The Amygdalo-Nigrostriatal Network Is Critical for an Optimal Temporal Performance

ERIC Educational Resources Information Center

Es-seddiqi, Mouna; El Massioui, Nicole; Samson, Nathalie; Brown, Bruce L.; Doyère, Valérie

2016-01-01

The amygdalo-nigrostriatal (ANS) network plays an essential role in enhanced attention to significant events. Interval timing requires attention to temporal cues. We assessed rats having a disconnected ANS network, due to contralateral lesions of the medial central nucleus of the amygdala (CEm) and dopaminergic afferents to the lateral striatum,…

Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease

PubMed Central

Betts, Matthew J; O'Neill, Michael J; Duty, Susan

2012-01-01

BACKGROUND AND PURPOSE We recently reported that broad spectrum agonist-induced activation of presynaptic group III metabotropic glutamate (mGlu) receptors within the substantia nigra pars compacta using L-2-amino-4-phosphonobutyrate provided functional neuroprotection in the 6-hydroxydopamine lesion rat model of Parkinson's disease. The aim of this study was to establish whether selective activation of the mGlu4 receptor alone could afford similar functional neuroprotection. EXPERIMENTAL APPROACH The neuroprotective effects of 8 days of supranigral treatment with a positive allosteric modulator of mGlu4 receptors, (+/−)-cis-2-(3,5-dichlorphenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041), were investigated in rats with unilateral 6-hydroxydopamine lesions. The effects of VU0155041 treatment on motor function were assessed using both habitual (cylinder test) and forced (adjusted stepping, amphetamine-induced rotations) behavioural tests. Nigrostriatal tract integrity was examined by analysis of tyrosine hydroxylase, dopa decarboxylase or dopamine levels in the striatum and tyrosine hydroxylase-positive cell counts in the substantia nigra pars compacta. KEY RESULTS VU0155041 provided around 40% histological protection against a unilateral 6-hydroxydopamine lesion as well as significant preservation of motor function. These effects were inhibited by pre-treatment with (RS)-α-cyclopropyl-4-phosphonophenylglycine, confirming a receptor-mediated response. Reduced levels of inflammatory markers were also evident in the brains of VU0155041-treated animals. CONCLUSIONS AND IMPLICATIONS Allosteric potentiation of mGlu4 receptors in the substantia nigra pars compacta provided neuroprotective effects in the 6-hydroxydopamine rat model A reduced inflammatory response may contribute, in part, to this action. In addition to the reported symptomatic effects, activation of mGlu4 receptors may also offer a novel approach for slowing the progressive degeneration observed in Parkinson's disease. PMID:22404342

Both pre- and post-lesion experiential therapy is beneficial in 6-hydroxydopamine dopamine-depleted female rats.

PubMed

Jadavji, N M; Metz, G A

2009-01-23

Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. Two groups of female rats were placed in an EE while two groups were housed in a standard environment (SE) for 6 weeks prior to receiving a unilateral nigrostriatal bundle infusion of the neurotoxin 6-hydroxydopamine. After the lesion, one group remained in EE, while the second EE group (Pre-Lesion EE) was moved into SE conditions. In addition, a third group of rats was now moved into EE (Post-lesion EE). A fourth group remained in SE throughout the experimental period. Rats were tested in skilled reaching and skilled walking tasks and in non-skilled motor function up to 4 weeks after lesion. The observations demonstrated beneficial effects of both pre- and post-lesion exposure to EE on skilled movement performance by promoting compensatory limb use and partial protection or restoration of skilled movement. Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat.

PubMed

Goldstein, L B

1997-01-01

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.

Silencing Alpha Synuclein in Mature Nigral Neurons Results in Rapid Neuroinflammation and Subsequent Toxicity

PubMed Central

Benskey, Matthew J.; Sellnow, Rhyomi C.; Sandoval, Ivette M.; Sortwell, Caryl E.; Lipton, Jack W.; Manfredsson, Fredric P.

2018-01-01

Human studies and preclinical models of Parkinson’s disease implicate the involvement of both the innate and adaptive immune systems in disease progression. Further, pro-inflammatory markers are highly enriched near neurons containing pathological forms of alpha synuclein (α-syn), and α-syn overexpression recapitulates neuroinflammatory changes in models of Parkinson’s disease. These data suggest that α-syn may initiate a pathological inflammatory response, however the mechanism by which α-syn initiates neuroinflammation is poorly understood. Silencing endogenous α-syn results in a similar pattern of nigral degeneration observed following α-syn overexpression. Here we aimed to test the hypothesis that loss of α-syn function within nigrostriatal neurons results in neuronal dysfunction, which subsequently stimulates neuroinflammation. Adeno-associated virus (AAV) expressing an short hairpin RNA (shRNA) targeting endogenous α-syn was unilaterally injected into the substantia nigra pars compacta (SNc) of adult rats, after which nigrostriatal pathology and indices of neuroinflammation were examined at 7, 10, 14 and 21 days post-surgery. Removing endogenous α-syn from nigrostriatal neurons resulted in a rapid up-regulation of the major histocompatibility complex class 1 (MHC-1) within transduced nigral neurons. Nigral MHC-1 expression occurred prior to any overt cell death and coincided with the recruitment of reactive microglia and T-cells to affected neurons. Following the induction of neuroinflammation, α-syn knockdown resulted in a 50% loss of nigrostriatal neurons in the SNc and a corresponding loss of nigrostriatal terminals and dopamine (DA) concentrations within the striatum. Expression of a control shRNA did not elicit any pathological changes. Silencing α-syn within glutamatergic neurons of the cerebellum did not elicit inflammation or cell death, suggesting that toxicity initiated by α-syn silencing is specific to DA neurons. These data provide evidence that loss of α-syn function within nigrostriatal neurons initiates a neuronal-mediated neuroinflammatory cascade, involving both the innate and adaptive immune systems, which ultimately results in the death of affected neurons. PMID:29497361

A Guide to Neurotoxic Animal Models of Parkinson’s Disease

PubMed Central

Tieu, Kim

2011-01-01

Parkinson’s disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway. PMID:22229125

Dopamine release in rat striatum - Physiological coupling to tyrosine supply

NASA Technical Reports Server (NTRS)

During, Matthew J.; Acworth, Ian N.; Wurtman, Richard J.

1989-01-01

Intracerebral microdialysis was used to monitor dopamine release in rat striatal extracellular fluid following the intraperitoneal administration of dopamine's precursor amino acid, L-tyrosine. Dopamine concentrations in dialysates increased transiently after tyrosine (50-100 mg/kg) administration. Pretreatment with haloperidol or the partial lesioning of nigrostriatal neurons enhanced the effect of tyrosine on dopamine release, and haloperidol also prolonged this effect. These data suggest that nigrostriatal dopaminergic neurons are responsive to changes in precursor availability under basal conditions, but that receptor-mediated feedback mechanisms limit the magnitude and duration of this effect.

Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death

PubMed Central

Wang, Yi-Ting; Lin, Hui-Ching; Zhao, Wei-Zhong; Huang, Hui-Ju; Lo, Yu-Li; Wang, Hsiang-Tsui; Maan-Yuh Lin, Anya

2017-01-01

Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson’s disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain. PMID:28401906

Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion

PubMed Central

Reyes-Corona, David; Vázquez-Hernández, Nallely; Escobedo, Lourdes; Orozco-Barrios, Carlos E.; Ayala-Davila, Jose; Moreno, Mario Gil; Amaro-Lara, Miriam E.; Flores-Martinez, Yazmin M.; Espadas-Alvarez, Armando J.; Fernandez-Parrilla, Manuel A.; Gonzalez-Barrios, Juan A.; Gutierrez-Castillo, ME; González-Burgos, Ignacio

2017-01-01

The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson’s disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system. We showed that the transgenic expression in dopaminergic neurons remained until the end of the study (12 weeks). Only animals expressing NRTN-His showed recovery of tyrosine hydroxylase (TH)+ cells (28 ± 2%), their neurites (32 ± 2%) and the neuron-specific cytoskeletal marker β-III-tubulin in the substantia nigra; striatal TH(+) fibers were also recovered (52 ± 3%), when compared to the healthy condition. Neurotensin receptor type 1 levels were also significantly recovered in the substantia nigra and striatum. Dopamine recovery was 70 ± 4% in the striatum and complete in the substantia nigra. The number of dendritic spines of striatal medium spiny neurons was also significantly increased, but the recovery was not complete. Drug-activated circling behavior decreased by 73 ± 2% (methamphetamine) and 89 ± 1% (apomorphine). Similar decrease was observed in the spontaneous motor behavior. Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion. However, those improvements did not reach the healthy condition, suggesting that NRTN exerts lesser neurotrophic effects than other neurotrophic approaches. PMID:29176874

Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion.

PubMed

Reyes-Corona, David; Vázquez-Hernández, Nallely; Escobedo, Lourdes; Orozco-Barrios, Carlos E; Ayala-Davila, Jose; Moreno, Mario Gil; Amaro-Lara, Miriam E; Flores-Martinez, Yazmin M; Espadas-Alvarez, Armando J; Fernandez-Parrilla, Manuel A; Gonzalez-Barrios, Juan A; Gutierrez-Castillo, M E; González-Burgos, Ignacio; Martinez-Fong, Daniel

2017-01-01

The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system. We showed that the transgenic expression in dopaminergic neurons remained until the end of the study (12 weeks). Only animals expressing NRTN-His showed recovery of tyrosine hydroxylase (TH)+ cells (28 ± 2%), their neurites (32 ± 2%) and the neuron-specific cytoskeletal marker β-III-tubulin in the substantia nigra; striatal TH(+) fibers were also recovered (52 ± 3%), when compared to the healthy condition. Neurotensin receptor type 1 levels were also significantly recovered in the substantia nigra and striatum. Dopamine recovery was 70 ± 4% in the striatum and complete in the substantia nigra. The number of dendritic spines of striatal medium spiny neurons was also significantly increased, but the recovery was not complete. Drug-activated circling behavior decreased by 73 ± 2% (methamphetamine) and 89 ± 1% (apomorphine). Similar decrease was observed in the spontaneous motor behavior. Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion. However, those improvements did not reach the healthy condition, suggesting that NRTN exerts lesser neurotrophic effects than other neurotrophic approaches.

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson's disease.

PubMed

Hoban, D B; Howard, L; Dowd, E

2015-09-10

Constraints involving the delivery method of glial cell line-derived neurotrophic factor (GDNF) have hampered its efficacy as a neuroprotectant in Parkinson's disease. Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), are genetically engineered to overexpress GDNF (GDNF-MSCs) prior to transplantation may be more beneficial than direct brain infusion of the neurotrophin. Previously, GDNF-MSCs have been assessed in the commonly employed 6-hydroxydopamine neurotoxic model of Parkinson's disease. In this study however, we used an emerging inflammatory model of Parkinson's disease (the lipopolysaccharide (LPS) model) to assess the ability of transplanted GDNF-MSCs to protect against LPS-induced neuroinflammation, neurodegeneration and behavioral impairment. Thirty male Sprague-Dawley rats were used in this experiment. Rats were performance matched based on baseline motor function tests into three groups (LPS lesion only, LPS lesion+GFP-MSCs, LPS lesion+GDNF-MSCs; n=10/group). Both cell groups received a unilateral intra-striatal transplant of either 200,000 GDNF-MSCs or 200,000 GFP-MSCs (as a control). One day post-transplantation, all rats received a unilateral intra-nigral infusion of LPS (10 μg in 2 μl sterile saline). Rats were sacrificed by transcardial perfusion-fixation and their brains were used for post mortem quantitative immunohistochemistry. Injection of LPS into the substantia nigra induced a pronounced local inflammatory response which resulted in 20% loss of nigrostriatal dopaminergic neurons and impaired contralateral motor function. Following transplantation of GDNF-MSCs to the striatum, dense areas of TH-positive staining directly proximal to the transplant site were observed. Most importantly, this effect was observed only in the GDNF-MSC transplanted group and not the GFP-MSC transplanted group demonstrating protection and/or sprouting of the dopaminergic terminals induced by the secreted GDNF. This study is the first to highlight the neurotrophic capability of GDNF in the inflammation-driven LPS model and, while future studies will endeavor to improve this approach by increasing cell survival, this work highlights the potential of GDNF delivery by ex vivo gene therapy using MSCs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease.

PubMed

Padel, Thomas; Özen, Ilknur; Boix, Jordi; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

2016-10-01

Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

PubMed

Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

2012-05-01

It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuronal network-based mathematical modeling of perceived verticality in acute unilateral vestibular lesions: from nerve to thalamus and cortex.

PubMed

Glasauer, S; Dieterich, M; Brandt, T

2018-05-29

Acute unilateral lesions of vestibular graviceptive pathways from the otolith organs and semicircular canals via vestibular nuclei and the thalamus to the parieto-insular vestibular cortex regularly cause deviations of perceived verticality in the frontal roll plane. These tilts are ipsilateral in peripheral and in ponto-medullary lesions and contralateral in ponto-mesencephalic lesions. Unilateral lesions of the vestibular thalamus or cortex cause smaller tilts of the perceived vertical, which may be either ipsilateral or contralateral. Using a neural network model, we previously explained why unilateral vestibular midbrain lesions rarely manifest with rotational vertigo. We here extend this approach, focussing on the direction-specific deviations of perceived verticality in the roll plane caused by acute unilateral vestibular lesions from the labyrinth to the cortex. Traditionally, the effect of unilateral peripheral lesions on perceived verticality has been attributed to a lesion-based bias of the otolith system. We here suggest, on the basis of a comparison of model simulations with patient data, that perceived visual tilt after peripheral lesions is caused by the effect of a torsional semicircular canal bias on the central gravity estimator. We further argue that the change of gravity coding from a peripheral/brainstem vectorial representation in otolith coordinates to a distributed population coding at thalamic and cortical levels can explain why unilateral thalamic and cortical lesions have a variable effect on perceived verticality. Finally, we propose how the population-coding network for gravity direction might implement the elements required for the well-known perceptual underestimation of the subjective visual vertical in tilted body positions.

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

PubMed

Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

PubMed

Scheck, Simon M; Pannek, Kerstin; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

2014-10-01

The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions. © 2014 Mac Keith Press.

Unilateral hippocampal inactivation or lesion selectively impairs remote contextual fear memory.

PubMed

Zhou, Heng; Zhou, Qixin; Xu, Lin

2016-10-01

Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.

Characteristics of learning voluntary control of posture in lesions of the pyramidal and nigrostriatal systems.

PubMed

Ioffe, M E; Ustinova, K I; Chernikova, L A; Luk'yanova, Yu A; Ivanova-Smolenskaya, I A; Kulikov, M A

2004-07-01

The aim of the study reported here was to investigate impairments on the learning of voluntary control of the center of pressures using visual feedback in patients with lesions of the corticospinal and nigrostriatal systems. Participants were 33 patients with Parkinson's disease and 20 patients with hemipareses due to circulatory lesions in the basin of the middle cerebral artery. Subjects stood on a stabilometric platform and used two computer games over 10 days to learn to shift the body relative to the foot to move the centre of pressures, indicated by the position of a cursor on the screen, with the target and to move the target to a specified part of the screen. The games differed in terms of the postural tasks. In one, the direction of movement of the center of pressures was not known to the subjects, and subjects learned a general strategy for posture control; the other formed a strictly defined postural coordination. Both groups of patients were found to have impairments of voluntary control of the position of the center of pressures. There were no differences between groups of patients, in terms of the severity of the initial performance deficit in the task involving shifts of the center of pressures in different directions (the general strategy for controlling the center of pressures), while learning of this task was more difficult for patients with Parkinson's disease. The initial deficit in the fine postural coordination task was more marked in patients with Parkinsonism, though learning in these patients was significantly better than in patients with hemipareses. It is suggested that the mechanisms of involvement of the nigrostriatal and corticospinal systems in learning the voluntary control of posture have elements in common as well as unique elements.

beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

PubMed Central

Cowen, P. J.; Grahame-Smith, D. G.; Green, A. R.; Heal, D. J.

1982-01-01

The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg) and the combination of tranylcypromine (10 mg/kg) and L-tryptophan (50 mg/kg). Salbutamol and terbutaline potentiated quipazine-induced hyperactivity only when given at the higher dose of 20 mg/kg. 3 The effect of clenbuterol in enhancing quipazine hyperactivity was blocked by the centrally acting beta 1-adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the beta 2-adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting beta 1-adrenoceptor antagonist, atenolol (5 mg/kg). 4 Clenbuterol (5 mg/kg) did not enhance the circling responses produced by methamphetamine (0.5 mg/kg) in unilateral nigrostriatal-lesioned rats. 5 The results suggest that beta-adrenoceptor agonists in common with some established antidepressant treatments produce enhancement of 5-HT-mediated behavioural responses. PMID:6124294

Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion

PubMed Central

Plowman, Emily K.; Maling, Nicholas; Rivera, Benjamin J.; Larson, Krista; Thomas, Nagheme J.; Fowler, Stephen C.; Manfredsson, Fredric P.; Shrivastav, Rahul; Kleim, Jeffrey A.

2012-01-01

The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n = 20) or control (n = 20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson’s disease are more effective for limb motor symptoms than cranial motor impairments. PMID:23018122

Effects of WR1065 on 6-hydroxydopamine-induced motor imbalance: Possible involvement of oxidative stress and inflammatory cytokines.

PubMed

Kheradmand, Afshin; Nayebi, Alireza M; Jorjani, Masoumeh; Khalifeh, Solmaz; Haddadi, Rasool

2016-08-03

Over production of reactive oxygen species (ROS) is postulated to be the main contributor in degeneration of nigrostriatal dopaminergic neurons. In this study we investigated the effects of WR1065, a free radical scavenger, on motor imbalance, oxidative stress parameters and inflammatory cytokines in CSF and brain of hemi-parkinsonian rats. Lesion of dopaminergic neurons was done by unilateral infusion of 6-hydroxydopamine into the central region of the substentia nigra pars compacta (SNc) to induce hemi-parkinsonism and motor imbalance in rats. WR1065 (20, 40 and 80μg/2μl/rat) was administered three days before 6-OHDA administration. After three weeks behavioral study was performed and then brain and CSF samples were collected to assess tumor necrosis factor (TNFα), interlukin (IL-1β), reduced glutathione (GSH), and malondialdehyde (MDA). WR1065 pre-treatment in rats before receiving 6-OHDA, improved significantly motor impairment and caused reduction of MDA and inflammatory cytokines TNFα and IL-1β levels, while GSH level significantly increased when compared with lesioned rats. Our study indicated that WR1065 could improve 6-OHDA-induced motor imbalance. Furthermore, it decreased lipid peroxidation and inflammatory cytokines and restored the level of GSH up to normal range. We suggest that WR1065 can be proposed as a potential neuroprotective agent in motor impairments of PD. However to prove this hypothesis more clinical trial studies should be done. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

PubMed

Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

2017-05-01

Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

PubMed

Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

2014-12-01

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

Differences Between Bilateral Adrenal Incidentalomas and Unilateral Lesions.

PubMed

Pasternak, Jesse D; Seib, Carolyn D; Seiser, Natalie; Tyrell, J Blake; Liu, Chienying; Cisco, Robin M; Gosnell, Jessica E; Shen, Wen T; Suh, Insoo; Duh, Quan-Yang

2015-10-01

Adrenal incidentalomas are found in 1% to 5% of abdominal cross-sectional imaging studies. Although the workup and management of unilateral lesions are well established, limited information exists for bilateral incidentalomas. To compare the natural history of patients having bilateral incidentalomas with those having unilateral incidentalomas. Retrospective analysis of a prospective database of consecutive patients referred to an academic multidisciplinary adrenal conference. The setting was a tertiary care university hospital among a cohort of 500 patients with adrenal lesions between July 1, 2009, and July 1, 2014. Prevalence, age, imaging characteristics, biochemical workup, any intervention, and final diagnosis. Twenty-three patients with bilateral incidentalomas and 112 patients with unilateral incidentalomas were identified. The mean age at diagnosis of bilateral lesions was 58.7 years. The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side. Bilateral incidentalomas were associated with a significantly higher prevalence of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009) and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6% [22 of 112]) (P = .003) compared with unilateral lesions, while rates of hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of 112]) (P > .99). Only one patient with bilateral incidentalomas underwent unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years). There were no occult adrenocortical carcinomas. Bilateral incidentalomas are more likely to be associated with subclinical Cushing syndrome and less likely to be pheochromocytomas. Although patients with bilateral incidentalomas undergo a workup similar to that in patients with unilateral lesions, differences in their natural history warrant a greater index of suspicion for subclinical Cushing syndrome.

A Case of Generalized Auditory Agnosia with Unilateral Subcortical Brain Lesion

PubMed Central

Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

2012-01-01

The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322

Chronic Nicotine Treatment Increases nAChRs and Microglial Expression in Monkey Substantia Nigra after Nigrostriatal Damage

PubMed Central

Campos, Carla; Parameswaran, Neeraja; William Langston, J.; Michael McIntosh, J.; Yeluashvili, Michael

2010-01-01

Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose MPTP for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in α3/α6β2* and α4β2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson’s disease. PMID:19685015

What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson's disease?

PubMed Central

Magnard, R; Vachez, Y; Carcenac, C; Krack, P; David, O; Savasta, M; Boulet, S; Carnicella, S

2016-01-01

In addition to classical motor symptoms, Parkinson's disease (PD) patients display incapacitating neuropsychiatric manifestations, such as apathy, anhedonia, depression and anxiety. These hitherto generally neglected non-motor symptoms, have gained increasing interest in medical and scientific communities over the last decade because of the extent of their negative impact on PD patients' quality of life. Although recent clinical and functional imaging studies have provided useful information, the pathophysiology of apathy and associated affective impairments remains elusive. Our aim in this review is to summarize and discuss recent advances in the development of rodent models of PD-related neuropsychiatric symptoms using neurotoxin lesion-based approaches. The data collected suggest that bilateral and partial lesions of the nigrostriatal system aimed at inducing reliable neuropsychiatric-like deficits while avoiding severe motor impairments that may interfere with behavioral evaluation, is a more selective and efficient strategy than medial forebrain bundle lesions. Moreover, of all the different classes of pharmacological agents, D2/D3 receptor agonists such as pramipexole appear to be the most efficient treatment for the wide range of behavioral deficits induced by dopaminergic lesions. Lesion-based rodent models, therefore, appear to be relevant tools for studying the pathophysiology of the non-motor symptoms of PD. Data accumulated so far confirm the causative role of dopaminergic depletion, especially in the nigrostriatal system, in the development of behavioral impairments related to apathy, depression and anxiety. They also put forward D2/D3 receptors as potential targets for the treatment of such neuropsychiatric symptoms in PD. PMID:26954980

Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation.

PubMed

Faure, Alexis; Haberland, Ulrike; Condé, Françoise; El Massioui, Nicole

2005-03-16

Acquisition and performance of instrumental actions are assumed to require both action-outcome and stimulus-response (S-R) habit processes. Over the course of extended training, control over instrumental performance shifts from goal-directed action-outcome associations to S-R associations that progressively gain domination over behavior. Lesions of the lateral part of the dorsal striatum disrupt this process, and rats with lesions to the lateral striatum showed selective sensitivity to devaluation of the instrumental outcome (Yin et al., 2004), indicating that this area is necessary for habit formation. The present experiment further explored the basis of this dysfunction by examining the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway to develop behavioral autonomy with overtraining. Rats were given extended training on two cued instrumental tasks associating a stimulus (a tone or a light) with an instrumental action (lever press or chain pull) and a food reward (pellets or sucrose). Both tasks were run daily in separate sessions. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. In control animals, one action (lever press) was insensitive to reward devaluation, indicating that it became a habit, whereas the second action (chain pull) was still sensitive to goal devaluation. This result provides evidence that the development of habit learning may depend on the characteristics of the response. In dopamine-depleted rats, lever press and chain pull remained sensitive to reward devaluation, evidencing a role of striatal dopamine transmission in habit formation.

Unilateral Superior Laryngeal Nerve Lesion in an Animal Model of Dysphagia and Its Effect on Sucking and Swallowing

PubMed Central

Campbell-Malone, Regina; Holman, Shaina D.; Lukasik, Stacey L.; Fukuhara, Takako; Gierbolini-Norat, Estela M.; Thexton, Allan J.; German, Rebecca Z.

2013-01-01

We tested two hypotheses relating to the sensory deficit that follows a unilateral superior laryngeal nerve (SLN) lesion in an infant animal model. We hypothesized that it would result in (1) a higher incidence of aspiration and (2) temporal changes in sucking and swallowing. We ligated the right-side SLN in six 2–3-week-old female pigs. Using videofluoroscopy, we recorded swallows in the same pre- and post-lesion infant pigs. We analyzed the incidence of aspiration and the duration and latency of suck and swallow cycles. After unilateral SLN lesioning, the incidence of silent aspiration during swallowing increased from 0.7 to 41.5 %. The durations of the suck containing the swallow, the suck immediately following the swallow, and the swallow itself were significantly longer in the post-lesion swallows, although the suck prior to the swallow was not different. The interval between the start of the suck containing a swallow and the subsequent epiglottal movement was longer in the post-lesion swallows. The number of sucks between swallows was significantly greater in post-lesion swallows compared to pre-lesion swallows. Unilateral SLN lesion increased the incidence of aspiration and changed the temporal relationships between sucking and swallowing. The longer transit time and the temporal coordinative dysfunction between suck and swallow cycles may contribute to aspiration. These results suggest that swallow dysfunction and silent aspiration are common and potentially overlooked sequelae of unilateral SLN injury. This validated animal model of aspiration has the potential for further dysphagia studies. PMID:23417250

Hand Function in Relation to Brain Lesions and Corticomotor-Projection Pattern in Children with Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

Holmstrom, Linda; Vollmer, Brigitte; Tedroff, Kristina; Islam, Mominul; Persson, Jonas Ke; Kits, Annika; Forssberg, Hans; Eliasson, Ann-Christin

2010-01-01

Aim: To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). Method: The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7-16y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability…

Gaze Behaviour during Interception in Children with Spastic Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

van Kampen, P. M.; Ledebt, A.; Smorenburg, A. R. P.; Vermeulen, R. J.; Kelder, M. E.; van der Kamp, J.; Savelsbergh, G. J. P.

2012-01-01

Anticipatory gaze behaviour during interceptive movements was investigated in children with Spastic Unilateral Cerebral Palsy (SUCP), and related to the side of the intracerebral lesion. Five children with lesions of the right hemisphere (RHL) and five children with lesions of the left hemisphere (LHL) had to walk towards and intercept a ball that…

Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Takahashi, Reinaldo N; Bertoglio, Leandro J; Cunha, Rodrigo A; Prediger, Rui D

2016-08-01

The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). The nigrostriatal dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC), which has been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Using behavioral, neurochemical, and electrophysiological approaches, we investigated the temporal dissociation between the role of the DLS and PFC in the appearance of anhedonia and defense behaviors relevant to depression in rats submitted to bilateral DLS lesions with 6-hydroxydopamine (6-OHDA; 10 μg/hemisphere). 6-OHDA induced partial dopaminergic nigrostriatal damage with no gross motor impairments. Anhedonic-like behaviors were observed in the splash and sucrose consumption tests only 7 days after 6-OHDA lesion. By contrast, defense behaviors relevant to depression evaluated in the forced swimming test and social withdrawal only emerged 21 days after 6-OHDA lesion when anhedonia was no longer present. These temporally dissociated behavioral alterations were coupled to temporal- and structure-dependent alterations in dopaminergic markers such as dopamine D1 and D2 receptors and dopamine transporter, leading to altered dopamine sensitivity in DLS and PFC circuits, evaluated electrophysiologically. These results provide the first demonstration of a dissociated involvement of the DLS and PFC in anhedonic-like and defense behaviors relevant to depression in 6-OHDA-lesioned rats, which was linked with temporal fluctuations in dopaminergic receptor density, leading to altered dopaminergic system sensitivity in these two brain structures. This sheds new light to the duality between depressive and anhedonic symptoms in PD.

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

PubMed Central

Rousseaux, Maxime W. C.; Marcogliese, Paul C.; Qu, Dianbo; Hewitt, Sarah J.; Seang, Sarah; Kim, Raymond H.; Slack, Ruth S.; Schlossmacher, Michael G.; Lagace, Diane C.; Mak, Tak W.; Park, David S.

2012-01-01

DJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse. A subset of DJ-1–nullizygous mice, when fully backcrossed to a C57BL/6J background, display dramatic early-onset unilateral loss of dopaminergic (DA) neurons in their substantia nigra pars compacta, progressing to bilateral degeneration of the nigrostriatal axis with aging. In addition, these mice exhibit age-dependent bilateral degeneration at the locus ceruleus nucleus and display mild motor behavior deficits at aged time points. These findings effectively recapitulate the early stages of PD. Therefore, the DJ1-C57 mouse provides a tool to study the preclinical aspects of neurodegeneration. Importantly, by exome sequencing, we identify candidate modifying genes that segregate with the phenotype, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice. PMID:23019375

Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying conditional learning.

PubMed

Dumont, Julie R; Petrides, Michael; Sziklas, Viviane

2010-05-01

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.

Use of prism adaptation in children with unilateral brain lesion: Is it feasible?

PubMed

Riquelme, Inmaculada; Henne, Camille; Flament, Benoit; Legrain, Valéry; Bleyenheuft, Yannick; Hatem, Samar M

2015-01-01

Unilateral visuospatial deficits have been observed in children with brain damage. While the effectiveness of prism adaptation for treating unilateral neglect in adult stroke patients has been demonstrated previously, the usefulness of prism adaptation in a pediatric population is still unknown. The present study aims at evaluating the feasibility of prism adaptation in children with unilateral brain lesion and comparing the validity of a game procedure designed for child-friendly paediatric intervention, with the ecological task used for prism adaptation in adult patients. Twenty-one children with unilateral brain lesion randomly were assigned to a prism group wearing prismatic glasses, or a control group wearing neutral glasses during a bimanual task intervention. All children performed two different bimanual tasks on randomly assigned consecutive days: ecological tasks or game tasks. The efficacy of prism adaptation was measured by assessing its after-effects with visual open loop pointing (visuoproprioceptive test) and subjective straight-ahead pointing (proprioceptive test). Game tasks and ecological tasks produced similar after-effects. Prismatic glasses elicited a significant shift of visuospatial coordinates which was not observed in the control group. Prism adaptation performed with game tasks seems an effective procedure to obtain after-effects in children with unilateral brain lesion. The usefulness of repetitive prism adaptation sessions as a therapeutic intervention in children with visuospatial deficits and/or neglect, should be investigated in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson’s is associated with histone acetylation and up-regulation of neurotrophic factors

PubMed Central

Harrison, Ian F; Crum, William R; Vernon, Anthony C; Dexter, David T

2015-01-01

Background and Purpose Histone hypoacetylation is associated with Parkinson's disease (PD), due possibly to an imbalance in the activities of enzymes responsible for histone (de)acetylation; correction of which may be neuroprotective/neurorestorative. This hypothesis was tested using the anti-epileptic drug sodium valproate, a known histone deacetylase inhibitor (HDACI), utilizing a delayed-start study design in the lactacystin rat model of PD. Experimental Approach The irreversible proteasome inhibitor lactacystin was unilaterally injected into the substantia nigra of Sprague–Dawley rats that subsequently received valproate for 28 days starting 7 days after lactacystin lesioning. Longitudinal motor behavioural testing, structural MRI and post-mortem assessment of nigrostriatal integrity were used to track changes in this model of PD and quantify neuroprotection/restoration. Subsequent cellular and molecular analyses were performed to elucidate the mechanisms underlying valproate's effects. Key Results Despite producing a distinct pattern of structural re-modelling in the healthy and lactacystin-lesioned brain, delayed-start valproate administration induced dose-dependent neuroprotection/restoration against lactacystin neurotoxicity, characterized by motor deficit alleviation, attenuation of morphological brain changes and restoration of dopaminergic neurons in the substantia nigra. Molecular analyses revealed that valproate alleviated lactacystin-induced histone hypoacetylation and induced up-regulation of brain neurotrophic/neuroprotective factors. Conclusions and Implications The histone acetylation and up-regulation of neurotrophic/neuroprotective factors associated with valproate treatment culminate in a neuroprotective and neurorestorative phenotype in this animal model of PD. As valproate induced structural re-modelling of the brain, further research is required to determine whether valproate represents a viable candidate for disease treatment; however, the results suggest that HDACIs could hold potential as disease-modifying agents in PD. PMID:26040297

Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson’s Disease

PubMed Central

Hsueh, Shih-Chang; Lai, Jing-Huei; Wu, Chung-Che; Yu, Yu-Wen; Luo, Yu; Hsieh, Tsung-Hsun; Chiang, Yung-Hsiao

2018-01-01

Background: Parkinson’s disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. Methods: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. Results: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. Conclusions: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH), Brain-derived neurotrophic factor (BDNF), bone marrow tyrosine kinase in chromosome X (BMX) protein expression level without affecting dopaminergic (DA) neuron loss in this PD rat model. PMID:29419747

Striatal Pleiotrophin Overexpression Provides Functional and Morphological Neuroprotection in the 6-Hydroxydopamine Model

PubMed Central

Gombash, Sara E; Lipton, Jack W; Collier, Timothy J; Madhavan, Lalitha; Steece-Collier, Kathy; Cole-Strauss, Allyson; Terpstra, Brian T; Spieles-Engemann, Anne L; Daley, Brian F; Wohlgenant, Susan L; Thompson, Valerie B; Manfredsson, Fredric P; Mandel, Ronald J; Sortwell, Caryl E

2012-01-01

Neurotrophic factors are integrally involved in the development of the nigrostriatal system and in combination with gene therapy, possess great therapeutic potential for Parkinson's disease (PD). Pleiotrophin (PTN) is involved in the development, maintenance, and repair of the nigrostriatal dopamine (DA) system. The present study examined the ability of striatal PTN overexpression, delivered via psueudotyped recombinant adeno-associated virus type 2/1 (rAAV2/1), to provide neuroprotection and functional restoration from 6-hydroxydopamine (6-OHDA). Striatal PTN overexpression led to significant neuroprotection of tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc) and THir neurite density in the striatum, with long-term PTN overexpression producing recovery from 6-OHDA-induced deficits in contralateral forelimb use. Transduced striatal PTN levels were increased threefold compared to adult striatal PTN expression and approximated peak endogenous developmental levels (P1). rAAV2/1 vector exclusively transduced neurons within the striatum and SNpc with approximately half the total striatal volume routinely transduced using our injection parameters. Our results indicate that striatal PTN overexpression can provide neuroprotection for the 6-OHDA lesioned nigrostriatal system based upon morphological and functional measures and that striatal PTN levels similar in magnitude to those expressed in the striatum during development are sufficient to provide neuroprotection from Parkinsonian insult. PMID:22008908

Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

PubMed

Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

2007-04-01

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

PubMed

Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

2016-12-01

Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). H max (H-wave maximum amplitude)/M max (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

Protective effect of resveratrol against nigrostriatal pathway injury in striatum via JNK pathway.

PubMed

Li, Dan; Liu, Nan; Zhao, Liang; Tong, Lei; Kawano, Hitoshi; Yan, Hong-Jing; Li, Hong-Peng

2017-01-01

Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot. Prior to the injury, mice were infused with resveratrol intracerebroventricularly with or without JNK-IN-8, a specific c-JNK pathway inhibitor for JNK1, JNK2 and JNK4. The study assessed modified improved neurological function score (mNSS) and beam/walking test, the level of inflammatory cytokines IL-1β, IL-6 and TNF-α, and striatal expression of Bax and Bcl-2 proteins associated with neuronal apoptosis. The results revealed that resveratrol exerted a neuroprotective effect as shown by the improved mNSS and beam latency, anti-inflammatory effects as indicated by the decreased level of IL-1β, TNF-α and IL-6. Furthermore, resveratrol up-regulated the protein expression of p-JNK and Bcl-2, down-regulated the expression of Bax and the number of Fluoro-Jade C (FJC) positive neurons. However, these advantages of resveratrol were abolished by JNK-IN-8 treatment. Overall, we demonstrated that resveratrol treatment attenuates the nigrostriatal pathway injury-induced neuronal apoptosis and inflammation via activation of c-JNK signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

Behavioural and biochemical responses following activation of midbrain dopamine pathways by receptor selective neurokinin agonists.

PubMed

Elliott, P J; Mason, G S; Stephens-Smith, M; Hagan, R M

1991-06-01

Preferential activation of mesolimbic and nigro-striatal dopamine (DA) pathways by receptor-selective and peptidase-resistant neurokinin (NK) agonists is reported. The DA cell body region of the mesolimbic pathway appears to be activated by NK agonists selective for NK-1 and NK-3 receptors whereas the DA cell bodies in the substantia nigra are under an excitatory NK-2 receptor-mediated influence. Stimulation of the mesolimbic DA pathway by NK-1 (Ava[L-Pro9,N-Me-Leu10]SP (7-11) [GR73632]) or NK-3 (Senktide) agonists increase locomotor activity. Additional studies showed that this elevated motor response observed after intra-VTA infusion of GR73632 was accompanied by a corresponding increase in DA turnover in the terminal fields of this pathway. Similarly, unilateral activation of the nigro-striatal DA pathway by NK-2 selective agonists (Ava (D-Pro9) SP (7-11) [GR51667] or [Lys3,Gly8,R-Lac-Leu9]NKA (3-10) [GR64349]) elicit contralateral rotational activity and an increase in DA turnover in the ipsilateral striatum. The rotational response was attenuated by prior administration of an NK-2 antagonist (cyclo (Gln, Trp, Phe, Gly, Leu, Met)] L-659877]) into the nigra. Peripheral injection of haloperidol, a DA antagonist, also blocked the NK-2 agonist induced rotations.

A Japanese Encephalitis Patient Presenting with Parkinsonism with Corresponding Laterality of Magnetic Resonance and Dopamine Transporter Imaging Findings.

PubMed

Tadokoro, Koh; Ohta, Yasuyuki; Sato, Kota; Maeki, Takahiro; Sasaki, Ryo; Takahashi, Yoshiaki; Shang, Jingwei; Takemoto, Mami; Hishikawa, Nozomi; Yamashita, Toru; Lim, Chang Kweng; Tajima, Shigeru; Abe, Koji

2018-03-09

Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using 123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ( 123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE.

Nicotine Reduces l-DOPA-Induced Dyskinesias by Acting at β2* Nicotinic Receptors

PubMed Central

Huang, Luping Z.; Grady, Sharon R.

2011-01-01

l-DOPA-induced dyskinesias or abnormal involuntary movements (AIMs) are a debilitating adverse complication associated with prolonged l-DOPA administration for Parkinson's disease. Few treatments are currently available for dyskinesias. Our recent data showed that nicotine reduced l-DOPA-induced AIMs in parkinsonian animal models. An important question is the nicotinic acetylcholine receptor (nAChR) subtypes through which nicotine exerts this beneficial effect, because such knowledge would allow for the development of drugs that target the relevant receptor population(s). To address this, we used β2 nAChR subunit knockout [β2(−/−)] mice because β2-containing nAChRs are key regulators of nigrostriatal dopaminergic function. All of the mice were lesioned by intracranial injection of 6-hydroxydopamine into the right medial forebrain bundle. Lesioning resulted in a similar degree of nigrostriatal damage and parkinsonism in β2(−/−) and wild-type mice. All of the mice then were injected with l-DOPA (3 mg/kg) plus benserazide (15 mg/kg) once daily for 4 weeks until AIMs were fully developed. l-DOPA-induced AIMs were approximately 40% less in the β2(−/−) mice compared with the wild-type mice. It is interesting to note that nicotine (300 μg/ml in drinking water) reduced l-DOPA-induced AIMs by 40% in wild-type mice but had no effect in β2(−/−) mice with partial nigrostriatal damage. The nicotine-mediated decline in AIMs was much less pronounced in wild-type mice with near-complete degeneration, suggesting that presynaptic nAChRs on dopaminergic terminals have a major influence. These data demonstrate an essential role for β2* nAChRs in the antidyskinetic effect of nicotine and suggest that drugs targeting these subtypes may be useful for the management of l-DOPA-induced dyskinesias in Parkinson's disease. PMID:21665941

Consequences of partial and severe dopaminergic lesion on basal ganglia oscillatory activity and akinesia.

PubMed

Tseng, Kuei Y; Kargieman, Lucila; Gacio, Sebastian; Riquelme, Luis A; Murer, M Gustavo

2005-11-01

Severe chronic dopamine (DA) depletion increases the proportion of neurons in the basal ganglia that fire rhythmic bursts of action potential (LFO units) synchronously with the cortical oscillations. Here we report on how different levels of mesencephalic DA denervation affect substantia nigra pars reticulata (SNpr) neuronal activity in the rat and its relationship to akinesia (stepping test). Chronic nigrostriatal lesion induced with 0 (control group), 4, 6 or 8 microg of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle resulted in a dose-dependent decrease of tyrosine hydroxylase positive (TH+) neurons in the SN and ventral tegmental area (VTA). Although 4 microg of 6-OHDA reduced the number of TH+ neurons in the SN by approximately 60%, both stepping test performance and SNpr neuronal activity remained indistinguishable from control animals. By contrast, animals that received 6 microg of 6-OHDA showed a marked reduction of TH+ cells in the SN ( approximately 75%) and VTA ( approximately 55%), a significant stepping test deficit and an increased proportion of LFO units. These changes were not dramatically enhanced with 8 microg 6-OHDA, a dose that induced an extensive DA lesion (> 95%) in the SN and approximately 70% reduction of DA neurons in the VTA. These results suggest a threshold level of DA denervation for both the appearance of motor deficits and LFO units. Thus, the presence of LFO activity in the SNpr is not related to a complete nigrostriatal DA neuron depletion (ultimate stage parkinsonism); instead, it may reflect a functional disruption of cortico-basal ganglia dynamics associated with clinically relevant stages of the disease.

Partial dopaminergic denervation-induced impairment in stimulus discrimination acquisition in parkinsonian rats: a model for early Parkinson's disease.

PubMed

Eagle, Andrew L; Olumolade, Oluyemi O; Otani, Hajime

2015-03-01

Parkinson's disease (PD) produces progressive nigrostriatal dopamine (DA) denervation resulting in cognitive and motor impairment. However, it is unknown whether cognitive impairments, such as instrumental learning deficits, are associated with the early stage PD-induced mild DA denervation. The current study sought to model early PD-induced instrumental learning impairments by assessing the effects of low dose (5.5μg), bilateral 6OHDA-induced striatal DA denervation on acquisition of instrumental stimulus discrimination in rats. 6OHDA (n=20) or sham (n=10) lesioned rats were tested for stimulus discrimination acquisition either 1 or 2 weeks post surgical lesion. Stimulus discrimination acquisition across 10 daily sessions was used to assess discriminative accuracy, or a probability measure of the shift toward reinforced responding under one stimulus condition (Sd) away from extinction, when reinforcement was withheld, under another (S(d) phase). Striatal DA denervation was assayed by tyrosine hydroxylase (TH) staining intensity. Results indicated that 6OHDA lesions produced significant loss of dorsal striatal TH staining intensity and marked impairment in discrimination acquisition, without inducing akinetic motor deficits. Rather 6OHDA-induced impairment was associated with perseveration during extinction (S(Δ) phase). These findings suggest that partial, bilateral striatal DA denervation produces instrumental learning deficits, prior to the onset of gross motor impairment, and suggest that the current model is useful for investigating mild nigrostriatal DA denervation associated with early stage clinical PD. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

PubMed

Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

2014-01-01

Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Behavioural changes induced by N,N-dimethyl-tryptamine in rodents.

PubMed Central

Jenner, P.; Marsden, C. D.; Thanki, C. M.

1980-01-01

1 N,N-Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose-dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking. 2 In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by L-tryptophan or quipazine, in the lack of forepaw treading and head-weaving and in the presence of only mild tremor. 3 The hyperactivity component of the DMT-induced behavioural syndrome in pargyline-pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67-sulphate and methysergide. 4 The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration. 5 DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6-hydroxy-dopamine lesion of the nigro-striatal pathway. 6 The DMT-induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5-hydroxytryptamine function. PMID:6769527

Nigrostriatal proteasome inhibition impairs dopamine neurotransmission and motor function in minipigs.

PubMed

Lillethorup, Thea P; Glud, Andreas N; Alstrup, Aage K O; Mikkelsen, Trine W; Nielsen, Erik H; Zaer, Hamed; Doudet, Doris J; Brooks, David J; Sørensen, Jens Christian H; Orlowski, Dariusz; Landau, Anne M

2018-05-01

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We translated this model to the Göttingen minipig by administering lactacystin into the medial forebrain bundle (MFB). Minipigs underwent positron emission tomography (PET) imaging with (+)-α-[ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a marker of vesicular monoamine transporter 2 availability, at baseline and three weeks after the unilateral administration of 100 μg lactacystin into the MFB. Compared to their baseline values, minipigs injected with lactacystin showed on average a 36% decrease in ipsilateral striatal binding potential corresponding to impaired presynaptic dopamine terminals. Behaviourally, minipigs displayed asymmetrical motor disability with spontaneous rotations in one of the animals. Immunoreactivity for tyrosine hydroxylase (TH) and HLA-DR-positive microglia confirmed asymmetrical reduction in nigral TH-positive neurons with an inflammatory response in the lactacystin-injected minipigs. In conclusion, direct injection of lactacystin into the MFB of minipigs provides a model of PD with reduced dopamine neurotransmission, TH-positive neuron reduction, microglial activation and behavioural deficits. This large animal model could be useful in studies of symptomatic and neuroprotective therapies with translatability to human PD. Copyright © 2018 Elsevier Inc. All rights reserved.

Fibroblast growth factor 20 is protective towards dopaminergic neurons in vivo in a paracrine manner.

PubMed

Boshoff, Eugene L; Fletcher, Edward J R; Duty, Susan

2018-04-23

Neuroprotective strategies are an unmet medical need for Parkinson's disease. Fibroblast growth factor 20 (FGF20) enhances survival of cultured dopaminergic neurons but little is known about its in vivo potential. We set out to examine whether manipulation of the FGF20 system affected nigrostriatal tract integrity in rats, to identify which fibroblast growth factor receptors (FGFRs) might reside on dopaminergic neurons and to discover the source of endogenous FGF20 in the substantia nigra (SN). Male Sprague Dawley rats were subject to a partial 6-OHDA lesion alongside treatment with exogenous FGF20 or an FGFR antagonist. Behavioural readouts and tyrosine-hydroxylase (TH) immunohistochemistry were used to evaluate nigrostriatal tract integrity. Fluorescent immunohistochemistry was used to examine FGFR subtype expression on TH-positive dopamine neurons and FGF20 cellular localisation within the SN. FGF20 (2.5 μg/day) significantly protected TH-positive cells in the SN and terminals in the striatum, while reducing the development of motor asymmetry at 5, 8 and 11 days post lesion. Conversely, the FGFR antagonist PD173074 (2 mg/kg) significantly worsened both the 6-OHDA lesion and resultant motor asymmetry. Within the SN, TH-positive cells expressed FGFR1, 3 and 4 while FGF20 co-localised with GFAP-positive astrocytes. In conclusion, FGF20 protects dopaminergic neurons in vivo, an action likely mediated through activation of FGFRs1, 3 or 4 found on these neurons. Given FGF20 is localised to astrocytes in the adult SN, endogenous FGF20 provides its protection of dopamine neurons through a paracrine action. Boosting the endogenous FGF20 production might offer potential as a future therapeutic strategy in Parkinson's disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

PubMed Central

Pannek, Kerstin; Boyd, Roslyn N.; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E.

2014-01-01

Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention. PMID:25003031

Unilateral giant cell lesion of the jaw in Noonan syndrome.

PubMed

Eyselbergs, M; Vanhoenacker, F; Hintjens, J; Dom, M; Devriendt, K; Van Dijck, H

2014-01-01

Noonan syndrome (NS) is an etiologically heterogeneous disorder caused by mutations in the RAS-MAPK signaling pathway. Noonan-Like/Multiple Giant Cell Lesion (NL/MGCL) syndrome is initially described as the occurrence of multiple gnathic giant cell lesions in patients with phenotypic features of NS. Nowadays, NS/MGCL syndrome is considered a variant of the NS spectrum rather than a distinct entity. We report the case of a 14-year-old female patient carrying a SOS1 mutation with a unilateral giant cell lesion of the right mandible. Cross-sectional imaging such as CT and MRI are not specific for the diagnosis of oral giant cell lesions. Nonetheless, intralesional scattered foci of low SI on T2-WI, corresponding to hemosiderin deposits due to hemorrhage, can help the radiologist in narrowing down the differential diagnosis of gnathic lesions in patients with NS.

A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions.

PubMed

Ikeda, Shigaku; Kawada, Juri; Yaguchi, Hitoshi; Ogawa, Hideoki

2003-01-01

Multiple hair follicle nevi are an extremely rare condition. In 1998, a case of unilateral multiple hair follicle nevi, ipsilateral alopecia and ipsilateral leptomeningeal angiomatosis of the brain was first reported from Japan. Very recently, hair follicle nevus in a distribution following Blaschko's lines has also been reported. In this paper, we observed a congenital case of unilateral, systematized linear hair follicle nevi associated with congenital, ipsilateral, multiple plaque lesions resembling epidermal nevi but lacking leptomeningeal angiomatosis of the brain. These cases implicate the possibility of a novel neurocutaneous syndrome. Additional cases should be sought in order to determine whether this condition is pathophysiologically distinct. Copyright 2003 S. Karger AG, Basel

The Metabotropic Glutamate Receptor 4-Positive Allosteric Modulator VU0364770 Produces Efficacy Alone and in Combination with l-DOPA or an Adenosine 2A Antagonist in Preclinical Rodent Models of Parkinson's Disease

PubMed Central

Jones, Carrie K.; Bubser, Michael; Thompson, Analisa D.; Dickerson, Jonathan W.; Turle-Lorenzo, Nathalie; Amalric, Marianne; Blobaum, Anna L.; Bridges, Thomas M.; Morrison, Ryan D.; Jadhav, Satyawan; Engers, Darren W.; Italiano, Kimberly; Bode, Jacob; Daniels, J. Scott; Lindsley, Craig W.; Hopkins, Corey R.; Conn, P. Jeffrey

2012-01-01

Parkinson's disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu4), including N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclinical models of PD. However, these early mGlu4 PAMs exhibited unsuitable physiochemical properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu4 in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacologic characterization of a systemically active mGlu4 PAM, N-(3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with l-DOPA or an adenosine 2A (A2A) receptor antagonist currently in clinical development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of l-DOPA, suggesting that mGlu4 PAMs may provide l-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu4 PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either l-DOPA or A2A antagonists. PMID:22088953

Direction discrimination learning in normal and visually deprived cats and the effects of lateral suprasylvian lesions.

PubMed

Burnat, K; Zernicki, B

1997-01-01

We used 5 binocularly deprived cats (BD cats), 4 control cats reared also in the laboratory (C cats) and 4 cats reared in a normal environment (N cats). The cats were trained to discriminate an upward or downward-moving light spot versus a stationary spot (detection task) and then an upward versus a downward spot (direction task). The N and C cats learned slowly. The learning was slower than in previously studied discriminations of stationary stimuli. However, all N and C cats mastered the detection task and except one C cat the direction task. In contrast, 4 BD cats failed in the detection task and all in the direction task. This result is consistent with single-cell recording data showing impairment of direction analysis in the visual system in BD cats. After completing the training the upper part of the middle suprasylvian sulcus was removed unilaterally in 7 cats and bilaterally in 6 cats. Surprisingly, the unilateral lesions were more effective: the clear-cut retention deficits were found in 5 cats lesioned unilaterally, whereas only in one cat lesioned bilaterally.

Unilateral proptosis as the initial manifestation of malignancy.

PubMed

Rakul Nambiar, K; Ajith, P S; Arjunan, Asha

2017-09-01

Proptosis, a common sign with a broad differential diagnosis, is defined as anterior displacement and protrusion of one or both orbital globes. Patients can present with varying degrees of chronicity, visual loss and associated symptoms. The etiology of acquired unilateral proptosis is diverse, ranging from benign to life-threatening. The causes of unilateral proptosis include traumatic, vascular, endocrine, inflammatory, infective and malignant. Breast carcinoma is the most common metastatic cause of proptosis; however, proptosis has never been reported as the initial manifestation of breast carcinoma. Our patient presented with unilateral proptosis secondary to an intraorbital lesion and histopathology of orbital lesion was suggestive of metastatic breast adenocarcinoma. She was later diagnosed to have primary breast carcinoma. We present this unusual case of a 56-year-old woman who presented with proptosis as the initial manifestation of a metastatic breast malignancy. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.

PubMed

Hadzagic-Catibusic, Feriha; Avdagic, Edin; Zubcevic, Smail; Uzicanin, Sajra

2017-02-01

Unilateral spastic cerebral palsy (US CP) is the second most common subtype of cerebral palsy. The aim of the study was to analyze neuroimaging findings in children with unilateral spastic cerebral palsy. The study was hospital based, which has included 106 patients with US CP (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified into 5 groups: Brain maldevelopment, predominant white matter injury, predominant gray matter injury, non specific findings and normal neuroimaging findings. Predominant white matter lesions where the most frequent (48/106,45.28%; term 35/preterm 13), without statistically significant difference between term and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically significant difference between term and preterm born children (x2=0.902; p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were term born. Other finding had 2/106 children, 1.89%, both of them were term born. Normal neuroimaging findings were present in14/106 patients (13.21%). Neuroimaging may help to understand morphological background of motor impairment in children with US CP. Periventricular white matter lesions were the most frequent, then gray matter lesions.

A behavioural analysis of spatial localization following electrolytic, kainate- or colchicine-induced damage to the hippocampal formation in the rat.

PubMed

Sutherland, R J; Whishaw, I Q; Kolb, B

1983-02-01

This experiment examines the notion that in the rat the hippocampal formation is an essential structure in the neurological representation of spatial abilities. Spatial localization by rats with different types of hippocampal damage, including bilateral electrolytic lesions, unilateral and bilateral kainic acid-induced CA3-CA4 lesions, and unilateral and bilateral colchicine-induced dentate gyrus lesions, was compared with vehicle-injected and normal control groups in the Morris water task. The task required the rats to escape from cold water by finding a submerged and hidden platform located at a fixed place within the room. The start point was varied randomly from trial to trial and there were no local cues available to indicate the position of the hidden platform. After training, the platform was moved. Escape latencies and the initial swimming headings revealed that all lesion groups, except the unilateral CA3-damaged group, were impaired at finding the platform: the dentate-damaged rats exhibited the greatest deficit. When the platform was moved the control rats swam mainly in the part of the pool that had previously contained the platform and, on finding it in the new location, they showed a marked dishabituation of rearing. None of the bilateral lesion groups showed these effects.

A virtual reality assessment and training system for unilateral neglect.

PubMed

Kim, Kwanguk; Kim, Jaehun; Ku, Jeonghun; Kim, Deog Young; Chang, Won Hyek; Shin, Dong Ik; Lee, Jang Han; Kim, In Young; Kim, Sun I

2004-12-01

Patients with unilateral neglect have problems reporting, responding, or orienting to novel or meaningful stimuli that is presented to the side opposite to that of a brain lesion. This creates a serous problem in regards to daily living activities. However, the established methods for assessing and training of unilateral neglect patients have several deficits. Recently, virtual reality (VR) technologies have been used as an assessment and treatment tool for rehabilitation. Hence, this study designed a VR system to assess and train unilateral neglect patients. In addition, the suitability and feasibility of our VR system for unilateral neglect patients was verified.

Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

PubMed

Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

2001-11-30

Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [35S]GTPgammaS binding) at cloned hD2 (and hD3) receptors. At rat striatal membranes, dopamine stimulated [35S]GTPgammaS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D2/D3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D2 receptor antagonist, L741,626. Further, novel antagonists selective for D3 and D4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D3 and D4 receptor-selective doses of S33084 and S18126, respectively. In functional ([35S]GTPgammaS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (approximately 50% stimulation), but significantly greater on the lesioned side (approximately 80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.

Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats.

PubMed

Marin, C; Aguilar, E; Rodríguez-Oroz, M C; Bartoszyk, G D; Obeso, J A

2009-06-01

Dyskinesia affects the majority of levodopa-treated parkinsonian patients within 5-10 years of treatment with levodopa. Clinical and preclinical observations suggest that an increase in serotoninergic transmission can contribute to the appearance of dyskinesias. It is thus conceivable that a modulation of synaptic dopamine (DA) levels induced by the inhibition of serotonin (5-HT) release, as a consequence of 5-HT(1A) agonists administration, might alleviate dyskinesias. Since 5-HT(1A) receptors are expressed in the subthalamic nucleus (STN), the aim of the present study was to assess the effect of the intrasubthalamic administration of sarizotan, a compound with full 5-HT(1A) agonist properties, on levodopa-induced dyskinesias in the 6-hydroxydopamine (6-OHDA) model of parkinsonism. Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. A test of apomorphine was performed to evaluate dopamine depletion. One week later, a cannula was implanted in the STN. Animals were treated with levodopa (6 mg/kg, i.p., twice at day) for 22 consecutive days. On day 23, several doses (1 ng, 10 ng, or 1 microg) of sarizotan were administered through the cannula to the STN. The higher doses of sarizotan effectively attenuated all levodopa-induced dyskinesias including axial, limb, and orolingual subtypes. These results suggest that the STN is a target structure for the antidyskinetic action of sarizotan and indicate that drug-mediated modulation of STN activity may be an alternative option for the treatment of levodopa-induced dyskinesias in Parkinson's disease.

1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity.

PubMed

Lorenc-Koci, Elzbieta; Gołembiowska, Krystyna; Wardas, Jadwiga

2005-07-27

Malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, is frequently used as a model neurotoxin to produce lesion of the nigrostriatal dopaminergic system in animals due to particular sensitivity of dopamine neurons to mild energy impairment. This model of neurotoxicity was applied in our study to explore neuroprotective potential of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance whose function in the mammalian brain, despite extensive studies, has not been elucidated so far. Injection of malonate at a dose of 3 mumol unilaterally into the rat left medial forebrain bundle resulted in the 54% decrease in dopamine (DA) concentration in the ipsilateral striatum and, depending on the examined striatum regions, caused 24-44% reduction in [3H]GBR12,935 binding to the dopamine transporter (DAT). TIQ (50 mg/kg i.p.) administered 4 h before malonate infusion and next once daily for successive 7 days prevented both these effects of malonate. Such TIQ treatment restored DA content and DAT binding almost to the control level. The results of the present study indicate that TIQ may act as a neuroprotective agent in the rat brain. An inhibition of the enzymatic activities of monoamine oxidase and gamma-glutamyl transpeptidase as well as an increase in the striatal levels of glutathione and nitric oxide found after TIQ administration and reported in our earlier studies are considered to be potential factors that may be involved in the TIQ-mediated protection of dopamine terminals from malonate toxicity.

How does the interaction of presumed timing, location and extent of the underlying brain lesion relate to upper limb function in children with unilateral cerebral palsy?

PubMed

Mailleux, Lisa; Klingels, Katrijn; Fiori, Simona; Simon-Martinez, Cristina; Demaerel, Philippe; Locus, Marlies; Fosseprez, Eva; Boyd, Roslyn N; Guzzetta, Andrea; Ortibus, Els; Feys, Hilde

2017-09-01

Upper limb (UL) function in children with unilateral cerebral palsy (CP) vary largely depending on presumed timing, location and extent of brain lesions. These factors might exhibit a complex interaction and the combined prognostic value warrants further investigation. This study aimed to map lesion location and extent and assessed whether these differ according to presumed lesion timing and to determine the impact of structural brain damage on UL function within different lesion timing groups. Seventy-three children with unilateral CP (mean age 10 years 2 months) were classified according to lesion timing: malformations (N = 2), periventricular white matter (PWM, N = 42) and cortical and deep grey matter (CDGM, N = 29) lesions. Neuroanatomical damage was scored using a semi-quantitative MRI scale. UL function was assessed at body function and activity level. CDGM lesions were more pronounced compared to PWM lesions (p = 0.0003). Neuroanatomical scores were correlated with a higher degree to UL function in the CDGM group (r s  = -0.39 to r s  = -0.84) compared to the PWM group (r rb  = -0.42 to r s  = -0.61). Regression analysis found lesion location and extent to explain 75% and 65% (p < 0.02) respectively, of the variance in AHA performance in the CDGM group, but only 24% and 12% (p < 0.03) in the PWM group. In the CDGM group, lesion location and extent seems to impact more on UL function compared to the PWM group. In children with PWM lesions, other factors like corticospinal tract (re)organization and structural connectivity may play an additional role. Copyright © 2017 European Paediatric Neurology Society. All rights reserved.

Assessment of ultrasonography and computed tomography for the evaluation of unilateral orbital disease in dogs.

PubMed

Boroffka, Susanne A E B; Verbruggen, Anne-Marie; Grinwis, Guy C M; Voorhout, George; Barthez, Paul Y

2007-03-01

To describe clinical, ultrasonographic, and computed tomographic (CT) features of confirmed neoplastic and nonneoplastic disease in dogs with unilateral orbital diseases, determine criteria to differentiate between the 2 conditions, and assess the relative value of ultrasonography and CT for the differential diagnosis of these 2 conditions. Prospective study. 29 dogs with unilateral neoplastic orbital disease and 16 dogs with unilateral nonneoplastic orbital disease. Clinical history and results of physical and ophthalmologic examinations were recorded. Ultrasonographic and CT images were evaluated, and discriminating factors were identified to differentiate neoplastic from nonneoplastic diseases. Diagnostic value of ultrasonography and CT was assessed. Dogs with neoplastic disease were significantly older; had clinical signs for a longer time before initial examination; had more progressive onset of clinical signs; and more frequently had protrusion of the nictitating membrane, fever, and anorexia. The most discriminating factor for both imaging modalities was delineation of the margins (odds ratio was 41.7 for ultrasonography and 45 for CT), with neoplastic lesions clearly delineated more often. Ultrasonographically, neoplastic lesions were more frequently hypoechoic and homogeneous, with indentation of the globe and bone involvement evident more frequently than for nonneoplastic lesions. Mineralization was detected only with neoplasia. Fluctuant fluid was seen more frequently in dogs with nonneoplastic disease. Computed tomography more frequently revealed extraorbital involvement. Diagnostic value was similar for both imaging modalities. Ultrasonography and CT are valuable imaging modalities to assist in differentiating neoplastic from nonneoplastic unilateral orbital disease in dogs.

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.

PubMed

Leem, Eunju; Nam, Jin Han; Jeon, Min-Tae; Shin, Won-Ho; Won, So-Yoon; Park, Sang-Joon; Choi, Myung-Sook; Jin, Byung Kwan; Jung, Un Ju; Kim, Sang Ryong

2014-07-01

This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Pleiotrophin over-expression provides trophic support to dopaminergic neurons in parkinsonian rats.

PubMed

Taravini, Irene Re; Chertoff, Mariela; Cafferata, Eduardo G; Courty, José; Murer, Mario G; Pitossi, Fernando J; Gershanik, Oscar S

2011-06-07

Pleiotrophin is known to promote the survival and differentiation of dopaminergic neurons in vitro and is up-regulated in the substantia nigra of Parkinson's disease patients. To establish whether pleiotrophin has a trophic effect on nigrostriatal dopaminergic neurons in vivo, we injected a recombinant adenovirus expressing pleiotrophin in the substantia nigra of 6-hydroxydopamine lesioned rats. The viral vector induced pleiotrophin over-expression by astrocytes in the substantia nigra pars compacta, without modifying endogenous neuronal expression. The percentage of tyrosine hydroxylase-immunoreactive cells as well as the area of their projections in the lesioned striatum was higher in pleiotrophin-treated animals than in controls. These results indicate that pleiotrophin over-expression partially rescues tyrosine hydroxylase-immunoreactive cell bodies and terminals of dopaminergic neurons undergoing 6-hydroxydopamine-induced degeneration.

Exposure of wide cerebellomedullary cisterns for vascular lesion surgeries in cerebellomedullary cisterns: opening of unilateral cerebellomedullary fissures combined with lateral foramen magnum approach.

PubMed

Matsushima, Toshio; Kawashima, Masatou; Inoue, Kohei; Matsushima, Ken; Miki, Koichi

2014-11-01

To clarify microsurgical anatomic features of the cerebellomedullary fissure (CMF), the natural cleavage plane between the cerebellum and the medulla, and its relationship to the cerebellomedullary cistern (CMC) and to describe a surgical technique that uses the unilateral trans-CMF approach for CMC surgeries. In the anatomic study, 2 formalin-fixed cadaver heads were used. In the clinical study, 3 patients with vertebral artery-posterior inferior cerebellar artery aneurysms and 3 patients with glossopharyngeal neuralgia were surgically treated through the unilateral trans-CMF approach combined with the transcondylar fossa approach, which is a lateral foramen magnum approach. The CMC was present at the lateral end of the CMF. The CMF was closed by arachnoidal adhesion, and the cerebellar hemisphere was superiorly attached to the cerebellar peduncle. After the unilateral CMF was completely opened, the cerebellar hemisphere was easily retracted rostrodorsally. Clinically, almost completely opening the unilateral CMF markedly enabled the retraction of the biventral lobule to obtain a wide surgical field safely for vascular CMC lesions. We present 2 representative cases. Combined unilateral trans-CMF/lateral foramen magnum approaches provide a wide and close surgical field in the CMC, allowing easy and safe CMC surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Upregulation of Ryk expression in rat dorsal root ganglia after peripheral nerve injury.

PubMed

Li, Xin; Li, Yao-hua; Yu, Shun; Liu, Yaobo

2008-10-22

To study changes of Ryk expression in dorsal root ganglia (DRG) after peripheral nerve injury, we set up an animal model of unilateral sciatic nerve lesioned rats. Changes of Ryk protein expression in DRG neurons after unilateral sciatic nerve injury were investigated by immunostaining. Changes of Ryk mRNA were also tested by semi-quantitative PCR concurrently. We found, both at the level of protein and mRNA, that Ryk could be induced in cells of ipsilateral DRG after unilateral sciatic nerve lesion. Further investigation by co-immunostaining confirmed that the Ryk-immunoreactive (Ryk-IR) cells were NeuN-immunoreactive (NeuN-IR) neurons of DRG. We also showed the pattern of Ryk induction in DRG neurons after sciatic nerve injury: the number of Ryk IR neurons peaked at 2 weeks post-lesion and decreased gradually by 3 weeks post-lesion. The proportions of different sized Ryk IR neurons were also observed and counted at various stages after nerve lesion. Analysis of Ryk mRNA by RT-PCR showed the same induction pattern as by immunostaining. Ryk mRNA was not expressed in normal or contralateral DRG, but was expressed 1, 2 and 3 weeks post-lesion in the ipsilateral DRG. Ryk mRNA levels increased slightly from 1 to 2 weeks, decreased then by 3 weeks post-lesion. These results indicate that Ryk might be involved in peripheral nerve plasticity after injury. This is a novel function apart from its well-known fundamental activity as a receptor mediating axon guidance and outgrowth.

Paradoxical ictal EEG lateralization in children with unilateral encephaloclastic lesions.

PubMed

Garzon, Eliana; Gupta, Ajay; Bingaman, William; Sakamoto, Americo C; Lüders, Hans

2009-09-01

Describe an ictal EEG pattern of paradoxical lateralization in children with unilateral encephaloclastic hemispheric lesion acquired early in life. Of 68 children who underwent hemispherectomy during 2003-2005, scalp video-EEG and brain MRI of six children with an ictal scalp EEG pattern discordant to the clinical and imaging data were reanalyzed. Medical charts were reviewed for clinical findings and seizure outcome. Age of seizure onset was 1 day-4 years. The destructive MRI lesion was an ischemic stroke in 2, a post-infectious encephalomalacia in 2, and a perinatal trauma and hemiconvulsive-hemiplegic syndrome in one patient each. Ictal EEG pattern was characterized by prominent ictal rhythms with either 3-7 Hz spike and wave complexes or beta frequency sharp waves (paroxysmal fast) over the unaffected (contralesional) hemisphere. Scalp video-EEG was discordant, however, other findings of motor deficits (hemiparesis; five severe, one mild), seizure semiology (4/6), interictal EEG abnormalities (3/6), and unilateral burden of MRI lesion guided the decision for hemispherectomy. After 12-39 months of post-surgery follow up, five of six patients were seizure free and one has brief staring spells. We describe a paradoxical lateralization of the EEG to the "good" hemisphere in children with unihemispheric encephaloclastic lesions. This EEG pattern is compatible with seizure free outcome after surgery, provided other clinical findings and tests are concordant with origin from the abnormal hemisphere.

Bronchial mucus properties in lung cancer: relationship with site of lesion.

PubMed

Zayas, J G; Rubin, B K; York, E L; Lien, D C; King, M

1999-01-01

To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

Distinct changes in evoked and resting globus pallidus activity in early and late Parkinson's disease experimental models.

PubMed

Zold, Camila L; Larramendy, Celia; Riquelme, Luis A; Murer, M Gustavo

2007-09-01

The main clinical manifestations of Parkinson's disease are caused by alterations of basal ganglia activity that are tied in with the progressive loss of mesencephalic dopaminergic neurons. Recent theoretical and modeling studies have suggested that changes in resting neuronal activity occurred later in the course of the disease than those evoked by phasic cortical input. However, there is no empirical support for this proposal. Here we report a marked increase in the responsiveness of globus pallidus neurons to electrical motor cortex stimulation, in the absence of noticeable changes in resting activity, in anesthetized rats that had consistently shown a deficit in forelimb use during behavioral testing before the experiments, and had approximately 45% dopamine neurons spared in the substantia nigra. Pallidal neurons were also over-responsive to motor cortex stimulation and lost spatial selectivity for cortical inputs in rats with extensive nigrostriatal damage. After partial lesions, over-responsiveness was mainly due to an increased proportion of neurons showing excitatory responses, while extensive lesions led to an increased likelihood of inhibitory responding neurons. Changes in resting neuronal activity, comprising pauses disrupting tonic discharge, occurred across different global brain states, including an activated condition which shares similarities with natural patterns of cortical activity seen in awake states and rapid eye-movement sleep, but only after massive nigrostriatal degeneration. These results suggest that a loss of functional segregation and an abnormal temporal encoding of phasic cortical inputs by globus pallidus neurons may contribute to inducing early motor impairment in Parkinson's disease.

Dissociation between memory accuracy and memory confidence following bilateral parietal lesions.

PubMed

Simons, Jon S; Peers, Polly V; Mazuz, Yonatan S; Berryhill, Marian E; Olson, Ingrid R

2010-02-01

Numerous functional neuroimaging studies have observed lateral parietal lobe activation during memory tasks: a surprise to clinicians who have traditionally associated the parietal lobe with spatial attention rather than memory. Recent neuropsychological studies examining episodic recollection after parietal lobe lesions have reported differing results. Performance was preserved in unilateral lesion patients on source memory tasks involving recollecting the context in which stimuli were encountered, and impaired in patients with bilateral parietal lesions on tasks assessing free recall of autobiographical memories. Here, we investigated a number of possible accounts for these differing results. In 3 experiments, patients with bilateral parietal lesions performed as well as controls at source recollection, confirming the previous unilateral lesion results and arguing against an explanation for those results in terms of contralesional compensation. Reducing the behavioral relevance of mnemonic information critical to the source recollection task did not affect performance of the bilateral lesion patients, indicating that the previously observed reduced autobiographical free recall might not be due to impaired bottom-up attention. The bilateral patients did, however, exhibit reduced confidence in their source recollection abilities across the 3 experiments, consistent with a suggestion that parietal lobe lesions might lead to impaired subjective experience of rich episodic recollection.

Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

PubMed

Pereira Bacares, Marcia E; Vemireddi, Vimala; Creasy, Dianne

2017-06-01

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilts, R.P. Jr.

In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDAmore » resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.« less

Pleiotrophin over-expression provides trophic support to dopaminergic neurons in parkinsonian rats

PubMed Central

2011-01-01

Background Pleiotrophin is known to promote the survival and differentiation of dopaminergic neurons in vitro and is up-regulated in the substantia nigra of Parkinson's disease patients. To establish whether pleiotrophin has a trophic effect on nigrostriatal dopaminergic neurons in vivo, we injected a recombinant adenovirus expressing pleiotrophin in the substantia nigra of 6-hydroxydopamine lesioned rats. Results The viral vector induced pleiotrophin over-expression by astrocytes in the substantia nigra pars compacta, without modifying endogenous neuronal expression. The percentage of tyrosine hydroxylase-immunoreactive cells as well as the area of their projections in the lesioned striatum was higher in pleiotrophin-treated animals than in controls. Conclusions These results indicate that pleiotrophin over-expression partially rescues tyrosine hydroxylase-immunoreactive cell bodies and terminals of dopaminergic neurons undergoing 6-hydroxydopamine-induced degeneration. PMID:21649894

Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.

PubMed

Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell

2005-02-08

The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.

A pathway in the brainstem for roll-tilt of the subjective visual vertical: evidence from a lesion-behavior mapping study.

PubMed

Baier, Bernhard; Thömke, Frank; Wilting, Janine; Heinze, Caroline; Geber, Christian; Dieterich, Marianne

2012-10-24

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion-behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucleus of Cajal. Thus, these structures constitute the anatomical pathway in the brainstem for verticality perception. Present data indicate that graviceptive otolith signals present a predominant role in the multisensory system of verticality perception.

Protection of dopaminergic neurons by electroconvulsive shock in an animal model of Parkinson's disease.

PubMed

Anastasia, Agustín; de Erausquin, Gabriel A; Wojnacki, José; Mascó, Daniel H

2007-11-01

Electroconvulsive shock (ECS) improves motor function in Parkinson's disease. In rats, ECS stimulates the expression of various factors some of which have been proposed to exert neuroprotective actions. We have investigated the effects of ECS on 6-hydroxydopamine (6-OHDA)-injected rats. Three weeks after a unilateral administration of 6-OHDA, 85-95% nigral dopaminergic neurons are lost. Chronic ECS prevented this cell loss, protect the nigrostriatal pathway (assessed by FloroGold retrograde labeling) and reduce motor impairment in 6-OHDA-treated animals. Injection of 6-OHDA caused loss of expression of glial cell-line derived neurotrophic factor (GDNF) in the substantia nigra. Chronic ECS completely prevented this loss of GDNF expression in 6-OHDA-treated animals. We also found that protected dopaminergic neurons co-express GDNF receptor proteins. These results strongly suggest that endogenous changes in GDNF expression may participate in the neuroprotective mechanism of ECS against 6-OHDA induced toxicity.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

PubMed

Hoare, Brian; Ditchfield, Michael; Thorley, Megan; Wallen, Margaret; Bracken, Jenny; Harvey, Adrienne; Elliott, Catherine; Novak, Iona; Crichton, Ali

2018-05-08

Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl) pyridine decreases striatal VGlut2 expression in association with an attenuation of L-DOPA-induced dyskinesias.

PubMed

Marin, C; Bonastre, M; Aguilar, E; Jiménez, A

2011-10-01

The striatal glutamatergic hyperactivity is considered critical in the development of levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). Pharmacological antagonism of the metabotropic glutamate receptors (mGluRs), in particular, the subtype mGluR5, can inhibit the expression of dyskinesia in both rodent and nonhuman primate models of PD. However, the exact mechanisms underlying the mGluR5 antagonism effects are not completely known. The vesicular glutamate transporters (VGluts) are localized in the synaptic vesicles of the striatal glutamatergic axonal terminals. The effects of mGluR5 antagonism modulating VGlut1 and VGlut2, as selective markers for the corticostriatal and thalamostriatal pathways, respectively, are still unknown. We investigated the effects of the mGluR5 antagonist, 2-methyl-6-(phenylethynyl) pyridine (MPEP) on the striatal expression of VGlut1 and VGlut2 in levodopa-treated hemiparkinsonian rats. Male Sprague-Dawley rats received a unilateral 6-hydroxydopamine (6-OHDA) administration in the nigrostriatal pathway. Rats were treated with: (a) levodopa (12 mg/kg/day with benserazide 15 mg/kg, ip) + vehicle; (b) MPEP (1.5 mg/kg/day, ip) + vehicle; (c) levodopa + MPEP, or (d) saline for 10 days. Levodopa treatment induced dyskinesias and did not modify the striatal expression of either VGlut1 or VGlut2. The administration of MPEP significantly attenuated LID and decreased the levels of VGlut2, but not the VGlut1, in the striatum ipsilateral to the lesion (P < 0.05). Our results suggest that the effects of MPEP on LID might be mediated by a modulating effect on VGlut 2 expression. Copyright © 2011 Wiley-Liss, Inc.

A stimulus-centered reading disorder for words and numbers: Is it neglect dyslexia?

PubMed

Arduino, Lisa S; Daini, Roberta; Caterina Silveri, Maria

2005-12-01

A single case, RCG, showing a unilateral reading disorder without unilateral spatial neglect was studied. The disorder was characterized by substitutions of the initial (left) letters of words, nonwords and Arabic numbers, independently of egocentered spatial coordinates. MRI showed a bilateral lesion with the involvement of the splenium. Although, within the framework of the visual word recognition model proposed by Caramazza and Hillis (1990), RCG disorder could be defined as a stimulus-centered neglect dyslexia, we discuss the hypothesis of a dissociation in neural correlates and mechanisms between the syndrome of unilateral spatial neglect and such a unilateral reading disorder.

Focal atrophy of the unilateral masticatory muscles caused by pure trigeminal motor neuropathy: case report.

PubMed

Kämppi, Antti; Kämppi, Leena; Kemppainen, Pentti; Kanerva, Mari; Toppila, Jussi; Auranen, Mari

2018-05-01

Patients with unknown clinical or radiological asymmetry in the face structures combined with atrophy and weakness of the masticatory muscles should be comprehensively examined clinically and with MRI, neurophysiological measurements, and serologically. Malignant lesions or benign idiopathic unilateral trigeminal motor neuropathy should be considered as an etiological explanation for the asymmetry.

Visual attention in posterior stroke and relations to alexia.

PubMed

Petersen, A; Vangkilde, S; Fabricius, C; Iversen, H K; Delfi, T S; Starrfelt, R

2016-11-01

Impaired visual attention is common following strokes in the territory of the middle cerebral artery, particularly in the right hemisphere, while attentional effects of more posterior lesions are less clear. Commonly, such deficits are investigated in relation to specific syndromes like visual agnosia or pure alexia. The aim of this study was to characterize visual processing speed and apprehension span following posterior cerebral artery (PCA) stroke. In addition, the relationship between these attentional parameters and single word reading is investigated, as previous studies have suggested that reduced visual speed and span may explain pure alexia. Eight patients with unilateral PCA strokes (four left hemisphere, four right hemisphere) were selected on the basis of lesion location, rather than the presence of any visual symptoms. Visual attention was characterized by a whole report paradigm allowing for hemifield-specific measurements of processing speed and apprehension span. All patients showed reductions in visual span contralateral to the lesion site, and four patients showed bilateral reductions in visual span despite unilateral lesions (2L; 2R). Six patients showed selective deficits in visual span, though processing speed was unaffected in the same field (ipsi- or contralesionally). Only patients with right hemifield reductions in visual span were impaired in reading, and this could follow either right or left lateralized stroke and was irrespective of visual field impairments. In conclusion, visual span may be affected bilaterally by unilateral PCA-lesions. Reductions in visual span may also be confined to one hemifield, and may be affected in spite of preserved visual processing speed. Furthermore, reduced span in the right visual field seems to be related to reading impairment in this group, regardless of lesion lateralization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Memory-enhancing activities of the aqueous extract of Albizia adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease

PubMed Central

2014-01-01

Background Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a traditional herb largely used in the African traditional medicine as analgesic, purgative, anti-inflammatory, antioxidant, antimicrobial and memory-enhancer drug. This study was undertaken in order to evaluate the possible cognitive-enhancing and antioxidative effects of the aqueous extract of A. adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease. Methods The effect of the aqueous extract of A. adianthifolia leaves (150 and 300 mg/kg, orally, daily, for 21 days) on spatial memory performance was assessed using Y-maze and radial arm-maze tasks, as animal models of spatial memory. Pergolide - induced rotational behavior test was employed to validate unilateral damage to dopamine nigrostriatal neurons. Also, in vitro antioxidant activity was assessed through the estimation of total flavonoid and total phenolic contents along with determination of free radical scavenging activity. Statistical analyses were performed using two-way analysis of variance (ANOVA). Significant differences were determined by Tukey’s post hoc test. F values for which p < 0.05 were regarded as statistically significant. Pearson’s correlation coefficient and regression analysis were used in order to evaluate the association between behavioral parameters and net rotations in rotational behavior test. Results The 6-OHDA-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors and reference memory errors within radial arm maze task. Administration of the aqueous extract of A. adianthifolia leaves significantly improved these parameters, suggesting positive effects on spatial memory formation. Also, the aqueous extract of A. adianthifolia leaves showed potent in vitro antioxidant activity. Furthermore, in vivo evaluation, the aqueous extract of A. adianthifolia leaves attenuated the contralateral rotational asymmetry observed by pergolide challenge in 6-OHDA-treated rats. Conclusions Taken together, our results suggest that the aqueous extract of A. adianthifolia leaves possesses antioxidant potential and might provide an opportunity for management neurological abnormalities in Parkinson’s disease conditions. PMID:24884469

Bilateral LMAN lesions cancel differences in HVC neuronal recruitment induced by unilateral syringeal denervation. Lateral magnocellular nucleus of the anterior neostriatum.

PubMed

Wilbrecht, L; Petersen, T; Nottebohm, F

2002-12-01

Twenty-six-day-old male zebra finches received (1) unilateral section of their tracheosyringeal nerve, (2) bilateral lesions of the lateral magnocellular nucleus of the anterior neostriatum (LMAN), and (3) both operations. All birds were kept with an adult, singing male as a tutor until day 65. Tracheo-syringeal nerve-cut birds were able to imitate this model, but LMAN-lesioned birds were not. Bromodeoxyuridine, a marker of cell division, was injected intramuscularly during post-hatching days 61-65 and all birds were killed at 91 days of age. The number of bromodeoxyuridine+ neurons in the high vocal center of the tracheosyringeal-cut birds was twice as high in the intact as in the nerve cut side. This asymmetry disappeared when nerve section was combined with bilateral LMAN lesions. The latter operation, by itself, had no effect on new neuron counts. We suggest that the single nerve cut produced a hemispheric asymmetry in learning, reflected in new neuron recruitment, which disappeared when LMAN lesions blocked learning.

Development of Endoscopic Diagnosis and Treatment for Chronic Unilateral Hematuria: 35 Years Experience.

PubMed

Tanimoto, Ryuta; Kumon, Hiromi; Bagley, Demetrius H

2017-04-01

Chronic unilateral hematuria (CUH) is also called lateralizing essential hematuria, benign essential hematuria, and benign lateralizing hematuria, which was defined as intermittent or continuous gross hematuria that cannot be diagnosed with standard radiology and hematology studies, together with unilateral bloody efflux by cystoscopy. CUH is rare, but sometimes confused with malignancy or life-threatening hemorrhage. Therefore, it can cause considerable anxiety to not only patients but also urologists. For this study, we summarized articles about endoscopic diagnosis and treatment of CUH, and discussed the development of endourology for CUH. We searched articles related to CUH that were indexed in the PubMed database and published in English. Key terms used were "unilateral," "lateralizing," "chronic," "benign," and "idiopathic" hematuria. We found 15 pertinent articles reporting CUH. Endoscopically, CUH can be classified into three categories: discrete lesion, diffuse lesion, or no (unidentified) lesion. Currently, endoscopic techniques for CUH are similar to the techniques for upper tract urothelial carcinoma, using semi-rigid and flexible ureteroscopes with diathermy fulguration or laser ablation for treatment. The overall success rate of endoscopic treatment for CUH, defined as resolution of gross hematuria after treatment, was 93% (190/205). The recurrence rate, defined as recurrent gross hematuria after treatment, was 10% (19/189). Advancements in endoscopic devices and techniques have enabled more accurate and less invasive diagnosis and treatment of CUH. Once CUH is defined, flexible ureteroscopy is the diagnostic and therapeutic technique of choice.

Automated, quantitative measures of grey and white matter lesion burden correlates with motor and cognitive function in children with unilateral cerebral palsy.

PubMed

Pagnozzi, Alex M; Dowson, Nicholas; Doecke, James; Fiori, Simona; Bradley, Andrew P; Boyd, Roslyn N; Rose, Stephen

2016-01-01

White and grey matter lesions are the most prevalent type of injury observable in the Magnetic Resonance Images (MRIs) of children with cerebral palsy (CP). Previous studies investigating the impact of lesions in children with CP have been qualitative, limited by the lack of automated segmentation approaches in this setting. As a result, the quantitative relationship between lesion burden has yet to be established. In this study, we perform automatic lesion segmentation on a large cohort of data (107 children with unilateral CP and 18 healthy children) with a new, validated method for segmenting both white matter (WM) and grey matter (GM) lesions. The method has better accuracy (94%) than the best current methods (73%), and only requires standard structural MRI sequences. Anatomical lesion burdens most predictive of clinical scores of motor, cognitive, visual and communicative function were identified using the Least Absolute Shrinkage and Selection operator (LASSO). The improved segmentations enabled identification of significant correlations between regional lesion burden and clinical performance, which conform to known structure-function relationships. Model performance was validated in an independent test set, with significant correlations observed for both WM and GM regional lesion burden with motor function (p < 0.008), and between WM and GM lesions alone with cognitive and visual function respectively (p < 0.008). The significant correlation of GM lesions with functional outcome highlights the serious implications GM lesions, in addition to WM lesions, have for prognosis, and the utility of structural MRI alone for quantifying lesion burden and planning therapy interventions.

Investigation of brachial plexus traction lesions by peripheral and spinal somatosensory evoked potentials.

PubMed Central

Jones, S J

1979-01-01

Peripheral, spinal and cortical somatosensory evoked potentials were recorded in 26 patients with unilateral traction injuries of the brachial plexus ganglia. Of 10 cases explored surgically the recordings correctly anticipated the major site of the lesion in eight. PMID:422958

Unilateral purpura annularis telangiectodes of majocchi in an elderly male: an atypical presentation.

PubMed

Wang, Apphia; Shuja, Fareesa; Chan, Audrey; Wasko, Carina

2013-08-15

Purpura annularis telangiectodes (PAT), also known as Majocchi purpura, is a rare form of pigmented purpuric dermatosis characterized by non-palpable red-brown, occasionally pruritic patches which progress to hyperpigmented halos. Purpura annularis telangiectodes usually presents in female adolescents as benign symmetric lesions with a predilection for the lower extremities. We present an atypical case of unilateral PAT in an elderly male. To our knowledge, our patient at 85-years-old is the oldest PAT and first unilateral purpura annularis telangiectodes case described in the literature.

MOG antibody–positive, benign, unilateral, cerebral cortical encephalitis with epilepsy

PubMed Central

Ogawa, Ryo; Takahashi, Toshiyuki; Kaneko, Kimihiko; Akaishi, Tetsuya; Takai, Yoshiki; Sato, Douglas Kazutoshi; Nishiyama, Shuhei; Misu, Tatsuro; Kuroda, Hiroshi; Aoki, Masashi; Fujihara, Kazuo

2017-01-01

Objective: To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody. Methods: In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody–positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008–2014). We then analyzed the findings in MOG antibody–positive cases. Results: Three more patients, as well as the index case, were MOG antibody–positive, and all were adult men (median age 37 years, range 23–39 years). The main symptom was generalized epileptic seizure with or without abnormal behavior or consciousness disturbance. Two patients also developed unilateral benign optic neuritis (before or after seizure). In all patients, brain MRI demonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense lesions, which were swollen and corresponded to hyperperfusion on SPECT. CSF studies showed moderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated total protein levels, but myelin basic protein was not elevated. A screening of encephalitis-associated autoantibodies, including aquaporin-4, glutamate receptor, and voltage-gated potassium channel antibodies, was negative. All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone, and the unilateral cortical MRI lesions subsequently disappeared. No patient experienced relapse. Conclusions: These MOG antibody–positive cases represent unique benign unilateral cortical encephalitis with epileptic seizure. The pathology may be autoimmune, although the findings differ from MOG antibody–associated demyelination and Rasmussen and other known immune-mediated encephalitides. PMID:28105459

The feeling of familiarity for music in patients with a unilateral temporal lobe lesion: A gating study.

PubMed

Huijgen, Josefien; Dellacherie, Delphine; Tillmann, Barbara; Clément, Sylvain; Bigand, Emmanuel; Dupont, Sophie; Samson, Séverine

2015-10-01

Previous research has indicated that the medial temporal lobe (MTL), and more specifically the perirhinal cortex, plays a role in the feeling of familiarity for non-musical stimuli. Here, we examined contribution of the MTL to the feeling of familiarity for music by testing patients with unilateral MTL lesions. We used a gating paradigm: segments of familiar and unfamiliar musical excerpts were played with increasing durations (250, 500, 1000, 2000, 4000 ms and complete excerpts), and participants provided familiarity judgments for each segment. Based on the hypothesis that patients might need longer segments than healthy controls (HC) to identify excerpts as familiar, we examined the onset of the emergence of familiarity in HC, patients with a right MTL resection (RTR), and patients with a left MTL resection (LTR). In contrast to our hypothesis, we found that the feeling of familiarity was relatively spared in patients with a right or left MTL lesion, even for short excerpts. All participants were able to differentiate familiar from unfamiliar excerpts as early as 500 ms, although the difference between familiar and unfamiliar judgements was greater in HC than in patients. These findings suggest that a unilateral MTL lesion does not impair the emergence of the feeling of familiarity. We also assessed whether the dynamics of the musical excerpt (linked to the type and amount of information contained in the excerpts) modulated the onset of the feeling of familiarity in the three groups. The difference between familiar and unfamiliar judgements was greater for high than for low-dynamic excerpts for HC and RTR patients, but not for LTR patients. This indicates that the LTR group did not benefit in the same way from dynamics. Overall, our results imply that the recognition of previously well-learned musical excerpts does not depend on the integrity of either right or the left MTL structures. Patients with a unilateral MTL resection may compensate for the effects of unilateral damage by using the intact contralateral temporal lobe. Moreover, we suggest that remote semantic memory for music might depend more strongly on neocortical structures rather than the MTL. Copyright © 2015. Published by Elsevier Ltd.

Anatomical physiology of spatial extinction.

PubMed

Ciçek, Metehan; Gitelman, Darren; Hurley, Robert S E; Nobre, Anna; Mesulam, Marsel

2007-12-01

Neurologically intact volunteers participated in a functional magnetic resonance imaging experiment that simulated the unilateral (focal) and bilateral (global) stimulations used to elicit extinction in patients with hemispatial neglect. In peristriate areas, attentional modulations were selectively sensitive to contralaterally directed attention. A higher level of mapping was observed in the intraparietal sulcus (IPS), inferior parietal lobule (IPL), and inferior frontal gyrus (IFG). In these areas, there was no distinction between contralateral and ipsilateral focal attention, and the need to distribute attention globally led to greater activity than either focal condition. These physiological characteristics were symmetrically distributed in the IPS and IFG, suggesting that the effects of unilateral lesions in these 2 areas can be compensated by the contralateral hemisphere. In the IPL, the greater activation by the bilateral attentional mode was seen only in the right hemisphere. Its contralateral counterpart displayed equivalent activations when attention was distributed to the right, to the left, or bilaterally. Within the context of this experiment, the IPL of the right hemisphere emerged as the one area where unilateral lesions can cause the most uncompensated and selective impairment of global attention (without interfering with unilateral attention to either side), giving rise to the phenomenon of extinction.

Differential effects of unilateral lesions in the medial amygdala on spontaneous and induced ovulation.

PubMed

Sanchez, M A; Dominguez, R

1995-01-01

The possible existence of asymmetry in the control of ovulation by the medial amygdala was explored. Unilateral lesions of the medial amygdala were performed on each day of the estrous cycle. The estral index diminished in almost all animals with a lesion in the right side of medial amygdala. Lesions of the right medial amygdala, when performed on diestrus-1, resulted in a significant decrease in the number of rats ovulating compared to controls (4/8 vs. 8/8, p < 0.05). In ovulating animals a significant reduction in the number of ova shed by the left ovary was found (2.2 +/- 0.8 vs. 6.3 +/- 0.8, p < 0.05). Lesions of the stria terminalis performed on diestrus-1 did not affect ovulation. In a second experiment, administration of GnRH did not restore ovulation in rats with lesions of the right medial amygdala. However, sequential injections of PMSG-hCG did result in ovulation by all members of a group of lesioned animals. In this last condition a significant decrease in the number of ova shed by the right ovary was found compared to animals in the lesion-only condition (1.5 +/- 0.5 vs. 6.0 +/- 1.5, p < 0.05). These data suggest that control of ovulation by the medial amygdala is asymmetric and varies during the estrous cycle.

Effect of motor imagery in children with unilateral cerebral palsy: fMRI study.

PubMed

Chinier, Eva; N'Guyen, Sylvie; Lignon, Grégoire; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickaël

2014-01-01

Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions.

Amygdala central nucleus interacts with dorsolateral striatum to regulate the acquisition of habits

PubMed Central

Lingawi, Nura W.; Balleine, Bernard W.

2012-01-01

The role of the amygdala central nucleus (CeN) in habit learning was assessed in two experiments. First we examined the effects of bilateral lesions of the anterior CeN on an overtraining-induced lever press habit evaluated using an outcome devaluation protocol. Overtraining generated habitual performance and rendered sham lesioned rats insensitive to outcome devaluation, an effect that was also found in rats given control lesions of the posterior CeN. In contrast, rats with lesions of the anterior CeN did not show normal habit acquisition and their performance remained goal-directed and sensitive to outcome devaluation. Nevertheless, lesions of either the posterior or the anterior CeN abolished the general excitatory influence of a Pavlovian CS on instrumental performance. Next we assessed the functional interaction between the CeN and dorsolateral striatum (DLS), a region previously implicated in the acquisition of habits, using asymmetrical lesions to disconnect these structures. Rats were given a unilateral lesion of anterior CeN and a unilateral lesion of the DLS, made either ipsilateral (control) or contralateral (disconnection) to the CeN lesion, and given overtraining followed by outcome devaluation. Although the ipsilateral lesioned rats were insensitive to devaluation, the contralateral CeN-DLS lesion impaired habit acquisition rendering performance sensitive to the devaluation treatment. These results are the first to implicate the CeN and its connection with a circuit involving DLS in habit learning. They imply that, in instrumental conditioning, regions of amygdala parse the instrumental outcome into the reward and reinforcement signals mediating goal-directed and habitual actions, respectively. PMID:22262905

Unilateral phrenic nerve lesion in Lyme neuroborreliosis

PubMed Central

2013-01-01

Background Among a variety of more common differential diagnoses, the aetiology of acute respiratory failure includes Lyme neuroborreliosis. Case presentation We report an 87-years old huntsman with unilateral phrenic nerve palsy as a consequence of Lyme neuroborreliosis. Conclusion Although Lyme neuroborreliosis is a rare cause of diaphragmatic weakness, it should be considered in the differential workup because of its potentially treatable nature. PMID:23327473

Increased expression of c-fos in the medial preoptic area after mating in male rats: role of afferent inputs from the medial amygdala and midbrain central tegmental field.

PubMed

Baum, M J; Everitt, B J

1992-10-01

Immunocytochemical methods were used to localize the protein product of the immediate-early gene, c-fos, in male rats after exposure to, or direct physical interaction with, oestrous females. Increasing amounts of physical contact with a female, with resultant olfactory-vomeronasal and/or genital-somatosensory inputs, caused corresponding increments in c-fos expression in the medial preoptic area, the caudal part of the bed nucleus of the stria terminalis, the medial amygdala, and the midbrain central tegmental field. Males bearing unilateral electrothermal lesions of the olfactory peduncle showed a significant reduction in c-fos expression in the ipsilateral medial amygdala, but not in other structures, provided their coital interaction with oestrous females was restricted to mount-thrust and occasional intromissive patterns due to repeated application of lidocaine anaesthetic to the penis. No such lateralization of c-fos expression occurred in other males with unilateral olfactory lesions which were allowed to intromit and ejaculate with a female. These results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala. However, lesion-induced deficits in this type of afferent input to the nervous system appear to be readily compensated for by the genital somatosensory input derived from repeated intromissions. Unilateral excitotoxic lesions of the medial preoptic area, made by infusing quinolinic acid, failed to reduce c-fos expression in the ipsilateral or contralateral medial amygdala or central tegmental field following ejaculation. By contrast, combined, unilateral excitotoxic lesions of the medial amygdala and the central tegmental field significantly reduced c-fos expression in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area after mating; no such asymmetry in c-fos expression occurred when lesions were restricted to either the medial amygdala or central tegmental field. This suggests that afferent inputs from the central tegmental field (probably of genital-somatosensory origin) and from the medial amygdala (probably of olfactory-vomeronasal origin) interact to promote cellular activity, and the resultant induction of c-fos, in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area. The monitoring of neuronal c-fos expression provides an effective means of studying the role of sensory factors in governing the activity of integrated neural structures which control the expression of a complex social behaviour.

[Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

PubMed

Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

2018-02-07

Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in patients with unilateral multifocal microcarcinoma, and generally a routine dissection of the LN-prRLN-CLN is not required, however for bilateral non-microcarcinoma and the the non-microcarcinoma on the right side, the LN-prRLN-CLN dissection should be conducted.

Olivocochlear Efferent Control in Sound Localization and Experience-Dependent Learning

PubMed Central

Irving, Samuel; Moore, David R.; Liberman, M. Charles; Sumner, Christian J.

2012-01-01

Efferent auditory pathways have been implicated in sound localization and its plasticity. We examined the role of the olivocochlear system (OC) in horizontal sound localization by the ferret and in localization learning following unilateral earplugging. Under anesthesia, adult ferrets underwent olivocochlear bundle section at the floor of the fourth ventricle, either at the midline or laterally (left). Lesioned and control animals were trained to localize 1 s and 40ms amplitude-roved broadband noise stimuli from one of 12 loudspeakers. Neither type of lesion affected normal localization accuracy. All ferrets then received a left earplug and were tested and trained over 10 d. The plug profoundly disrupted localization. Ferrets in the control and lateral lesion groups improved significantly during subsequent training on the 1 s stimulus. No improvement (learning) occurred in the midline lesion group. Markedly poorer performance and failure to learn was observed with the 40 ms stimulus in all groups. Plug removal resulted in a rapid resumption of normal localization in all animals. Insertion of a subsequent plug in the right ear produced similar results to left earplugging. Learning in the lateral lesion group was independent of the side of the lesion relative to the earplug. Lesions in all reported cases were verified histologically. The results suggest the OC system is not needed for accurate localization, but that it is involved in relearning localization during unilateral conductive hearing loss. PMID:21325517

Lesion of the Centromedian Thalamic Nucleus in MPTP-Treated Monkeys

PubMed Central

Lanciego, Jose L.; Rodríguez-Oroz, Maria C.; Blesa, Francisco J.; Alvarez-Erviti, Lydia; Guridi, Jorge; Barroso-Chinea, Pedro; Smith, Yoland; Obeso, Jose A.

2015-01-01

The caudal intralaminar nuclei are a major source of glutamatergic afferents to the basal ganglia. Experiments in the 6-hydroxydopamine rat model have shown that the parafascicular nucleus is overactive and its lesion alleviates basal ganglia neurochemical abnormalities associated with dopamine depletion. Accordingly, removal of this excitatory innervation of the basal ganglia could have a beneficial value in the parkinsonian state. To test this hypothesis, unilateral kainate-induced chemical ablation of the centromedian thalamic nucleus (CM) has been performed in MPTP-treated monkeys. Successful lesions restricted to the CM boundaries (n = 2) without spreading over other neighboring thalamic nuclei showed an initial, short-lasting, and mild change in the parkinsonian motor scale but no effect against levodopa-induced dyskinesias. The lack of significant and persistent motor improvement leads us to conclude that unilateral selective lesion of the CM alone cannot be considered as a suitable surgical approach for the treatment of PD or levo-dopa-induced dyskinesias. The role of the caudal intralaminar nuclei in the pathophysiology of movement disorders of basal ganglia origin remains to be clarified. PMID:18175345

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Evidence for a Specific Integrative Mechanism for Episodic Memory Mediated by AMPA/kainate Receptors in a Circuit Involving Medial Prefrontal Cortex and Hippocampal CA3 Region.

PubMed

de Souza Silva, Maria A; Huston, Joseph P; Wang, An-Li; Petri, David; Chao, Owen Yuan-Hsin

2016-07-01

We asked whether episodic-like memory requires neural mechanisms independent of those that mediate its component memories for "what," "when," and "where," and if neuronal connectivity between the medial prefrontal cortex (mPFC) and the hippocampus (HPC) CA3 subregion is essential for episodic-like memory. Unilateral lesion of the mPFC was combined with unilateral lesion of the CA3 in the ipsi- or contralateral hemispheres in rats. Episodic-like memory was tested using a task, which assesses the integration of memories for "what, where, and when" concomitantly. Tests for novel object recognition (what), object place (where), and temporal order memory (when) were also applied. Bilateral disconnection of the mPFC-CA3 circuit by N-methyl-d-aspartate (NMDA) lesions disrupted episodic-like memory, but left the component memories for object, place, and temporal order, per se, intact. Furthermore, unilateral NMDA lesion of the CA3 plus injection of (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX) (AMPA/kainate receptor antagonist), but not AP-5 (NMDA receptor antagonist), into the contralateral mPFC also disrupted episodic-like memory, indicating the mPFC AMPA/kainate receptors as critical for this circuit. These results argue for a selective neural system that specifically subserves episodic memory, as it is not critically involved in the control of its component memories for object, place, and time. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Restoring penis sensation in patients with low spinal cord lesions: the role of the remaining function of the dorsal nerve in a unilateral or bilateral TOMAX procedure.

PubMed

Overgoor, Max L E; Braakhekke, Jan P; Kon, Moshe; De Jong, Tom P V M

2015-04-01

The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of the glans but this entails cutting both DNPs, risking patients' erection/ejaculation ability. The objective was to select patients for a bilateral TOMAX-procedure by measuring remaining DNP function, and perform the first bilateral cases. In 30 LSL patients with no penile- but normal groin sensation selected for a unilateral TOMAX-procedure the integrity of the sacral-reflex-arc and DNP function was tested pre-operatively using bilateral needle electromyography (EMG)-bulbocavernosus reflex (BCR) measurements, and an interview about reflex erections (RE) ability. In 13 spina bifida- and 17 spinal cord injury patients [median age 29.5 years (range 13-59 years), spinal lesion T12 (incomplete) to sacral], seven (23%) patients reported RE, four (57%) with intact BCR, and of nine (30%) patients with intact BCR, four reported RE (44%). Even patients with a LSL and no penile sensation can have signs of remaining DNP function, but cutting both DNPs to restore full glans sensation in a bilateral TOMAX-procedure might interfere with their RE/ejaculation. To avoid this risk, we propose a selecting-protocol for a unilateral- or bilateral procedure using RE and BCR measurements. Using this protocol, three patients were bilaterally operated with promising preliminary results. Full sensation of the glans could lead to further improvement in sexual function. © 2014 Wiley Periodicals, Inc.

Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy.

PubMed

Sadeghi, Soroush G; Minor, Lloyd B; Cullen, Kathleen E

2007-02-01

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1-12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5-15 Hz (20-80 degrees /s) and fast whole-body rotations reaching velocities of 500 degrees /s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of < or =2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

Dynamic nigrostriatal dopamine biases action selection

PubMed Central

Howard, Christopher D.; Li, Hao; Geddes, Claire E.; Jin, Xin

2017-01-01

Summary Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here, we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons, or optogenetic manipulation of dopamine concentration, alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions and have important implications for neurological disorders including Parkinson’s disease and substance dependence. PMID:28285820

Dynamic Nigrostriatal Dopamine Biases Action Selection.

PubMed

Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin

2017-03-22

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

Ambiguous genitalia in a fertile, unilaterally cryptorchid male miniature schnauzer dog.

PubMed

Breshears, M A; Peters, J L

2011-09-01

A 7-year-old male miniature schnauzer dog with unilateral cryptorchidism was presented for elective orchiectomy. Surgery to remove the cryptorchid testis revealed a fully formed uterus with horns attached to both testis and the body and cervix terminating at the prostate gland. The gross and microscopic diagnosis for the genital tract was persistent Müllerian duct syndrome with unilateral cryptorchidism. Additional associated lesions included cystic endometrial hyperplasia and a solitary, intratubular seminoma within the undescended testis. Persistent Müllerian duct syndrome is rare among domestic animals but is more common in miniature schnauzer dogs because of inheritance as an autosomal recessive trait.

Subchronic intermittent caffeine administration to unilaterally 6-hydroxydopamine-lesioned rats sensitizes turning behaviour in response to dopamine D(1) but not D(2) receptor agonists.

PubMed

Cauli, Omar; Pinna, Annalisa; Morelli, Micaela

2005-12-01

The effects of caffeine, an antagonist of adenosine A(1) and A(2A) receptors, are significantly influenced by modifications in dopamine transmission. Administration of caffeine to unilaterally 6-hydroxydopamine-lesioned rats induces ipsilateral turning behaviour in rats never exposed to a dopamine receptor agonist, whereas contralateral turning is elicited if rats are repeatedly primed with a dopamine receptor agonist. In this study, rats unilaterally lesioned with 6-hydroxydopamine and subchronically treated with an intermittent administration of caffeine (15 mg/kg) or vehicle, were administered, 3 days after discontinuations of the treatment, with the dopamine D(1) receptor agonist 1-phenyl 1,2,3,4,5-tetrahydro(1H)-3-benzazepine-7,8-diolhydrochloride (SKF 38393), the D(2)/D(3) receptor agonist quinpirole, the D(2) receptor agonist R(-)-propylnorapomorphine or the dopamine precursor L-3,4-dihydroxyphenyl-alanine. Administration of SKF 38393 (1.5 mg/kg) or L-3,4-dihydroxyphenyl-alanine (6 mg/kg), but not quinpirole (0.15 mg/kg) or R(-)-propylnorapomorphine (0.01 mg/kg), induced a significantly higher contralateral turning behaviour in rats subchronically treated with caffeine than in vehicle-pretreated rats. The results show that repeated intermittent caffeine exposure enhances the motor stimulant effects elicited by dopamine agonists by a preferential sensitization of dopamine D(1) receptors.

Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

PubMed

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-09-01

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binukumar, BK; Gupta, Nidhi; Bal, Amanjit

Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q{sub 10} (CoQ{sub 10}) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, {alpha}-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg bodymore » weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, {alpha}-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q{sub 10} (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q{sub 10} administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, {alpha}-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: > CoQ{sub 10} administration attenuates dichlorvos induced nigrostriatal neurodegenaration. > CoQ{sub 10} pre treatment leads to preservation of TH-IR neurons. > CoQ{sub 10} may decrease oxidative damage and {alpha}-synuclin aggregation. > CoQ{sub 10} treatment enhances motor function and protects rats from catalepsy.« less

Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys.

PubMed

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F; Mir, Anis; Schwab, Martin E; Belhaj-Saif, Abderraouf; Rouiller, Eric M

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns ("true" recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

Comparison of Functional Recovery of Manual Dexterity after Unilateral Spinal Cord Lesion or Motor Cortex Lesion in Adult Macaque Monkeys

PubMed Central

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F.; Mir, Anis; Schwab, Martin E.; Belhaj-Saif, Abderraouf; Rouiller, Eric M.

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns (“true” recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex. PMID:23885254

[Facial nerve injuries cause changes in central nervous system microglial cells].

PubMed

Cerón, Jeimmy; Troncoso, Julieta

2016-12-01

Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

Relationship Between Laryngeal Electromyography and Video Laryngostroboscopy in Vocal Fold Paralysis.

PubMed

Maamary, Joel A; Cole, Ian; Darveniza, Paul; Pemberton, Cecilia; Brake, Helen Mary; Tisch, Stephen

2017-09-01

The objective of this study was to better define the relationship of laryngeal electromyography and video laryngostroboscopy in the diagnosis of vocal fold paralysis. Retrospective diagnostic cohort study with cross-sectional data analysis METHODS: Data were obtained from 57 patients with unilateral vocal fold paralysis who attended a large tertiary voice referral center. Electromyographic findings were classified according to recurrent laryngeal nerve, superior laryngeal nerve, and high vagal/combined lesions. Video laryngostroboscopy recordings were classified according to the position of the immobile fold into median, paramedian, lateral, and a foreshortened/hooded vocal fold. The position of the paralyzed vocal fold was then analyzed according to the lesion as determined by electromyography. The recurrent laryngeal nerve was affected in the majority of cases with left-sided lesions more common than right. Vocal fold position differed between recurrent laryngeal and combined vagal lesions. Recurrent laryngeal nerve lesions were more commonly associated with a laterally displaced immobile fold. No fold position was suggestive of a combined vagal lesion. The inter-rater reliability for determining fold position was high. Laryngeal electromyography is useful in diagnosing neuromuscular dysfunction of the larynx and best practice recommends its continued implementation along with laryngostroboscopy. While recurrent laryngeal nerve lesions are more likely to present with a lateral vocal fold, this does not occur in all cases. Such findings indicate that further unknown mechanisms contribute to fold position in unilateral paralysis. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

AAV1/2-induced overexpression of A53T-α-synuclein in the substantia nigra results in degeneration of the nigrostriatal system with Lewy-like pathology and motor impairment: a new mouse model for Parkinson's disease.

PubMed

Ip, Chi Wang; Klaus, Laura-Christin; Karikari, Akua A; Visanji, Naomi P; Brotchie, Jonathan M; Lang, Anthony E; Volkmann, Jens; Koprich, James B

2017-02-01

α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson's disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5.16 x 10 12 gp/ml were unilaterally injected into the right SN of male adult C57BL/6 mice. Post-mortem examinations included immunohistochemistry to analyze nigral α-synuclein, Ser129 phosphorylated α-synuclein and TH expression, striatal dopamine transporter (DAT) levels by autoradiography and dopamine levels by high performance liquid chromatography. At 10 weeks, in AAV1/2-A53T α-synuclein mice there was a 33% reduction in TH+ dopaminergic nigral neurons (P < 0.001), 29% deficit in striatal DAT binding (P < 0.05), 38% and 33% reductions in dopamine (P < 0.001) and DOPAC (P < 0.01) levels and a 60% increase in dopamine turnover (homovanilic acid/dopamine ratio; P < 0.001). Immunofluorescence showed that the AAV1/2-A53T α-synuclein injected mice had widespread nigral and striatal expression of vector-delivered A53T-α-synuclein. Concurrent staining with human PD SN samples using gold standard histological methodology for Lewy pathology detection by proteinase K digestion and application of specific antibody raised against human Lewy body α-synuclein (LB509) and Ser129 phosphorylated α-synuclein (81A) revealed insoluble α-synuclein aggregates in AAV1/2-A53T α-synuclein mice resembling Lewy-like neurites and bodies. In the cylinder test, we observed significant paw use asymmetry in the AAV1/2-A53T α-synuclein group when compared to EV controls at 5 and 9 weeks post injection (P < 0.001; P < 0.05). These data show that unilateral injection of AAV1/2-A53T α-synuclein into the mouse SN leads to persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system and development of Lewy-like pathology, thereby reflecting clinical and pathological hallmarks of human PD.

Ultra-High Resolution Optical Coherence Tomography Imaging of Unilateral Drusen in a 31 Year Old Woman.

PubMed

de Carlo, Talisa E; Adhi, Mehreen; Lu, Chen D; Duker, Jay S; Fujimoto, James G; Waheed, Nadia K

We report a case of widespread unilateral drusen in a healthy 31 year old Caucasian woman using multi-modal imaging including ultra-high resolution optical coherence tomography (UHR-OCT). Dilated fundus exam showed multiple drusen-like lesions in the posterior pole without heme or fluid. Fundus auto fluorescence demonstrated hyperautofluorescent at the deposits. Fluorescein angiography revealed mild hyperfluorescence and staining of the lesions. Spectral-domain optical coherence tomography (SD-OCT) OS showed accumulations in the temporal macula at Bruch's membrane. UHR-OCT provided improved axial resolution compared to the standard 5 μm on the commercial SD-OCT and confirmed the presence of deposits in Bruch's membrane, consistent with drusen. The retinal layers were draped over the excrescences but did not show any disruption.

Differential Impact of Posterior Lesions in the Left and Right Hemisphere on Visual Category Learning and Generalization to Contrast Reversal

ERIC Educational Resources Information Center

Langguth, Berthold; Juttner, Martin; Landis, Theodor; Regard, Marianne; Rentschler, Ingo

2009-01-01

Hemispheric differences in the learning and generalization of pattern categories were explored in two experiments involving sixteen patients with unilateral posterior, cerebral lesions in the left (LH) or right (RH) hemisphere. In each experiment participants were first trained to criterion in a supervised learning paradigm to categorize a set of…

Somitic disruption of GNAS in chick embryos mimics progressive osseous heteroplasia

PubMed Central

Cairns, Dana M.; Pignolo, Robert J.; Uchimura, Tomoya; Brennan, Tracy A.; Lindborg, Carter M.; Xu, Meiqi; Kaplan, Frederick S.; Shore, Eileen M.; Zeng, Li

2013-01-01

Progressive osseous heteroplasia (POH) is a rare developmental disorder of heterotopic ossification (HO) caused by heterozygous inactivating germline mutations in the paternal allele of the GNAS gene. Interestingly, POH lesions have a bewildering mosaic distribution. Using clinical, radiographic, and photographic documentation, we found that most of the 12 individuals studied had a lesional bias toward one side or the other, even showing exclusive sidedness. Most strikingly, all had a dermomyotomal distribution of HO lesions. We hypothesized that somatic mutations in a progenitor cell of somitic origin may act on a background of germline haploinsufficiency to cause loss of heterozygosity at the GNAS locus and lead to the unilateral distribution of POH lesions. Taking advantage of the chick system, we examined our hypothesis by mimicking loss of heterozygosity of GNAS expression using dominant-negative GNAS that was introduced into a subset of chick somites, the progenitors that give rise to dermis and muscle. We observed rapid ectopic cartilage and bone induction at the axial and lateral positions in a unilateral distribution corresponding to the injected somites, which suggests that blocking GNAS activity in a targeted population of progenitor cells can lead to mosaic ectopic ossification reminiscent of that seen in POH. PMID:23863715

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

PubMed

Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

2018-01-01

Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

Callosal disconnection syndrome in a left-handed patient due to infarction of the total length of the corpus callosum.

PubMed

Lausberg, H; Göttert, R; Münssinger, U; Boegner, F; Marx, P

1999-03-01

We report on a left-handed patient with an ischemic infarction affecting exclusively the total length of the corpus callosum. This lesion clinically correlated with an almost complete callosal disconnection syndrome as described in callosotomy subjects, including unilateral verbal anosmia, hemialexia, unilateral ideomotor apraxia, unilateral agraphia, unilateral tactile anomia, unilateral constructional apraxia, lack of somesthetic transfer and dissociative phenomena. Despite the patient's left-handedness, his pattern of deficits was similar to the disconnection syndrome found in right-handers. Our report focusses on motor dominance and praxis. We followed-up the improvement in left apraxia and investigated the ability to initiate and learn a new visuo-motor skill. The results permit two tentative assumptions: (1) that the improvement in left apraxia was due to a compensatory increase in ipsilateral proximal muscle control, and (2) that motor dominance, i.e. the competence to initiate and learn a new movement pattern, was hemispherically dissociable from manual dominance in the sense of praxis control.

Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

PubMed

Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

2017-07-01

Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke

PubMed Central

Vahid-Ansari, F; Lagace, D C; Albert, P R

2016-01-01

Post-stroke depression (PSD) is a common outcome following stroke that is associated with poor recovery. To develop a preclinical model of PSD, we targeted a key node of the depression–anxiety circuitry by inducing a unilateral ischemic lesion to the medial prefrontal cortex (mPFC) stroke. Microinjection of male C57/BL6 mice with endothelin-1 (ET-1, 1600 pmol) induced a small (1 mm3) stroke consistently localized within the left mPFC. Compared with sham control mice, the stroke mice displayed a robust behavioral phenotype in four validated tests of anxiety including the elevated plus maze, light–dark, open-field and novelty-suppressed feeding tests. In addition, the stroke mice displayed depression-like behaviors in both the forced swim and tail suspension test. In contrast, there was no effect on locomotor activity or sensorimotor function in the horizontal ladder, or cylinder and home cage activity tests, indicating a silent stroke due to the absence of motor abnormalities. When re-tested at 6 weeks post stroke, the stroke mice retained both anxiety and depression phenotypes. Surprisingly, at 6 weeks post stroke the lesion site was infiltrated by neurons, suggesting that the ET-1-induced neuronal loss in the mPFC was reversible over time, but was insufficient to promote behavioral recovery. In summary, unilateral ischemic lesion of the mPFC results in a pronounced and persistent anxiety and depression phenotype with no evident sensorimotor deficits. This precise lesion of the depression circuitry provides a reproducible model to study adaptive cellular changes and preclinical efficacy of novel interventions to alleviate PSD symptoms. PMID:27483381

Osteochondritis Dissecans Lesions in Family Members: Does a Positive Family History Impact Phenotypic Potency?

PubMed

Gornitzky, Alex L; Mistovich, R Justin; Atuahuene, Brittany; Storey, Eileen P; Ganley, Theodore J

2017-06-01

Although repetitive microtrauma and athletic overuse patterns are most commonly associated with osteochondritis dissecans (OCD), recent studies have identified a potential genetic predisposition for OCD. Several case series have documented family pedigrees that support autosomal-dominant inheritance, but the families in these studies were all selected as a result of unique histories that may not accurately represent OCD inheritance patterns at large. Because there has been little investigation beyond these case reports, we aimed to describe a broader, more representative pattern of OCD inheritance applicable to all affected patients. (1) What proportion of patients treated for OCD of the knee have one or more immediate and/or extended family members with a history of OCD lesions? (2) Do patients with more phenotypically potent lesions, which we defined as patients with bilateral OCD lesions or patients who have undergone multiple procedures for OCD, have a higher frequency of affected relatives than those with less potent lesions? This retrospective study queried patient databases, diagnosis codes (International Classification of Diseases, 9th Revision), and surgical logs at a regional, tertiary care children's hospital to identify all patients treated over a 10-year period (March 2004-March 2014) by the senior author for OCD of the knee. All patients aged 0-18 years at the time of diagnosis were included. At our institution, patients with intact lesions are treated with a trial of conservative therapy; conversely, patients with a break in the articular cartilage and/or loose fragments of bone/cartilage are treated surgically. There were no OCD-specific contraindications to surgery. This search identified 543 patients. After patient identification, a questionnaire was designed that asked for the number, age, and gender of all immediate family members and the history of OCD lesions in any family member (immediate or extended). For all positive family members, patients were further queried regarding relevant clinical details to affirm a history of OCD. Patients were contacted by mailed questionnaires and phone calls for survey completion. All 543 patients received the survey, of which 103 (19%) responded to it and were included here. Responders were approximately 1 year younger than nonresponders; there was no difference in gender distribution. A retrospective chart review was then conducted to collect demographic information, phenotypic disease severity, and treatment details. Of the 103 included patients, 20 patients (19%) with unilateral lesions were managed nonoperatively ("conservative" group), 50 patients (49%) had unilateral lesions advanced to surgery ("unilateral" group), 21 patients (20%) had bilateral lesions managed either conservatively or surgically ("bilateral" group), and 12 patients (12%) underwent multiple procedures for the same lesion ("multiple" group). Of those included, 75 patients (73%) were treated surgically. With the numbers available, there were no baseline differences among the groups in terms of gender, lesion laterality, lesion location, or number of secondary procedures at the time of the initial surgical intervention. In total, 14 of 103 (14%) patients treated for OCD in this study had an immediate and/or extended family member with a history of OCD lesions. This included four of 20 (20%) patients in the conservative group, five of 50 (10%) in the unilateral group, four of 21 (19%) in the bilateral group, and one of 12 (8%) in the multiple group. With the numbers available, we did not identify a higher proportion of immediate and/or extended family members with a positive history of OCD in those patients with phenotypically potent lesions (bilateral and multiple) as compared with those with patients phenotypically less potent lesions (conservative and unilateral; five of 33 [15%] versus nine of 70 [13%]; odds ratio, 1.2; 95% confidence interval, 0.4-3.9; p = 0.751). In this broad, heterogeneous cohort of pediatric patients with OCD, the proportion of patients with a positive family history of OCD was 14%, which appeared to be much higher than the reported prevalence of OCD in the general population according to prior research. Therefore, our data provide preliminary support for a familial inheritance pattern for OCD, suggesting that further clinical, biologic, and genomic investigation might help to improve our understanding of who is at highest risk for OCD and what moderating factors might influence their disease severity and risk of progression. Furthermore, our data suggest that expanded patient education and screening regarding inheritance patterns might enhance identification of potential familial disease burden and improve access to timely and appropriate treatment. Level IV, prognostic study.

Diabetic muscle infarction: two cases: one with recurrent and bilateral lesions and one with usual unilateral involvement.

PubMed

Arroyave, Jorge A; Aljure, Dahyana Cadavid; Cañas, Carlos A; Vélez, Juan D; Abadía, Fabio Bonilla

2013-04-01

Diabetic muscle infarction is a rare complication of diabetes. We describe 2 cases of diabetic muscle infarction, each one of them with a particular form of clinical presentation: recurrence, bilateral engagement, and unilateral compromise. Both cases had history of poorly controlled diabetes mellitus and diabetic nephropathy. The diagnosis was based on clinical, imaging, and anatomopathological features. The treatment was with a close control of diabetes mellitus, analgesics, short-term immobilization, and physical therapy.

An incidental finding on a diagnostic CBCT: a case report.

PubMed

Lyros, Ioannis; Fora, Eleni; Damaskos, Spyridon; Stanko, Peter; Tsolakis, Apostolos

2014-05-01

It is known that Cone Beam Computed Tomography (CBCT) provides reliable spatial data and has many clinical applications for dental and particularly orthodontic patients. The present article provides a short review of the literature and reports an unusual CBCT finding in an orthodontic patient referred for the assessment of impacted upper canines. A unilateral lesion in the left maxillary sinus, was an incidental finding. Following a histological examination, which revealed unilateral nasal polyps, surgical removal was performed as the treatment of choice.

Nanoformulation: A Useful Therapeutic Strategy for Improving Neuroprotection and the Neurorestorative Potential in Experimental Models of Parkinson's Disease.

PubMed

Lafuente, Jose V; Requejo, Catalina; Carrasco, Alejandro; Bengoetxea, Harkaitz

2017-01-01

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle (MFB) or into the striatum in rats affords to study various stages of PD depending on the evolution time lapsed. A promising alternative to address the neurodegenerative process is the use of neurotrophic factors; but its clinical use has been limited due to its short half-life and rapid degradation after in vivo administration, along with difficulties for crossing the blood-brain barrier (BBB). Tyrosine hydroxylase (TH) immunostaining revealed a significant decrease of the TH-immunopositive striatal volume in 6-OHDA group from rostral to caudal one. The loss of TH-ir neurons and axodendritic network (ADN) was higher in caudal sections showing a selective vulnerability of the topological distributed dopaminergic system. In addition to a remarkable depletion of dopamine in the nigrostriatal system, the administration of 6-OHDA into MFB induces some other neuropathological changes such as an increase of glial fibrillary acidic protein (GFAP) positive cells in substantia nigra (SN) as well as in striatum. Intrastriatal implantation of micro- or nanosystems delivering neurotrophic factor in parkinsonized rats for bypassing BBB leads to a significative functional and morphological recovery. Neurorestorative morphological changes (preservation of the TH-ir cells and ADN) along the rostrocaudal axis of caudoputamen complex and SN have been probed supporting a selective recovering after the treatment as well. Others innovative therapeutic strategies, such as the intranasal delivery, have been recently assessed in order to search the NTF effects. In addition some others methodological key points are reviewed. © 2017 Elsevier Inc. All rights reserved.

Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988).

PubMed

O'Brien, R T; Evans, S M; Wortman, J A; Hendrick, M J

1996-02-01

To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Retrospective study. Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia.

Surgical treatment of lumbosacral foraminal stenosis using a lateral approach in twenty dogs with degenerative lumbosacral stenosis.

PubMed

Gödde, Thomas; Steffen, Frank

2007-10-01

To describe clinical signs, magnetic resonance imaging (MRI) and surgical findings using a lateral approach to the lumbosacral intervertebral foramen and to evaluate clinical outcomes in dogs with or without concurrent dorsal decompression and annulectomy. Retrospective study. Dogs (n=20) with degenerative lumbosacral stenosis (DLSS). Medical records (2002-2006) of dogs that had lumbosacral lateral foraminotomy alone or in combination with dorsal decompression were reviewed. Degree of dysfunction was assessed separately for each pelvic limb; dogs with unilateral signs were included in group A, those with bilateral signs in group B. Retrieved data were: signalment, history, neurologic status on admission, 3 days, 6 weeks, and 6 months postoperatively, duration of clinical signs, results of MRI, surgical site(s), intraoperative findings, and outcome. Based on the clinical and MRI findings unilateral foraminotomy was performed in 8 dogs, bilateral foraminotomy in 1 dog, unilateral foraminotomy with concurrent dorsal decompression in 7 dogs, and bilateral foraminotomy with concomitant dorsal decompression in 4 dogs. Surgery confirmed the presence of foraminal stenosis in all dogs, with osteophyte formation and soft tissue proliferations being the most common lesions. Outcome was good to excellent in 19 dogs and poor in 1 dog. Mean follow-up was 15.2 months (range, 6-42 months). Lateral foraminotomy addresses compressive lesions within exit and middle zones of the lumbosacral foramen. Successful surgical management of DLSS is dependent on recognition and correction of each of the compressive lesions within the lumbosacral junction.

Treadmill exercise alleviates nigrostriatal dopaminergic loss of neurons and fibers in rotenone-induced Parkinson rats.

PubMed

Shin, Mal-Soon; Kim, Tae-Woon; Lee, Jae-Min; Ji, Eun-Sang; Lim, Baek-Vin

2017-02-01

Parkinson disease is one of the common brain diseases caused by dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. In the present study, the effects of treadmill exercise on motor performance, dopaminergic loss of neurons and fibers, and α-synuclein expression in the nigrostriatum were evaluated using rotenone-induced Parkinson rats. For the induction of Parkinson rats, 3-mg/kg rotenone was injected, once a day for 14 consecutive days. Treadmill running was conducted for 30 min once a day during 14 consecutive days. Rota-rod test for motor balance and coordination and immunohistochemistry for tyrosine hydroxylase and α-synuclein in the nigrostriatum were performed. In the present study, motor balance and coordination was disturbed by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated motor dysfunction in the rotenone-induced Parkinson rats. Nigrostriatal dopaminergic loss of neurons and fibers was occurred by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated nigrostriatal dopaminergic loss of neurons and fibers in the rotenone-induced Parkinson rats. α-Synuclein expression in the nigrostriatum was enhanced by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise suppressed α-synuclein expression in the rotenone-induced Parkinson rats. Treadmill exercise improved motor function through preservation of nigrostriatal dopaminergic neurons and fibers and suppression of nigrostriatal formation of Lewy bodies in rotenone-induced Parkinson rats.

Primate translational vestibuloocular reflexes. IV. Changes after unilateral labyrinthectomy

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; Newlands, S. D.; Dickman, J. D.

2000-01-01

The effects of unilateral labyrinthectomy on the properties of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient displacements. During small-amplitude, steady-state sinusoidal lateral oscillations, a small decrease in the horizontal trVOR sensitivity and its dependence on viewing distance was observed during the first week after labyrinthectomy. These deficits gradually recovered over time. In addition, the vertical response component increased, causing a tilt of the eye velocity vector toward the lesioned side. During large, transient lateral displacements, the deficits were larger and longer lasting. Responses after labyrinthectomy were asymmetric, with eye velocity during movements toward the side of the lesion being more compromised. The most profound effect of the lesions was observed during fore-aft motion. Whereas responses were kinematically appropriate for fixation away from the side of the lesion (e.g., to the left after right labyrinthectomy), horizontal responses were anticompensatory during fixation at targets located ipsilateral to the side of the lesion (e.g., for targets to the right after right labyrinthectomy). This deficit showed little recovery during the 3-mo post-labyrinthectomy testing period. These results suggest that inputs from both labyrinths are important for the proper function of the trVORs, although the details of how bilateral signals are processed and integrated remain unknown.

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

PubMed

Lane, E L; Cheetham, S; Jenner, P

2008-01-01

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

PubMed

Hiasa, Y; Konishi, N; Nakaoka, S; Nakamura, T; Nishii, K; Ohshima, M

1992-07-01

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

Promoting Effects of Potassium Dibasic Phosphate on Early‐stage Renal Carcinogenesis in Unilaterally Nephrectomized Rats Treated with N‐Ethyl‐N‐hydroxyethylnitrosamine

PubMed Central

Konishi, Noboru; Nakaoka, Shingo; Nakamura, Toshimitsu; Nishii, Kiyoji; Ohshima, Masato

1992-01-01

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early‐stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not. PMID:1517146

Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis and subluxated lens: case report and review of literature.

PubMed

Vanathi, M; Sen, Seema; Panda, Anita; Dada, Tanuj; Behera, Geeta; Khokhar, Sudharshan

2007-01-01

To report the unusual association of unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens. A 20-year old man presented with a mass lesion involving the left cornea. The corneal lesion had been present since birth. On biomicroscopic examination, a well-defined vascularized, grayish-white mass occupying the whole of the left cornea was seen. The right eye showed multiple peripheral corneal opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a subluxated lens. Excision biopsy of the mass was done for histopathologic examination. Histopathologic examination of the excised corneal mass showed features consistent with that of a corneal keloid: thickened keratinized epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed of hyalinized collagen fibers with irregular orientation of the collagen lamellae. During penetrating keratoplasty of the left eye, an anomalous iris pattern with poorly defined angle and a supranasal subluxated lens was also observed. Extraction of the subluxated lens was also done. The graft failed subsequent to a nonhealing persistent epithelial defect. Our case report highlights the rare association of a unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

Efficacy of baby-CIMT: study protocol for a randomised controlled trial on infants below age 12 months, with clinical signs of unilateral CP

PubMed Central

2014-01-01

Background Infants with unilateral brain lesions are at high risk of developing unilateral cerebral palsy (CP). Given the great plasticity of the young brain, possible interventions for infants at risk of unilateral CP deserve exploration. Constraint-induced movement therapy (CIMT) is known to be effective for older children with unilateral CP but is not systematically used for infants. The development of CIMT for infants (baby-CIMT) is described here, as is the methodology of an RCT comparing the effects on manual ability development of baby-CIMT versus baby-massage. The main hypothesis is that infants receiving baby-CIMT will develop manual ability in the involved hand faster than will infants receiving baby-massage in the first year of life. Method and design The study will be a randomised, controlled, prospective parallel-group trial. Invited infants will be to be randomised to either the baby-CIMT or the baby-massage group if they: 1) are at risk of developing unilateral CP due to a known neonatal event affecting the brain or 2) have been referred to Astrid Lindgren Children’s Hospital due to asymmetric hand function. The inclusion criteria are age 3–8 months and established asymmetric hand use. Infants in both groups will receive two 6-weeks training periods separated by a 6-week pause, for 12 weeks in total of treatment. The primary outcome measure will be the new Hand Assessment for Infants (HAI) for evaluating manual ability. In addition, the Parenting Sense of Competence scale and Alberta Infant Motor Scale will be used. Clinical neuroimaging will be utilized to characterise the brain lesion type. To compare outcomes between treatment groups generalised linear models will be used. Discussion The model of early intensive intervention for hand function, baby-CIMT evaluated by the Hand Assessment for Infants (HAI) will have the potential to significantly increase our understanding of how early intervention of upper limb function in infants at risk of developing unilateral CP can be performed and measured. Trial registration SFO-V4072/2012, 05/22/2013 PMID:24903062

Nuclear microscopy in Parkinson's disease

NASA Astrophysics Data System (ADS)

Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.

1995-09-01

Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

PubMed

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

Lateral parabrachial nucleus mediates shortening of expiration during hypoxia.

PubMed

Song, Gang; Poon, Chi-Sang

2009-01-01

Acute hypoxia elicits complex time-dependent responses including rapid augmentation of inspiratory drive, shortening of inspiratory and expiratory durations (T(I), T(E)), and short-term potentiation and depression. The central pathways mediating these varied effects are largely unknown. Here, we show that the lateral parabrachial nucleus (LPBN) of the dorsolateral pons specifically mediates T(E)-shortening during hypoxia and not other hypoxic response components. Twelve urethane-anesthetized and vagotomized adult Sprague-Dawley rats were exposed to 1-min poikilocapnic hypoxia before and after unilateral kainic acid or bilateral electrolytic lesioning of the LPBN. Bilateral lesions resulted in a significant increase in baseline T(E) under hyperoxia. After unilateral or bilateral lesions, the decrease in T(E) during hypoxia was markedly attenuated without appreciable changes in all other hypoxic response components. These findings add to the mounting evidence that the central processing of peripheral chemoafferent inputs is segregated into parallel integrator and differentiator (low-pass and high-pass filter) pathways that separately modulate inspiratory drive, T(I), T(E) and resultant short-term potentiation and depression.

Ipsilateral visual illusion after unilateral posterior cerebral artery infarction: a report of two cases.

PubMed

Hong, Yoon Hee; Lim, Tae-Sung; Yong, Suk Woo; Moon, So Young

2010-08-15

In cases of unilateral posterior cerebral artery (PCA) infarction, abnormal visual perception in the ipsilateral visual field, which is usually believed to be intact, is not met frequently and may confuse doctors during evaluation. Recently, we observed two patients who presented with contralateral hemianopsia accompanied by ipsilateral visual illusions after acute unilateral PCA infarctions. Their visual illusion was characterized by zooming in, macropsia or micropsia. These symptoms appeared to be related to deficits in size constancy. Lesions of both patients commonly involved the ipsilateral forceps major. The consistent presentation observed in these two patients suggests that dominance of size constancy can be located in the left hemisphere in some individuals. Copyright (c) 2010 Elsevier B.V. All rights reserved.

A cavernous sinus lesion clinically responsive to steroids.

PubMed

Ruff, M W; Carabenciov, I D; Johnson, D R; Pollock, B E; Parisi, J E; Klaas, J P

2018-04-20

Tolosa Hunt syndrome (THS) is characterized by painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus. The characteristic finding on MRI is an enhancing T1 isointense and T2 hypo- or hyperintense cavernous sinus mass lesion, which may result in focal narrowing of the ipsilateral internal carotid artery. Although the incidence is quite rare, it is a common diagnostic consideration in cases that present with multiple cranial neuropathies. However, the differential diagnosis for a unilateral cavernous sinus lesion in adults is broad and includes neoplastic, inflammatory (such as sarcoidosis and immunoglobulin G4-related disease [IgG4-RD]), infectious etiologies (such as syphilis and leprosy), as well as vascular lesions. We describe a patient presenting with neurologic symptoms referable to a persistent unilateral cavernous sinus MRI abnormality, initially thought to be consistent with Tolosa-Hunt syndrome, that was clinically but not radiographically responsive to steroids. Following reevaluation due to the presence of new symptoms, pathology revealed that the abnormality was most consistent with chordoma, a rare skull based tumor. In patients with a presumed diagnosis of Tolosa-Hunt syndrome, close clinical and radiographic follow-up is imperative, with early consideration for biopsy in patients that fail to respond to treatment both clinically and radiographically. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rat brain sagittal organotypic slice cultures as an ex vivo dopamine cell loss system.

PubMed

McCaughey-Chapman, Amy; Connor, Bronwen

2017-02-01

Organotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures. Building on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss. We show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture. Using Fluoro-Gold axonal tracing, we demonstrate that the slice 3-dimensional cytoarchitecture is maintained over a 4 week culturing period, with particular focus on the nigrostriatal pathway. Treatment of the cultures with 6-hydroxydopamine and desipramine induces a progressive loss of Fluoro-Gold-positive nigral cells with a sustained loss of tyrosine hydroxylase-positive nigral cells. This recapitulates the pattern of dopaminergic degeneration observed in the rat partial 6-hydroxydopamine lesion model and, most importantly, the progressive pathology of Parkinson's disease. Our slice culture platform provides an advance over other systems, as we demonstrate for the first time 3-dimensional cytoarchitecture maintenance of rat nigrostriatal sagittal slices for up to 6 weeks. Our ex vivo organotypic slice culture system provides a long term cellular platform to model Parkinson's disease, allowing for the elucidation of mechanisms involved in dopaminergic neuron degeneration and the capability to study cellular integration and plasticity ex vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

PubMed

Fernández-Espejo, Emilio; Bis-Humbert, Cristian

2018-06-06

3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in cellular, enteric and brain approaches of Parkinsonism in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

The behavioural and neuropathological impact of intranigral AAV-α-synuclein is exacerbated by systemic infusion of the Parkinson's disease-associated pesticide, rotenone, in rats.

PubMed

Mulcahy, Pádraig; O'Doherty, Aideen; Paucard, Alexia; O'Brien, Timothy; Kirik, Deniz; Dowd, Eilís

2013-04-15

Despite the widely held belief that Parkinson's disease is caused by both underlying genetics and exposure to environmental risk factors, it is still widely modelled in preclinical models using a single genetic or neurotoxic insult. This single-insult approach has resulted in a variety of models that are limited with respect to their aetiological, construct, face and/or predictive validity. Thus, the aim of the current study was to investigate the interplay between genes and the environment as an alternative approach to modelling Parkinson's disease. To do so, rats underwent stereotaxic surgery for unilateral delivery of the Parkinson's disease-associated gene, α-synuclein, into the substantia nigra (using AAV vectors). This was followed 13 weeks later by subcutaneous implantation of an osmotic minipump delivering the Parkinson's disease-associated pesticide, rotenone (2.5mgkg(-1)day(-1) for 4 weeks). The effect of the genetic and environmental insults alone or in combination on lateralised motor performance (Corridor, Stepping and Whisker Tests), nigrostriatal integrity (tyrosine hydroxylase immunohistochemistry) and α-synucleinopathy (α-synuclein immunohistochemistry) was assessed. We found that exposing AAV-α-synuclein-treated rats to rotenone led to a model in which the classical Parkinson's disease triad of progressive motor dysfunction, nigrostriatal neurodegeneration and α-synucleinopathy was evident. However, delivering rotenone systemically was also associated with bilateral motor dysfunction and loss of body weight. Thus, although we have shown that Parkinson's disease can be modelled in experimental animals by combined exposure to both genetic and environmental risk factors, this approach is limited by systemic toxicity of the pesticide rotenone. Direct intracerebral delivery of rotenone may be more useful in longer-term studies as we have previously shown that it overcomes this limitation. Copyright © 2013 Elsevier B.V. All rights reserved.

Clinical, Dopaminergic, and Metabolic Correlations in Parkinson Disease: A Dual-Tracer PET Study.

PubMed

Liu, Feng-Tao; Ge, Jing-Jie; Wu, Jian-Jun; Wu, Ping; Ma, Yilong; Zuo, Chuan-Tao; Wang, Jian

2018-05-31

Neuroimaging indicators of Parkinson disease have been developed and applied in clinical practices. Dopaminergic imaging reflects nigrostriatal dopaminergic dysfunction, and metabolic network imaging offers disease-related metabolic changes at a system level. We aimed to elucidate the association between Parkinsonian symptoms and neuroimaging, and interactions between different imaging techniques. We conducted a dual-tracer PET study for the combined assessments of dopaminergic binding (C-CFT) and glucose metabolism (F-FDG) in 103 participants with Parkinson disease (65 male and 38 female subjects). The detailed clinical rating scores were systematically collected in all members. The interactions among dopaminergic bindings, metabolic changes, and clinical manifestations were evaluated at voxel, regional, and network levels. Striatal DAT binding correlated with akinesia-rigidity (P < 0.001) but not with tremor; the metabolic PET imaging, nonspecific to the dopaminergic dysfunction, disclosed a set of brain regions correlating with the cardinal symptoms, including tremor. In addition, the unilateral symptom correlated with the contralateral nigrostriatal dopamine loss, but with bilateral metabolic changes, suggesting their differences in the application of disease-related mechanistic studies. Further imaging-imaging correlation study revealed that dopaminergic dysfunction correlated with widely distributed metabolic changes in Parkinson disease, and the modest correlations supported the findings on the clinical-imaging correlation. In this dual-tracer PET study, we demonstrated the robust interactions among dopaminergic dysfunction, metabolic brain changes and clinical manifestations at voxel, regional, and network levels. Our findings might promote the understanding in the proper application of dopaminergic and metabolic PET imaging in Parkinson disease and offer more evidence in support of Parkinsonian pathophysiological mechanisms.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Alteration of Striatal Tetrahydrobiopterin in Iron-Induced Unilateral Model of Parkinson's Disease

PubMed Central

Aryal, Bijay; Lee, Jin-Koo; Kim, Hak Rim

2014-01-01

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin (BH4) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of BH4 into neuron would induce the neuronal toxicity in vitro. To elucidate a role of BH4 in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and BH4 at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and BH4 levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of BH4 was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of BH4 in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both BH4 and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of BH4 can deteriorate the disease progression in early phase of PD, and the inhibition of BH4 increase could be a strategy for PD treatment. PMID:24757374

Absence of Ret Signaling in Mice Causes Progressive and Late Degeneration of the Nigrostriatal System

PubMed Central

Kramer, Edgar R; Aron, Liviu; Ramakers, Geert M. J; Seitz, Sabine; Zhuang, Xiaoxi; Beyer, Klaus; Smidt, Marten P; Klein, Rüdiger

2007-01-01

Support of ageing neurons by endogenous neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. GDNF has been tested in clinical trials for the treatment of Parkinson disease (PD), a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA neurons in PD animal models. The physiological roles of GDNF and BDNF signaling in the adult nigrostriatal DA system are unknown. We generated mice with regionally selective ablations of the genes encoding the receptors for GDNF (Ret) and BDNF (TrkB). We find that Ret, but not TrkB, ablation causes progressive and adult-onset loss of DA neurons specifically in the substantia nigra pars compacta, degeneration of DA nerve terminals in striatum, and pronounced glial activation. These findings establish Ret as a critical regulator of long-term maintenance of the nigrostriatal DA system and suggest conditional Ret mutants as useful tools for gaining insights into the molecular mechanisms involved in the development of PD. PMID:17298183

Influence of gravity on the spatial orientation of eye nystagmus induced by unilateral lesion of horizontal semicircular canal.

PubMed

Pettorossi, V E; Ermanno, M; Pierangelo, E; Silvarosa, G

2000-03-01

The influence of gravity in the orientation and slow phase eye velocity of the ocular nystagmus following unilateral damage of the cupula in the ampulla of the horizontal semicircular canal (UHCD) was investigated. The nystagmus was analysed at different sagittal head positions using the x-y infrared eye monitor technique. The nystagmus was almost horizontal at 0 degrees head pitch angle and remained partially fixed in space when the head was pitched upward or downward. The reorientation gain of the slow and quick phases was high (about 0.75) within +/- 45 degrees of head pitch angle, but beyond this range, it decreased greatly. The gain value depended on the lesion extension to otolithic receptors. The absolute value of the slow phase eye velocity of UHCD nystagmus was also modified systematically by the head pitch, showing a reduction in the upward and an increase in the downward.

A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

PubMed

Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

2004-06-01

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson's disease.

PubMed

Caminiti, Silvia Paola; Presotto, Luca; Baroncini, Damiano; Garibotto, Valentina; Moresco, Rosa Maria; Gianolli, Luigi; Volonté, Maria Antonietta; Antonini, Angelo; Perani, Daniela

2017-01-01

A progressive loss of dopamine neurons in the substantia nigra (SN) is considered the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological evidence however suggests that the axons of the nigrostriatal dopaminergic system are the earliest target of α-synuclein accumulation in PD, thus the principal site for vulnerability. Whether this applies to in vivo PD, and also to the mesolimbic system has not been investigated yet. We used [ 11 C]FeCIT PET to measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and mesolimbic systems, in 36 early PD patients (mean disease duration in months ± SD 21.8 ± 10.7) and 14 healthy controls similar for age. We also performed anatomically-driven partial correlation analysis to evaluate possible changes in the connectivity within both the dopamine networks at an early clinical phase. In the nigrostriatal system, we found a severe DAT reduction in the afferents to the dorsal putamen (DPU) (η 2  = 0.84), whereas the SN was the less affected region (η 2  = 0.31). DAT activity in the ventral tegmental area (VTA) and the ventral striatum (VST) were also reduced in the patient group, but to a lesser degree (VST η 2  = 0.71 and VTA η 2  = 0.31). In the PD patients compared to the controls, there was a marked decrease in dopamine network connectivity between SN and DPU nodes, supporting the significant derangement in the nigrostriatal pathway. These results suggest that neurodegeneration in the dopamine pathways is initially more prominent in the afferent axons and more severe in the nigrostriatal system. Considering PD as a disconnection syndrome starting from the axons, it would justify neuroprotective interventions even if patients have already manifested clinical symptoms.

What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

PubMed Central

Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

2014-01-01

One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

PubMed

Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

2011-01-01

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

PubMed Central

Simmons, Camilla; Mesquita, Michel B.; Wood, Tobias C.; Williams, Steve C. R.; Vernon, Anthony C.; Cash, Diana

2017-01-01

Resting-state functional MRI (rsfMRI) is an imaging technology that has recently gained attention for its ability to detect disruptions in functional brain networks in humans, including in patients with Parkinson’s disease (PD), revealing early and widespread brain network abnormalities. This methodology is now readily applicable to experimental animals offering new possibilities for cross-species translational imaging. In this context, we herein describe the application of rsfMRI to the unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat, a robust experimental model of the dopamine depletion implicated in PD. Using graph theory to analyse the rsfMRI data, we were able to provide meaningful and translatable measures of integrity, influence and segregation of the underlying functional brain architecture. Specifically, we confirm that rats share a similar functional brain network topology as observed in humans, characterised by small-worldness and modularity. Interestingly, we observed significantly reduced functional connectivity in the 6-OHDA rats, primarily in the ipsilateral (lesioned) hemisphere as evidenced by significantly lower node degree, local efficiency and clustering coefficient in the motor, orbital and sensorimotor cortices. In contrast, we found significantly, and bilaterally, increased thalamic functional connectivity in the lesioned rats. The unilateral deficits in the cortex are consistent with the unilateral nature of this model and further support the validity of the rsfMRI technique in rodents. We thereby provide a methodological framework for the investigation of brain networks in other rodent experimental models of PD, as well as of animal models in general, for cross-comparison with human data. PMID:28249008

Calf enlargement associated with neurologic disease: two uncommon cases.

PubMed

Harwood, S C; Honet, J C

1988-01-01

Muscle enlargement and hypertrophy are rare findings in neurogenic lesions. The two in combination have been reported in cases of peripheral nerve lesions, polyneuropathy, and poliomyelitis. True and pseudo muscle hypertrophy are the two possible etiologies, whereas infiltration, stretch, or exercise of the muscle are the causative factors. We report two cases of unilateral calf enlargement, one occurring after surgery for S1 radiculopathy with associated cramping, and the other after poliomyelitis.

Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.

PubMed

Sonsalla, P K; Nicklas, W J; Heikkila, R E

1989-01-20

The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.

Effect of sensory and motor connectivity on hand function in pediatric hemiplegia.

PubMed

Gupta, Disha; Barachant, Alexandre; Gordon, Andrew M; Ferre, Claudio; Kuo, Hsing-Ching; Carmel, Jason B; Friel, Kathleen M

2017-11-01

We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions. Twenty-four children with unilateral cerebral palsy had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked electroencephalographic potentials. Tractography of the corticospinal tract and the medial lemniscus was performed with diffusion tensor imaging, and lesions were classified by magnetic resonance imaging. Anatomical and physiological results were correlated with measures of hand function using 2 independent statistical methods. Children with disruptions in the somatosensory connectivity and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function. Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. Ann Neurol 2017;82:766-780. © 2017 American Neurological Association.

Facial recognition in children after perinatal stroke.

PubMed

Ballantyne, A O; Trauner, D A

1999-04-01

To examine the effects of prenatal or perinatal stroke on the facial recognition skills of children and young adults. It was hypothesized that the nature and extent of facial recognition deficits seen in patients with early-onset lesions would be different from that seen in adults with later-onset neurologic impairment. Numerous studies with normal and neurologically impaired adults have found a right-hemisphere superiority for facial recognition. In contrast, little is known about facial recognition in children after early focal brain damage. Forty subjects had single, unilateral brain lesions from pre- or perinatal strokes (20 had left-hemisphere damage, and 20 had right-hemisphere damage), and 40 subjects were controls who were individually matched to the lesion subjects on the basis of age, sex, and socioeconomic status. Each subject was given the Short-Form of Benton's Test of Facial Recognition. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and multiple regression. The lesion subjects performed significantly more poorly than did matched controls. There was no clear-cut lateralization effect, with the left-hemisphere group performing significantly more poorly than matched controls and the right-hemisphere group showing a trend toward poorer performance. Parietal lobe involvement, regardless of lesion side, adversely affected facial recognition performance in the lesion group. Results could not be accounted for by IQ differences between lesion and control groups, nor was lesion severity systematically related to facial recognition performance. Pre- or perinatal unilateral brain damage results in a subtle disturbance in facial recognition ability, independent of the side of the lesion. Parietal lobe involvement, in particular, has an adverse effect on facial recognition skills. These findings suggest that the parietal lobes may be involved in the acquisition of facial recognition ability from a very early point in brain development, but that there is sufficient potential to reorganize or compensate such that the residual deficits, though significant, are subtle.

Pan-brachial plexus neuropraxia following lightning: A rare case report.

PubMed

Patnaik, Ashis; Mahapatra, Ashok Kumar; Jha, Menka

2015-01-01

Neurological complications following lightning are rare and occur in form of temporary neurological deficits of central origin. Involvement of peripheral nervous system is extremely rare and only a few cases have been described in the literature. Isolated unilateral pan-brachial plexus neuropraxia has never been reported in the literature. Steroids have long been used for treatment of neuropraxia. However, their use in lightning neural injury is unique and requires special mention. We report a rare case of lightning-induced unilateral complete flaccid paralysis along with sensory loss in a young patient. Lightning typically causes central nervous involvement in various types of motor and sensory deficit. Surprisingly, the nerve conduction study showed the involvement of peripheral nervous system involvement. Steroids were administered and there was significant improvement in neurological functions within a short span of days. Patients' functions in the affected limb were normal in one month. Our case was interesting since it is the first such case in the literature where lightning has caused such a rare instance of unilateral pan-brachial plexus lesion. Such cases when seen, raises the possibility of more common central nervous system pathology rather than peripheral involvement. However, such lesions can be purely benign forms of peripheral nerve neuropraxia, which can be managed by steroid treatment without leaving any long-term neurological deficits.

Asymmetric vestibular stimulation reveals persistent disruption of motion perception in unilateral vestibular lesions.

PubMed

Panichi, R; Faralli, M; Bruni, R; Kiriakarely, A; Occhigrossi, C; Ferraresi, A; Bronstein, A M; Pettorossi, V E

2017-11-01

Self-motion perception was studied in patients with unilateral vestibular lesions (UVL) due to acute vestibular neuritis at 1 wk and 4, 8, and 12 mo after the acute episode. We assessed vestibularly mediated self-motion perception by measuring the error in reproducing the position of a remembered visual target at the end of four cycles of asymmetric whole-body rotation. The oscillatory stimulus consists of a slow (0.09 Hz) and a fast (0.38 Hz) half cycle. A large error was present in UVL patients when the slow half cycle was delivered toward the lesion side, but minimal toward the healthy side. This asymmetry diminished over time, but it remained abnormally large at 12 mo. In contrast, vestibulo-ocular reflex responses showed a large direction-dependent error only initially, then they normalized. Normalization also occurred for conventional reflex vestibular measures (caloric tests, subjective visual vertical, and head shaking nystagmus) and for perceptual function during symmetric rotation. Vestibular-related handicap, measured with the Dizziness Handicap Inventory (DHI) at 12 mo correlated with self-motion perception asymmetry but not with abnormalities in vestibulo-ocular function. We conclude that 1 ) a persistent self-motion perceptual bias is revealed by asymmetric rotation in UVLs despite vestibulo-ocular function becoming symmetric over time, 2 ) this dissociation is caused by differential perceptual-reflex adaptation to high- and low-frequency rotations when these are combined as with our asymmetric stimulus, 3 ) the findings imply differential central compensation for vestibuloperceptual and vestibulo-ocular reflex functions, and 4 ) self-motion perception disruption may mediate long-term vestibular-related handicap in UVL patients. NEW & NOTEWORTHY A novel vestibular stimulus, combining asymmetric slow and fast sinusoidal half cycles, revealed persistent vestibuloperceptual dysfunction in unilateral vestibular lesion (UVL) patients. The compensation of motion perception after UVL was slower than that of vestibulo-ocular reflex. Perceptual but not vestibulo-ocular reflex deficits correlated with dizziness-related handicap. Copyright © 2017 the American Physiological Society.

Dilatation of the Virchow-Robin spaces as an indicator of unilateral carotid artery stenosis: correlation with white matter lesions.

PubMed

Sahin, Neslin; Solak, Aynur; Genc, Berhan; Akpinar, Mehmet Besir

2015-07-01

Virchow-Robin space (VRS) dilatation is related to many pathologic conditions, mostly associated with vascular abnormalities. White matter lesions (WMLs) are commonly seen on brain magnetic resonance imaging (MRI) with advancing age and generally considered as potential markers for vascular disease. To investigate if asymmetric dilatation of VRSs and WMLs are associated with unilateral internal carotid artery stenosis (ICAS) and to test the relationship between dilated VRSs and common vascular risk factors. Twenty-nine patients (18 men, 11 women; mean age, 68.62 years) with unilateral ICAS (≥70% carotid stenosis) undergoing carotid endarterectomy were identified for this Health Insurance Portability and Accountability Act (HIPAA) compliant prospective study and assessed with brain MRI. Two experienced radiologists scored VRSs and WMLs and evaluated old infarcts, chronic lacunar infarcts, and cerebral atrophy. Asymmetry of WML and VRS scores between two cerebral hemispheres was assessed and associations between VRS scores, WML scores, and explanatory variables (e.g. age, sex, vascular risk factors, and atrophy) were tested. In this study, WMLs and basal ganglia VRSs were significantly greater in the unilateral hemisphere with ICA stenosis than contralateral hemisphere. Basal ganglia VRSs were associated with WMLs and internal cerebral atrophy. No association between the severity of VRSs and vascular risk factors was found. ICA stenosis may contribute as a factor in the development of WMLs and dilatation of VRSs by causing chronic hypoperfusion. VRS dilatation may be an additional MRI marker of ICAS. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Congenital syphilis: an unusual presentation.

PubMed

Dzebolo, N N

1980-08-01

Congenital syphilis was discovered in a neonate with the unusual radiographic presentation of unilateral involvement of three bones showing lytic lesions and periostitis. Congenital syphilis should be considered in a newborn infant with these radiographic manifestations, especially when a suggestive history is obtained.

Epilepsy surgery in patients with malformations of cortical development.

PubMed

Lüders, Hans; Schuele, Stephan U

2006-04-01

Patients with malformations of cortical development often suffer from intractable focal epilepsy. This review considers recent progress in the selection and seizure outcome of patients undergoing resective epilepsy surgery for this condition. Patients with malformations of cortical development restricted to part or even a whole hemisphere may be candidates for epilepsy surgery even when, due to microscopic malformations, magnetic resonance imaging shows no detectable lesion. Despite recent advances in structural and functional imaging, the majority of patients with this condition undergo invasive evaluation. Patients with focal cortical dysplasia, with and without a detectable lesion on magnetic resonance imaging, often have a favorable outcome with epilepsy surgery. The underlying pathological substrate seems to be a better predictor for surgical outcome in patients with focal cortical dysplasia than the presence of a lesion on magnetic resonance imaging. Epilepsy surgery can be offered in a highly selected subgroup of patients with unilateral nodular heterotopia. Seizures in hemimegalencephaly may respond favorably to hemispherectomy, although most children will continue to have seizures and significant functional impairments. Patients with focal epilepsy due to malformations of cortical development are often intractable to medical management. Resective epilepsy surgery can be beneficial, particularly for patients with focal cortical dysplasia and unilateral hemispheric malformations.

Behavioral, neurochemical, and electrophysiological changes in an early spontaneous mouse model of nigrostriatal degeneration.

PubMed

Sgadò, Paola; Viaggi, Cristina; Pinna, Annalisa; Marrone, Cristina; Vaglini, Francesca; Pontis, Silvia; Mercuri, Nicola Biagio; Morelli, Micaela; Corsini, Giovanni Umberto

2011-08-01

In idiopathic Parkinson's disease, clinical symptoms do not emerge until consistent neurodegeneration has occurred. The late appearance of symptoms implies the existence of a relatively long preclinical period during which several disease-induced neurochemical changes take place to mask the existence of the disease and delay its clinical manifestations. The aim of this study was to examine the neurochemical, neurophysiological, and behavioral changes induced by the loss of nigrostriatal innervation in the En1+/-;En2-/- mouse, in the 10 months following degeneration, compared to En2 null mutant mice. Behavioral analysis (Pole-test, Beam-walking test, and Inverted grid test) and field potential recordings in the striatum indicated that loss of ~70% of nigrostriatal neurons produced no significant functional effects until 8 months of age, when En1+/-;En2-/- animals started to show frank motor deficits and electrophysiological alterations in corticostriatal plasticity. Similarly, alterations in dopamine homeostasis, dopamine turnover, and dopamine innervation were observed in aged animals compared to young En1+/-;En2-/- mice. These data suggests that in En1+/-;En2-/- mice nigrostriatal degeneration in the substantia nigra is functionally compensated.

Paroxetine prevents loss of nigrostriatal dopaminergic neurons by inhibiting brain inflammation and oxidative stress in an experimental model of Parkinson's disease.

PubMed

Chung, Young C; Kim, Sang R; Jin, Byung K

2010-07-15

The present study examined whether the antidepressant paroxetine promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Real-time PCR, Western blotting, and immunohistochemistry showed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase and astroglial myeloperoxidase, and subsequent reactive oxygen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with paroxetine prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by paroxetine was associated with the suppression of astroglial myeloperoxidase expression and/or NADPH oxidase-derived reactive oxygen species production and reduced expression of proinflammatory cytokines, including IL-1beta, TNF-alpha, and inducible NO synthase, by activated microglia. The present findings show that paroxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress, suggesting that paroxetine and its analogues may have therapeutic value in the treatment of aspects of Parkinson's disease related to neuroinflammation.

Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

PubMed

Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

2007-02-09

Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward a lesion area in the striatum.

Enlarged thalamostriate vein causing unilateral Monro foramen obstruction. Case report.

PubMed

Leonardo, Jody; Grand, Walter

2009-06-01

Causes of unilateral hydrocephalus resulting from an obstruction at the Monro foramen include foraminal atresia, tumors, gliosis, contralateral shunting, and infectious and inflammatory conditions. However, few reports in the literature cite vascular lesions as the cause of the obstruction. To their knowledge, the authors present the first report of unilateral hydrocephalus occurring due to an abnormally enlarged thalamostriate vein independent of an arteriovenous malformation or developmental venous angioma. The condition was treated successfully by endoscopic septum pellucidum fenestration. A 28-year-old man was referred for evaluation due to a 10-year history of chronic headaches that worsened in severity over the past year. A CT scan of the head revealed unilateral right ventricular dilation. Cranial MR imaging with and without contrast administration showed a dilated right thalamostriate-internal vein complex without any evidence of associated arteriovenous malformation or venous angioma. Endoscopic exploration of the right lateral ventricle showed an enlarged subependymal thalamostriate vein obstructing the Monro foramen. An endoscopic fenestration of the septum pellucidum was performed, resulting in alleviation of the patient's symptoms. Abnormally enlarged venous structures may cause obstructive unilateral hydrocephalus and can be a rare cause of chronic, intermittent headaches in adults. Endoscopic fenestration of the septum pellucidum is an effective treatment.

Plasticity of spontaneous excitatory and inhibitory synaptic activity in morphologically defined vestibular nuclei neurons during early vestibular compensation

PubMed Central

Shao, Mei; Hirsch, June C.

2012-01-01

After unilateral peripheral vestibular lesions, the brain plasticity underlying early recovery from the static symptoms is not fully understood. Principal cells of the chick tangential nucleus offer a subset of morphologically defined vestibular nuclei neurons to study functional changes after vestibular lesions. Chickens show posture and balance deficits immediately after unilateral vestibular ganglionectomy (UVG), but by 3 days most subjects begin to recover, although some remain uncompensated. With the use of whole cell voltage-clamp, spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) and miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were recorded from principal cells in brain slices 1 and 3 days after UVG. One day after UVG, sEPSC frequency increased on the lesion side and remained elevated at 3 days in uncompensated chickens only. Also by 3 days, sIPSC frequency increased on the lesion side in all operated chickens due to major increases in GABAergic events. Significant change also occurred in decay time of the events. To determine whether fluctuations in frequency and kinetics influenced overall excitatory or inhibitory synaptic drive, synaptic charge transfer was calculated. Principal cells showed significant increase in excitatory synaptic charge transfer only on the lesion side of uncompensated chickens. Thus compensation continues when synaptic charge transfer is in balance bilaterally. Furthermore, excessive excitatory drive in principal cells on the lesion side may prevent vestibular compensation. Altogether, this work is important for it defines the time course and excitatory and inhibitory nature of changing spontaneous synaptic inputs to a morphologically defined subset of vestibular nuclei neurons during critical early stages of recovery after UVG. PMID:21957228

Macrostructural and Microstructural Brain Lesions Relate to Gait Pathology in Children With Cerebral Palsy.

PubMed

Meyns, Pieter; Van Gestel, Leen; Leunissen, Inge; De Cock, Paul; Sunaert, Stefan; Feys, Hilde; Duysens, Jacques; Desloovere, Kaat; Ortibus, Els

2016-10-01

Background Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP. © The Author(s) 2016.

Implied functional crossed cerebello-cerebral diaschisis and interhemispheric compensation during hand grasping more than 20 years after unilateral cerebellar injury in early childhood.

PubMed

Nakahachi, Takayuki; Ishii, Ryouhei; Canuet, Leonides; Iwase, Masao

2015-01-01

Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to unilateral cerebellar damage.

[Unilateral exophthalmos as the debut of a non-secretory multiple myeloma].

PubMed

Castro-Rebollo, M; Cañones-Zafra, R; Vleming-Pinilla, E N; Drake-Rodríguez-Casanova, P; Pérez-Rico, C

2009-12-01

A 56 year-old male presented blurred vision and diplopia for 2 months, left unilateral exophthalmos, restricted ocular motility and papilledema. The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth rib and fourth dorsal vertebral body with associated masses of soft tissues. Biopsy was performed and the diagnosis of plasma cell neoplasm was established. The diagnosis of non-secretory multiple myeloma was made by analytical criteria and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed. The ophthalmologist can play an important role in the diagnosis of systemic neoplasms that require the intervention of a multidisciplinary team.

Constructing a new nigrostriatal pathway in the Parkinsonian model with bridged neural transplantation in substantia nigra.

PubMed

Zhou, F C; Chiang, Y H; Wang, Y

1996-11-01

The physical repair and restoration of a completely damaged pathway in the brain has not been achieved previously. In a previous study, using excitatory amino acid bridging and fetal neural transplantation, we demonstrated that a bridged mesencephalic transplant in the substantia nigra generated an artificial nerve pathway that reinnervated the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the current study, we report that a bridged mesencephalic transplant can anatomically, neurochemically, and functionally reinstate the 6-OHDA-eradicated nigro-striatal pathway. An excitatory amino acid, kainic acid, laid down in a track during the transplant generated a trophic environment that effectively guided the robust growth of transplanted neuronal fibers in a bundle to innervate the distal striatum. Growth occurred at the remarkable speed of approximately 200 microm/d. Two separate and distinct types of dopamine (DA) innervation from the transplant have been achieved for the first time: (1) DA innervation of the striatum, and (2) DA innervation of the pars reticularis of the substantia nigra. In addition, neuronal tracing revealed that reciprocal connections were achieved. The grafted DA neurons in the SNr innervated the host's striatum, whereas the host's striatal neurons, in turn, innervated the graft within 3-8 weeks. Electrochemical volt- ammetry recording revealed the restoration of DA release and clearance in a broad striatal area associated with the DA reinnervation. Furthermore, the amphetamine-induced rotation was attenuated, which indicates that the artificial pathways were motor functional. This study provides additional evidences that our bridged transplantation technique is a potential means for the repair of a completely damaged neuronal pathway.

Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

PubMed Central

Hou, Lijuan; Chen, Wei; Liu, Xiaoli; Qiao, Decai; Zhou, Fu-Ming

2017-01-01

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients. PMID:29163139

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM.

PubMed

Donnemiller, E; Brenneis, C; Wissel, J; Scherfler, C; Poewe, W; Riccabona, G; Wenning, G K

2000-09-01

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats.

PubMed

Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

2007-05-01

During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague-Dawley rats with 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans-striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.

Psychological symptoms and spatial orientation during the first 3 months after acute unilateral vestibular lesion.

PubMed

Gómez-Alvarez, Fatima B; Jáuregui-Renaud, Kathrine

2011-02-01

We undertook this study to assess the correlation between the results of simple tests of spatial orientation and the occurrence of common psychological symptoms during the first 3 months after an acute, unilateral, peripheral, vestibular lesion. Ten vestibular patients were selected and accepted to participate in the study. During a 3-month follow-up, we recorded the static visual vertical (VV), the estimation error of reorientation in the yaw plane and the responses to a standardized questionnaire of balance symptoms, the Dizziness Handicap Inventory (DHI), the depersonalization/derealization inventory by Cox and Swinson (DD), the Dissociative Experiences Scale (DES), the 12-item General Health Questionnaire (GHQ-12), the Zung Instrument for Anxiety Disorders and the Hamilton Depression Rating Scale. At week 1, all patients showed a VV >2° and failed to reorient themselves effectively. They reported several balance symptoms and handicap as well as DD symptoms, including attention/concentration difficulties; 80% of the patients had a Hamilton score ≥8. At this time the balance symptom score correlated with the DHI. After 3 months, all scores decreased. Multiple regression analysis of the differences from baseline showed that the DD score difference was related to the difference on the balance score, the reorientation error and the DHI score (p <0.01). No other linear relationships were observed (p >0.5). During the acute phase of a unilateral, peripheral, vestibular lesion, patients may show poor spatial orientation concurrent with DD symptoms including attention/concentration difficulties, and somatic depression symptoms. After vestibular rehabilitation, DD symptoms decrease as the spatial orientation improves, even if somatic symptoms of depression persist. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

Intractable bone marrow edema syndrome of the hip.

PubMed

Gao, Fuqiang; Sun, Wei; Li, Zirong; Guo, Wanshou; Kush, Nepali; Ozaki, Koji

2015-04-01

There is a need for an effective and noninvasive treatment for intractable bone marrow edema syndrome of the hip. Forty-six patients with intractable bone marrow edema syndrome of the hip were retrospectively studied to compare the short-term clinical effects of treatment with high-energy extracorporeal shock wave therapy vs femoral head core decompression. The postoperative visual analog scale score decreased significantly more in the extracorporeal shock wave therapy group compared with the femoral head core decompression group (P<.05). For unilateral lesions, postoperative Harris Hip Scores for all hips in the extracorporeal shock wave therapy group were more significantly improved than Harris Hip Scores for all hips in the femoral head core decompression group (P<.05). Patients who underwent extracorporeal shock wave therapy also resumed daily activities significantly earlier. Average overall operative time was similar in both groups. Symptoms disappeared significantly sooner in the extracorporeal shock wave therapy group in patients with both unilateral (P<.01) and bilateral lesions (P<.05). Hospital costs were significantly lower with extracorporeal shock wave therapy compared with femoral head core decompression. The intraoperative fluoroscopy radiation dose was lower in extracorporeal shock wave therapy than in femoral head core decompression for both unilateral (P<.05) and bilateral lesions (P<.01). On magnetic resonance imaging (MRI), bone marrow edema improved in all patients during the follow-up period. After extracorporeal shock wave therapy, all patients remained pain-free and had normal findings on posttreatment radiographs and MRI scans. Extracorporeal shock wave therapy appears to be a valid, reliable, and noninvasive tool for rapidly resolving intractable bone marrow edema syndrome of the hip, and it has a low complication rate and relatively low cost compared with other conservative and surgical treatment approaches. Copyright 2015, SLACK Incorporated.

Identifying relevant biomarkers of brain injury from structural MRI: Validation using automated approaches in children with unilateral cerebral palsy

PubMed Central

Dowson, Nicholas; Doecke, James; Fiori, Simona; Bradley, Andrew P.; Boyd, Roslyn N.; Rose, Stephen

2017-01-01

Previous studies have proposed that the early elucidation of brain injury from structural Magnetic Resonance Images (sMRI) is critical for the clinical assessment of children with cerebral palsy (CP). Although distinct aetiologies, including cortical maldevelopments, white and grey matter lesions and ventricular enlargement, have been categorised, these injuries are commonly only assessed in a qualitative fashion. As a result, sMRI remains relatively underexploited for clinical assessments, despite its widespread use. In this study, several automated and validated techniques to automatically quantify these three classes of injury were generated in a large cohort of children (n = 139) aged 5–17, including 95 children diagnosed with unilateral CP. Using a feature selection approach on a training data set (n = 97) to find severity of injury biomarkers predictive of clinical function (motor, cognitive, communicative and visual function), cortical shape and regional lesion burden were most often chosen associated with clinical function. Validating the best models on the unseen test data (n = 42), correlation values ranged between 0.545 and 0.795 (p<0.008), indicating significant associations with clinical function. The measured prevalence of injury, including ventricular enlargement (70%), white and grey matter lesions (55%) and cortical malformations (30%), were similar to the prevalence observed in other cohorts of children with unilateral CP. These findings support the early characterisation of injury from sMRI into previously defined aetiologies as part of standard clinical assessment. Furthermore, the strong and significant association between quantifications of injury observed on structural MRI and multiple clinical scores accord with empirically established structure-function relationships. PMID:28763455

[A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis co-occurring with unilateral cerebral cortical encephalitis].

PubMed

Fukushima, Naoya; Suzuki, Miki; Ogawa, Ryo; Hayashi, Kitami; Takanashi, Jun-Ichi; Ohashi, Takashi

2017-11-25

A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM) at 11 years of age. At 17 years of age, she was hospitalized due to generalized seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she was admitted to our hospital, diagnosed with multifocal disseminated encephalomyelitis (MDEM). MDEM has been observed in patients that are seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex encephalitis with epilepsy has also been reported in such patients. The co-occurrence of MDEM and cortical encephalitis in the same patient has important implications for the pathogenesis of anti-MOG antibody-associated autoimmune diseases.

Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction.

PubMed

Saito, Tsukasa; Hayashi, Keisuke; Nakazawa, Hajime; Ota, Tetsuo

2016-08-01

Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition.

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

PubMed Central

Hutson, Che Brown; Lazo, Carlos R.; Mortazavi, Farzad; Giza, Christopher C.; Hovda, David

2011-01-01

Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. In an acute study, rats received moderate TBI by lateral fluid percussion (LFP) injury, were injected with saline or paraquat (10 mg/kg IP) 3 and 6 days after LFP, were sacrificed 5 days later, and their brains processed for immunohistochemistry. TBI alone increased microglial activation in the substantia nigra, and caused a 15% loss of dopaminergic neurons ipsilaterally. Paraquat increased the TBI effect, causing a 30% bilateral loss of dopaminergic neurons, reduced striatal tyrosine hydroxylase (TH) immunoreactivity more than TBI alone, and induced alpha-synuclein accumulation in the substantia nigra pars compacta. In a long-term study, rats received moderate LFP, were injected with saline or paraquat at 21 and 22 weeks post-injury, and were sacrificed 4 weeks later. At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk. PMID:21644813

Torpedo maculopathy: Two case reports and a literature review.

PubMed

de Manuel-Triantafilo, S; Gili, P; Bañuelos Bañuelos, J

2016-08-01

The cases concern a 4 year-old boy and 25 year-old female with 20/20 visual acuity, who presented with a unilateral non-pigmented macular lesion, temporal to the fovea, a torpedo shaped defect in the retinal pigment epithelium (RPE). Optical coherence tomography showed attenuation of the RPE signal, and in the second patient there proved to be a neurosensory detachment, RPE atrophy, and thinning of the retinal layers. The lesion was hypoautofluorescent and hyperfluorescent on fluorescein angiography. Torpedo maculopathy is an asymptomatic characteristic lesion which should be considered in the differential diagnosis of macular lesions in children and young patients. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

PubMed

Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

2009-01-01

The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and Review of the Literature.

PubMed

Brar, Rupinder Kaur; Singh, Ashok; Deshpande, Archana Hemant; Gargade, Chitrawati Bal; Das, Sujit

2017-11-01

Primary conjunctival tuberculosis is very rare in the developed countries. In an endemic country like India, it should be considered in the differential diagnosis of any unusual conjunctival lesion with unilaterality, chronicity, and nonresolution of symptoms after steroid use. We present the case of a 52-year-old female who presented with unilateral itching and blurring of vision for 20 days. There were irregular nodular elevated areas with shrinkage of the lower palpebral conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell granulomas along with Langhans type of giant cells. However, no acid-fast bacilli were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal, and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of conjunctival scrapings was positive for Mycobacterium tuberculosis . The patient was started on antitubercular drugs. We present this very rare case of primary tuberculosis of the conjunctiva presenting with dryness of the eye.

Insulin resistance impairs nigrostriatal dopamine function.

PubMed

Morris, J K; Bomhoff, G L; Gorres, B K; Davis, V A; Kim, J; Lee, P-P; Brooks, W M; Gerhardt, G A; Geiger, P C; Stanford, J A

2011-09-01

Clinical studies have indicated a link between Parkinson's disease (PD) and Type 2 Diabetes. Although preclinical studies have examined the effect of high-fat feeding on dopamine function in brain reward pathways, the effect of diet on neurotransmission in the nigrostriatal pathway, which is affected in PD and parkinsonism, is less clear. We hypothesized that a high-fat diet, which models early-stage Type 2 Diabetes, would disrupt nigrostriatal dopamine function in young adult Fischer 344 rats. Rats were fed a high fat diet (60% calories from fat) or a normal chow diet for 12 weeks. High fat-fed animals were insulin resistant compared to chow-fed controls. Potassium-evoked dopamine release and dopamine clearance were measured in the striatum using in vivo electrochemistry. Dopamine release was attenuated and dopamine clearance was diminished in the high-fat diet group compared to chow-fed rats. Magnetic resonance imaging indicated increased iron deposition in the substantia nigra of the high fat group. This finding was supported by alterations in the expression of several proteins involved in iron metabolism in the substantia nigra in this group compared to chow-fed animals. The diet-induced systemic and basal ganglia-specific changes may play a role in the observed impairment of nigrostriatal dopamine function. Copyright © 2011 Elsevier Inc. All rights reserved.

Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

PubMed

Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

2011-09-14

Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

The diagnostic value of earlier and later components of Vestibular Evoked Myogenic Potentials (VEMP) in multiple sclerosis.

PubMed

Eleftheriadou, A; Deftereos, S N; Zarikas, V; Panagopoulos, G; Sfetsos, S; Karageorgiou, C L; Ferekidou, E; Kandiloros, D; Korres, S

2009-01-01

To evaluate the ability of VEMP to disclose spatial dissemination of Multiple Sclerosis. Forty-six MS patients with auditory and/or vestibular symptoms were studied. Patients were divided in two groups. Group 1 included 24 patients with brainstem MRI findings, and Group 2 included 22 patients without MRI findings. VEMP and BAEP have been recorded and assessed. Abnormal p13n23 wave was observed in 50%, while unilateral absence or bilateral delay of the n34p44 in 43% of the patients. The overall diagnostic value considering abnormal cases suggested by both first and second VEMP waves was increased to 71%. Statistically significant differences revealed between patients and controls for p13 latency (p=0.018). The p13n23 was abnormal in 7 patients, although MRI scanning did not reveal brainstem lesions. In 9 out of 18 MS patients suffering from unilateral hearing loss, n34p44 was present in the unaffected ears and absent in the affected side, although p13n23 was normal. Abnormal VEMP imply the presence of lesions undetected by MRI neuroimaging, which verifies the diagnostic value of the method. Unilateral absence of n34p44 complex was related with sensorineural hearing loss, supporting the hypothesis that n34p44 is of cochlear origin.

Evidence that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei to inhibit maternal behavior in rats.

PubMed

Sheehan, T; Paul, M; Amaral, E; Numan, M J; Numan, M

2001-01-01

The maternal behaviors shown by a rat that has given birth are not shown by a virgin female rat when she is first presented with young. This absence of maternal behavior in virgins has been attributed to the activity of a neural circuit that inhibits maternal behavior in nulliparae. The medial amygdala and regions of the medial hypothalamus such as the anterior and ventromedial hypothalamic nuclei have previously been shown to inhibit maternal behavior, in that lesions to these regions promote maternal responding. Furthermore, we have recently shown that these and other regions, such as the principal bed nucleus of the stria terminalis, the ventral lateral septum, and the dorsal premammillary nucleus, show higher pup-induced Fos-immunoreactivity in non-maternal rats exposed to pups than during the performance of maternal behavior, indicating that they too could be involved in preventing maternal responsiveness. The current study tested whether the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, as well as to see what other brain regions could participate in this circuit. Bilateral excitotoxic lesions of the medial amygdala, or of the anterior/ventromedial hypothalamic nuclei, promoted maternal behavior. Unilateral medial amygdala lesions caused a reduction of pup-induced Fos-immunoreactivity in the anterior/ventromedial hypothalamic nuclei in non-maternal rats ipsilateral to the lesion, as well as in the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus. Finally, unilateral medial amygdala lesions paired with contralateral anterior/ventromedial hypothalamic nuclei lesions promoted maternal behavior, although ipsilateral lesion placements were also effective.Together, these results indicate that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, and that the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus could also be involved in this circuit.

Converging levels of analysis in the cognitive neuroscience of visual attention.

PubMed Central

Duncan, J

1998-01-01

Experiments using behavioural, lesion, functional imaging and single neuron methods are considered in the context of a neuropsychological model of visual attention. According to this model, inputs compete for representation in multiple visually responsive brain systems, sensory and motor, cortical and subcortical. Competition is biased by advance priming of neurons responsive to current behavioural targets. Across systems competition is integrated such that the same, selected object tends to become dominant throughout. The behavioural studies reviewed concern divided attention within and between modalities. They implicate within-modality competition as one main restriction on concurrent stimulus identification. In contrast to the conventional association of lateral attentional focus with parietal lobe function, the lesion studies show attentional bias to be a widespread consequence of unilateral cortical damage. Although the clinical syndrome of unilateral neglect may indeed be associated with parietal lesions, this probably reflects an assortment of further deficits accompanying a simple attentional imbalance. The functional imaging studies show joint involvement of lateral prefrontal and occipital cortex in lateral attentional focus and competition. The single unit studies suggest how competition in several regions of extrastriate cortex is biased by advance priming of neurons responsive to current behavioural targets. Together, the concepts of competition, priming and integration allow a unified theoretical approach to findings from behavioural to single neuron levels. PMID:9770224

Delayed Unilateral Soft Palate Palsy without Vocal Cord Involvement after Microvascular Decompression for Hemifacial Spasm

PubMed Central

Park, Jae Han; Jo, Kyung Il

2013-01-01

Microvascular decompression is a very effective and relatively safe surgical modality in the treatment of hemifacial spasm. But rare debilitating complications have been reported such as cranial nerve dysfunctions. We have experienced a very rare case of unilateral soft palate palsy without the involvement of vocal cord following microvascular decompression. A 33-year-old female presented to our out-patient clinic with a history of left hemifacial spasm for 5 years. On postoperative 5th day, patient started to exhibit hoarsness with swallowing difficulty. Symptoms persisted despite rehabilitation. Various laboratory work up with magnetic resonance image showed no abnormal lesions. Two years after surgery patient showed complete recovery of unitaleral soft palate palsy. Various etiologies of unilateral soft palate palsy are reviewed as the treatment and prognosis differs greatly on the cause. Although rare, it is important to keep in mind that such complication could occur after microvascular decompression. PMID:24003372

[A case of bilateral medial medullary infarction caused by unilateral vertebral artery dissection].

PubMed

Akimoto, Takayoshi; Hara, Makoto; Saito, Mari; Takahashi, Keiko; Kamei, Satoshi

2015-01-01

A 34-year-old man developed right neck pain. Several hours later, he felt numbness of his extremities and presented at our hospital. He developed right hemiparesis and hypoesthesia of the right extremities. A few hours later, upbeat nystagmus and dysarthria appeared along with a sensory disturbance that spread to all extremities, and right hemiparesis progressed to tetraplegia. Brain MR diffusion-weighted images revealed a high-intensity lesion in the bilateral medial medulla oblongata and we diagnosed this bilateral medial medullary infarction. Three dimentional CT angiography revealed dissection of the right VA. We administered intravenous argatroban, edaravone, glycerin and oral clopidogrel. He was assessed as having modified Rankin scale 4 and was transferred to another hospital for rehabilitation on day 30. When the medial medulla oblongata is supplied by the unilateral VA, a unilateral VA dissection can cause bilateral medial medullary infarction.

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

PubMed Central

Gagnon, D.; Petryszyn, S.; Sanchez, M. G.; Bories, C.; Beaulieu, J. M.; De Koninck, Y.; Parent, A.; Parent, M.

2017-01-01

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease. PMID:28128287

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice.

PubMed

Gagnon, D; Petryszyn, S; Sanchez, M G; Bories, C; Beaulieu, J M; De Koninck, Y; Parent, A; Parent, M

2017-01-27

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D 1 or D 2 dopamine receptor. Consequences on MSNs expressing both receptors (D 1 /D 2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D 1 /D 2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D 1 /D 2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D 1 and D 2 MSNs, D 1 /D 2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D 1 /D 2 MSNs, but also of D 1 and D 2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D 1 and D 2 MSNs, the extent of dendritic arborization of D 1 /D 2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D 1 /D 2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.

Severe amnesia following a unilateral temporal lobe stroke.

PubMed

Grewal, Raji P

2003-01-01

A 60 year old right-handed man developed severe amnesia following a left medial temporal stroke as documented by cerebral MRI, MRA and SPECT scans. Neuropsychological evaluation 13 weeks after the stroke showed a profound retrograde amnesia characterised by memory loss for public facts and events over the previous four decades. In addition, autobiographical memory showed selective loss of personal episodic memory with relative preservation of personal semantic memory. The development of this degree of amnesia with these features following a unilateral temporal lobe lesion is unusual. The possible neuroanatomical mechanisms underlying the amnesia and how they relate to current theories of memory loss are discussed.

Fractionating the Binding Process: Neuropsychological Evidence from Reversed Search Efficiencies

ERIC Educational Resources Information Center

Humphreys, Glyn W.; Hodsoll, John; Riddoch, M. Jane

2009-01-01

The authors present neuropsychological evidence distinguishing binding between form, color, and size (cross-domain binding) and binding between form elements. They contrasted conjunctive search with difficult feature search using control participants and patients with unilateral parietal or fronto/temporal lesions. To rule out effects of task…

Contrasting expressions of aggressive behavior released by lesions of the central nucleus of the amygdala during wakefulness and rapid eye movement sleep without atonia in cats.

PubMed

Zagrodzka, J; Hedberg, C E; Mann, G L; Morrison, A R

1998-06-01

Whether damage to the central nucleus of the amygdala (Ace) contributes to the predatorylike attack sometimes observed in rapid eye movement sleep without atonia (REM-A), created in cats by bilateral pontine lesions, was examined. Such lesions eliminate REM sleep skeletal muscle atonia and release elaborate behavior. Unilateral damage to the Ace alone increased affective defensive aggressive behavior toward humans and conspecifics without altering predatory behavior in wakefulness. Pontine lesions added at loci normally not leading to aggression induced predatorylike attacks in REM-A as well as the waking affective defense. Alterations of autonomic activity, the absence of relevant environmental stimuli in REM-A, or both may explain the state-related differences.

The myth of the 'unaffected' side after unilateral stroke: is reorganisation of the non-infarcted corticospinal system to re-establish balance the price for recovery?

PubMed

Graziadio, S; Tomasevic, L; Assenza, G; Tecchio, F; Eyre, J A

2012-12-01

Bilateral changes in the hemispheric reorganisation have been observed chronically after unilateral stroke. Our hypotheses were that activity dependent competition between the lesioned and non-lesioned corticospinal systems would result in persisting asymmetry and be associated with poor recovery. Eleven subjects (medium 6.5 years after stroke) were compared to 9 age-matched controls. The power spectral density (PSD) of the sensorimotor electroencephalogram (SM1-EEG) and electromyogram (EMG) and corticomuscular coherence (CMC) were studied during rest and isometric contraction of right or left opponens pollicis (OP). Global recovery was assessed using NIH score. There was bilateral loss of beta frequency activity in the SM1-EEGs and OP-EMGs in strokes compared to controls. There was no difference between strokes and controls in symmetry indices estimated between the two corticospinal systems for SM1-EEG, OP-EMG and CMC. Performance correlated with preservation of beta frequency power in OP-EMG in both hands. Symmetry indices for the SM1-EEG, OP-EMG and CMC correlated with recovery. Significant changes occurred at both cortical and spinomuscular levels after stroke but to the same degree and in the same direction in both the lesioned and non-lesioned corticospinal systems. Global recovery correlated with the degree of symmetry between corticospinal systems at all three levels - cortical and spinomuscular levels and their connectivity (CMC), but not with the absolute degree of abnormality. Re-establishing balance between the corticospinal systems may be important for overall motor function, even if it is achieved at the expense of the non-lesioned system. Copyright © 2012 Elsevier Inc. All rights reserved.

Spondylolysis in young tennis players

PubMed Central

Ruiz‐Cotorro, A; Balius‐Matas, R; Estruch‐Massana, A; Angulo, J Vilaró

2006-01-01

The general aetiology, diagnosis, and treatment of spondylolysis, a bone defect in the pars interarticularis of the vertebra, are reviewed. A retrospective study of young tennis players diagnosed between 2000 and 2004 with spondylolysis with or without spondylolisthesis, assessed by radiography and planar bone scintigraphy, is described. If the radiographic results were negative, computed tomography was performed. Sixty six cases were evaluated: 53 L5 lesions, eight L4 lesions, two L3 lesions, and one bilateral lesion at the L2 level. Two more lesions at two levels were found (bilateral L5 and unilateral L4 and L3 on the right side). Classification, treatment, and outcome of the cases are reported. A combination of radiography, planar bone scintigraphy, and SPECT is useful for evaluating spondylolysis in tennis players and recommending treatment. Use of a brace did not appear to achieve significant results. PMID:16632576

Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.

PubMed

Dluzen, D E; Gao, X; Story, G M; Anderson, L I; Kucera, J; Walro, J M

2001-07-01

Deletion of a single copy of the BDNF gene has been shown to affect the nigrostriatal dopaminergic system of young adult BDNF mice. In the present report we evaluated various indices of nigrostriatal dopaminergic function between 9-month-old wild-type (+/+) and heterozygous (+/-) BDNF mutant mice. Performance in a sensorimotor beam walking task was significantly decreased in +/- mice as indicated by increased times required to traverse both a wide (21 mm) and narrow (6 mm) beam. No differences in spontaneous locomotor behavior were observed between the +/+ and +/- mice. Amphetamine-stimulated (5 mg/kg) locomotor behavior was increased to a greater degree in the +/- mice, with the number of movements performed by these mice being significantly greater than their +/+ controls. Corpus striatal dopamine concentrations were significantly greater in the +/- BDNF mice. The absence of any significant differences for dopamine concentrations within the hypothalamus and olfactory bulb of these mice, as well as an absence of any difference in striatal norepinephrine concentrations, suggested a relative specificity of these effects to the corpus striatum. Both the +/- and +/+ mice showed similar reductions in striatal dopamine concentrations in response to a neurotoxic regimen of methamphetamine (20 mg/kg). Collectively these data show increased levels of striatal dopamine concentrations associated with altered behavioral responses involving the nigrostriatal dopaminergic system within the heterozygous BDNF mutant mice. Copyright 2001 Academic Press.

Tamoxifen protects male mice nigrostriatal dopamine against methamphetamine-induced toxicity.

PubMed

Bourque, Mélanie; Liu, Bin; Dluzen, Dean E; Di Paolo, Thérèse

2007-11-01

The selective estrogen receptor modulator tamoxifen and estradiol were shown to protect nigrostriatal dopamine concentration loss by methamphetamine in female mice whereas male mice were protected only by tamoxifen. The present study examined the protective properties of tamoxifen in male mice on several nigrostriatal dopaminergic markers and body temperature. Intact male mice were administered 12.5 or 50 microg tamoxifen 24 h before methamphetamine treatment. Basal body temperatures of male mice remained unchanged by the tamoxifen treatment. Methamphetamine reduced striatal dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations, striatal and substantia nigra dopamine and vesicular monoamine transporter specific binding as well substantia nigra dopamine and vesicular monoamine transporter mRNA levels and increased striatal preproenkephalin mRNA levels. These methamphetamine effects were not altered by 12.5 microg tamoxifen except for increased striatal dopamine metabolites and turnover. Tamoxifen at 50 microg reduced the methamphetamine effect on striatal dopamine concentration, dopamine transporter specific binding and prevented the increase in preproenkephalin mRNA levels; in the substantia nigra tamoxifen prevented the decrease of dopamine transporter mRNA levels. The present results show a tamoxifen dose-dependent prevention of loss of various dopaminergic markers against methamphetamine-induced toxicity in male mice. Since this is the only known hormonal protection of male mice against methamphetamine toxicity, these findings provide important new information on specific parameters of nigrostriatal dopaminergic function preserved by tamoxifen.

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?

PubMed

Laloux, C; Gouel, F; Lachaud, C; Timmerman, K; Do Van, B; Jonneaux, A; Petrault, M; Garcon, G; Rouaix, N; Moreau, C; Bordet, R; Duce, J A; Devedjian, J C; Devos, D

2017-07-01

In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

CD24 expression does not affect dopamine neuronal survival in a mouse model of Parkinson's disease.

PubMed

Stott, Simon R W; Hayat, Shaista; Carnwath, Tom; Garas, Shaady; Sleeman, Jonathan P; Barker, Roger A

2017-01-01

Parkinson's disease (PD) is a progressive neurodegenerative condition that is characterised by the loss of specific populations of neurons in the brain. The mechanisms underlying this selective cell death are unknown but by using laser capture microdissection, the glycoprotein, CD24 has been identified as a potential marker of the populations of cells that are affected in PD. Using in situ hybridization and immunohistochemistry on sections of mouse brain, we confirmed that CD24 is robustly expressed by many of these subsets of cells. To determine if CD24 may have a functional role in PD, we modelled the dopamine cell loss of PD in Cd24 mutant mice using striatal delivery of the neurotoxin 6-OHDA. We found that Cd24 mutant mice have an anatomically normal dopamine system and that this glycoprotein does not modulate the lesion effects of 6-OHDA delivered into the striatum. We then undertook in situ hybridization studies on sections of human brain and found-as in the mouse brain-that CD24 is expressed by many of the subsets of the cells that are vulnerable in PD, but not those of the midbrain dopamine system. Finally, we sought to determine if CD24 is required for the neuroprotective effect of Glial cell-derived neurotrophic factor (GDNF) on the dopaminergic nigrostriatal pathway. Our results indicate that in the absence of CD24, there is a reduction in the protective effects of GDNF on the dopaminergic fibres in the striatum, but no difference in the survival of the cell bodies in the midbrain. While we found no obvious role for CD24 in the normal development and maintenance of the dopaminergic nigrostriatal system in mice, it may have a role in mediating the neuroprotective aspects of GDNF in this system.

Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location.

PubMed

Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; Deveber, Gabrielle

2010-04-01

Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at injury, lesion location and intellectual outcome. Using age-appropriate Wechsler scales of intellectual ability, we explored this issue by evaluating a large group (n=145) of children (89 males, 56 females) who experienced unilateral arterial ischaemic stroke during the perinatal period (diagnosed mean 73d, SD 29d), between the ages of 1 month and 5 years (mean 2y 10mo, SD 1y 9mo), or between the ages of 6 and 16 years (mean 11y 1mo SD 3y 6mo). The mean age at assessment was 8 years (SD 3y 10mo) in the perinatal group, 7 years 5 months (SD 2y 9mo) in the 1 month to 5 years group, and 12 years 5 months (SD 3y 9mo) in the 6 to 16 years group. The mean time interval between stroke and assessment was 8 years (SD 18d) for perinatal, 4 years 6 months (SD 1y 5mo) for 1 month to 5 years, and 1 year 4 months (SD 2y 9mo) for 6 to 16 years. The relationship between age at stroke and lesion location (subcortical, cortical, or combined) as it pertains to cognitive outcome was also examined. Measures of overall intelligence, verbal ability, working memory, and processing speed were significantly lower in children who had had a stroke than in the normative sample (all z>2.5, all p<0.01). The perinatal group performed more poorly than the other two groups on most cognitive measures, regardless of lesion location. The combined lesion location group performed more poorly than those with damage to either cortical or subcortical areas alone. Further investigation revealed different periods of peak vulnerability for subcortical lesions (perinatal) and cortical lesions (1mo-5y). Lesion location modulates the relationship between age at stroke and cognitive outcome.

Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration.

PubMed

Snider, Jonathan; Müller, Martijn L T M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J H; Frey, Kirk A; Albin, Roger L; Bohnen, Nicolaas I

2015-10-01

To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Cross-sectional study. PD subjects, n = 48 (40 M); 69.4 ± 7.4 (56-84) years old; 8.4 ± 4.2 (2.5-20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7-53) and mean MMSE score 28.4 ± 1.9 (22-30) underwent [(11)C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R = -0.37, P = 0.0099) but not with duration of exercise physical activity (R = -0.05, P = 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F = 6.15, P = 0.017) while accounting for effects of nigrostriatal degeneration (F = 4.93, P = 0.032), levodopa-equivalent dose (LED; F = 1.07, P = 0.31), age (F = 4.37, P = 0.043) and duration of disease (F = 1.46, P = 0.23; total model (F = 5.76, P = 0.0004). Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. Published by Elsevier Ltd.

Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration

PubMed Central

Snider, Jon; Müller, Martijn L.T.M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J.H.; Frey, Kirk A; Albin, Roger L.; Bohnen, Nicolaas I.

2015-01-01

Objective To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Background Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Methods Cross-sectional study. PD subjects, n=48 (40M); 69.4±7.4 (56–84) years old; 8.4±4.2 (2.5–20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7–53) and mean MMSE score 28.4 ± 1.9 (22–30) underwent [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Results Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R= −0.37, P=0.0099) but not with duration of exercise physical activity (R= −0.05, P= 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F=6.15, P=0.017) while accounting for effects of nigrostriatal degeneration (F=4.93, P=0.032), levodopa-equivalent dose (LED; F=1.07, P=0.31), age (F=4.37, P=0.043) and duration of disease (F=1.46, P=0.23; total model (F=5.76, P=0.0004). Conclusions Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. PMID:26330028

Rapid compensatory changes in GABA receptor efficacy in rat vestibular neurones after unilateral labyrinthectomy

PubMed Central

Yamanaka, Toshiaki; Him, Aydin; Cameron, Susan A; Dutia, Mayank B

2000-01-01

The inhibitory effects of the GABAA agonist muscimol and the GABAB agonist baclofen on tonically active medial vestibular nucleus (MVN) neurones were recorded in slices of the rat dorsal brainstem in vitro, to determine whether any changes occurred in the functional efficacy of GABAergic inhibition in these cells during the initial rapid stage of ‘vestibular compensation’, the behavioural recovery that takes place after unilateral labyrinthectomy (UL). These experiments were carried out in preparations where the midline was cut, severing all commissural connections between the two vestibular nuclei. Slices of the MVN were prepared from normal animals and animals that had been unilaterally labyrinthectomised 4 h earlier. The mean in vitro discharge rate of MVN neurones in the rostral region of the ipsi-lesional nucleus after UL was significantly higher than that in control slices, confirming our earlier reports of an increase in intrinsic excitability of these cells in the early stage of vestibular compensation. The in vitro discharge rates of caudal ipsi-lesional MVN cells, and rostral and caudal contra-lesional MVN cells, were not different from controls. Muscimol and baclofen caused reversible, dose-related inhibition of the tonic discharge rate of MVN cells in control slices. In slices prepared from UL animals, MVN cells in the rostral region of the ipsi-lesional nucleus showed a marked downregulation of their response to both muscimol and baclofen, seen as a rightward shift and a decrease in slope of the dose-response relationships for the two agonists. In the contra-lesional nucleus, there was a small but significant upregulation of the responsiveness of both rostral and caudal MVN cells to baclofen, and a marked upregulation of the responsiveness of caudal MVN cells to muscimol. In slices from animals that had undergone bilateral labyrinthectomy 4 h earlier, the downregulation of the functional efficacy of GABA receptors in the rostral MVN cells did not occur. The changes in GABA receptor efficacy after UL are therefore not due to the vestibular de-afferentation itself, but are instead due to the imbalance in excitability of the vestibular nuclei of the lesioned and intact sides, and the enhanced commissural inhibition of the ipsi-lesional MVN cells that follows UL. The downregulation of GABA receptor efficacy in the ipsi-lesional MVN neurones is functionally compensatory, in that their response to commissural and cerebellar inhibitory drive will be significantly reduced after UL. Their intrinsic membrane conductances, and their remaining excitatory synaptic inputs, will consequently be more effective in causing depolarisation and the restoration of resting activity. Simultaneously the upregulation of GABAergic efficacy in the contra-lesional MVN will tend to reduce the hyperactivity on the contralateral side. These adaptive changes therefore represent a plausible cellular mechanism for the recovery of resting discharge in the ipsi-lesional MVN neurones, and the ‘re-balancing’ of the excitability of the vestibular neurones of the lesioned and intact sides, as occurs after UL in vivo. We propose that the adaptive regulation of the functional efficacy of GABA receptors in the MVN neurones may be an important cellular mechanism for the ‘homeostasis of bilateral excitability’ of the vestibular nuclei of the two sides. PMID:10699085

Nuclear microscopic investigations into the elemental changes in the substantia nigra of unilaterally MPTP-lesioned Parkinsonian monkeys

NASA Astrophysics Data System (ADS)

Thong, P. S. P.; He, Y.; Lee, T.; Watt, F.

1997-07-01

Various transition metals, particularly iron, have been implicated in the aetiology of the neurodegenerative disease, Parkinson's disease, in which there is a characteristic loss of cells in the substantia nigra (SN) region of the brain. In this study, monkeys were unilaterally lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to obtain primate models of parkinsonism, with the non-lesioned side of the brain serving as controls. The monkeys were sacrificed at one day, one week, two weeks, one month and one year after lesioning to investigate the time dependent elemental changes in the parkinsonian SN. Sections of the brain encompassing both the lesioned and non-lesioned SNs were analysed using the National University of Singapore nuclear microscope. Adjacent sections were tyrosine hydroxylase (TH) immunohistochemically stained to provide complementary information on dopaminergic cell loss and to facilitate definition of the SN boundaries during data analysis. In one-day and one-week monkeys (representing early stages of the disease), there were no changes in elemental concentrations within experimental errors and the adjacent TH-stained sections did not show apparent cell loss in the SN. At two weeks, cell loss was seen in the lesioned SN compared to the control SN. Although there was no bulk increase in SN iron, localised accumulation of iron in granules containing up to 15% by weight iron was observed in the lesioned SN of one of the two-week monkeys. An average 15% increase in nigral iron, significant at the 90% confidence level ( p < 0.1), was seen in the one-month monkeys. TH-stained sections for the one-month monkeys showed cell loss in the lesioned SN. In one-year samples (representing the advanced stage of the disease) there was a significant ( p < 0.05) 56% increase in iron, 14% increase in phosphorous and a 20% decrease in copper. Here an almost complete loss of cells in the lesioned SN was apparent from the adjacent TH-stained sections. These preliminary results suggest that while bulk increase in iron may seem to follow cell death, localised accumulation of SN iron in the early stages of the disease may play an important role in initiating and/or accelerating nigral cell death.

Multimodal Integration After Unilateral Labyrinthine Lesion: Single Vestibular Nuclei Neuron Responses and Implications for Postural Compensation

PubMed Central

Sadeghi, Soroush G.; Minor, Lloyd B.

2011-01-01

Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of neurons that mediate these pathways at the functional and cellular levels. PMID:21148096

Multimodal integration after unilateral labyrinthine lesion: single vestibular nuclei neuron responses and implications for postural compensation.

PubMed

Sadeghi, Soroush G; Minor, Lloyd B; Cullen, Kathleen E

2011-02-01

Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of neurons that mediate these pathways at the functional and cellular levels.

Persistent Left Unilateral Mirror Writing: A Neuropsychological Case Study

ERIC Educational Resources Information Center

Angelillo, Valentina G.; De Lucia, Natascia; Trojano, Luigi; Grossi, Dario

2010-01-01

Mirror writing (MW) is a rare disorder in which a script runs in direction opposite to normal and individual letters are reversed. The disorder generally occurs after left-hemisphere lesions, is transient and is observed on the left hand, whereas usually motor impairments prevent assessment of direction of right handwriting. We describe a…

Gesturing with an Injured Brain: How Gesture Helps Children with Early Brain Injury Learn Linguistic Constructions

ERIC Educational Resources Information Center

Ozcaliskan, Seyda; Levine, Susan C.; Goldin-Meadow, Susan

2013-01-01

Children with pre/perinatal unilateral brain lesions (PL) show remarkable plasticity for language development. Is this plasticity characterized by the same developmental trajectory that characterizes typically developing (TD) children, with gesture leading the way into speech? We explored this question, comparing eleven children with PL -- matched…

Unilateral Postoperative Deep Cerebral Venous Thrombosis with Complete Recovery: A Report of 2 Cases.

PubMed

Benifla, Mony; Laughlin, Suzzanne; Tovar-Spinoza, Zulma S; Rutka, James T; Dirks, Peter B

2017-01-01

Postsurgical deep brain venous thrombosis has not been well described in children before. When approaching thalamic or intraventricular lesions, extra care should be taken to prevent injury to the internal cerebral veins (ICVs) and the vein of Galen. However, even when they are well preserved during surgery, postoperative hemodynamic changes, mainly in the first 24 h, or surgical manipulation can cause thrombosis of these veins. We report 2 children with unilateral postoperative ICV thrombosis; in 1 of the patients the vein of Galen was also thrombosed. Although both patients had altered sensorium initially, no anticoagulation therapy was given, and they both recovered well. When approaching thalamic or intraventricular lesions, extra care should be taken to prevent injury to the ICV and the vein of Galen. The surgeon should respect the deep brain venous system when approaching midline structures. Both the neurosurgeon and the neuroradiologist should be aware of this possible complication in order to make a prompt diagnosis and to offer proper treatment if needed. © 2017 S. Karger AG, Basel.

Studies on the cellular localization of spinal cord substance P receptors.

PubMed

Helke, C J; Charlton, C G; Wiley, R G

1986-10-01

Substance P-immunoreactivity and specific substance P binding sites are present in the spinal cord. Receptor autoradiography showed the discrete localization of substance P binding sites in both sensory and motor regions of the spinal cord and functional studies suggested an important role for substance P receptor activation in autonomic outflow, nociception, respiration and somatic motor function. In the current studies, we investigated the cellular localization of substance P binding sites in rat spinal cord using light microscopic autoradiography combined with several lesioning techniques. Unilateral injections of the suicide transport agent, ricin, into the superior cervical ganglion reduced substance P binding and cholinesterase-stained preganglionic sympathetic neurons in the intermediolateral cell column. However, unilateral electrolytic lesions of ventral medullary substance P neurons which project to the intermediolateral cell column did not alter the density of substance P binding in the intermediolateral cell column. Likewise, 6-hydroxydopamine and 5,7-dihydroxytryptamine, which destroy noradrenergic and serotonergic nerve terminals, did not reduce the substance P binding in the intermediolateral cell column. It appears, therefore, that the substance P binding sites are located postsynaptically on preganglionic sympathetic neurons rather than presynaptically on substance P-immunoreactive processes (i.e. as autoreceptors) or on monoamine nerve terminals. Unilateral injections of ricin into the phrenic nerve resulted in the unilateral destruction of phrenic motor neurons in the cervical spinal cord and caused a marked reduction in the substance P binding in the nucleus. Likewise, sciatic nerve injections of ricin caused a loss of associated motor neurons in the lateral portion of the ventral horn of the lumbar spinal cord and a reduction in the substance P binding. Sciatic nerve injections of ricin also destroyed afferent nerves of the associated dorsal root ganglia and increased the density of substance P binding in the dorsal horn. Capsaicin, which destroys small diameter primary sensory neurons, similarly increased the substance P binding in the dorsal horn. These studies show that the cellular localization of substance P binding sites can be determined by analysis of changes in substance P binding to discrete regions of spinal cord after selective lesions of specific groups of neurons. The data show the presence of substance P binding sites on preganglionic sympathetic neurons in the intermediolateral cell column and on somatic motor neurons in the ventral horn, including the phrenic motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Sensorimotor assessment of the unilateral 6-hydroxydopamine mouse model of Parkinson’s disease

PubMed Central

Glajch, Kelly E.; Fleming, Sheila M.; Surmeier, D. James; Osten, Pavel

2012-01-01

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by marked impairments in motor function caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Animal models of PD have traditionally been based on toxins, such as 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that selectively lesion dopaminergic neurons. Motor impairments from 6-OHDA lesions of SNc neurons are well characterized in rats, but much less work has been done in mice. In this study, we compare the effectiveness of a series of drug-free behavioral tests in assessing sensorimotor impairments in the unilateral 6-OHDA mouse model, including six tests used for the first time in this PD mouse model (the automated treadmill “DigiGait” test, the challenging beam test, the adhesive removal test, the pole test, the adjusting steps test, and the test of spontaneous activity) and two tests used previously in 6-OHDA-lesioned mice (the limb-use asymmetry “cylinder” test and the manual gait test). We demonstrate that the limb-use asymmetry, challenging beam, pole, adjusting steps, and spontaneous activity tests are all highly robust assays for detecting sensorimotor impairments in the 6-OHDA mouse model. We also discuss the use of the behavioral tests for specific experimental objectives, such as simple screening for well-lesioned mice in studies of PD cellular pathophysiology or comprehensive behavioral analysis in preclinical therapeutic testing using a battery of sensorimotor tests. PMID:22178078

MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice.

PubMed

Adén, Ulrika; Dahlberg, Viktoria; Fredholm, Bertil B; Lai, Li-Ju; Chen, Zhengguan; Bjelke, Börje

2002-05-01

Severe perinatal asphyxia is an important cause of brain injury in the newborn infant. We examined early events after hypoxic ischemia (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional effects and histopathology in the same animals at 4 to 5 weeks of age. HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analyzed after 3 weeks. Four weeks after HI, the mice were killed, and cresyl violet-stained brain sections were examined morphologically. A decrease in apparent diffusion coefficient values in cortex on the affected side was found at 3 hours after HI. T2 values were significantly increased after 6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3 to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions had decreased forward locomotion, performed worse than controls in the beam-walking test, and showed a unilateral hypotrophy in the cresyl violet-stained brain sections 4 weeks later. The temporal progression of the damage after HI in 7-day-old mice differs from that of the adult brain as judged by MRI. The early lesions detected by MRI were related to functional impairments for these mice in near-adult life.

Diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults.

PubMed

Focquet, A; Péréon, Y; Ségura, S; Ferron, C; Malard, O; Espitalier, F

2017-02-01

To study the diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults. A retrospective study included patients with unilateral vocal-fold immobility undergoing laryngeal electromyography between 2007 and 2015. Neurogenic, normal or myogenic findings were compared to the clinical aspect. Prognosis for recovery was assessed from motor unit potentials on laryngeal electromyography, and compared to subsequent progress on laryngoscopy. Sixty-three patients (mean age, 59 years) were initially included; 2 were subsequently excluded from analysis. Mean time from onset of immobility to laryngeal electromyography was 7 months. 85% of the 61 patients showed neurogenic findings, indicating neural lesion; 13% showed normal electromyography, indicating cricoarytenoid joint ankylosis; and 1 patient showed a myogenic pattern. Neurogenic cases were usually secondary to cervical surgery. Thirty-eight patients were followed up. In total, 75% of patients showing reinnervation potentials recovered. The positive predictive value of laryngeal electromyography was 69.2%. Laryngeal electromyography is effective in specifying the origin of unilateral vocal-fold immobility in adults. It also has a prognostic role, lack of reinnervation potentials being a possible indication for early medialization surgery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Structural Brain Damage and Upper Limb Kinematics in Children with Unilateral Cerebral Palsy.

PubMed

Mailleux, Lisa; Simon-Martinez, Cristina; Klingels, Katrijn; Jaspers, Ellen; Desloovere, Kaat; Demaerel, Philippe; Fiori, Simona; Guzzetta, Andrea; Ortibus, Els; Feys, Hilde

2017-01-01

Background: In children with unilateral cerebral palsy (uCP) virtually nothing is known on the relation between structural brain damage and upper limb (UL) kinematics quantified with three-dimensional movement analysis (3DMA). This explorative study aimed to (1) investigate differences in UL kinematics between children with different lesion timings, i.e., periventricular white matter (PWM) vs. cortical and deep gray matter (CDGM) lesions and (2) to explore the relation between UL kinematics and lesion location and extent within each lesion timing group. Methods: Forty-eight children (age 10.4 ± 2.7 year; 29 boys; 21 right-sided; 33 PWM; 15 CDGM) underwent an UL 3DMA during a reach-to-grasp task. Spatiotemporal parameters [movement duration, (timing of) maximum velocity, trajectory straightness], the Arm Profile Score (APS) and Arm Variable Scores (AVS) were extracted. The APS and AVS refer to the total amount of movement pathology and movement deviations of the wrist, elbow, shoulder, scapula and trunk respectively. Brain lesion location and extent were scored based on FLAIR-images using a semi-quantitative MRI-scale. Results: Children with CDGM lesions showed more aberrant spatiotemporal parameters ( p < 0.03) and more movement pathology (APS, p = 0.003) compared to the PWM group, mostly characterized by increased wrist flexion ( p = 0.01). In the CDGM group, moderate to high correlations were found between lesion location and extent and duration, timing of maximum velocity and trajectory straightness ( r = 0.53-0.90). Lesion location and extent were further moderately correlated with distal UL movement pathology (wrist flexion/extension, elbow pronation/supination, elbow flexion/extension; r = 0.50-0.65) and with the APS ( r = 0.51-0.63). In the PWM group, only a few and low correlations were observed, mostly between damage to the PLIC and higher AVS of elbow flexion/extension, shoulder elevation and trunk rotation ( r = 0.35-0.42). Regression analysis revealed damage to the temporal lobe with lesion timing as interactor (27%, p = 0.002) and the posterior limb of the internal capsule (PLIC) (7%, p = 0.04) as the strongest predictors, explaining 34% of the variance in APS. Conclusion: UL kinematic deviations are more influenced by lesion location and extent in children with later (CDGM) versus earlier lesions (PWM), except for proximal movement pathology. Damage to the PLIC is a significant predictor for UL movement pathology irrespective of lesion timing.

The Small GTP-Binding Protein Rhes Influences Nigrostriatal-Dependent Motor Behavior During Aging.

PubMed

Pinna, Annalisa; Napolitano, Francesco; Pelosi, Barbara; Di Maio, Anna; Wardas, Jadwiga; Casu, Maria Antonietta; Costa, Giulia; Migliarini, Sara; Calabresi, Paolo; Pasqualetti, Massimo; Morelli, Micaela; Usiello, Alessandro

2016-04-01

Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of Rhes deletion on the number of dopamine neurons, (3) nigrostriatal-sensitive behavior during aging in knockout mice. Radioactive in situ hybridization was assessed in adult mice. The beam-walking test was executed in 3-, 6- and 12-month-old mice. Immunohistochemistry of midbrain tyrosine hydroxylase (TH)-positive neurons was performed in 6- and 12-month-old mice. Rhes mRNA is expressed in TH-positive neurons of SNpc and the ventral tegmental area. Moreover, lack of Rhes leads to roughly a 20% loss of nigral TH-positive neurons in both 6- and 12-month-old mutants, when compared with their age-matched controls. Finally, lack of Rhes triggers subtle alterations in motor performance and coordination during aging. Our findings indicate a fine-tuning role of Rhes in regulating the number of TH-positive neurons of the substantia nigra and nigrostriatal-sensitive motor behavior during aging. © 2016 International Parkinson and Movement Disorder Society.

Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.

PubMed

Lin, Yin Chiu; Kuo, Yu-Min; Liao, Pao-Chi; Cherng, Chianfang G; Su, Su-Wen; Yu, Lung

2007-04-30

Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.

Dental Caries Experience in Texan Children with Cleft Lip and Palate.

PubMed

Sunderji, Sabrina; Acharya, Bhavini; Flaitz, Catherine; Chiquet, Brett

2017-09-15

The purpose of this study was to assess the caries experience in the primary dentition of children born with cleft lip and palate (CLP). A retrospective chart review was conducted on subjects between two and six years old recruited from a university-based pediatric dentistry residency clinic. The number of dental visits and professional fluoride applications, the plaque index and treatment modality, and the presence/location of caries, white spot lesions, and enamel hypoplastic lesions were compared between CLP patients and healthy age- and gender-matched controls. Descriptive statistics, Student's t test, Mann-Whitney U test, and regression analysis were completed. A total of 183 charts were reviewed. Compared to healthy children, CLP children had increases in number of dental visits (P<0.001), decayed-missing-filled surfaces (dmfs; P<0.001), decayed-missing-filled teeth (dmft; P<0.001), enamel hypoplastic lesions (P=0.003), treatment completed under general anesthesia (P<0.001), plaque score (P<0.001), and caries increment between baseline and most recent oral examination (P=0.003). Regression analysis revealed a positive association between age and dmft scores within the CLP group (P=0.018). The caries experience of unilateral and bilateral CLP cases was the same (P>0.05). Children with cleft lip and palate are at a greater risk of enamel hypoplasia and dental caries. No significant caries experience difference was found between unilateral or bilateral CLP cases.

Temporal lobe developmental malformations and epilepsy: dual pathology and bilateral hippocampal abnormalities.

PubMed

Ho, S S; Kuzniecky, R I; Gilliam, F; Faught, E; Morawetz, R

1998-03-01

Temporal lobe developmental malformations (TLDM) with focal cortical dysplasia and balloon cells may coexist with mesial temporal sclerosis. The true incidence of this dual pathology is unknown. Our aim was to assess the frequency of amygdala (AM)-hippocampal abnormality in a homogeneous population with this specific developmental malformation. MRI-based volumetry of the AM and hippocampal formation (HF) in 30 patients with unilateral TLDM and intractable partial epilepsy was performed. A volume normalization process defined a normal range of HF and AM volumes in control subjects, and enabled the detection of bilateral volume loss. Normalized volumes detected HF atrophy in 26 patients (nine unilateral and 17 bilateral) and AM atrophy in 18 patients (three unilateral and 15 bilateral). Visual analysis detected unilateral HF abnormality in 21 patients and bilateral abnormality in two. When compared with a group of patients with temporal lobe epilepsy and pure hippocampal sclerosis (N = 92), where volumetry revealed bilateral HF atrophy in 18%, a significant difference in the frequency of bilateral HF atrophy was found (p < 0.0001). Dual pathology is frequent in patients with TLDM (87%), and the AM-HF abnormality is often bilateral (57%). Our data suggest that more widespread and potentially epileptogenic lesions coexist with visibly detectable unilateral TLDM. This has implications for the selection of patients for temporal lobe surgery and may influence surgical strategies.

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects.

PubMed

Cerri, Silvia; Greco, Rosaria; Levandis, Giovanna; Ghezzi, Cristina; Mangione, Antonina Stefania; Fuzzati-Armentero, Marie-Therese; Bonizzi, Arianna; Avanzini, Maria Antonietta; Maccario, Rita; Blandini, Fabio

2015-09-01

Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for Parkinson's disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study, we evaluated homing of intraarterially infused rat MSCs (rMSCs) in the brain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establish whether the toxin-induced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBB disruption is necessary. The rMSC distribution in peripheral organs and the effects of cell infusion on neurodegenerative process and motor deficits were also investigated. rMSCs were infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioral impairment was assessed by adjusting step test and response to apomorphine. Animals were sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brain of 6-OHDA-lesioned animals can be obtained only after mannitol pretreatment. A notable percentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did not modify the progression of 6-OHDA-induced damage or the motor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest that many aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment. This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in rats with a Parkinson's disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent (e.g., mannitol) is used. The infusion did not reduce the neuronal damage and associated motor impairment, but abolished the motor abnormalities these animals typically show when challenged with a dopaminergic agonist. Therefore, although arterially infused mesenchymal stem cells did not show neurorestorative effects in this study's Parkinson's disease model, they appeared to normalize the pathological responsiveness of striatal neurons to dopaminergic stimulation. This capability should be further explored in future studies. ©AlphaMed Press.

Severity of post-stroke aphasia according to aphasia type and lesion location in Koreans.

PubMed

Kang, Eun Kyoung; Sohn, Hae Min; Han, Moon-Ku; Kim, Won; Han, Tai Ryoon; Paik, Nam-Jong

2010-01-01

To determine the relations between post-stroke aphasia severity and aphasia type and lesion location, a retrospective review was undertaken using the medical records of 97 Korean patients, treated within 90 days of onset, for aphasia caused by unilateral left hemispheric stroke. Types of aphasia were classified according to the validated Korean version of the Western Aphasia Battery (K-WAB), and severities of aphasia were quantified using WAB Aphasia Quotients (AQ). Lesion locations were classified as cortical or subcortical, and were determined by magnetic resonance imaging. Two-step cluster analysis was performed using AQ values to classify aphasia severity by aphasia type and lesion location. Cluster analysis resulted in four severity clusters: 1) mild; anomic type, 2) moderate; Wernicke's, transcortical motor, transcortical sensory, conduction, and mixed transcortical types, 3) moderately severe; Broca's aphasia, and 4) severe; global aphasia, and also in three lesion location clusters: 1) mild; subcortical 2) moderate; cortical lesions involving Broca's and/or Wernicke's areas, and 3) severe; insular and cortical lesions not in Broca's or Wernicke's areas. These results revealed that within 3 months of stroke, global aphasia was the more severely affected type and cortical lesions were more likely to affect language function than subcortical lesions.

GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function.

PubMed

Horvath, Tamas L; Erion, Derek M; Elsworth, John D; Roth, Robert H; Shulman, Gerald I; Andrews, Zane B

2011-07-01

Guanidinopropionic acid (GPA) increases AMPK activity, mitochondrial function and biogenesis in muscle and improves physiological function, for example during aging. Mitochondrial dysfunction is a major contributor to the pathogenesis of Parkinson's disease. Here we tested whether GPA prevents neurodegeneration of the nigrostriatal dopamine system in MPTP-treated mice. Mice were fed a diet of 1% GPA or normal chow for 4 weeks and then treated with either MPTP or saline. Indices of nigrostriatal function were examined by HPLC, immunohistochemistry, stereology, electron microscopy and mitochondrial respiration. MPTP intoxication decreased TH neurons in the SNpc of normal chow-fed mice; however GPA-fed mice remarkably exhibited no loss of TH neurons in the SNpc. MPTP caused a decrease in striatal dopamine of both normal chow- and GPA-fed mice, although this effect was significantly attenuated in GPA-fed mice. GPA-fed mice showed increased AMPK activity, mitochondrial respiration and mitochondrial number in nigrostriatal TH neurons, suggesting that the neuroprotective effects of GPA involved AMPK-dependent increases in mitochondrial function and biogenesis. MPTP treatment produced a decrease in mitochondrial number and volume in normal chow-fed mice but not GPA-fed mice. Our results show the neuroprotective properties of GPA in a mouse model of Parkinson's disease are partially mediated by AMPK and mitochondrial function. Mitochondrial dysfunction is a common problem in neurodegeneration and thus GPA may slow disease progression in other models of neurodegeneration. Copyright © 2011 Elsevier Inc. All rights reserved.

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

Progranulin gene delivery protects dopaminergic neurons in a mouse model of Parkinson's disease.

PubMed

Van Kampen, Jackalina M; Baranowski, David; Kay, Denis G

2014-01-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity and akinesia/bradykinesia resulting from the progressive loss of nigrostriatal dopaminergic neurons. To date, only symptomatic treatment is available for PD patients, with no effective means of slowing or stopping the progression of the disease. Progranulin (PGRN) is a 593 amino acid multifunction protein that is widely distributed throughout the CNS, localized primarily in neurons and microglia. PGRN has been demonstrated to be a potent regulator of neuroinflammation and also acts as an autocrine neurotrophic factor, important for long-term neuronal survival. Thus, enhancing PGRN expression may strengthen the cells resistance to disease. In the present study, we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of PGRN gene delivery as a therapy for the prevention or treatment of PD. Viral vector delivery of the PGRN gene was an effective means of elevating PGRN expression in nigrostriatal neurons. When PGRN expression was elevated in the SNC, nigrostriatal neurons were protected from MPTP toxicity in mice, along with a preservation of striatal dopamine content and turnover. Further, protection of nigrostriatal neurons by PGRN gene therapy was accompanied by reductions in markers of MPTP-induced inflammation and apoptosis as well as a complete preservation of locomotor function. We conclude that PGRN gene therapy may have beneficial effects in the treatment of PD.

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

PubMed Central

Li, Hong-Peng; Komuta, Yukari; Kimura-Kuroda, Junko; van Kuppevelt, Toin H.

2013-01-01

Abstract Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration. PMID:23438307

A dual task priming investigation of right hemisphere inhibition for people with left hemisphere lesions

PubMed Central

2012-01-01

Background During normal semantic processing, the left hemisphere (LH) is suggested to restrict right hemisphere (RH) performance via interhemispheric suppression. However, a lesion in the LH or the use of concurrent tasks to overload the LH's attentional resource balance has been reported to result in RH disinhibition with subsequent improvements in RH performance. The current study examines variations in RH semantic processing in the context of unilateral LH lesions and the manipulation of the interhemispheric processing resource balance, in order to explore the relevance of RH disinhibition to hemispheric contributions to semantic processing following a unilateral LH lesion. Methods RH disinhibition was examined for nine participants with a single LH lesion and 13 matched controls using the dual task paradigm. Hemispheric performance on a divided visual field lexical decision semantic priming task was compared over three verbal memory load conditions, of zero-, two- and six-words. Related stimuli consisted of categorically related, associatively related, and categorically and associatively related prime-target pairs. Response time and accuracy data were recorded and analyzed using linear mixed model analysis, and planned contrasts were performed to compare priming effects in both visual fields, for each of the memory load conditions. Results Control participants exhibited significant bilateral visual field priming for all related conditions (p < .05), and a LH advantage over all three memory load conditions. Participants with LH lesions exhibited an improvement in RH priming performance as memory load increased, with priming for the categorically related condition occurring only in the 2- and 6-word memory conditions. RH disinhibition was also reflected for the LH damage (LHD) group by the removal of the LH performance advantage following the introduction of the memory load conditions. Conclusions The results from the control group are consistent with suggestions of an age related hemispheric asymmetry reduction and indicate that in healthy aging compensatory bilateral activation may reduce the impact of inhibition. In comparison, the results for the LHD group indicate that following a LH lesion RH semantic processing can be manipulated and enhanced by the introduction of a verbal memory task designed to engage LH resources and allow disinhibition of RH processing. PMID:22429687

Left hand tactile agnosia after posterior callosal lesion.

PubMed

Balsamo, Maddalena; Trojano, Luigi; Giamundo, Arcangelo; Grossi, Dario

2008-09-01

We report a patient with a hemorrhagic lesion encroaching upon the posterior third of the corpus callosum but sparing the splenium. She showed marked difficulties in recognizing objects and shapes perceived through her left hand, while she could appreciate elementary sensorial features of items tactually presented to the same hand flawlessly. This picture, corresponding to classical descriptions of unilateral associative tactile agnosia, was associated with finger agnosia of the left hand. This very unusual case report can be interpreted as an instance of disconnection syndrome, and allows a discussion of mechanisms involved in tactile object recognition.

Acoustic input and efferent activity regulate the expression of molecules involved in cochlear micromechanics

PubMed Central

Lamas, Veronica; Arévalo, Juan C.; Juiz, José M.; Merchán, Miguel A.

2015-01-01

Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels. PMID:25653600

Superimposed Segmental Manifestation of Juvenile Amyopathic Dermatomyositis in a 9-year-old Boy

PubMed Central

Bulur, Isil; Erdogan, Hilal Kaya; Saracoglu, Zeynep Nurhan; Happle, Rudolf; Canaz, Funda

2017-01-01

Dermatomyositis is a well-known autoimmune disorder. On the other hand, juvenile amyopathic dermatomyositis (JADM) occurs rather rarely. Here, we report an unusual case in a 9-year-old Turkish boy showing a unilateral linear inflammatory skin lesion that was followed, after 16 months, by the appearance of bilateral disseminated features JADM. PMID:28794565

Post-Training Unilateral Amygdala Lesions Selectively Impair Contextual Fear Memories

ERIC Educational Resources Information Center

Flavell, Charlotte R.; Lee, Jonathan L. C.

2012-01-01

The basolateral amygdala (BLA) and the dorsal hippocampus (dHPC) are both structures with key roles in contextual fear conditioning. During fear conditioning, it is postulated that contextual representations of the environment are formed in the hippocampus, which are then associated with foot shock in the amygdala. However, it is not known to what…

Cognitive Outcome following Unilateral Arterial Ischaemic Stroke in Childhood: Effects of Age at Stroke and Lesion Location

ERIC Educational Resources Information Center

Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; deVeber, Gabrielle

2010-01-01

Aim: Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at…

Auditory/visual Duration Bisection in Patients with Left or Right Medial-Temporal Lobe Resection

ERIC Educational Resources Information Center

Melgire, Manuela; Ragot, Richard; Samson, Severine; Penney, Trevor B.; Meck, Warren H.; Pouthas, Viviane

2005-01-01

Patients with unilateral (left or right) medial temporal lobe lesions and normal control (NC) volunteers participated in two experiments, both using a duration bisection procedure. Experiment 1 assessed discrimination of auditory and visual signal durations ranging from 2 to 8 s, in the same test session. Patients and NC participants judged…

Lymphoscintigraphic findings in chylous reflux in a lower extremity.

PubMed

Berenji, Gholam R; Iker, Emily; Glass, Edwin C

2007-09-01

Lymphoscintigraphy is a useful and safe tool for the diagnostic evaluation of a swollen extremity. Unilateral leg swelling with cutaneous chylous vesicles is a common manifestation of chylous reflux. The authors present a case of chylous reflux in an 11-year-old boy who presented with swelling and skin lesions of the left lower extremity.

Herpes zoster of gingiva in an older woman: a rare case report.

PubMed

Chopra, Aditi; Sivaraman, Karthik; Thomas, Betsy S

2017-06-01

The aim of the article is to highlight the distinguishing features of secondary varicella gingival infection in an older women. Herpes zoster is an acute sporadic, painful viral infection in older people caused by the reactivation of the latent varicella zoster virus. Herpes zoster affecting the gingiva without any dermal lesions is a rare pathological condition that mimics many intraoral vesiculobullous lesions. The ambiguous nature of this condition creates a diagnostic dilemma. A 58-year-old woman presented with an acute, unilateral and persistent burning sensation and pain in the gingiva with desqaumating vesicullobulous lesion. The women was diagnosed with secondary varicella zoster infection. Herpes zoster of the gingiva could manifest as painful desquamative vesicular lesions, pulpal or other painful neuralgic condition in older individuals which need careful diagnosis before formulating appropiate treatment plan. © 2016 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Unilateral robotic hybrid mini-maze: a novel experimental approach.

PubMed

Moslemi, Mohammad; Rawashdeh, Badi; Meyer, Mark; Nguyen, Duy; Poston, Robert; Gharagozloo, Farid

2016-03-01

A complete Cox maze IV procedure is difficult to accomplish using current endoscopic and minimally invasive techniques. These techniques are hampered by inability to adequately dissect the posterior structures of the heart and place all necessary lesions. We present a novel approach, using robotic technology, that achieves placement of all the lesions of the complete maze procedure. In three cadaveric human models, the technical feasibility of using robotic instruments through the right chest to dissect the posterior structures of the heart and place all Cox maze lesions was performed. The entire posterior aspect of the heart was dissected in the cadaveric model facilitating successful placement of all Cox maze IV lesions with robotic assistance through minimally invasive incisions. The robotic Cox maze IV procedure through the novel right thoracic approach is feasible. This obviates the need for sternotomy and avoids the associated morbidity of the conventional Cox-maze procedure. Copyright © 2015 John Wiley & Sons, Ltd.

Neuropsychological outcome after traumatic temporal lobe damage.

PubMed

Formisano, R; Schmidhuber-Eiler, B; Saltuari, L; Cigany, E; Birbamer, G; Gerstenbrand, F

1991-01-01

The most frequent sequelae after severe brain injury include changes in personality traits, disturbances of emotional behaviour and impairment of cognitive functions. In particular, emotional changes and/or verbal and non verbal dysfunctions were found in patients with bilateral or unilateral temporal lobe lesions. The aim of our study is to correlate the localization of the brain damage after severe brain injury, in particular of the temporal lobe, with the cognitive impairment and the emotional and behavioural changes resulting from these lesions. The patients with right temporal lobe lesions showed significantly better scores in verbal intelligence and verbal memory in comparison with patients with left temporal lobe lesions and those with other focal brain lesions or diffuse brain damage. In contradistinction, study of the personality and the emotional changes (MMPI and FAF) failed to demonstrate pathological scores in the 3 groups with different CT lesions, without any significant difference being found between the groups with temporal lesions and those with other focal brain lesions or diffuse brain damage. The severity of the brain injury and the prolongation of the disturbance of consciousness could, in our patients, account for prevalence of congnitive impairment on personality and emotional changes.

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal–temporal interaction

PubMed Central

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2008-01-01

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure. PMID:18702721

Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion.

PubMed

Timmer, Marco; Cesnulevicius, Konstantin; Winkler, Christian; Kolb, Julia; Lipokatic-Takacs, Esther; Jungnickel, Julia; Grothe, Claudia

2007-01-17

Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.

Recovery From Experimental Parkinsonism by Semaphorin-guided Axonal Growth of Grafted Dopamine Neurons

PubMed Central

Díaz-Martínez, N Emmanuel; Tamariz, Elisa; Díaz, N Fabián; García-Peña, Claudia M; Varela-Echavarría, Alfredo; Velasco, Iván

2013-01-01

Cell therapy in animal models of Parkinson's disease (PD) is effective after intrastriatal grafting of dopamine (DA) neurons, whereas intranigral transplantation of dopaminergic cells does not cause consistent behavioral recovery. One strategy to promote axonal growth of dopaminergic neurons from the substantia nigra (SN) to the striatum is degradation of inhibitory components such as chondroitin sulphate proteoglycans (CSPG). An alternative is the guidance of DA axons by chemotropic agents. Semaphorins 3A and 3C enhance axonal growth of embryonic stem (ES) cell–derived dopaminergic neurons in vitro, while Semaphorin 3C also attracts them. We asked whether intranigral transplantation of DA neurons, combined with either degradation of CSPG or with grafts of Semaphorin 3–expressing cells, towards the striatum, is effective in establishing a new nigrostriatal dopaminergic pathway in rats with unilateral depletion of DA neurons. We found depolarization-induced DA release in dorsal striatum, DA axonal projections from SN to striatum, and concomitant behavioral improvement in Semaphorin 3–treated animals. These effects were absent in animals that received intranigral transplants combined with Chondroitinase ABC treatment, although partial degradation of CSPG was observed. These results are evidence that Semaphorin 3–directed long-distance axonal growth of dopaminergic neurons, resulting in behavioral improvement, is possible in adult diseased brains. PMID:23732989

Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nouraei, Negin; Zarger, Lauren; Weilnau, Justin N.

The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 μg) and administered NAC intraperitoneally (100 mg/kg). NAC-treated animals exhibited higher levels of the dopaminergic terminal marker tyrosine hydroxylase (TH) in the striatum 10d after 6-OHDA. As TH expression is subject to stress-induced modulation, we infusedmore » the tracer FluoroGold into the striatum to retrogradely label nigrostriatal projection neurons. As expected, nigral FluoroGold staining and cell counts of FluoroGold{sup +} profiles were both more sensitive measures of nigrostriatal degeneration than measurements relying on TH alone. However, NAC failed to protect dopaminergic neurons 3 weeks following 6-OHDA, an effect verified by four measures: striatal TH levels, nigral TH levels, nigral TH{sup +} cell counts, and nigral FluoroGold levels. Some degree of mild toxicity of FluoroGold and NAC was evident, suggesting that caution must be exercised when relying on FluoroGold as a neuron-counting tool and when designing experiments with long-term delivery of NAC—such as clinical trials on patients with chronic disorders. Finally, the strengths and limitations of the tools used to define nigrostriatal degeneration are discussed. - Highlights: • N-acetyl cysteine (NAC) was injected into animals infused with the toxicant 6-OHDA. • Retrograde tracing with FluoroGold was used to define nigrostriatal cell loss. • Infrared Odyssey imaging and cell counts were used to screen for nigral cell loss. • NAC protected transiently against 6-OHDA but this effect waned over time. • Mildly toxic effects of chronic NAC delivery may influence future clinical trials.« less

Vertebral growth modulation by hemicircumferential electrocoagulation: an experimental study in pigs.

PubMed

Caballero, Alberto; Barrios, Carlos; Burgos, Jesús; Hevia, Eduardo; Correa, Carlos

2011-08-01

This experimental study in pigs was aimed at evaluating spinal growth disorders after partial arrest of the vertebral epiphyseal plates (EP) and neurocentral cartilages (NCC). Unilateral and multisegmental single or combined lesions of the physeal structures were performed by electrocoagulation throughout a video-assisted thoracoscopical approach. Thirty 4-week-old domestic pigs (mean weight 16 kg) were included in the experiments. The superior and inferior epiphyseal plates of T5 to T9 vertebra were damaged in ten animals by hemicircumferential electrocoagulation (group I). In other ten pigs (group II), right NCC at the same T5-T9 levels were damaged. Ten other animals underwent combined lesions of the ipsilateral hemiepiphyseal plates and NCC at the T5-T9 levels. A total of 26 animals could be evaluated after 12 weeks of follow-up using conventional X-rays, CT scans and histology. The pigs with hemicircumferential EP damage developed very slight concave non-structured scoliotic deformities without vertebral rotation.(mean 12° Cobb; range10-16°). Some of the damaged vertebra showed a marked wedgening with unilateral development alteration of the vertebral body, including the adjacent discs The animals with damage of the NCC developed mild scoliotic curves (mean 19° Cobb; range 16-24°) with convexity opposite to the damaged side and loss of physiological kyphosis. The injured segments showed an asymmetric growth with hypoplasia of the pedicle and costovertebral joints at the damaged side. The pigs undergoing combined EP and NCC lesions developed minimal non-structured curves, ranging from 10 to 12° Cobb. In these animals there was a lack of growth of a vertebral hemibody and disc hypoplasia at the damaged segments. Both damage of the NCC and the EP affect the height of the vertebral body. No spinal stenosis was found in any case. In most cases, the adjacent superior and inferior vertebral EP to damaged segments had a compensatory growth that maintained the straight spinal shape. In summary, unilateral direct lesion of the EP by hemicircumferential thoracoscopic electrocoagulation modifies vertebral growth, but is not able to induce true scoliostic curves in pigs. Only animals with damaged NCC developed mild scoliotic curves of lordotic type. This work rediscovers and emphasizes the decisive role of the neurocentral cartilage in the ethiopatogeny of idiopathic scoliosis.

A short review of primary aldosteronism in a question and answer fashion.

PubMed

Farrugia, Frederick-Anthony; Zavras, Nicolaos; Martikos, Georgios; Tzanetis, Panagiotis; Charalampopoulos, Anestis; Misiakos, Evangelos P; Sotiropoulos, Dimitrios; Koliakos, Nikolaos

2018-01-01

The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

Responses of non-eye movement central vestibular neurons to sinusoidal horizontal translation in compensated macaques after unilateral labyrinthectomy

PubMed Central

Lin, Nan; Wei, Min

2014-01-01

After vestibular labyrinth injury, behavioral deficits partially recover through the process of vestibular compensation. The present study was performed to improve our understanding of the physiology of the macaque vestibular system in the compensated state (>7 wk) after unilateral labyrinthectomy (UL). Three groups of vestibular nucleus neurons were included: pre-UL control neurons, neurons ipsilateral to the lesion, and neurons contralateral to the lesion. The firing responses of neurons sensitive to linear acceleration in the horizontal plane were recorded during sinusoidal horizontal translation directed along six different orientations (30° apart) at 0.5 Hz and 0.2 g peak acceleration (196 cm/s2). This data defined the vector of best response for each neuron in the horizontal plane, along which sensitivity, symmetry, detection threshold, and variability of firing were determined. Additionally, the responses of the same cells to translation over a series of frequencies (0.25–5.0 Hz) either in the interaural or naso-occipital orientation were obtained to define the frequency response characteristics in each group. We found a decrease in sensitivity, increase in threshold, and alteration in orientation of best responses in the vestibular nuclei after UL. Additionally, the phase relationship of the best neural response to translational stimulation changed with UL. The symmetry of individual neuron responses in the excitatory and inhibitory directions was unchanged by UL. Bilateral central utricular neurons still demonstrated two-dimension tuning after UL, consistent with spatio-temporal convergence from a single vestibular end-organ. These neuronal data correlate with known behavioral deficits after unilateral vestibular compromise. PMID:24717349

Restoring tactile and erogenous penile sensation in low-spinal-lesion patients: procedural and technical aspects following 43 TOMAX nerve transfer procedures.

PubMed

Overgoor, Max L E; de Jong, Tom P V M; Kon, Moshe

2014-08-01

The "TOMAX" (TO MAX-imize sensation, sexuality, and quality of life) procedure restores genital sensation in men with low spinal lesions, improving sexual health, as shown previously. It connects the dorsal nerve of the penis to the intact ipsilateral ilioinguinal nerve, unilaterally or bilaterally. This study reports on the technical aspects based on 43 TOMAX nerve transfers. In 40 patients with no penile but intact groin sensation, 43 nerve transfers were performed. Data on patient selection, surgical history, anatomy of the ilioinguinal nerve and dorsal nerve of the penis, unilateral or bilateral surgery, surgical technique, complications, and patient information were collected prospectively. Regardless of origin, all patients with no penile but good groin sensation are eligible for the procedure, provided the ilioinguinal nerve is not damaged because of former inguinal surgery or absent because of anatomical variations. Selection of a unilateral or bilateral procedure depends on the presence or absence of reflex erections and bulbocavernosus reflex. Preliminary experience with the first three bilateral cases shows that it is technically feasible, with encouraging results. The surgical technique has evolved (described in detail, including video) to enhance outcome and reduce complications. Patients are better informed, resulting in realistic expectations. This article synthesizes the procedural and technical experience of 43 TOMAX nerve transfers. Anyone skilled in peripheral nerve surgery and microsurgery can adopt this concept and further develop it. The TOMAX procedure can then be used to restore erogenous penile sensation and improve the quality of sexual health in patients with absent penile but good groin sensation.

Effects of acidic fibroblast growth factor on cholinergic neurons of nucleus basalis magnocellularis and in a spatial memory task following cortical devascularization.

PubMed

Figueiredo, B C; Piccardo, P; Maysinger, D; Clarke, P B; Cuello, A C

1993-10-01

The ability of acidic fibroblast growth factor to elicit a trophic response in the nervous system of the rat was tested in vitro and in vivo. Treatment of cultured septal cells with acidic fibroblast growth factor resulted in an elongation of glial processes as assessed by immunostaining for glial fibrillary acidic protein. Increased choline acetyltransferase was also observed. The responses to acidic fibroblast growth factor in vivo were studied in rats trained in a spatial memory task, using the Morris water maze. Randomly selected animals were subjected to unilateral cortical devascularization. This lesion results in partial unilateral infarction of the neocortex, and in retrograde degeneration of the nucleus basalis magnocellularis. Animals were tested post-lesion for memory retention and were then killed for morphological studies. Intracerebroventricular administration of acidic fibroblast growth factor (0.6 microgram/h for seven days starting at surgery) prevented the lesion-induced impairment in this test, and reduced the nucleus basalis magnocellularis cholinergic degeneration, as assessed by morphometric choline acetyltransferase-like immunoreactivity and radioenzymatic assay for choline acetyltransferase activity. The preservation of the phenotype of injured cholinergic neurons of the nucleus basalis magnocellularis by acidic fibroblast growth factor was indicated by the maintenance of the cross-sectional area of cell bodies and mean length of neuritic processes one month after surgery. The effect of acidic fibroblast growth factor in non-cholinergic cells remains to be investigated. It is suggested that acidic fibroblast growth factor may alleviate the lesion-induced deficit in the memory retention task by preventing disruption of functional connections between nucleus basalis magnocellularis and intact cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical utility of a complete diagnostic protocol for the ocular evaluation of free-living raptors.

PubMed

Labelle, Amber L; Whittington, Julia K; Breaux, Carrie B; Labelle, Philippe; Mitchell, Mark A; Zarfoss, Mitzi K; Schmidt, Stephanie A; Hamor, Ralph E

2012-01-01

  To describe a protocol for the examination of free-living raptors and report the ophthalmic examination findings of seven raptor species native to central Illinois, namely the barred owl, Cooper's hawk, eastern screech owl, great horned owl, American kestrel, red-tailed hawk, and turkey vulture and to determine if the findings relative to visual prognosis affected eligibility for future release.   Seventy-nine free-living raptors.   Under manual restraint, complete ophthalmic examination including slit-lamp biomicroscopy and indirect funduscopy, applanation tonometry, rebound tonometry, ocular morphometrics, B-mode ultrasound, and electroretinography (ERG) were performed on each bird. Histopathology of enucleated globes was performed after euthanasia or death in selected cases.   The examination protocol was easily performed using manual restraint alone on all birds. Ocular lesions were detected in 48.1% of birds, with 47.3% affected unilaterally and 52.6% affected bilaterally. Ocular lesions were considered to be vision threatening in 29.0% of the unilaterally affected birds and 29.0% of the bilaterally affected birds. The most common case outcomes were discharge from hospital to rehabilitation facility (45.6%) followed by euthanasia (43.0%). The presence of an ocular lesion or a vision-threatening ocular lesion was not significantly associated with outcome. Reference ranges are reported for B-mode ultrasound, ocular morphometrics, and horizontal corneal diameter in all species.   Complete ophthalmic examination can be supplemented by the use of ocular morphometrics, ultrasound, and ERG in the manually restrained raptor. These advanced diagnostic techniques may be useful in developing more objective criteria for evaluating eligibility for release following rehabilitation of free-living birds of prey. © 2011 American College of Veterinary Ophthalmologists.

Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy.

PubMed

Lv, Rui-Juan; Sun, Zhen-Rong; Cui, Tao; Shao, Xiao-Qiu

2014-02-01

This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis.

PubMed

Juenger, Hendrik; Koerte, Inga K; Muehlmann, Marc; Mayinger, Michael; Mall, Volker; Krägeloh-Mann, Ingeborg; Shenton, Martha E; Berweck, Steffen; Staudt, Martin; Heinen, Florian

2014-11-01

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo

PubMed Central

Nouraei, Negin; Zarger, Lauren; Weilnau, Justin N.; Han, Jimin; Mason, Daniel M.; Leak, Rehana K.

2016-01-01

The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 μg) and administered NAC intraperitoneally (100 mg/kg). NAC-treated animals exhibited higher levels of the dopaminergic terminal marker tyrosine hydroxylase (TH) in the striatum 10d after 6-OHDA. As TH expression is subject to stress-induced modulation, we infused the tracer FluoroGold into the striatum to retrogradely label nigrostriatal projection neurons. As expected, nigral FluoroGold staining and cell counts of FluoroGold+ profiles were both more sensitive measures of nigrostriatal degeneration than measurements relying on TH alone. However, NAC failed to protect dopaminergic neurons 3 weeks following 6-OHDA, an effect verified by four measures: striatal TH levels, nigral TH levels, nigral TH+ cell counts, and nigral FluoroGold levels. Some degree of mild toxicity of FluoroGold and NAC was evident, suggesting that caution must be exercised when relying on FluoroGold as a neuron-counting tool and when designing experiments with long-term delivery of NAC—such as clinical trials on patients with chronic disorders. Finally, the strengths and limitations of the tools used to define nigrostriatal degeneration are discussed. PMID:26879220

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

PubMed

Kim, H C; Jhoo, W K; Choi, D Y; Im, D H; Shin, E J; Suh, J H; Floyd, R A; Bing, G

1999-12-18

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Mucosal Melanoma Originating From the Eustachian Tube.

PubMed

Kim, Jeong Hong; Lim, Gil-Chai; Kang, Ju Wan

2017-11-01

A 77-year-old man was referred with a 4-month history of hearing impairment and ear fullness of the left ear. Otoscopic examination revealed an effusion in the left middle ear, and nasal endoscopic examination revealed a dark polypoid lesion at the opening of the left Eustachian tube. In addition to the lesion of the Eustachian tube, a dark mucosal lesion was seen at the posterior choana and the posterior end of the nasal septum. Endoscopic biopsy was done and pathologic result was consistent with malignant melanoma. Wide surgical excision with postoperative radiotherapy was performed; multiple metastases were detected 4 months after the treatment. Mucosal melanoma originating from nasopharynx was extremely rare, but careful examination of nasopharyngeal area should be considered when the patient presents with unilateral middle ear effusion, especially in older age.

Unilateral or bilateral punctate hippocampal hyperintensities on DW-MRI: seizures, amnesia, or both?

PubMed

Bocos-Portillo, Jone; Escalza-Cortina, Inés; Gómez-Beldarrain, Marian; Rodriguez-Sainz, Aida; Garcia-Monco, Juan Carlos

2018-06-02

The presence of small hippocampal hyperintense lesions on diffusion-weighted (DW) MRI can respond to different etiologies and represents a challenge where clinical judgment is imperative, since therapeutic approach may be quite different.We here report three patients with similar neuroradiological findings, i.e., hyperintense punctate hippocampal lesions on diffusion-weighted MRI sequences, yet of different origin. The first one presented with isolated amnesia (transient global amnesia), the second one with amnesia and seizures, and the third one with seizures.Thus, hippocampal punctate lesions appear after transient global amnesia, but the same pattern may be present after seizures, either focal-onset or generalized seizures. This peculiar radiological MRI pattern could indicate a pathogenic link between transient global amnesia (TGA) and seizures which should be further studied.

Optic radiations are thinner and show signs of iron deposition in patients with long-standing remitting-relapsing multiple sclerosis: an enhanced T2*-weighted angiography imaging study.

PubMed

Zeng, Chun; Du, Silin; Han, Yongliang; Fu, Jialiang; Luo, Qi; Xiang, Yayun; Chen, Xiaoya; Luo, Tianyou; Li, Yongmei; Zheng, Yineng

2018-04-30

This study aimed to investigate iron deposition and thickness and signal changes in optic radiation (OR) by enhanced T 2 * -weighted angiography imaging (ESWAN) in patients with relapsing-remitting multiple sclerosis (RRMS) with unilateral and bilateral lesions or no lesions. Fifty-one RRMS patients (42 patients with a disease duration [DD] ≥ 2 years [group Mor], nine patients with a DD < 2 years [group Les]) and 51 healthy controls (group Con) underwent conventional magnetic resonance imaging (MRI) and ESWAN at 3.0 T. The mean phase value (MPV) of the OR was measured on the phase image, and thickness and signal changes of the OR were observed on the magnitude image. The average MPVs for the OR were 1,981.55 ± 7.75 in group Mor, 1,998.45 ± 2.01 in group Les, and 2,000.48 ± 5.53 in group Con. In group Mor, 28 patients with bilateral OR lesions showed bilateral OR thinning with a heterogeneous signal, and 14 patients with unilateral OR lesions showed ipsilateral OR thinning with a heterogeneous signal. In the remaining nine patients without OR lesions and in group Con, the bilateral OR had a normal appearance. In the patients, a negative correlation was found between DD and OR thickness and a positive correlation was found between MPV and OR thickness. We confirmed iron deposition in the OR in the RRMS patients, and the OR thickness was lower in the patients than in the controls. • Enhanced T 2 * -weighted magnetic resonance angiography (ESWAN) provides new insights into multiple sclerosis (MS). • Focal destruction of the optic radiation (OR) is detectable by ESWAN. • Iron deposition in OR can be measured on ESWAN phase image in MS patients. • OR thickness was lower in the patients than in the controls. • Iron deposition and thickness changes of the OR are associated with disease duration.

Lesions that functionally disconnect the anterior and posterodorsal sub-regions of the medial amygdala eliminate opposite-sex odor preference in male Syrian hamsters (Mesocricetus auratus)

PubMed Central

Maras, Pamela M.; Petrulis, Aras

2009-01-01

In many rodent species, such as Syrian hamsters, reproductive behavior requires neural integration of chemosensory information and steroid hormone cues. The medial amygdala processes both of these signals through anatomically distinct sub-regions; the anterior region (MeA) receives substantial chemosensory input, but contains few steroid receptor-labeled neurons, whereas the posterodorsal region (MePD) receives less chemosensory input, but contains a dense population of steroid receptors. Importantly, these sub-regions have considerable reciprocal connections, and the goal of this experiment was therefore to determine whether interactions between MeA and MePD are required for male hamsters’ preference to investigate female over male odors. To functionally disconnect MeA and MePD, males received unilateral lesions of MeA and MePD within opposite brain hemispheres. Control males received either unilateral lesions of MeA and MePD within the same hemisphere or sham surgery. Odor preferences were measured using a 3-choice apparatus, which simultaneously presented female, male and clean odor stimuli; all tests were done under conditions that either prevented or allowed contact with the odor sources. Under non-contact conditions, males with asymmetrical lesions investigated female and male odors equally, whereas males in both control groups preferred to investigate female odors. Under contact conditions, all groups investigated female odors longer than male odors, although males with asymmetrical lesions displayed decreased investigation of female odors compared to sham males. These data suggest that MeA-MePD interactions are critical for processing primarily the volatile components of social odors and highlight the importance of input from the main olfactory system to these nuclei in the regulation of reproductive behavior. More broadly, these results support the role of the medial amygdala in integrating chemosensory and hormone information, a process that may underlie social odor processing in a variety of behavioral contexts. PMID:19931356

Tic douloureux.

PubMed

Sweeney, P J

1981-02-01

Tic douloureux (trigerminal neuralgia) usually has its onset in the sixth or seventh decade and is characterized by severe, excruciating facial pain which is almost always unilateral. The mandibular division and the maxillary division of the fifth cranial nerve are most commonly affected. Carbamazepine is the drug of choice. Currently popular surgical procedures include decompression of the fifth cranial nerve and percutaneous thermal lesioning of the gasserian ganglion.

Severity of Post-stroke Aphasia According to Aphasia Type and Lesion Location in Koreans

PubMed Central

Kang, Eun Kyoung; Sohn, Hae Min; Han, Moon-Ku; Kim, Won; Han, Tai Ryoon

2010-01-01

To determine the relations between post-stroke aphasia severity and aphasia type and lesion location, a retrospective review was undertaken using the medical records of 97 Korean patients, treated within 90 days of onset, for aphasia caused by unilateral left hemispheric stroke. Types of aphasia were classified according to the validated Korean version of the Western Aphasia Battery (K-WAB), and severities of aphasia were quantified using WAB Aphasia Quotients (AQ). Lesion locations were classified as cortical or subcortical, and were determined by magnetic resonance imaging. Two-step cluster analysis was performed using AQ values to classify aphasia severity by aphasia type and lesion location. Cluster analysis resulted in four severity clusters: 1) mild; anomic type, 2) moderate; Wernicke's, transcortical motor, transcortical sensory, conduction, and mixed transcortical types, 3) moderately severe; Broca's aphasia, and 4) severe; global aphasia, and also in three lesion location clusters: 1) mild; subcortical 2) moderate; cortical lesions involving Broca's and/or Wernicke's areas, and 3) severe; insular and cortical lesions not in Broca's or Wernicke's areas. These results revealed that within 3 months of stroke, global aphasia was the more severely affected type and cortical lesions were more likely to affect language function than subcortical lesions. PMID:20052357

Interaction between the medial prefrontal cortex and hippocampal CA1 area is essential for episodic-like memory in rats.

PubMed

Chao, Owen Y; Nikolaus, Susanne; Lira Brandão, Marcus; Huston, Joseph P; de Souza Silva, Maria A

2017-05-01

The interplay between medial prefrontal cortex (mPFC) and hippocampus, particularly the hippocampal CA3 area, is critical for episodic memory. To what extent the mPFC also interacts with the hippocampus CA1 subregion still requires elucidation. To investigate this issue, male rats received unilateral N-methyl- D -aspartate lesions of the mPFC together with unilateral lesions of the hippocampal CA1 area, either in the same (control) or in the opposite hemispheres (disconnection). They underwent an episodic-like memory test, combining what-where-when information, and separate tests for novel object preference (what), object place preference (where) and temporal order memory (when). Compared to controls, the disconnected mPFC-CA1 rats exhibited disrupted episodic-like memory with an impaired integration of the what-where-when elements. Both groups showed intact memories for what and when, while only the control group showed intact memory for where. These findings suggest that the functional interaction of the mPFC-CA1 circuit is crucial for the processing of episodic memory and, in particular, for the integration of the spatial memory component. Copyright © 2017 Elsevier Inc. All rights reserved.

Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

PubMed

Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

2014-04-01

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effect of unilateral versus bilateral electrostimulation in subthalamic nucleus on speech in Parkinsons disease

NASA Astrophysics Data System (ADS)

Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

2004-05-01

Previously, it was found that 16 right-handed patients with idiopathic Parkinsons disease who underwent unilateral implantation of deep brain stimulator in subthalamic nucleus (STN) showed significant improvement in their nonspeech motor functions. Eight of the 16 patients had stimulator in the left STN and eight in the right STN. In contrast, their speech function showed very mild improvement that was limited to the respiratory/phonotory subsystems. Further, there seemed a trend that the patients with right STN stimulation did better than those with left STN stimulation. It was speculated that the difference might be due to a micro lesion caused by the surgical procedure to the corticobulbar fibers run in the left internal capsule. This paper reports speech changes associated with bilateral DBS in STN in four of the 16 subjects who elected to have deep brain stimulator implanted in STN on the opposite side of the brain at a later time. Results show negative changes in speech after bilateral DBS in STN. The changes were not limited to the micro lesion effect due to the surgery itself, but also related to the active stimulation on the dominant hemisphere for speech processing. [Work supported by NIH.

Bone scintigraphy in the investigation of occult lameness in the dog.

PubMed

Schwarz, T; Johnson, V S; Voute, L; Sullivan, M

2004-05-01

99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in 14 dogs of different breeds after clinical lameness examination, radiography and synovial fluid analysis failed to localise lameness to a specific area of pain. The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc-MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised positions with a low-energy all-purpose collimator. Confirmation of diagnosis was achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography, computed tomography and response to treatment. In seven cases, bone phase scans showed single elbow uptakes, in two cases unilateral limb uptake, and in one case each a single shoulder and tibia uptake; in three cases there was no increased uptake. Vascular and soft tissue phase images did not reveal additional information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid process, panosteitis and arthropathy was possible in nine cases. Skeletal pathology was ruled out in three normal scintigrams. In two dogs with unilateral uptake of multiple joints, no diagnostic benefit was gained from scintigraphy. The highly sensitive and relatively specific uptake allowed localisation and characterisation or exclusion of skeletal lesions in most dogs.

The effect of contextual auditory stimuli on virtual spatial navigation in patients with focal hemispheric lesions.

PubMed

Cogné, Mélanie; Knebel, Jean-François; Klinger, Evelyne; Bindschaedler, Claire; Rapin, Pierre-André; Joseph, Pierre-Alain; Clarke, Stephanie

2018-01-01

Topographical disorientation is a frequent deficit among patients suffering from brain injury. Spatial navigation can be explored in this population using virtual reality environments, even in the presence of motor or sensory disorders. Furthermore, the positive or negative impact of specific stimuli can be investigated. We studied how auditory stimuli influence the performance of brain-injured patients in a navigational task, using the Virtual Action Planning-Supermarket (VAP-S) with the addition of contextual ("sonar effect" and "name of product") and non-contextual ("periodic randomised noises") auditory stimuli. The study included 22 patients with a first unilateral hemispheric brain lesion and 17 healthy age-matched control subjects. After a software familiarisation, all subjects were tested without auditory stimuli, with a sonar effect or periodic random sounds in a random order, and with the stimulus "name of product". Contextual auditory stimuli improved patient performance more than control group performance. Contextual stimuli benefited most patients with severe executive dysfunction or with severe unilateral neglect. These results indicate that contextual auditory stimuli are useful in the assessment of navigational abilities in brain-damaged patients and that they should be used in rehabilitation paradigms.

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

PubMed

Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

2012-09-01

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

Antidepressant-like properties of sarizotan in experimental Parkinsonism.

PubMed

Zhang, Xiaoqun; Egeland, Martin; Svenningsson, Per

2011-12-01

Depression and anxiety are common symptoms in Parkinson's disease for which there are no optimal treatments. Sarizotan, an agonist at serotonin receptors and partial agonist at dopamine D₂-like receptors, has shown antidyskinetic effects in Parkinson's disease. Based on its pharmacological profile, we hypothesized that sarizotan could also have antidepressant-like properties. Examine effects of sarizotan on behavioral and histological measures known to be regulated by established antidepressants in normal and unilaterally 6-hydroxydopamine-lesioned rats. Sarizotan was found to significantly reduce immobility in the modified forced swim test, a measure of antidepressant-like activity, but had no effects on thigmotaxis or corner time, measures of anxiety-like behavior, in the unilaterally 6-hydroxydopamine-lesioned rats. At the same dose, sarizotan counteracted L: -DOPA/benserazide-induced supersentitized rotational behavior and dyskinesias without significantly affecting L: -DOPA/benserazide-induced locomotion. At the histological level, sarizotan alone or in combination with L: -DOPA/benserazide stimulated cell proliferation, measured by bromodeoxyuridine incorporation or Ki-67 staining, both in the subgranular zone of the dentate gyrus and in the subventricular zone of the striatum in the 6-hydroxydopamine-lesioned hemisphere. Likewise, combined sarizotan and L: -DOPA/benserazide treatment stimulated doublecortin levels in the subgranular zone of the dentate gyrus. These significant effects of sarizotan in the modified forced swim test and on cell proliferation are reminiscent of those found after various antidepressant therapies. These data suggest that sarizotan may have some antidepressant-like and restorative properties in Parkinsonism.

Parahippocampal epilepsy with subtle dysplasia: A cause of "imaging negative" partial epilepsy.

PubMed

Pillay, Neelan; Fabinyi, Gavin C A; Myles, Terry S; Fitt, Gregory J; Berkovic, Samuel F; Jackson, Graeme D

2009-12-01

Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T(1)- and T(2)-weighted images with relative preservation of the gray-white matter boundary on T(1)-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.

Comparison of two models of hemispheric specialization with unilaterally lesioned patients: material-specific impairment vs response-bias distortion.

PubMed

Guimond, Anik; Braun, Claude M J; Daigneault, Sylvie; Farmer, Jean-Pierre

2013-10-01

Validity of two models of hemispheric specialization was compared. The "material-specific impairment" model was radicalized as postulating that left hemisphere (LH) lesions impair processing of verbal material and that right hemisphere (RH) lesions impair processing of visuospatial material, independently of response-bias distortions. The "response-bias distortion" model was radicalized as postulating that LH lesions distort response style toward omissiveness and that RH lesions distort response style toward commissiveness, regardless of material-specific impairments. Participants had comparable left (N=27) or right (N=24) hemisphere cortical lesions having occurred between birth and early adolescence. Four cognitive neuropsychological tests were adjusted to optimize applicability and comparability of the two theoretical models: Rey Complex Figure, Kimura's Recurring Figures, the Story Recall subtest of the Children's Memory Scale, and the California Verbal Learning Test. Both models significantly, independently, and equally distinguished the LH from the RH patients. Both these forms of hemispheric specialization seemed to be implemented very early in life and very rigidly. Intrahemispheric lesion sites, e.g., frontal vs nonfrontal, held no significant relation to the effects described above. © 2013 Elsevier Inc. All rights reserved.

Penile herpes zoster: an unusual location for a common disease.

PubMed

Bjekic, Milan; Markovic, Milica; Sipetic, Sandra

2011-01-01

Herpes zoster is a common dermatological condition which affects up to 20% of the population, most frequently involving the thoracic and facial dermatomes with sacral lesions occurring rarely and only a few reported cases of penile shingles. We report two cases of unusual penile clinical presentations of varicella zoster virus infection in immunocompetent men. The patients presented with grouped clusters of vesicles and erythema on the left side of penile shaft and posterior aspect of the left thigh and buttock, involving s2-s4 dermatomes. The lesions resolved quickly upon administration of oral antiviral therapy. Penile herpes zoster should not be overlooked in patients with unilateral vesicular rash.

Biphasic effects of oxotremorine-M on turning behavior induced by caffeine in 6-OHDA-lesioned rats.

PubMed

Núñez-Taltavull, Juan Francisco; Prat, Gemma; Rubio, Antonia; Robledo, Patricia; Casas, Miguel

2004-12-03

This work studied the interactions between cholinergic and adenosine systems in the denervated striatum. For that purpose, we evaluated the effects of an intrastriatal administration of the muscarincic receptor agonist, oxotremorine-M on turning behavior induced by systemic caffeine in unilaterally 6-hydroxydopamine-lesioned rats. Low doses of oxotremorine-M (0.1 ng/microl) enhanced, whereas high doses (100 ng/microl) attenuated contralateral turning induced by caffeine. These results support a functional link between muscarinic and adenosinergic systems in the denervated striatum and suggest opposite actions of muscarinic M2 and M1 receptors on caffeine-induced turning behavior.

Stimulation of the Rat Subthalamic Nucleus is Neuroprotective Following Significant Nigral Dopamine Neuron Loss

PubMed Central

Spieles-Engemann, A. L.; Behbehani, M. M.; Collier, T. J.; Wohlgenant, S. L.; Steece-Collier, K.; Paumier, K.; Daley, B. F.; Gombash, S.; Madhavan, L.; Mandybur, G. T.; Lipton, J.W.; Terpstra, B.T.; Sortwell, C.E.

2010-01-01

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson’s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between two and four weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID:20307668

Extracellular Zn2+ Influx into Nigral Dopaminergic Neurons Plays a Key Role for Pathogenesis of 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

PubMed

Tamano, Haruna; Nishio, Ryusuke; Morioka, Hiroki; Takeda, Atsushi

2018-04-29

Parkinson's disease (PD) is a progressive neurological disease characterized by a selective loss of nigrostriatal dopaminergic neurons. The exact cause of the neuronal loss remains unclear. Here, we report a unique mechanism of nigrostriatal dopaminergic neurodegeneration, in which extracellular Zn 2+ influx plays a key role for PD pathogenesis induced with 6-hydroxydopamine (6-OHDA) in rats. 6-OHDA rapidly increased intracellular Zn 2+ only in the substantia nigra pars compacta (SNpc) of brain slices and this increase was blocked in the presence of CaEDTA, an extracellular Zn 2+ chelator, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, indicating that 6-OHDA rapidly increases extracellular Zn 2+ influx via AMPA receptor activation in the SNpc. Extracellular Zn 2+ concentration was decreased under in vivo SNpc perfusion with 6-OHDA and this decrease was blocked by co-perfusion with CNQX, supporting 6-OHDA-induced Zn 2+ influx via AMPA receptor activation in the SNpc. Interestingly, both 6-OHDA-induced loss of nigrostriatal dopaminergic neurons and turning behavior to apomorphine were ameliorated by co-injection of intracellular Zn 2+ chelators, i.e., ZnAF-2DA and N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Co-injection of TPEN into the SNpc blocked 6-OHDA-induced increase in intracellular Zn 2+ but not in intracellular Ca 2+ . These results suggest that the rapid influx of extracellular Zn 2+ into dopaminergic neurons via AMPA receptor activation in the SNpc induces nigrostriatal dopaminergic neurodegeneration, resulting in 6-OHDA-induced PD in rats.

The nigrostriatal dopamine system of aging GFRα-1 heterozygous mice: neurochemistry, morphology and behavior

PubMed Central

Zaman, Vandana; Boger, Heather A.; Granholm, Ann-Charlotte; Rohrer, Baerbel; Moore, Alfred; Buhusi, Mona; Gerhardt, Greg A.; Hoffer, Barry J.; Middaugh, Lawrence D.

2009-01-01

Given the established importance of glial cell line-derived neurotrophic factor (GDNF) in maintaining dopaminergic neurotransmitter systems, the nigrostriatal system and associated behaviors of mice with genetic reduction of its high-affinity receptor, GDNF receptor (GFR)α-1 (GFRα-1+/−), were compared with wild-type controls. Motor activity and the stimulatory effects of a dopamine (DA) D1 receptor agonist (SKF 82958) were assessed longitudinally at 8 and 18 months of age. Monoamine concentrations and dopaminergic nerve terminals in the striatum and the number of dopaminergic neurons in the substantia nigra (SN) were assessed. The results support the importance of GFRα-1 in maintaining normal function of the nigrostriatal dopaminergic system, with deficits being observed for GFRα-1+/− mice at both ages. Motor activity was lower and the stimulatory effects of the DA agonist were enhanced for the older GFRα-1+/− mice. DA in the striatum was reduced in the GFRα-1+/− mice at both ages, and tyrosine hydroxylase-positive cell numbers in the SN were reduced most substantially in the older GFRα-1+/− mice. The combined behavioral, pharmacological probe, neurochemical and morphological measures provide evidence of abnormalities in GFRα-1+/− mice that are indicative of an exacerbated aging-related decline in dopaminergic system function. The noted deficiencies, in turn, suggest that GFRα-1 is necessary for GDNF to maintain normal function of the nigrostriatal dopaminergic system. Although the precise mechanism(s) for the aging-related changes in the dopaminergic system remain to be established, the present study clearly establishes that genetic reductions in GFRα-1 can contribute to the degenerative changes observed in this system during the aging process. PMID:18973577

[Lesions in the pars compacta substantiae nigra and the subthalamic nucleus modify the density of muscarinic receptors in different nuclei of the basal ganglia].

PubMed

Blanco-Lezcano, L; Rocha-Arrieta, L L; Martínez-Martí, L; Alvarez-González, L; Pavón-Fuentes, N; Macías-González, R; Serrano-Sánchez, T; Rosillo-Martí, J C; Coro-Grave de Peralta, Y; Bauza-Calderín, Y; Briones, M

Several studies that has focused to the dopaminergic transmission in the basal ganglia in parkinsonian condition, but only a few article has taking into account the imbalance between dopaminergic and cholinergic transmission. To evaluate the muscarinic cholinergic receptors density in SNc and PPN in the 6-OHDA model. Were organized five experimental groups in correspondence to the place of the lesion: I. Non treated rats, II. 6-OHDA lesion in SNc, III. 6-OHDA lesion in SNc + quinolinic acid lesion in NST, IV. Sham operated rats, V. Quinolinic acid in STN. Were obtained coronal sections of 20 microm thickness of SNc and PPN from rats and in these sections was evaluated the muscarinic receptors density through autoradiographic technique with [3H]quinuclidinylbenzilate (QNB) (1.23 nM). The muscarinic antagonist atropine (1 microM) was utilized as non-specific union. The density was evaluated in both hemispheres and the density optical was converted in fentomolas/mg of tissue with base to values obtained from tritium standards. Significant diminution of the muscarinic receptors density was found in the SNc ipsilateral to the 6-OHDA lesion from experimental groups II (t=2.76; p<0.05) and III (t=4.06; p<0.05). In the group V, was seen a significant increase of muscarinic receptor density in the SNc ipsilateral to the 6-OHDA lesion. The comparison between experimental groups evidenced significant differences among them (F=13.13; p<0.001) with a significant decrease in the density from SNc of groups II and III and significant increase in the density from SNc of group V in comparison of the others groups. In relation to PPN, muscarinic receptors density from right PPN ipsilateral to the 6-OHDA lesion, shown significant differences (F=3.93; p<0.01) between the experimental groups with a significant increase of this variable in the group II. These results signal a modification of cholinergic activity after 6-OHDA lesion. The changes in the muscarinic receptors populations located in SNc and PPN could be part of different compensatory mechanisms to attempt ameliorate the imbalance between dopaminergic and cholinergic transmission that it was installed after denervation of nigrostriatal forebrain bundle. The excitotoxic lesion of STN impose a new adjust mechanism for cell from PPN, which could be expressed in the changes of muscarinic cholinergic receptors population at the level of SNc.

Effects of optokinetic stimulation induced by virtual reality on locomotion: a preliminary study.

PubMed

Ohyama, Seizo; Nishiike, Suetaka; Watanabe, Hiroshi; Matsuoka, Katsunori; Takeda, Noriaki

2008-11-01

Exposure to a virtual environment for 20 min was sufficient to cause adaptive changes in locomotion in healthy subjects, suggesting that virtual environments might improve locomotor deviation in patients with unilateral labyrinthine defects. Postural and locomotor control in patients with unilateral labyrinthine defects deviates towards the lesion side. The aim of this study was to examine whether active locomotion within a virtual environment can increase the functionality of rehabilitation. We examined the effects of optokinetic stimulation produced by a virtual reality environment on ocular movement and locomotor tracks in 10 healthy subjects. During the 20 min experiment, the mean locomotor deviation and the mean frequency and mean amplitude of optokinetic nystagmus during the last period of the experiment were significantly higher than those during the initial period.

The Development of Complex Sentence Interpretation in Typically Developing Children Compared with Children with Specific Language Impairments or Early Unilateral Focal Lesions

ERIC Educational Resources Information Center

Dick, Frederic; Wulfeck, Beverly; Krupa-Kwiatkowski, Magda; Bates, Elizabeth

2004-01-01

This study compared sentence comprehension skills in typically developing children 5-17 years of age, children with language impairment (LI) and children with focal brain injuries (FL) acquired in the pre/perinatal period. Participants were asked to process sentences "on-line", choosing the agent in sentences that varied in syntactic complexity…

Unilateral visual neglect overcome by cues implicit in stimulus arrays.

PubMed Central

Kartsounis, L D; Warrington, E K

1989-01-01

The case of a man with a right hemisphere lesion and with evidence of left-sided visuospatial neglect is reported. On a variety of verbal and nonverbal tasks his performance was significantly modified by information implicit in stimulus configurations. Neglect deficits were present on tests involving spatially distinct or meaningless stimulus arrays but almost absent when stimuli were continuous or meaningfully integrated. PMID:2592968

Iron concentrations and distributions in the parkinsonian substantia nigra of aged and young primate models

NASA Astrophysics Data System (ADS)

Ren, M. Q.; Xie, J. P.; Wang, X. S.; Ong, W. Y.; Leong, S. K.; Watt, F.

2001-07-01

Parkinson's disease (PD) is a progressive neuronal degenerative brain disease of the elderly, and is caused by the selective degeneration of neurons in the substantia nigra (SN) region of the brain, resulting in a reduced production of the neurotransmitter dopamine. Iron has been linked to dopaminergic cell death in Parkinson's disease because of its potential to promote free radicals, leading to oxidative stress. The present study is aimed at using the techniques of nuclear microscopy to elucidate the iron concentrations and distributions in the SN of both young and old monkeys following unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioning. A group of three old monkeys (older than 7 years) and a group of three young monkeys (younger than 7 years) were unilaterally MPTP-lesioned (right side) to induce parkinsonism and sacrificed after 35 days. The left side SN was used as a control. This time interval was chosen to correspond to an average 50% loss of dopamine producing cells in the lesioned right side SN. We have observed a significant difference in iron concentrations between the SNs of the young and old monkeys (increasing from an average of 233 to 1092 parts per million dry weight). When comparing the lesioned and non-lesioned SNs of the same animal, we found no significant difference in iron levels for each young monkey. However we have found a slight increase in iron (approximately 10%) between the lesioned SN and control SN for old monkeys. We have also observed that in the SN of younger primates, there is a weak anti-correlation in the SN iron levels with the neuron distribution. In the older monkeys, however, we have observed a proliferation of iron-rich granules, which appear to be more strongly anti-correlated with the distribution of neurons. The iron-cell anti-correlation occurs both in the control as well as the lesioned SN. Our results suggest that iron, particularly in the form of iron-rich deposits, accumulates in specific sites in the SN with age. Since Parkinson's disease mainly occurs in the elderly, this may implicate iron as a factor in dopaminergic cell death through iron-catalysed free radical production.

Right vs. left sensorimotor cortex suction-ablation in the rat: no difference in beam-walking recovery.

PubMed

Goldstein, L B

1995-03-13

The ability of rats to traverse a narrow elevated beam has been used to quantitate recovery of hindlimb motor function after unilateral injury to the sensorimotor cortex. We tested the hypothesis that the rate of spontaneous beam-walking recovery varies with the side of the cortex lesion. Groups of rats that were trained at the beam-walking task underwent suction-ablation of either the right or left hindlimb sensorimotor cortex. There was no difference in hindlimb motor function between the groups on the first post-operative beam-waking trial carried out the day after cortex ablation and no difference between the groups in overall recovery rates over the next two weeks. Subsequent analyses of lesion surface parameters showed no differences in lesion size or extent. Regardless of the side of the lesion, there were also no differences between the right and left hemispheres in norepinephrine content of the lesioned or contralateral cortex. We conclude that the side of sensorimotor cortex ablation injury does not differentially affect the rate of spontaneous motor recovery as measured with the beam-walking task.

Ulcerative dermatitis in wild dusky grouper Epinephelus marginatus (Lowe) from Libyan waters.

PubMed

Rizgalla, J; Bron, J E; Shinn, A P; Herath, T K; Paladini, G; Ferguson, H W

2016-12-01

In the period 2013-2015, wild dusky grouper, Epinephelus marginatus (Lowe), caught in Libyan coastal waters and ranging in size from 42 to 92 cm in total length, were observed to have distinctive skin lesions of unknown aetiology. Histopathologically, the lesions comprised a multifocal, unilateral or bilateral dermatitis, involving the epidermis, superficial dermis and scale pockets, and sometimes, in severe cases, the hypodermis. Severe lesions had marked epidermal spongiosis progressing to ulceration. Healing was observed in some fish. Bacteria and fungi could be isolated from severe lesions, although they were not seen histopathologically in early-stage lesions. By contrast, metazoan parasite eggs were observed in the dermis and epidermis of some fish with mild and moderate dermatitis. Unidentified gravid digenean trematode parasites carrying similar eggs were also seen within the blood vessels of the deep and superficial dermis. The cause of this distinctive condition, termed dusky grouper dermatitis (DGD), and its potential impact upon already threatened Mediterranean wild dusky grouper populations and upon cultured grouper more widely have yet to be established. © 2016 John Wiley & Sons Ltd.

Mirror therapy in unilateral neglect after stroke (MUST trial): a randomized controlled trial.

PubMed

Pandian, Jeyaraj D; Arora, Rajni; Kaur, Paramdeep; Sharma, Deepika; Vishwambaran, Dheeraj K; Arima, Hisatomi

2014-09-09

We explored the effectiveness of mirror therapy (MT) in the treatment of unilateral neglect in stroke patients. This is an open, blinded endpoint, randomized controlled trial carried out from January 2011 to August 2013. We included stroke patients with thalamic and parietal lobe lesions with unilateral neglect 48 hours after stroke. Patients were randomized to the MT group or the control group (sham MT), and both the groups received limb activation. Patients received treatment for 1-2 hours a day 5 days a week for 4 weeks. The primary outcome was unilateral neglect assessed by a blinded assessor using the star cancellation test, the line bisection test, and a picture identification task at 1, 3, and 6 months. This study was registered at http://clinicaltrials.gov (NCT 01735877). Forty-eight patients were randomized to MT (n = 27) or the control group (n = 21). Improvement in scores on the star cancellation test over 6 months was greater in the MT group (mean difference 23, 95% confidence interval [CI] 19-28; p < 0.0001). Similarly, improvement in the MT group was observed in the scores on the picture identification task (mean difference 3.2, 95% CI 2.4-4.0; p < 0.0001) and line bisection test (mean difference 8.6, 95% CI 2.7-14.6; p = 0.006). In patients with stroke, MT is a simple treatment that improves unilateral neglect. This study provides Class I evidence that for patients with neglect from thalamic and parietal lobe strokes, MT improves neglect. © 2014 American Academy of Neurology.

Mirror Therapy in Unilateral Neglect After Stroke (MUST trial)

PubMed Central

Arora, Rajni; Kaur, Paramdeep; Sharma, Deepika; Vishwambaran, Dheeraj K.; Arima, Hisatomi

2014-01-01

Objective: We explored the effectiveness of mirror therapy (MT) in the treatment of unilateral neglect in stroke patients. Methods: This is an open, blinded endpoint, randomized controlled trial carried out from January 2011 to August 2013. We included stroke patients with thalamic and parietal lobe lesions with unilateral neglect 48 hours after stroke. Patients were randomized to the MT group or the control group (sham MT), and both the groups received limb activation. Patients received treatment for 1–2 hours a day 5 days a week for 4 weeks. The primary outcome was unilateral neglect assessed by a blinded assessor using the star cancellation test, the line bisection test, and a picture identification task at 1, 3, and 6 months. This study was registered at http://clinicaltrials.gov (NCT 01735877). Results: Forty-eight patients were randomized to MT (n = 27) or the control group (n = 21). Improvement in scores on the star cancellation test over 6 months was greater in the MT group (mean difference 23, 95% confidence interval [CI] 19–28; p < 0.0001). Similarly, improvement in the MT group was observed in the scores on the picture identification task (mean difference 3.2, 95% CI 2.4–4.0; p < 0.0001) and line bisection test (mean difference 8.6, 95% CI 2.7–14.6; p = 0.006). Conclusions: In patients with stroke, MT is a simple treatment that improves unilateral neglect. Classification of evidence: This study provides Class I evidence that for patients with neglect from thalamic and parietal lobe strokes, MT improves neglect. PMID:25107877

Susceptibility of ascending dopamine projections to 6-hydroxydopamine in rats: effect of hypothermia.

PubMed

Grant, R J; Clarke, P B S

2002-01-01

The aims of this study were to determine (1) whether mesolimbic and nigrostriatal DA cell bodies degenerate to different extents after 6-hydroxydopamine (6-OHDA) is administered into their respective terminal fields and (2) whether hypothermia, associated with sodium pentobarbital anesthesia, protects DA neurons from the toxic effects of 6-OHDA. To address these questions, 6-OHDA or vehicle was infused into either the ventral or dorsal striatum or into the medial forebrain bundle, under conditions of brain normothermia or hypothermia. Two weeks post-surgery, tyrosine hydroxylase-positive cell bodies were counted in the ventral tegmental area (VTA) and substantia nigra. In addition, autoradiographic labeling of tyrosine hydroxylase protein and dopamine transporter was quantified in dopamine terminal fields and cell body areas. Overall, DA cell bodies in the VTA were substantially less susceptible than those in the substantia nigra to depletion of dopaminergic markers. Hypothermia provided two types of neuroprotection. The first occurred when 6-OHDA was administered into the dorsal striatum, and was associated with a 30-50% increase in residual dopaminergic markers in the lateral portion of the VTA. The second neuroprotective effect of hypothermia occurred when 6-OHDA was given into the medial forebrain bundle. This was associated with a 200-300% increase in residual dopaminergic markers in the mesolimbic and nigrostriatal terminal fields; no significant protection occurred in the cell body regions.Collectively, these findings show that (1) the dopaminergic somata in the substantia nigra are more susceptible than those in the VTA to 6-OHDA-induced denervation, and (2) hypothermia can provide anatomically selective neuroprotection within the substantia nigra-VTA cell population. The continued survival of mesolimbic dopamine cell bodies after a 6-OHDA lesion may have functional implications relating to drugs of abuse, as somatodendritic release of dopamine in the VTA has been shown to play a role in the effectiveness of cocaine reward.

Gastric pentadecapeptide BPC 157 promotes corneal epithelial defects healing in rats.

PubMed

Lazić, Ratimir; Gabrić, Nikica; Dekaris, Iva; Bosnar, Damir; Boban-Blagaić, Alenka; Sikirić, Predrag

2005-06-01

We evaluated the role of human gastric pentadecapeptide BPC 157 in corneal epithelial defects healing in rats. 48 rats, in 4 groups (N=12). Total debridement of corneal epithelium preformed unilaterally and lesions stained and photographed. Animals medicated as follows: distilled water (control group) or BPC 157 2 pg/ml, 2 ng/ml, 2 microg/ml, 2 drops/rat eye started immediately after injury induction, every 8 hours up to 40 hours (i.e., at 0, 8, 16, 24, 32, 40 h). Lesions were photographed before application or sacrifice (at 48 h). Defect area was analyzed using a special program. Through 48 hour period a steady recovery is noted in controls. Recovery was markedly accelerated in eyes on microg- or ng-topical regimen of BPC 157 (p < 0.05). Of note, unlike control lesion present also after 48 h, these lesions disappeared already following 40 h (microg) or 48 h (ng) post-injury. BPC 157 was shown to be effective in promoting corneal defects healing in rats. Results were dose dependent.

Posterior insular cortex - a site of vestibular-somatosensory interaction?

PubMed

Baier, Bernhard; Zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-09-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact.

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

PubMed Central

Hatcher, Jaime M.; Richardson, Jason R.; Guillot, Thomas S.; McCormack, Alison L.; Di Monte, Donato A.; Jones, Dean P.; Pennell, Kurt D.; Miller, Gary W.

2007-01-01

Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson’s disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3H-WIN 35,428 binding and 3H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. PMID:17291500

Development of "material-specific" hemispheric specialization from beginning to end.

PubMed

Gingras, Benjamin; Braun, Claude M J

2018-07-01

Disparity of verbal and performance intelligence (VIQ, PIQ) on the Wechsler scales of intelligence is a conceptually cluttered and empirically weak measure of hemispheric specialization (HS). However, in the context of life span research, it is the only measure that can be exploited meta-analytically with the lesion method from prenatal life to late senescence. We assembled 1917 cases with a unilateral cortical focal brain lesion occurring at all ages and a post-lesion VIQ and PIQ. Lesion locus, volume and side were documented for each case, as well as age at lesion onset, age at first symptoms and age at the IQ test, presence/absence of epilepsy, lesion aetiology, gender, date of publication or of transfer of medical file. With and without covariate adjustment, HS was significant across the life span though its pattern changed. HS increased linearly and highly significantly until late senescence. Only in early adulthood did VIQ appear to vacate the right temporal lobe and occupy the left and PIQ vacate the left parietal lobe and occupy the right until late senescence. Biomaturational factors are more important in the ontogeny of material-specific HS over the whole life span than previously established.

Epidemiology of Ocular Toxoplasmosis in Three Community Surveys in the Central Region of Ghana, West Africa.

PubMed

Abu, Emmanuel Kwasi; Boampong, Johnson Nyarko; Amoabeng, Joseph Kwame; Ilechie, Alex A; Kyei, Samuel; Owusu-Ansah, Andrew; Boadi-Kusi, Samuel Bert; Amoani, Benjamin; Ayi, Irene

2016-01-01

To conduct the first ever population-based survey on ocular toxoplasmosis in the Central Region of Ghana. A cross-sectional population-based study was conducted in three randomly selected communities in the Central Region, Ghana. Visual acuity (VA) measurement, dilated fundus examination by indirect ophthalmoscopy and serology testing were performed on all participants. Ocular toxoplasmosis was diagnosed based on characteristic retinal lesions and supported by positive serologic testing using commercial enzyme-linked immunosorbent assay (ELISA) kits. A total of 390 subjects aged 10-100 years (mean age 47 years) were examined; 118 (30.3%) were male and 272 (69.7%) female. Ten subjects (6 females and 4 males) had toxoplasmic ocular lesions (prevalence 2.6%). Of these, two had bilateral lesions and eight had unilateral lesions. Subjects with toxoplasmic ocular lesions were older than those without lesions (p = 0.028). The development of ocular toxoplasmosis was not associated with rural dwelling, sex, keeping cats, or consumption of meat. The prevalence of ocular toxoplasmosis in our Ghanaian study population was lower than findings from Southern Brazil, where there is a similar prevalence of infection in the general population.

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

PubMed Central

Mencacci, Niccolò E.; Isaias, Ioannis U.; Reich, Martin M.; Ganos, Christos; Plagnol, Vincent; Polke, James M.; Bras, Jose; Hersheson, Joshua; Stamelou, Maria; Pittman, Alan M.; Noyce, Alastair J.; Mok, Kin Y.; Opladen, Thomas; Kunstmann, Erdmute; Hodecker, Sybille; Münchau, Alexander; Volkmann, Jens; Samnick, Samuel; Sidle, Katie; Nanji, Tina; Sweeney, Mary G.; Houlden, Henry; Batla, Amit; Zecchinelli, Anna L.; Pezzoli, Gianni; Marotta, Giorgio; Lees, Andrew; Alegria, Paulo; Krack, Paul; Cormier-Dequaire, Florence; Lesage, Suzanne; Brice, Alexis; Heutink, Peter; Gasser, Thomas; Lubbe, Steven J.; Morris, Huw R.; Taba, Pille; Koks, Sulev; Majounie, Elisa; Raphael Gibbs, J.; Singleton, Andrew; Hardy, John; Klebe, Stephan

2014-01-01

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson’s disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson’s disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson’s disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher’s exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4–25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson’s disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson’s disease. PMID:24993959

Progressive nigrostriatal terminal dysfunction and degeneration in the engrailed1 heterozygous mouse model of Parkinson's disease.

PubMed

Nordströma, Ulrika; Beauvais, Geneviève; Ghosh, Anamitra; Pulikkaparambil Sasidharan, Baby Chakrapani; Lundblad, Martin; Fuchs, Julia; Joshi, Rajiv L; Lipton, Jack W; Roholt, Andrew; Medicetty, Satish; Feinstein, Timothy N; Steiner, Jennifer A; Escobar Galvis, Martha L; Prochiantz, Alain; Brundin, Patrik

2015-01-01

Current research on Parkinson's disease (PD) pathogenesis requires relevant animal models that mimic the gradual and progressive development of neuronal dysfunction and degeneration that characterizes the disease. Polymorphisms in engrailed 1 (En1), a homeobox transcription factor that is crucial for both the development and survival of mesencephalic dopaminergic neurons, are associated with sporadic PD. This suggests that En1 mutant mice might be a promising candidate PD model. Indeed, a mouse that lacks one En1 allele exhibits decreased mitochondrial complex I activity and progressive midbrain dopamine neuron degeneration in adulthood, both features associated with PD. We aimed to further characterize the disease-like phenotype of these En1(+/-) mice with a focus on early neurodegenerative changes that can be utilized to score efficacy of future disease modifying studies. We observed early terminal defects in the dopaminergic nigrostriatal pathway in En1(+/-) mice. Several weeks before a significant loss of dopaminergic neurons in the substantia nigra could be detected, we found that striatal terminals expressing high levels of dopaminergic neuron markers TH, VMAT2, and DAT were dystrophic and swollen. Using transmission electron microscopy, we identified electron dense bodies consistent with abnormal autophagic vacuoles in these terminal swellings. In line with these findings, we detected an up-regulation of the mTOR pathway, concurrent with a downregulation of the autophagic marker LC3B, in ventral midbrain and nigral dopaminergic neurons of the En1(+/-) mice. This supports the notion that autophagic protein degradation is reduced in the absence of one En1 allele. We imaged the nigrostriatal pathway using the CLARITY technique and observed many fragmented axons in the medial forebrain bundle of the En1(+/-) mice, consistent with axonal maintenance failure. Using in vivo electrochemistry, we found that nigrostriatal terminals in the dorsal striatum were severely deficient in dopamine release and reuptake. Our findings support a progressive retrograde degeneration of En1(+/-) nigrostriatal neurons, akin to what is suggested to occur in PD. We suggest that using the En1(+/-) mice as a model will provide further key insights into PD pathogenesis, and propose that axon terminal integrity and function can be utilized to estimate dopaminergic neuron health and efficacy of experimental PD therapies. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The effects of anterior arcuate and dorsomedial frontal cortex lesions on visually guided eye movements: 2. Paired and multiple targets.

PubMed

Schiller, P H; Chou, I

2000-01-01

This study examined the effects of anterior arcuate and dorsomedial frontal cortex lesions on the execution of saccadic eye movements made to paired and multiple targets in rhesus monkeys. Identical paired targets were presented with various temporal asynchronies to determine the temporal offset required to yield equal probability choices to either target. In the intact animal equal probability choices were typically obtained when the targets appeared simultaneously. After unilateral anterior arcuate lesions a major shift arose in the temporal offset required to obtain equal probability choices for paired targets that necessitated presenting the target in the hemifield contralateral to the lesion more than 100 ms prior to the target in the ipsilateral hemifield. This deficit was still pronounced 1 year after the lesion. Dorsomedial frontal cortex lesions produced much smaller but significant shifts in target selection that recovered more rapidly. Paired lesions produced deficits similar to those observed with anterior arcuate lesions alone. Major deficits were also observed on a multiple target temporal discrimination task after anterior arcuate but not after dorsomedial frontal cortex lesions. These results suggest that the frontal eye fields that reside in anterior bank of the arcuate sulcus play an important role in temporal processing and in target selection. Dorsomedial frontal cortex, that contains the medial eye fields, plays a much less important role in the execution of these tasks.

Regenerative effects of peptide nanofibers in an experimental model of Parkinson's disease.

PubMed

Sever, Melike; Turkyilmaz, Mesut; Sevinc, Cansu; Cakir, Aysen; Ocalan, Busra; Cansev, Mehmet; Guler, Mustafa O; Tekinay, Ayse B

2016-12-01

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic nigrostriatal neurons and reduction in striatal dopamine levels. Although there are few treatment options for PD such as Levodopa, they are used just to relieve and modify the symptoms. There are no therapies available for PD to slow down the degeneration process in the brain and recover the lost function. In this study, we used extracellular matrix (ECM) mimetic peptide amphiphile (PA) nanofibers as a potential therapeutic approach in a PD rat model. We demonstrated the effect of heparan sulfate mimetic and laminin mimetic PA nanofibers on reducing striatal injury and enhancing functional recovery after unilateral striatal injection of 6-hydroxydopamine (6-OHDA). The bioactive self-assembled PA nanofibers significantly reduced forelimb asymmetry, contralateral forelimb akinesia and d-amphetamine-induced rotational behavior in cylinder, stepping and rotation tests, respectively, in 6-OHDA-lesioned rats after 6 weeks. The behavioral improvement with PA nanofiber administration was associated with enhanced striatal dopamine and tyrosine hydroxylase content as well as reduced cleaved-Caspase-3 levels. Histological assessment also showed that PA nanofiber injection to the striatum resulted in better tissue integrity compared to control groups. In addition, PA nanofibers reduced the progressive cell loss in SH-SY5Y cells caused by 6-OHDA treatment. These data showed that the bioactive peptide nanofibers improve neurochemical and behavioral consequences of Parkinsonism in rats and provide a promising new strategy for treatment of PD. Biomimetic nanomaterials bearing natural bioactive signals which are derived from extracellular matrix components like laminin and heparan sulfates provide promising therapeutic strategies for regeneration of the nervous system. However, no research has been reported exploring the use of biomimetic materials against degeneration in Parkinson's disease. In this work, we investigated potential therapeutic effects of heparan sulfate and laminin mimetic PA nanofibers on reduction of striatal injury in experimental Parkinson's disease model. PA nanofibers enhanced functional recovery associated with enhanced striatal dopamine and tyrosine hydroxylase content as well as reduced cleaved-Caspase-3 levels. Overall, this study shows the improvement in consequences of Parkinsonism in rats and provides a new platform for treatment of Parkinson's disease. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Management of irreducible unilateral facet joint dislocations in subaxial cervical spine: two case reports and a review of the literature.

PubMed

Zhou, Yu; Zhou, Zhenyu; Liu, Lifeng; Cao, Xuecheng

2018-03-21

Skeletal and soft tissue damage are often associated with unilateral facet dislocations, which undoubtedly lead to instability of the spine and further increase difficulties in cervical reduction. This type of irreducible facet dislocation is usually accompanied with potential catastrophic consequences including neurological deficit and severe disability. Therefore, a consistent and evidence-based treatment plan is imperative. The literature regarding the management of traumatic unilateral locked cervical facet dislocations was reviewed. Two patient cases (a 30-year-old Asian man and a 25-year-old Asian woman) who suffered irreducible cervical facet dislocations were presented. These two patients received surgical treatments including posterior reduction by poking facet joints, adjacent spinous process fixation by wire rope banding, anterior plate fixation, and intervertebral fusion after the failure of skull traction and closed reduction. At the postoperative 24-month follow-up, intervertebral fusion was achieved and our patients' neurological status improved based on the American Spinal Injury Association scale, compared with their preoperative status. Unilateral facet joint dislocations of subaxial cervical spine are difficult to reduce when complicated with posterior facet fractures or ligamentous injury. Magnetic resonance imaging can be beneficial for identifying ventral and dorsal compressive lesions, as well as ligamentous or capsule rupture. The combination of posterior reduction and anterior fixation with fusion has advantages in terms of clinical safety, ease of operation, and less iatrogenic damage.

[A clinical analysis of 5 patients with infratentorial primary angiitis of central nervous system].

PubMed

Peng, L J; Qian, H R; Mao, L L; Xia, D Y; Qi, X K

2017-04-01

Objective: To explore the clinical characteristics of infratentorial primary angiitis in central nervous system(PACNS). Methods: A total of 5 cases diagnosed as infratentorial PACNS in the neurology department of Navy General Hospital of PLA in 2015 were enrolled in the study. The clinical, imaging and pathological data were collected and analyzed. Results: All the 5 cases were male with the median onset age of thirty-four. Five cases presented with dizziness, two with headache, three with walking unstable, two with facial numbness and one with dysarthria. Rising pressure of cerebrospinal fluid (CSF) (190-245 cmH(2)O, 1 cmH(2)O=0.098 kPa) was found in 4 cases by the lumbar puncture, mildly increased number of leukocyte in 2 cases [(12-28)×10(6)/L], increased CSF protein in 3 cases(540-979 mg/L) and increased IgG index in 3 cases(0.84-1.45). Pons lesions were revealed by magnetic resonance imaging(MRI)in 4 cases, brachium pontis lesions in 2 cases, cerebellum lesions in 2 cases, one with midbrain lesion in 1 case, unilateral lesions in 4 cases and bilateral lesion in 1 case. Different degree of edema and mass effect were shown in all lesions by MRI. Patch like enhancement was found by contrast MRI in 5 cases and meningeal enhancement in 2 cases. Elevation of choline(Cho)peak was found by magnetic resonance spectroscopy(MRS)in 4 cases, reduction of N-acetyl aspartate(NAA) peak in 3 cases, appearance of lactate peak in 1 case and lipid peak in another case. Arterial spin labeling(ASL) was performed in 4 cases and no hyperperfusion was found. Susceptibility weighted imaging(SWI) was performed in 3 cases and microhemorrhage in the lesions was found in 2 cases and normal in 1 case. Magnetic resonance arteriography(MRA) was performed in 1 case and no stenosis was found. Digital subtraction arteriography(DSA) was performed in 1 case and multiple stenosis of the intracranial arteries was showed. Two cases had taken the stereotactic brain biopsy and the histopathologic diagnosis was angiitis. Five cases were treated with methylprednisolone and cyclophosphamide was added on in 1 case. Good prognosis was found in all cases. Conclusions: Infratentorial PACNS mostly attacks middle-aged males. The lesions tend to locate in unilateral pons, brachium pontis, cerebellum and midbrain. Hemorrhage or microhemorrhage in lesions is often found by SWI and no hyperperfusion is shown by ASL, which would be useful to distinguish PACNS from malignant tumors. Given the limitations of brain biopsy in clinical practice, clinical and imaging features would be helpful to diagnose PACNS.

Evaluation of local bone turnover in painful hip by 18F-fluoride positron emission tomography.

PubMed

Kobayashi, Naomi; Inaba, Yutaka; Tezuka, Taro; Ike, Hiroyuki; Kubota, So; Kawamura, Masaki; Saito, Tomoyuki

2016-04-01

The diagnosis of painful hip without remarkable radiographic findings is still challenging. In recent years, femoroacetabular impingement (FAI) has been recognized as an important cause of painful hip. The hypothesis of this study was that local bone turnover may be accelerated in painful hip, especially in FAI lesions. To test this, patients with unilateral symptomatic hip underwent F-fluoride PET, which directly correlates with osteoblast activity and therefore bone turnover. In total, 27 patients with unilateral symptomatic painful hip were enrolled. The diagnosis included 15 cam-type FAI cases, six labral tear cases, and six early-stage osteoarthritis cases. The region of interest for cam and pincer lesions was identified and the maximum standardized uptake value (SUVmax) in these regions and the contralateral asymptomatic regions were measured by F-fluoride PET. The SUVmax ratio was defined as symptomatic side SUVmax/asymptomatic side SUVmax. The α angle and center-edge angle were measured by plain radiograph. The SUVmax of both cam and pincer lesions were significantly higher than the SUVmax of the contralateral regions (P<0.0001). The cam SUVmax ratio correlated positively with the α angle (r=0.5, P=0.007). Patients with an α angle of more than or equal to 60° had a significantly higher cam SUVmax ratio than the less than 60° group (P=0.017). This study showed the accelerated local bone turnover in painful hip, partly in FAI cases. Accelerated bone turnover may play a significant role in FAI pathophysiology; therefore, its recognition by imaging modality may contribute toward a more sensitive diagnosis in painful hip.

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?

PubMed

Eyre, Janet A; Smith, Martin; Dabydeen, Lyvia; Clowry, Gavin J; Petacchi, Eliza; Battini, Roberta; Guzzetta, Andrea; Cioni, Giovanni

2007-11-01

Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity-dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment. Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects. Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development. Rather than representing "reparative plasticity," increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life.

Adenocarcinoma arising in warthin tumor of the parotid gland.

PubMed

Sayar, Hamide; Öztarakçi, Hüseyin; Sayar, Çağdaş; Ağirbaş, Şule

2012-01-01

Warthin tumor is a well-defined benign salivary gland neoplasm consisting of both epithelial and lymphoid components. The tumor is the second most common benign tumor next to pleomorphic adenoma. We present a case of adenocarcinoma, not otherwise classified, arising in unilateral Warthin tumor of the parotid gland in a 63-year-old male patient. Carcinomas arising in or from the epithelial component of a preexisting parotid Warthin tumor are rare and differential diagnosis of metastasis from an adenocarcinoma in Warthin tumor is important. The patient underwent a complete and thorough work-up, and no other primary malignant lesion was found. No other primary malignant lesion had manifested at the last one year follow-up period.

Congenital Becker's nevus with a familial association.

PubMed

Book, S E; Glass, A T; Laude, T A

1997-01-01

Becker's nevus is a unilateral, hyperpigmented cutaneous hamartoma usually with hypertrichosis. It occurs predominantly in boys, becoming apparent during adolescence, although several cases of congenital Becker's nevus have been reported. Rarely it may be familial and as such is transmitted in an autosomal dominant pattern. We report a 16-month-old black boy with a hyperpigmented patch on his right shoulder and upper pectoral area that extended down his arm. The patient's father has a similar lesion with hair on his left shoulder which has been present since childhood. Histology of the child's lesion was consistent with Becker's nevus. We believe this to be the first reported case of a congenital Becker's nevus with a familial association.

Recurrent unilateral headache associated with SAPHO syndrome.

PubMed

Tsugawa, Jun; Ouma, Shinji; Fukae, Jiro; Tsuboi, Yoshio

2014-01-01

A 57-year-old woman was admitted with recurrent episodes of right frontal headache. Head magnetic resonance imaging (MRI) revealed extensive thickening and enhancement of the right frontal dura, muscle and fascia, as well as abnormal signal intensity and enhancement of bone marrow at the lesions. Synovitis-acne-pustulosis-hyperostosis osteomyelitis (SAPHO) syndrome was diagnosed based on the patient's 8-year history of treatment of palmoplantar pustulosis and abnormal accumulations in the right temporal, sternum, and left medial clavicula on bone scintigraphy. SAPHO syndrome may be associated with skull lesions, which can contribute to the onset of repeated headache or dural thickening, thus these symptoms should be recognized as manifestations of this syndrome.

Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study.

PubMed

Juenger, Hendrik; Kuhnke, Nicola; Braun, Christoph; Ummenhofer, Frank; Wilke, Marko; Walther, Michael; Koerte, Inga; Delvendahl, Igor; Jung, Nikolai H; Berweck, Steffen; Staudt, Martin; Mall, Volker

2013-10-01

Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise-induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but 'healthy' contralateral motor projections (contra). Sixteen children and young adults with congenital hemiparesis participated in the study (contralateral [Contra] group: n=7, four females, three males; age range 10-30y, median age 16y; ipsilateral [Ipsi] group: n=9, four females, five males; age range 11-31y, median age 12y; Manual Ability Classification System levels I to II in all individuals in both groups). The participants underwent a 12-day intervention of constraint-induced movement therapy (CIMT), consisting of individual training (2h/d) and group training (8h/d). Before and after CIMT, hand function was tested using the Wolf Motor Function Test (WMFT) and diverging neuroplastic effects were observed by transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Statistical analysis of TMS data was performed using the non-parametric Wilcoxon signed-rank test for pair-wise comparison; for fMRI standard statistical parametric and non-parametric mapping (SPM5, SnPM3) procedures (first level/second level) were carried out. Statistical analyses of MEG data involved analyses of variance (ANOVA) and t-tests. While MEG demonstrated a significant increase in S1 activation in both groups (p=0.012), TMS showed a decrease in M1 excitability in the Ipsi group (p=0.036), but an increase in M1 excitability in the Contra group (p=0.043). Similarly, fMRI showed a decrease in M1 activation in the Ipsi group, but an increase in activation in the M1-S1 region in the Contra group (for both groups p<0.001 [SnPM3] within the search volume). Different patterns of sensorimotor (re)organization in individuals with early unilateral lesions show, on a cortical level, different patterns of exercise-induced neuroplasticity. The findings help to improve the understanding of the general principles of sensorimotor learning and will help to develop more specific therapies for different pathologies in congenital hemiparesis. © 2013 Mac Keith Press.

Breast disease in the male: galactographic evaluation.

PubMed

Detraux, P; Benmussa, M; Tristant, H; Garel, L

1985-03-01

Seven men with unilateral nipple discharge underwent galactography. In two patients the diagnosis was carcinoma, two were benign papillomas, one was a breast abscess, and two were ductal ectasia. Galactography is useful in men and women with nipple discharge, especially when the discharge is bloody and there is no palpable tumor. The precise location of an intraductal lesion through the use of galactography guides the biopsy and makes conservative surgery easier.

The natural history of the anterior knee instability by stress radiography

PubMed Central

de Rezende, Márcia Uchôa; Hernandez, Arnaldo José; Camanho, Gilberto Luis

2014-01-01

OBJECTIVE: To analyze the anteroposterior displacement of the knee by means of stress radiography in individuals with unilateral anterior knee instability and relate to time of instability. METHODS: Sixty individuals with intact knees (control group) and 125 patients with unilateral anterior instability (AI group) agreed to participate in the study. Gender, age, weight, height, age at injury, time between injury and testing, and surgical findings are studied. Both groups are submitted to anterior and posterior stress radiographies of both knees. Anterior (ADD) and posterior displacement difference (PDD) were calculated between sides. RESULTS: In the control group ADD and PDD are in average, zero, whereas in the AI group ADD averaged 9.8mm and PDD, 1.92mm. Gender, age, weight, height, age at trauma and presence of menisci's lesions do not intervene in the values of ADD and PDD. Meniscal injuries increase with time. ADD and PDD do not relate with the presence or absence of associated menisci's lesions. The ADD and the PDD are related to each other and increase with time. CONCLUSION: There is a permanent anterior subluxation of the injured knee that is related to the amount of anterior displacement that increases with time. Level of Evidence III, Study Types Case-control study. PMID:25246846

Bias in Magnitude Estimation Following Left Hemisphere Injury

PubMed Central

Woods, Adam J.; Mennemeier, Mark; Garcia-Rill, Edgar; Meythaler, Jay; Mark, Victor W.; Jewel, George R.; Murphy, Heather

2015-01-01

There is a growing interest both in identifying the neural mechanisms of magnitude estimation and in identifying forms of bias that can explain aspects of behavioral syndromes like unilateral neglect. Magnitude estimation is associated with activation of temporo-parietal cortex in both cerebral hemispheres of normal subjects; however, it is unclear if and how left hemisphere lesions bias magnitude estimation because the infrequency of neglect and the presence of aphasia in these subjects confound examination. In contrast, we examined magnitude estimation using 12 different types of sensory stimuli that spanned five sensory domains in two patients with very different clinical presentations following unilateral left hemisphere stroke. One patient had neglect sub-acutely without aphasia. The other had aphasia chronically after a temporo-parietal lesion but not neglect. The neglect patient was re-examined 48 hours after being treated with modafinil (Provigil) for decreased arousal. Both patients demonstrated bias in magnitude estimation relative to normal subjects (n=83). Alertness improved in the neglect patient after taking modafinil. His neglect also resolved and his magnitude estimates more closely resembled those of normal subjects. This is the first evidence, to our knowledge, that the left hemisphere injury can bias magnitude estimation in a manner similar but not identical to that associated with right hemisphere injury. PMID:16434066

Cortical oscillations scan using chirp-evoked potentials in 6-hydroxydopamine rat model of Parkinson's disease.

PubMed

Pérez-Alcázar, Marta; Nicolás, María Jesús; Valencia, Miguel; Alegre, Manuel; López-Azcárate, Jon; Iriarte, Jorge; Artieda, Julio

2010-01-15

There has been a growing interest during the last years on the relationship between Parkinson's disease and changes in the oscillatory activity, mostly in the cortico-basal motor loop. As Parkinson's disease (PD) is not limited to motor symptoms, it is logical to assume that the changes in oscillatory activity are not limited to this loop. Steady-state responses (SSR) are the result of averaging individual responses to trains of rhythmic stimuli delivered at a constant frequency. The amplitude of the response varies depending on the stimulus modality and stimulation rate, with a frequency of maximal response that is probably associated to the working frequency of the pathway involved. The study of SSR may be of interest in PD as a non-invasive test of cortical oscillatory activity. Our aim was to study the changes in auditory steady-state responses (ASSR) in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease in rats. We recorded the ASSR over the auditory cortex in a group of 10 control and 17 6-OHDA lesioned rats (the latter before and after the administration of the dopaminergic agonist apomorphine) both awake and under anesthesia with ketamine/xylazine, using chirp-modulated stimuli. The three conditions (control, lesion, lesion plus apomorphine) were compared with special emphasis on the amplitude, inter-trial phase coherence, and frequency of maximal response. A reduction in the frequency of maximal response (between 40 and 60 Hz) was observed in the 6-OHDA lesioned rats that was normalized after apomorphine injection. The administration of this dopaminergic agonist also reduced the inter-trial phase coherence of the response in frequencies above 170 Hz. These findings suggest that the nigrostriatal dopaminergic system may be involved in the regulation of oscillatory activity not only in motor circuits, but also in sensory responses. Copyright 2009 Elsevier B.V. All rights reserved.

Nicergoline facilitates vestibular compensation in aged male rats with unilateral labyrinthectomy.

PubMed

Rampello, L; Drago, F

1999-05-28

The ergoline derivatives, nicergoline (NIC) or dihydroergocristine (DHE) were administered at various doses (0.1, 0.5 and 1 mg/kg) to aged male rats subjected to labyrinth unilateral lesion (LBX). The nystagmus rate appeared to be lower in animals treated with DHE or NIC 1mg/kg than in saline-injected rats, when observed on day 1 and 2 after operation. The number of falls in the rotorod test of LBX animals was decreased by NIC 0.5 or 1 mg/kg at all observation times. This parameter was affected by DHE only at the higher dose. These results suggest that NIC facilitates vestibular compensation of LBX rats. DHE appeared to be less potent in this respect. Since both drugs act on central dopaminergic neurotransmission, it is possible that this neurotransmission may be involved in their mechanism of action.

Postradiation ureteral obstruction: a reappraisal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muram, D.; Oxorn, H.; Curry, R.H.

1981-02-01

Thirty-four patients who received radiation therapy for carcinoma of the cervix developed hydronephrosis. Twelve of 34 (35%) had no evidence of pelvic malignancy, and the obstruction was caused by periureteral fibrosis. The incidence of obstructive uropathy due to periureteral fibrosis not associated with recurrent tumor increased when the obstructing lesion was unilateral, the clinical staging of the cervical carcinoma prior to therapy was Stage IB or Stage II rather than Stage III or Stage IV, and the obstructing lesion appeared 2 or more years after the completion of radiation therapy. The appearance of hydronephrosis in association with ipsilateral leg edema,more » and sciatic pain in these patients strongly suggest a recurrent tumor. The diagnosis of periureteral fibrosis should be considered in all patients who develop obstruction of the urinary tract after radiation therapy for carcinoma of the cervix. Laparotomy is indicated if all other methods of investigation fail to confirm the presence of a malignant lesion.« less

Isolated thalamic tuberculoma presenting as ataxic hemiparesis

PubMed Central

Sahu, Ritesh; Patil, Tushar B; Kori, Prakash; Shukla, Rakesh

2013-01-01

Lacunar syndrome is a neurodeficit secondary to a deep cerebral lesion, usually because of microatheroma of small arteries. Ataxic hemiparesis (AH) is a lacunar syndrome with unilateral pyramidal weakness and ipsilateral ataxia. Thalamic tuberculoma, as a cause of AH, has not been previously described in the literature. We describe an elderly man who presented with left hemiparesis and ipsilateral ataxia. Clinical examination revealed upper motor neuron left facial paresis and left-sided hemiparesis. The patient had incoordination in left upper and lower limbs. Mantoux test was positive and erythrocyte sedimentation rate was elevated. MRI of brain showed a conglomerated hypointense lesion in the right thalamus with a peripheral hyperintensity on T1-weighted imaging and a hyperintense lesion in T2-weighted imaging with significant perilesional oedema, suggesting a tuberculoma. The patient was treated with antitubercular therapy and was symptomatically better at the 9 months follow-up. PMID:23580686

Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

PubMed

Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

2013-07-24

Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, T.M.; Dawson, V.L.; Gage, F.H.

1991-03-01

Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative (3H)BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of (3H)SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in themore » number (Bmax) of (3H)sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of (3H)BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat.« less

Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats.

PubMed

Singh, Shamsher; Kumar, Puneet

2017-02-01

6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.

Correlation Between White Matter Lesions and Intelligence Quotient in Patients With Congenital Cytomegalovirus Infection.

PubMed

Inaba, Yuji; Motobayashi, Mitsuo; Nishioka, Makoto; Kaneko, Tomoki; Yamauchi, Shoko; Kawasaki, Yoichiro; Shiba, Naoko; Nishio, Shin-ya; Moteki, Hideaki; Miyagawa, Maiko; Takumi, Yutaka; Usami, Shin-ichi; Koike, Kenichi

2016-02-01

It is well known that congenital cytomegalovirus infection exhibits white matter and other types of lesions in magnetic resonance imaging (MRI), but little is known on the clinical significance of white matter lesions because they are also present in asymptomatic congenital cytomegalovirus infection. We investigated for relationships among white matter lesions, intelligence quotient, and other neurodevelopmental features. Nine children (five boys and four girls; mean age: 87.4 months, range: 63-127 months) with sensorineural hearing loss (five bilateral and four unilateral) had been diagnosed as having congenital cytomegalovirus infection by positive polymerase chain reaction findings of dried umbilical cords. They were evaluated for the presence of autistic features, tested using Wechsler Intelligence Scale for Children-Fourth Edition for intelligence quotient, and underwent brain MRI to measure white matter lesion localization and volume. At the time of MRI examination (mean age: 69.4 months, range: 19-92 months), white matter lesions were detected in eight of nine patients. Five subjects were diagnosed as having autism spectrum disorders. We observed increased white matter lesion volume was associated with lower intelligence quotient scores (R(2) = 0.533, P = 0.026) but not with autism spectrum disorders. In individuals with congenital cytomegalovirus, an increased white matter lesion volume is associated with lower intelligence quotient scores but not with an increased likelihood of autistic behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences in swallow physiology in patients with left and right hemispheric strokes.

PubMed

Wilmskoetter, Janina; Martin-Harris, Bonnie; Pearson, William G; Bonilha, Leonardo; Elm, Jordan J; Horn, Janet; Bonilha, Heather S

2018-05-11

We sought to determine the impact of lesion lateralization and lesion volume on swallow impairment on group-level by comparing patients with left and right hemisphere strokes and on patient-level by analyzing patients individually. We performed a retrospective, observational, cross-sectional study of 46 patients with unilateral (22 left, 24 right), acute, first-ever, ischemic strokes who received a diffusion weighted MRI (DW-MRI) and modified barium swallow study (MBSS) during their acute hospital stay. We determined lesion side on the DW-MRI and measured swallow physiology using the Modified Barium Swallow Impairment Profile (MBSImP™©), Penetration-Aspiration Scale (PAS), swallow timing, distance, area, and speed measures. We performed Pearson's Chi-Square and Wilcoxon Rank-Sum tests to compare patients with left and right hemisphere strokes, and Pearson or Spearman correlation, simple logistic regression, linear, and logistic multivariable regression modeling to assess the relationship between variables. At the group-level, there were no differences in MBSImP oral swallow impairment scores between patients with left and right hemisphere stroke. In adjusted analyses, patients with right hemisphere strokes showed significantly worse MBSImP pharyngeal total scores (p = 0.02), worse MBSImP component specific scores for laryngeal vestibular closure (Bonferroni adjusted alpha p ≤ 0.0029), and worse PAS scores (p = 0.03). Patients with right hemisphere strokes showed worse timing, distance, area, and speed measures. Lesion volume was significantly associated with MBSImP pharyngeal residue (p = 0.03) and pharyngeal total scores (p = 0.04). At the patient-level, 24% of patients (4 left, 7 right) showed opposite patterns of MBSImP oral and pharyngeal swallow impairment than seen at group-level. Our study showed differences in swallow physiology between patients with right and left unilateral strokes with patients with right hemisphere strokes showing worse pharyngeal impairment. Lesion lateralization seems to be a valuable marker for the severity of swallowing impairment at the group-level but less informative at the patient-level. Copyright © 2018 Elsevier Inc. All rights reserved.

Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

PubMed

Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

2005-12-01

We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

Unilateral spatial neglect in the acute phase of ischemic stroke can predict long-term disability and functional capacity.

PubMed

Luvizutto, Gustavo José; Moliga, Augusta Fabiana; Rizzatti, Gabriela Rizzo Soares; Fogaroli, Marcelo Ortolani; Moura Neto, Eduardo de; Nunes, Hélio Rubens de Carvalho; Resende, Luiz Antônio de Lima; Bazan, Rodrigo

2018-05-21

The aim of this study was to assess the relationship between the degree of unilateral spatial neglect during the acute phase of stroke and long-term functional independence. This was a prospective study of right ischemic stroke patients in which the independent variable was the degree of spatial neglect and the outcome that was measured was functional independence. The potential confounding factors included sex, age, stroke severity, topography of the lesion, risk factors, glycemia and the treatment received. Unilateral spatial neglect was measured using the line cancellation test, the star cancellation test and the line bisection test within 48 hours of the onset of symptoms. Functional independence was measured using the modified Rankin and Barthel scales at 90 days after discharge. The relationship between unilateral spatial neglect and functional independence was analyzed using multiple logistic regression that was corrected for confounding factors. We studied 60 patients with a median age of 68 (34-89) years, 52% of whom were male and 74% of whom were Caucasian. The risk for moderate to severe disability increased with increasing star cancellation test scores (OR=1.14 [1.03-1.26], p=0.01) corrected for the stroke severity, which was a confounding factor that had a statistically positive association with disability (OR=1.63 [1.13-2.65], p=0.01). The best chance of functional independence decreased with increasing star cancellation test scores (OR=0.86 [0.78-0.96], p=0.006) corrected for the stroke severity, which was a confounding factor that had a statistically negative association with independence (OR=0.66 [0.48-0.92], p=0.017). The severity of unilateral spatial neglect in acute stroke worsens the degree of long-term disability and functional independence.

Individual MRI and radiographic features of knee OA in subjects with unilateral knee pain: Health ABC study

PubMed Central

Javaid, MK; Kiran, A; Guermazi, A; Kwoh, K; Zaim, S; Carbone, L; Harris, T.; McCulloch, C.E.; Arden, NK; Lane, NE; Felson, D; Nevitt, M

2012-01-01

Strong associations between radiographic features of knee OA and pain have been demonstrated in persons with unilateral knee symptoms. Our objectives were to compare radiographic with MRI features of knee OA and assess the discrimination between painful and non-painful knees in persons with unilateral symptoms. 283 individuals with unilateral knee pain aged 71 to 80 years from Health ABC, a study of weight-related diseases and mobility, had bilateral knee radiographs, read for KL grade and individual radiographic features, and 1.5T MRIs, read using WORMS. The association of structural features with pain was assessed using a within-person case/control design and conditional logistic regression. Receiver operator characteristics (ROC) were then used to test the discriminatory performance of structural features. In conditional logistic analyses, knee pain was significantly associated with both radiographic (any JSN grade >=1: OR 3.20 (1.79 – 5.71) and MRI (any cartilage defect:>=2: OR 3.67 (1.49 – 9.04)) features. However, most subjects had MR detected osteophytes, cartilage and bone marrow lesions in both knees and no individual structural feature discriminated well between painful and non-painful knees using ROC. The best performing MRI feature (synovitis/effusion) was not significantly more informative than KL grade >=2 (p=0.42). In persons with unilateral knee pain, MR and radiographic features were associated with knee pain confirming an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating painful from non-painful knees. Further work is needed to examine how structural and non-structural factors influence knee pain. PMID:22736267

Age-related pathophysiological changes in rats with unilateral renal agenesis.

PubMed

Amakasu, Kohei; Suzuki, Katsushi; Katayama, Kentaro; Suzuki, Hiroetsu

2011-06-01

Affected rats of the unilateral urogenital anomalies (UUA) strain show renal agenesis restricted to the left side. To determine whether unilateral renal agenesis is a risk factor for the progression of renal insufficiency, we studied age-related pathophysiological alterations in affected rats. Although body growth and food intake were normal, polydipsia and polyuria with low specific gravity were present at 10 weeks and deteriorated further with age. Blood hemoglobin concentrations were normal, though there was slight erythropenia with increased MCV and MCH. Although hypoalbuminemia, hypercholesterolemia, azotemia, and hypermagnesemia were manifested after age 20 weeks, neither hyperphosphatemia nor hypocalcemia was observed. Plasma Cre and UN concentrations gradually increased with age. Cre clearance was almost normal, whereas fractional UN excretion was consistently lower than normal. Proteinuria increased with age, and albumin was the major leakage protein. In addition to cortical lesions, dilated tubules, cast formation, and interstitial fibrosis were observed in the renal medulla of 50 week-old affected rats. Renal weight was increased 1.7-fold and glomerular number 1.2-fold compared with normal rats. These findings show that the remaining kidney in UUA rats is involved not only in compensatory reactions but experiences pathophysiological alterations associated with progressive renal insufficiency.

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism

PubMed Central

Sonsalla, Patricia K.; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L.; Richardson, Jason R.; Gadad, Bharathi S.; Li, Wenhao; German, Dwight C.

2013-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. PMID:24184050

Assessment of Two Depth Perception Tests to Predict Undergraduate Pilot Training Completion

DTIC Science & Technology

1991-05-22

degrees of 5 stereoacuity and less amblyopia (a unilateral or bilateral reduction in corrected central visual acuity without a visible organic lesion...and would markedly reduce the power o1 the study. Such a stratification could generate new hypotheses about reasons for attrition but these would be...and treatment ). In: Perdriel G ed. AGARD. NATO 1974. 152: All-1 - 9. ten Doesschate G. Heterophoria. In: Collected papers on Aviation Medicine (AGARD

Comprehensive analysis of area-specific and time-dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury.

PubMed

Higo, Noriyuki; Sato, Akira; Yamamoto, Tatsuya; Oishi, Takao; Nishimura, Yukio; Murata, Yumi; Onoe, Hirotaka; Isa, Tadashi; Kojima, Toshio

2018-05-01

The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l-CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l-CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l-CST lesion. These area-specific and time-dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l-CST. © 2018 Wiley Periodicals, Inc.

Extraocular muscle proprioception and eye position.

PubMed

Pettorossi, V E; Ferraresi, A; Draicchio, F; Errico, P; Santarelli, R; Manni, E

1995-03-01

In the lamb, acute unilateral section of the ophthalmic branch induced in the ipsilateral eye occasional oscillations of the resting position and misalignment of the horizontal vestibulo-ocular reflex (HVOR) with respect to the stimulus. Additional electrolytic lesion of the cells innervating the proprioceptors of the medial rectus muscle, or of the lateral rectus muscle in the contralateral semilunar ganglion, provoked a 4 degrees-7 degrees consensual eye deviation towards and away from the lesioned side, respectively. The optokinetic beating field was similarly deviated. Under these experimental conditions, HVOR showed enhanced gain and marked misalignment in both eyes. Therefore, the selective suppression of muscular proprioceptive input deviated both eyes towards the direction opposite to the muscle whose gangliar proprioceptive representation has been destroyed.

Effects of a facial nerve lesion on responses in forehead microvessels to conjunctival irritation and paced breathing.

PubMed

Drummond, Peter D

2012-08-16

To investigate parasympathetic influences on the forehead microvasculature, blood flow was monitored bilaterally in seven participants with a unilateral facial nerve lesion during conjunctival irritation with Schirmer's strips and while breathing at 0.15 Hz. Blood flow and slow-wave frequency increased on the intact side of the forehead during Schirmer's test but did not change on the denervated side. However, a 0.15 Hz vascular wave strengthened during paced breathing, particularly on the denervated side. These findings indicate that parasympathetic activity in the facial nerve increases forehead blood flow during minor conjunctival irritation, but may interfere with the 0.15 Hz vascular wave. Copyright © 2012 Elsevier B.V. All rights reserved.

Gallium-67 uptake by a benign adrenocortical adenoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, J.A.; Naul, L.G.; Montgomery, J.L.

1988-08-01

A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by /sup 67/Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because /sup 67/Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormalmore » /sup 67/Ga uptake and atypical MR findings.« less

Differential regulation of preprotachykinin-A mRNA expression in striatum by excitation of hippocampal neurons.

PubMed

Brené, S; Lindefors, N; Herrera-Marschitz, M; Persson, H

1993-07-01

In this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine-induced lesion caused a decrease of preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a similar kainic acid-mediated increase in preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum the decreased preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid-mediated excitation of hippocampal neurons causes a dopamine-independent induction of preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation-induced decrease of preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.

Smokeless Tobacco Use and Periodontal Health in a Rural Male Population

PubMed Central

Chu, Yong H.; Tatakis, Dimitris N.

2010-01-01

Background Despite the reported effects of smokeless tobacco (ST) on the periodontium and high prevalence of ST use in rural populations and in men, studies on this specific topic are limited. The purpose of this cross-sectional investigation is to evaluate the periodontal health status of male ST users from a rural population. Methods Adult male residents of two rural Appalachian Ohio counties and daily ST users, with a unilateral mandibular oral ST keratosis lesion, were recruited. Subjects completed a questionnaire and received oral examination. Teeth present, ST keratosis lesion, plaque and gingival index, probing depth (PD), recession depth (RD), and attachment level were recorded. Statistical analysis compared ST-site mandibular teeth (teeth adjacent to the subject’s unilateral ST keratosis lesion) to NST-site teeth (contralateral corresponding teeth). Results This study includes 73 ST users. Recession prevalence is much greater in ST-site quadrants (36%) compared to NST-site quadrants (18%; P <0.001). Twice as many teeth had recession on ST-site (approximately 20%) than NST-site (approximately 10%; P = 0.0001). Average buccal RD on ST-site teeth did not differ from that on the NST-site teeth (P = 0.0875). Although average buccal attachment loss is greater on ST-site teeth (P = 0.016), the mean difference is <0.5 mm. When stratified by years of ST use, subjects using ST for 10 to 18 years exhibit the most differences between ST and NST sites, whereas subjects using ST for <10 years show no differences. Conclusion The results indicate that greater gingival recession prevalence and extent are associated with ST placement site in rural male ST users. PMID:20350155

Correlation of VHI-30 to Acoustic Measurements Across Three Common Voice Disorders.

PubMed

Dehqan, Ali; Yadegari, Fariba; Scherer, Ronald C; Dabirmoghadam, Peyman

2017-01-01

Voice disorders that affect the quality of voice also result in varying degrees of psychological and social problems. The research question here is whether the correlations between Voice Handicap Index (VHI)-30 scores and objective acoustic measures differ in patients with different types of voice disorders. The subjects were divided into three groups: muscle tension dysphonia (MTD), benign mid-membranous vocal fold lesions, and unilateral vocal fold paralysis (UVFP). All participants were male. The mean age for the groups were 32.85 ± 8.6 years in the MTD group, 33.24 ± 7.32 years in the benign lesions group, and 34.24 ± 7.51 years in the UVFP group. The participants completed the Persian VHI-30 questionnaire. PRAAT software was used to obtain acoustic analyses. There was a significant correlation between the physical subscale of the VHI-30 and the total score of the VHI-30 and maximum phonation time (MPT) in the MTD group. Also, there was a significant correlation between the total VHI-30 score and the MPT value. There were relatively strong and significant correlations between the physical subscale of the VHI-30 with jitter and shimmer, harmonics-to-noise ratio (HNR) for the group with benign lesions such as nodules and polyps. Also, in this group, there was a significant correlation between the total VHI-30 score and the jitter value. The physical scale had strong and significant correlations between jitter, shimmer, and HNR in the unilateral paralysis group. Findings suggest that although the VHI-30 and the acoustic measurements of voice provide independent information, they are associated to some extent. Copyright © 2017 The Voice Foundation. All rights reserved.

Relationship between somatosensory deficit and brain somatosensory system after early brain lesion: A morphometric study.

PubMed

Perivier, Maximilien; Delion, Matthieu; Chinier, Eva; Loustau, Sebastien; Nguyen, Sylvie; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickael

2016-05-01

Cerebral Palsy (CP) is a group of permanent motor disorders due to non-progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, -0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Sturge-Weber syndrome: Continued vigilance is needed.

PubMed

Hassan, Saeed; Babiker, Amir; Bashiri, Fahad A; Hassan, Hamdi H; Husseini, Maha El; Salih, Mustafa A

2015-01-01

Sturge-Weber syndrome (SWS) is a non-hereditary congenital disorder due to somatic mosaic mutations in the GNAQ gene. The classical presentation relates to the brain lesion (cerebral angiomatous lesion of leptomeninges, which is responsible for epileptic seizures, hemiparesis and mental retardation), skin lesion (unilateral facial nevus), ocular and oral involvement. We present a 12-year-old boy who was referred to the Division of Pediatric Neurology, King Saud University Medical City, Riyadh, Saudi Arabia with left-sided hemiparesis. Physical examination showed a port wine stain involving the right side of the face, extending to the upper thorax, and enlargement of both the right eye globe and cornea (megalocornea), indicating the presence of glaucoma. Following urgent referral to ophthalmology service, his eye condition improved dramatically post surgery. Neuroradiological investigations, including cranial computed tomography (CT) and magnetic resonance angiography (MRI) revealed the classical brain lesions of SWS, as well as right leptomeningeal choroidal angioma. Ten months later, he developed focal-onset seizures which responded to treatment. His cognition is normal with good school performance. Continued vigilance is needed to identify and manage the complications of SWS.

Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions.

PubMed

Baier, Bernhard; Dieterich, Marianne

2011-01-25

Disorders of gaze-holding--organized by a neural network located in the brainstem or the cerebellum--may lead to nystagmus. Based on previous animal studies it was concluded that one key player of the cerebellar part of this gaze-holding neural network is the flocculus. Up to now, in humans there are no systematic studies in patients with cerebellar lesions examining one of the most common forms of nystagmus: gaze-evoked nystagmus (GEN). The aim of our present study was to clarify which cerebellar structures are involved in the generation of GEN. Twenty-one patients with acute unilateral cerebellar stroke were analyzed by means of modern MRI-based voxel-wise lesion-behavior mapping. Our data indicate that cerebellar structures such as the vermal pyramid, the uvula, and the tonsil, but also parts of the biventer lobule and the inferior semilunar lobule, were affected in horizontal GEN. It seems that these structures are part of a gaze-holding neural integrator control system. Furthermore, GEN might present a diagnostic sign pointing toward ipsilesionally located lesions of midline and lower cerebellar structures.

Posterior insular cortex – a site of vestibular–somatosensory interaction?

PubMed Central

Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-01-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

PubMed

Iyer, Rajesh Shankar; Wattamwar, Pandurang; Thomas, Bejoy

2017-07-27

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Partial recovery of hemiparesis following hemispherectomy in infant monkeys.

PubMed

Burke, Mark W; Zangenehpour, Shahin; Ptito, Maurice

2010-01-22

Hemiparesis, unilateral weakness or partial paralysis, is a common outcome following hemispherectomy in humans. We use the non-human primate as an invaluable translational model for our understanding of developmental plasticity in response to hemispherectomy. Three infant vervet monkeys (Chlorocebus sabeus) underwent hemispherectomy at a median age of 9 weeks and two additional monkeys at 48 months. Gross motor assessment was conducted in a large open field that contained a horizontal bar spanning the width of the cage. Subjects were assessed yearly following surgery in infantile lesions for a period of 3 years. Adult-lesioned subjects were assessed 40 months following surgery. Shortly after surgery both infant and adult-lesioned subjects were unable to move the contralateral side of their body, but all subjects were able to walk within 6 months following surgery. At each time point the lower limb gait was normal in infant-lesioned subjects with no apparent limp or dragging, however the upper limb demonstrated significant impairment. Horizontal bar crossing was significantly impaired during the first 24 months following surgery. Adult-lesioned subjects also displayed upper limb movement impairments similar to infant-lesioned subjects. In addition the adult-lesioned subjects displayed a noticeable lower limb limp, which was not observed in the infant-lesioned group. Both groups at each time point showed a propensity for ipsiversive turning. The upper limb gait impairment and horizontal bar crossing of lesioned subjects are reminiscent of hemiparesis seen in hemisperectomized humans with the young-lesioned subjects showing a greater propensity for recovery. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Methamphetamine fails to alter the noradrenergic integrity of the heart.

PubMed

Ruffoli, Riccardo; Soldani, Paola; Pasquali, Livia; Ruggieri, Stefano; Paparelli, Antonio; Fornai, Francesco

2008-10-01

The chronic use of methamphetamine leads to cardiomyopathy and a nigrostriatal dopamine deficiency that partly mimics what occurs in Parkinson's disease. This study examines the cardiac effects occurring after chronic administration of methamphetamine and parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Despite the similarities concerning the nigrostriatal dopamine denervation, methamphetamine failed to produce chronic norepinephrine depletion in the heart, thus contrasting with what occurs in Parkinson's disease or after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These data suggest that the chronic cardiovascular effects induced by methamphetamine rely on biochemical changes which differ from those activated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or during the course of Parkinson's disease.

Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain

PubMed Central

Jung, Un Ju; Kim, Sang Ryong

2014-01-01

Recently, we have demonstrated the ability of naringin, a well-known flavanone glycoside of grapefruits and citrus fruits, to prevent neurodegeneration in a neurotoxin model of Parkinson's disease. Intraperitoneal injection of naringin protected the nigrostriatal dopaminergic projection by increasing glial cell line-derived neurotrophic factor expression and decreasing the level of tumor necrosis factor-alpha in dopaminergic neurons and microglia, respectively. These results suggest that naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson's disease with anti-inflammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson's disease. PMID:25317167

A beam-walking apparatus to assess behavioural impairments in MPTP-treated mice: pharmacological validation with R-(-)-deprenyl.

PubMed

Quinn, Leann P; Perren, Marion J; Brackenborough, Kim T; Woodhams, Peter L; Vidgeon-Hart, Martin; Chapman, Helen; Pangalos, Menelas N; Upton, Neil; Virley, David J

2007-08-15

A beam-walking apparatus has been evaluated for its ability to detect motor impairments in mice acutely treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg, s.c., single or double administration). Mice subjected to MPTP lesioning showed deficits in motor performance on the beam-walking task, for up to 6 days post-MPTP administration, as compared to saline-treated controls. In addition, MPTP-treated mice were detected to have a marked depletion in striatal dopamine levels and a concomitant reduction in substantia nigra (SN) tyrosine hydroxylase (TH) immunoreactivity, at 7 days post-MPTP administration, indicative of dopaminergic neuronal loss. Pre-administration of the potent MAO-B inhibitor R-(-)-deprenyl at 3 or 10 mg/kg, 30 min, s.c, significantly inhibited the MPTP-induced reduction in SN TH-immunoreactivity, striatal dopamine depletions and impairments in mouse motor function. The data described in the present study provides further evidence that functional deficits following an acute MPTP dosing schedule in mice can be quantified and are related to nigro-striatal dopamine function.

Murine motor and behavior functional evaluations for acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication.

PubMed

Hutter-Saunders, Jessica A L; Gendelman, Howard E; Mosley, R Lee

2012-03-01

Acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces nigrostriatal neurodegeneration that reflects Parkinson's disease (PD) pathobiology. The model is commonly used for rodent studies of PD pathogenesis and diagnostics and for developmental therapeutics. However, tests of motor function in MPTP-intoxicated mice have yielded mixed results. This unmet need reflects, in part, lesion severity, animal variability, and the overall test sensitivity and specificity. In attempts to standardize rodent motor function and behavioral tests, mice were trained on the rotarod or habituated in an open field test chamber, and baseline performance measurements were collected prior to MPTP intoxication. One week following MPTP intoxication, motor function and behavior were assessed and baseline measurements applied to post-MPTP measurements with normalization to PBS controls. Rotarod and open field tests assessed in this manner demonstrated significant differences between MPTP- and saline-treated mice, while tests of neuromuscular strength and endurance did not. We conclude that the rotarod and open field tests provide reliable measures of motor function for MPTP-intoxicated mice.

Burning mouth syndrome: a review and update.

PubMed

Silvestre, Francisco J; Silvestre-Rangil, Javier; López-Jornet, Pía

2015-05-16

Burning mouth syndrome (BMS) is mainly found in middle aged or elderly women and is characterized by intense burning or itching sensation of the tongue or other regions of the oral mucosa. It can be accompanied by xerostomia and dysgeusia. The syndrome generally manifests spontaneously, and the discomfort is typically of a continuous nature but increases in intensity during the evening and at night. Although BMS classically has been attributed to a range of factors, in recent years evidence has been obtained relating it peripheral (sensory C and/or trigeminal nerve fibers) or central neuropathic disturbances (involving the nigrostriatal dopaminergic system). The differential diagnosis requires the exclusion of oral mucosal lesions or blood test alterations that can produce burning mouth sensation. Patient management is based on the avoidance of causes of oral irritation and the provision of psychological support. Drug treatment for burning sensation in primary BMS of peripheral origin can consist of topical clonazepam, while central type BMS appears to improve with the use of antidepressants such as duloxetine, antiseizure drugs such as gabapentin, or amisulpride.

Alteration of striatal [11C]raclopride and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine uptake precedes development of methamphetamine-induced rotation following unilateral 6-hydroxydopamine lesions of medial forebrain bundle in rats.

PubMed

Ishida, Yasushi; Kawai, Keiichi; Magata, Yasuhiro; Abe, Hiroshi; Yoshimoto, Mitsuyoshi; Takeda, Ryuichiro; Hashiguchi, Hiroyuki; Mukai, Takahiro; Saji, Hideo

2005-11-25

We studied the positron emission tomography (PET) tracer distributions of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and of the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than at 3 days after the 6-OHDA lesions. The brains of 6-OHDA-treated rats were analyzed by tissue dissection following i.v. bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [11C]Raclopride, but not [11C]SCH23390, showed higher accumulation in the striatum on the lesion side than on the non-lesion (intact) side both at 3 days and 3 weeks postlesion. On the other hand, lower accumulation of [18F]FDOPA was observed in the striatum on the lesion side at 3 days postlesion and in both the striatum and cerebral cortex on the lesion side at 3 weeks postlesion. Our studies demonstrate that an increase in [11C]raclopride and a decrease in [18F]FDOPA uptake in the denervated striatum is evident even at 3 days after the 6-OHDA lesions when the methamphetamine-induced rotational behavior is not established.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Mesocortical dopamine depletion and anxiety-related behavior in the rat: sex and hemisphere differences.

PubMed

Sullivan, R M; Dufresne, M M; Siontas, D; Chehab, S; Townsend, J; Laplante, F

2014-10-03

The mesocortical dopamine (DA) system of the rat plays an important role in prefrontal cortex (PFC) regulation of stress and emotion and exhibits functional hemispheric asymmetry for such processing. Since few studies examine sex differences in this context, we compared the effects of left vs. right unilateral PFC DA depletion in males and females in several behavioral situations associated with anxiety or aversion. Adult rats received unilateral injections of 6-hydroxydopamine (6-OHDA) or vehicle in the ventromedial (vm) PFC. Behavioral tests included a predator odor burying test, elevated plus maze and sucrose consumption with simple taste aversion. Tissue analysis confirmed that vmPFCs injected with 6-OHDA were depleted of DA (75-85%) compared to controls. Burying behavior and sucrose consumption were affected only by left lesions, similarly in both sexes. However, risk assessment behaviors were affected by right lesions in opposite directions in males and females. Behaviors modified preferentially by the left cortex thus showed less evidence of sex differences than those modulated by the right. While mesocortical DA depletion effects are lateralized, the nature of these effects can vary with sex and specific behavior. Such findings may be clinically significant, given the large gender differences in the incidence of mood and anxiety disorders, which also show many lateralized prefrontal abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional study of hands among patients dialysed for more than 10 years.

PubMed

Chazot, C; Chazot, I; Charra, B; Terrat, J C; Vanel, T; Calemard, E; Ruffet, M; Laurent, G

1993-01-01

Sixty-six haemodialysed (HD) in centre patients (24 h/m2/week, acetate bath, cuprophane membrane), with a mean age of 59.2 years, treated for 16.7 +/- 4.5 years, underwent clinical examination of their hands to determine anatomical and functional alterations. For each hand a functional score was calculated from a medicolegal technique based on sensitivity and angulation amplitude (rating from 0 to 100). Dialysis-related arthropathy (DRA), including carpal-tunnel (CT) syndrome, was scored as well as hand muscle amyotrophia. Trigger fingers, abnormal synovial hypertrophy, and one or more non-functional tendons were found in 15, 26, and 33% of the patients respectively. Thirteen percent had pseudoporphyria. Amyotrophy was moderate or severe in 39%. The global functional score (mean of the two unilateral functional scores) decreased with time spent on haemodialysis and was correlated with the DRA score. The unilateral functional score was linked to tendinous lesions, amyotrophy, and presence of pulses, but not to CT surgery or presence of AV fistula. Hands with ulnar insult at the elbow shown by electromyography had significantly lower functional scores. Repercussions of hand functional alteration may have an important social and psychological impact in daily life. The responsibility of amyloidosis is evidenced by tendinous lesions and nervous entrapment. Ulnar palsy is also important because of the vital motor role of that nerve in hand function.

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

NASA Technical Reports Server (NTRS)

Kaufman, G. D.; Shinder, M. E.; Perachio, A. A.

1999-01-01

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation. Copyright 1999 Elsevier Science B.V.

Pure word deafness following left temporal damage: Behavioral and neuroanatomical evidence from a new case.

PubMed

Maffei, Chiara; Capasso, Rita; Cazzolli, Giulia; Colosimo, Cesare; Dell'Acqua, Flavio; Piludu, Francesca; Catani, Marco; Miceli, Gabriele

2017-12-01

Pure Word Deafness (PWD) is a rare disorder, characterized by selective loss of speech input processing. Its most common cause is temporal damage to the primary auditory cortex of both hemispheres, but it has been reported also following unilateral lesions. In unilateral cases, PWD has been attributed to the disconnection of Wernicke's area from both right and left primary auditory cortex. Here we report behavioral and neuroimaging evidence from a new case of left unilateral PWD with both cortical and white matter damage due to a relatively small stroke lesion in the left temporal gyrus. Selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading and writing. Performance on dichotic listening was characterized by a reversal of the right-ear advantage typically observed in healthy subjects. Cortical thickness and gyral volume were severely reduced in the left superior temporal gyrus (STG), although abnormalities were not uniformly distributed and residual intact cortical areas were detected, for example in the medial portion of the Heschl's gyrus. Diffusion tractography documented partial damage to the acoustic radiations (AR), callosal temporal connections and intralobar tracts dedicated to single words comprehension. Behavioral and neuroimaging results in this case are difficult to integrate in a pure cortical or disconnection framework, as damage to primary auditory cortex in the left STG was only partial and Wernicke's area was not completely isolated from left or right-hemisphere input. On the basis of our findings we suggest that in this case of PWD, concurrent partial topological (cortical) and disconnection mechanisms have contributed to a selective impairment of speech sounds. The discrepancy between speech and non-speech sounds suggests selective damage to a language-specific left lateralized network involved in phoneme processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed-onset progressive movement disorders after static brain lesions.

PubMed

Scott, B L; Jankovic, J

1996-01-01

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Feasibility of a Semi-computerized Line Bisection Test for Unilateral Visual Neglect Assessment.

PubMed

Jee, H; Kim, J; Kim, C; Kim, T; Park, J

2015-01-01

Commonly used paper-and-pencil based test modalities for assessing the degree of unilateral visual neglect (ULN) in patients with hemispheric cerebral lesions consume human resources with a significant inter and intra-rater variability. To explore the feasibility of a semi-computerized electronic-pen based ULN assessment system (e-system) to improve assessment quality without altering the conventional user interface. Thirty cognitively healthy participants (HG) and 11 participants diagnosed with right-hemispheric lesion and unilateral visual neglect (NG) were recruited to evaluate the e-system. Line bisection tests (LBT) were repeatedly conducted twice for the inter-rater and intra-rater (reliability) comparisons. The LBT results were assessed by the e-system and the golden standard methods (manual rater assessment). The percent deviation (%), assessment duration (sec), and number of neglected line (each) were evaluated. The inter-rater comparisons of the assessed deviation (%) variable showed excellent interrater reliabilities (CCCs) ranging from .84 (.59 to .95 (p < .001)) to .99 (.90 to .99 (p < .001)) for HG and NG. The Bland Altman mean difference (B-A) plots with bias (95% LOA (limits of agreement)) showed similar agreements between the e-system and the raters ranging from -.04 % (-2.10 to 1.97) to 1.30 % (-2.23 to 4.84) for HG and NG. The effect sizes (ES), which show similarities between the assessment methods, yielded smaller ranges from .01 to .30 for HG and NG. The reliability (test-retest) comparisons showed similar assessment results between the e-system, rater 1, and rater 2. The manual rater assessment time ranging from 5.85 to 6.00 minutes and inter- and intraassessment variations were virtually eliminated with the e-system. The semi-computerized system with the conventional paper-and pencil user-interface showed valid and reliable assessment results. It may be a feasible replacement for the manual rater assessment modality even in a clinical setting.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) in patients with familial adenomatous polyposis (FAP); a polyposis registry experience.

PubMed

Nusliha, Anwer; Dalpatadu, Ushantha; Amarasinghe, Binara; Chandrasinghe, Pramodh Chitral; Deen, Kemal Ismail

2014-10-18

Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition giving rise to multiple adenomatous polyps in the colon which invariably become malignant by the fourth decade. Congenital hypertrophy of retinal pigment epithelium (CHRPE) is one of its extra intestinal manifestations early in childhood seen, present in 90% of FAP population and is easy to detect. Patients diagnosed with FAP and at risk first degree family members were screened for CHRPE using a slit lamp and indirect ophthalmoscopy. The retina of 17 diagnosed FAP patients and 13 individuals at risk were examined. The site and size of CHRPE lesions were documented. Thirteen (76%) of 17 FAP patients (male-10, female - 7, median age - 30 years; range 15-55 years) had CHRPE lesions; seven (54%) had bilateral CHRPE lesions and six (46%) had unilateral lesions. A single lesion was detected in 6 (46%) while 7 (54%) patients had multiple lesions. Of 13 at risk individuals (7- male, female-6 ; median age 34; range 16-52 years), one was positive for CHRPE and 12 were free of retinal lesions. The sensitivity of the presence of a CHRPE lesion in association with colonic polyps in FAP was 76%, specificity 92%, positive predictive value 93%, and negative predictive value 75%. This study found a high sensitivity and specificity for a CHRPE lesion to be associated with colonic polyps of FAP and hence a useful screening method in a burdened health-care system. The method is minimally invasive and simple and would be of particular value in screening children at risk for FAP.

Common avian infection plagued the tyrant dinosaurs.

PubMed

Wolff, Ewan D S; Salisbury, Steven W; Horner, John R; Varricchio, David J

2009-09-30

Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name 'Sue') has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids. We conducted an extensive survey of tyrannosaurid specimens and identified ten individuals with full-thickness erosive lesions. These lesions were described, measured and photographed for comparison with one another. We also conducted an extensive survey of related archosaurs for similar lesions. We show here that these lesions are consistent with those caused by an avian parasitic infection called trichomonosis, which causes similar abnormalities on the mandible of modern birds, in particular raptors. This finding represents the first evidence for the ancient evolutionary origin of an avian transmissible disease in non-avian theropod dinosaurs. It also provides a valuable insight into the palaeobiology of these now extinct animals. Based on the frequency with which these lesions occur, we hypothesize that tyrannosaurids were commonly infected by a Trichomonas gallinae-like protozoan. For tyrannosaurid populations, the only non-avian dinosaur group that show trichomonosis-type lesions, it is likely that the disease became endemic and spread as a result of antagonistic intraspecific behavior, consumption of prey infected by a Trichomonas gallinae-like protozoan and possibly even cannibalism. The severity of trichomonosis-related lesions in specimens such as Tyrannosaurus rex FMNH PR2081 and Tyrannosaurus rex MOR 980, strongly suggests that these animals died as a direct result of this disease, mostly likely through starvation.

GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease

PubMed Central

d’Anglemont de Tassigny, Xavier; Pascual, Alberto; López-Barneo, José

2015-01-01

The glial cell line-derived neurotrophic factor (GDNF) is a well-established trophic agent for dopaminergic (DA) neurons in vitro and in vivo. GDNF is necessary for maintenance of neuronal morphological and neurochemical phenotype and protects DA neurons from toxic damage. Numerous studies on animal models of Parkinson’s disease (PD) have reported beneficial effects of GDNF on nigrostriatal DA neuron survival. However, translation of these observations to the clinical setting has been hampered so far by side effects associated with the chronic continuous intra-striatal infusion of recombinant GDNF. In addition, double blind and placebo-controlled clinical trials have not reported any clinically relevant effect of GDNF on PD patients. In the past few years, experiments with conditional Gdnf knockout mice have suggested that GDNF is necessary for maintenance of DA neurons in adulthood. In parallel, new methodologies for exogenous GDNF delivery have been developed. Recently, it has been shown that a small population of scattered, electrically interconnected, parvalbumin positive (PV+) GABAergic interneurons is responsible for most of the GDNF produced in the rodent striatum. In addition, cholinergic striatal interneurons appear to be also involved in the modulation of striatal GDNF. In this review, we summarize current knowledge on brain GDNF delivery, homeostasis, and its effects on nigrostriatal DA neurons. Special attention is paid to the therapeutic potential of endogenous GDNF stimulation in PD. PMID:25762899

Subareolar Sclerosing Ductal Hyperplasia.

PubMed

Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

2017-02-01

Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

Surgery of the vulva in vulvar cancer.

PubMed

Micheletti, Leonardo; Preti, Mario

2014-10-01

The standard radical mutilating surgery for the treatment of invasive vulval carcinoma is, today, being replaced by a conservative and individualised approach. Surgical conservative modifications that are currently considered safe, regarding vulval lesion, are separate skin vulval-groin incisions, drawn according to the lesion diameter, and wide local radical excision or partial radical vulvectomy with 1-2 cm of clinically clear surgical margins. Regarding inguinofemoral lymph nodes management, surgical conservative modifications not compromising patient survival are omission of groin lymphadenectomy only when tumour stromal invasion is ≤ 1 mm, unilateral groin lymphadenectomy only in well-lateralised early lesions and total or radical inguinofemoral lymphadenectomy with preservation of femoral fascia when full groin resection is needed. Sentinel lymph node dissection is a promising technique but it should not be routinely employed outside referral centres. Pelvic nodes are better managed by radiation. Locally advanced vulval carcinoma can be managed by ultraradical surgery, exclusive radiotherapy or chemoradiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Restorative Effects of Uridine Plus Docosahexaenoic Acid in a Rat Model of Parkinson’s Disease

PubMed Central

Cansev, Mehmet; Ulus, Ismail H.; Wang, Lei; Maher, Timothy J.; Wurtman, Richard J.

2008-01-01

Summary Administering uridine-5’-monophosphate (UMP) and docosahexaenoic acid (DHA) increases synaptic membranes (as characterized by pre-and post-synaptic proteins) and dendritic spines in rodents. We examined their effects on rotational behavior and dopaminergic markers in rats with partial unilateral 6-hydroxydopamine (6-OHDA)-induced striatal lesions. Rats receiving UMP, DHA, both, or neither, daily, and intrastriatal 6-OHDA 3 days after treatment onset, were tested for d-amphetamine-induced rotational behavior and dopaminergic markers after 24 and 28 days, respectively. UMP/DHA treatment reduced ipsilateral rotations by 57% and significantly elevated striatal dopamine, tyrosine hydroxylase (TH) activity, TH protein and Synapsin-1 on the lesioned side. Hence, giving uridine and DHA may partially restore dopaminergic neurotransmission in this model of Parkinson’s Disease. PMID:18761383

Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson's disease.

PubMed

Cansev, Mehmet; Ulus, Ismail H; Wang, Lei; Maher, Timothy J; Wurtman, Richard J

2008-11-01

Administering uridine-5'-monophosphate (UMP) and docosahexaenoic acid (DHA) increases synaptic membranes (as characterized by pre- and post-synaptic proteins) and dendritic spines in rodents. We examined their effects on rotational behavior and dopaminergic markers in rats with partial unilateral 6-hydroxydopamine (6-OHDA)-induced striatal lesions. Rats receiving UMP, DHA, both, or neither, daily, and intrastriatal 6-OHDA 3 days after treatment onset, were tested for d-amphetamine-induced rotational behavior and dopaminergic markers after 24 and 28 days, respectively. UMP/DHA treatment reduced ipsilateral rotations by 57% and significantly elevated striatal dopamine, tyrosine hydroxylase (TH) activity, TH protein and synapsin-1 on the lesioned side. Hence, giving uridine and DHA may partially restore dopaminergic neurotransmission in this model of Parkinson's disease.

Comminuted mandibular fracture in child victim of dog bite.

PubMed

de Carvalho, Matheus Furtado; Hardtke, Luiz Augusto Paixão; de Souza, Max Filipe Cota; de Oliveira Araujo, Vasco

2012-08-01

Dog bites represent lesions commonly found in Hospital Emergency Clinic. This type of lesion may cause severe harm to patients, but it rarely affects the underlying bone structure causes facial fracture. This study aims to illustrate a rare clinical case in which a pediatric patient presented a comminuted fracture in the mandible which evolved into a unilateral avulsion of the mandibular condyle, body fractures as well as a mandibular ramus and hemiface that had been deformed, with multiple lacerations and loss of soft-tissue mass. Intermaxillary fixation was performed using the Ivy method, followed by internal rigid fixation using miniplates and screws in attempt to reconstruct the child's mandible. After 2 years of follow-up, a satisfactory esthetics and functional results could be observed. © 2011 John Wiley & Sons A/S.

Functional organization of primate translational vestibulo-ocular reflexes and effects of unilateral labyrinthectomy

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; McHenry, M. Q.; Newlands, S. D.; Dickman, J. D.

1999-01-01

Translational vestibulo-ocular reflexes (trVORs) are characterized by distinct spatio-temporal properties and sensitivities that are proportional to the inverse of viewing distance. Anodal (inhibitory) labyrinthine stimulation (100 microA, < 2 s) during motion decreased the high-pass filtered dynamics, as well as horizontal trVOR sensitivity and its dependence on viewing distance. Cathodal (excitatory) currents had opposite effects. Translational VORs were also affected after unilateral labyrinthectomy. Animals lost their ability to modulate trVOR sensitivity as a function of viewing distance acutely after the lesion. These deficits partially recovered over time, albeit a significant reduction in trVOR sensitivity as a function of viewing distance remained in compensated animals. During fore-aft motion, the effects of unilateral labyrinthectomy were more dramatic. Both acute and compensated animals permanently lost their ability to modulate fore-aft trVOR responses as a function of target eccentricity. These results suggest that (1) the dynamics and viewing distance-dependent properties of the trVORs are very sensitive to changes in the resting firing rate of vestibular afferents and, consequently, vestibular nuclei neurons; (2) the most irregularly firing primary otolith afferents that are most sensitive to labyrinthine electrical stimulation might contribute to reflex dynamics and sensitivity; (3) inputs from both labyrinths are necessary for the generation of the translational VORs.

[Cervical cord infarction associated with unilateral vertebral artery dissection due to golf swing].

PubMed

Tokumoto, Kazuki; Ueda, Nobuhiko

2014-01-01

A-68-year-old man experienced nuchal pain and bilateral shoulder weakness that occurred suddenly after he performed a golf swing. He was conscious. His cranial nerves were normal, but bilateral deltoid and biceps muscle strengths weakened. Magnetic resonance image (MRI) showed no brain stem infarctions or cervical epidural hematoma. We tentatively diagnosed him with concussion of the spinal cord because of mild recovery of his bilateral upper limb weakness after several hours; he was later discharged. The next day, he suddenly developed serious tetraplegia and was admitted to the emergency department. His breathing was controlled by a respirator as he had expectoration difficulty and respiratory muscle paralysis. A lesion in the cervical cord became apparent on MRI; the right vertebral artery was not detected on magnetic resonance angiography. Cervical MRI showed the intimal flap and a lack of flow void in the right vertebral artery. These findings revealed a right vertebral artery dissection. Cervical cord infarction due to unilateral vertebral artery dissection is rarer than posterior cerebral infarction due to the same pathogenesis; however, some such cases have been reported. We consider the present case to be caused by cervical cord infarction associated with unilateral vertebral artery dissection resulting from golf swing.

Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration.

PubMed

Stichel, Christine C.; Lausberg, Friederike; Hermanns, Susanne; Müller, Hans Werner

1999-01-01

After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons.Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods.A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration.These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.

The role of the dorsolateral tegmentum in the control of male sexual behavior: a reevaluation.

PubMed

Romero-Carbente, J C; Camacho, F J; Paredes, R G

2006-06-30

The medial preoptic area/anterior hypothalamus (MPOA/AH) plays a key role in the control of male sexual behavior. Independently of the type, MPOA/AH lesions permanently eliminate male sexual behavior in the rat. The MPOA/AH projects among other structures to the dorsolateral tegmentum (DLT). Bilateral electrolytic lesions of the DLT or the unilateral electrolytic destruction of the MPOA/HA combined with a contralateral electrolytic lesion of the DLT eliminate male sexual behavior. In the present experiment, we evaluated if neurotoxic lesions of the DLT produce the same behavioral deficits as those observed after electrolytic lesions. This would allow us to evaluate if neurons of the DLT or the fibers passing through this area are important in the control of male sexual behavior. To this aim, sexually experience male rats were tested for socio-sexual behavior, partner preference and motor execution in order to determine if the possible behavioral changes could be attributed to alterations in sexual motivation or motor execution. One week after the bilateral DLT lesions the animals were evaluated in the same behavioral tests. The lesions were identified by glial fibrillary acidic protein (GFAP) and neuronal nuclear protein (Neu-N) immunohistochemistry. No significant consistent effects upon sexual behavior were observed in any of the groups, including the group with clear bilateral damage of the DLT. A reduction in the percentage of males displaying ejaculation in the first post-lesion test was observed for all groups injected with quinolinic acid. No effects upon partner preference or motor coordination were observed after the lesion in any of the groups. The lack of effect of DLT neurotoxic lesions upon mating suggests that neurons of this structure are not involved in the control of male sexual behavior.

Frontal Mucocele Extended Orbita and Endoscopic Marsupialization Technique.

PubMed

Erdogan, Banu Atalay; Unlu, Nazmiye; Aydin, Sedat; Avci, Hakan

2018-06-01

Mucocele is benign, slow-growing, mucous-filled cystic lesions that arise in the paranasal sinuses. It causes progressive distension of the bony walls and induces compressive symptoms. Surgical treatment of paranasal sinus mucoceles includes endoscopic approach or external approach. The authors report a patient of frontal mucocele who presented with a history of progressive unilateral protrusion. Computed tomography scan revealed a large mucocele of the frontal sinus with orbital extension on the same side. He was successfully treated with endoscopic marsupialization without any serious complications.

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2014-12-01

glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury. Simard JM, Popovich PG, Tsymbalyuk O, Caridi J , Gullapalli RP, Kilbourne MJ...ScienceDirect Experimental Neurology j ourna l homepage: www.e lsev ie r .com/ locate /yexnrSpinal cord injury with unilateral versus bilateral primary...hemorrhage — Effects of glibenclamide J . Marc Simard a,b,c,⁎, Phillip G. Popovich d, Orest Tsymbalyuk a, Volodymyr Gerzanich a a Department of

A rare case of unilateral discoid lupus erythematosus mimicking lupus vulgaris.

PubMed

Verma, Parul; Pathania, Sucheta; Kubba, Asha

2017-11-08

Discoidlupus erythematosus (DLE) is a chronic type of cutaneous lupus erythematosus which can present in various morphologies, and the diagnosis can be rather confounding. Prompt evaluation and treatment is necessary to prevent disfigurement and systemic involvement associated with DLE. The following case presented a diagnostic dilemma as the lesion mimicked lupus vulgaris. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Right attitude, right decision and timely planning in surgical pedodontics -scoop out or expose it.

PubMed

Kethineni, Balaji; Peddi, Ravigna; Puppala, Ravindar; Banavath, Sunitha; Chowdary, Uday Kumar; Raj, Deepak

2013-04-01

Radicular cysts are the most common odontogenic cystic lesions of inflammatory origin and are usually asymptomatic and are left unnoticed, until detected by routine radiography. It is managed either by surgical enucleation or marsupialization. Conventional nonsurgical endodontic treatment has a high degree of clinical success, but in certain cases surgical intervention becomes necessary. This is the case report of a patient presenting with unilateral radicular cyst. The lesion is managed by marsupialization using a novel and safe method of separating the soft tissue mass of the periapical lesion which was in proximity to vital and vulnerable anatomical tissue, emphasizing the need of application of treatment in the best interest of patients. The treatment of choice is dependent on the size and localization of the lesion, the bone integrity of the lesions wall and its proximity to vital structure. This case report of radicular cysts emphasis on the advantages and disadvantages of the leading criteria that should be taken into consideration when assessing the treatment modalities for radicular cyst. Odontogenic cysts, Radicular cyst, Marsupialization, Enucleation. How to cite this article: Kethineni B, Peddi R, Puppala R, Sunitha B, Chowdary U K, Raj D. Right Attitude, Right Decision and Timely Planning in Surgical Pedodontics -Scoop Out or Expose It. J Int Oral Health 2013; 5(2):50-54.

Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

PubMed

Akundi, Ravi S; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D; Zhi, Lianteng; Cass, Wayne A; Sullivan, Patrick G; Büeler, Hansruedi

2011-01-13

PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.

Cytomorphologic features of papillary lesions of the male breast: a study of 11 cases.

PubMed

Reid-Nicholson, Michelle D; Tong, Guoxia; Cangiarella, Joan F; Moreira, Andre L

2006-08-25

Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men. Copyright 2006 American Cancer Society.

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xu; Zhou, Jianying; Chin, Mark H

2010-02-15

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.« less

Image of a line is not shrunk but neglected. Absence of crossover in unilateral spatial neglect.

PubMed

Ishiai, Sumio; Koyama, Yasumasa; Nakano, Naomi; Seki, Keiko; Nishida, Yoichiro; Hayashi, Kazuko

2004-01-01

Patients with left unilateral spatial neglect following right hemisphere lesions usually err rightward when bisecting a horizontal line. For very short lines (e.g. 25 mm), however, leftward errors or seemingly 'right' neglect is often observed. To explain this paradox of crossover in the direction of errors, rather complicated models have been introduced as to the distribution of attention. Neglect may be hypothesized to occur in representational process of a line or estimation of the midpoint on the formed image, or both. We devised a line image task using a computer display with a touch panel and approached the representational image of a line to be bisected. Three patients with typical left neglect were presented with a line and forced to see its whole extent with cueing to the left endpoint. After disappearance of the line, they pointed to the right endpoint, the left endpoint, or the subjective midpoint according to their representational image. The line image between the reproduced right and left endpoints was appropriately formed for the 200 mm lines. However, the images for the shorter 25 and 100 mm lines were longer than the physical lengths with overextension to the left side. These results proved the context effect that short lines may be perceived longer when they are presented in combination with longer lines. One of our patients had an extensive lesion that involved the frontal, temporal, and parietal lobes, and the other two had a lesion restricted to the posterior right hemisphere. The image for a fully perceived line may be represented far enough into left space even when left neglect occurs after a lesion that involves the right parietal lobe. The patients with neglect placed the subjective midpoint rightward from the centre of the stimulus line for the 100 and 200 mm lines and leftward for the 25 mm lines. This crossover of bisection errors disappeared when the displacement of the subjective midpoint was measured from the centre of the representational line image. Left neglect may occur consistently in estimation of the subjective midpoint on the representational image, which may be explained by a simple rightward bias of attentional distribution.

Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy

PubMed Central

2011-01-01

Background Traditional magnetic resonance (MR) imaging can identify abnormal changes in ipsilateral thalamus in patients with unilateral middle cerebral artery (MCA) infarcts. However, it is difficult to demonstrate these early changes quantitatively. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (MRS) are potentially sensitive and quantitative methods of detection in examining changes of tissue microstructure and metabolism. In this study, We used both DTI and MRS to examine possible secondary damage of thalamus in patients with corona radiata infarction. Methods Twelve patients with unilateral corona radiata infarction underwent MR imaging including DTI and MRS at one week (W1), four weeks (W4), and twelve weeks (W12) after onset of stroke. Twelve age-matched controls were imaged. Mean diffusivity (MD), fractional anisotropy (FA), N-acetylaspartate (NAA), choline(Cho), and creatine(Cr) were measured in thalami. Results T1-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted, and T2-FLAIR imaging showed an infarct at unilateral corona radiate but no other lesion in each patient brain. In patients, MD was significantly increased at W12, compared to W1 and W4 (all P< 0.05). NAA was significantly decreased at W4 compared to W1, and at W12 compared to W4 (all P< 0.05) in the ipsilateral thalamus. There was no significant change in FA, Cho, or Cr in the ipsilateral thalamus from W1 to W12. Spearman's rank correlation analysis revealed a significant negative correlation between MD and the peak area of NAA, Cho, and Cr at W1, W4, and W12 and a significant positive correlation of FA with NAA at W1. Conclusions These findings indicate that DTI and MRS can detect the early changes indicating secondary damage in the ipsilateral thalamus after unilateral corona radiata infarction. MRS may reveal the progressive course of damage in the ipsilateral thalamus over time. PMID:21542942

Functional asymmetry of left and right avian piriform cortex in homing pigeons' navigation.

PubMed

Gagliardo, Anna; Odetti, Francesca; Ioalè, Paolo; Pecchia, Tommaso; Vallortigara, Giorgio

2005-07-01

It has been shown that homing pigeons rely on olfactory cues to navigate over unfamiliar areas and that any kind of olfactory impairment produces a dramatic reduction of navigational performance from unfamiliar sites. The avian piriform cortex is the main projection field of olfactory bulbs and it is supposed to process olfactory information; not surprisingly bilateral lesions to this telencephalic region disrupt homing pigeon navigation. In the present study, we attempted to assess whether the left and right piriform cortex are differentially involved in the use of the olfactory navigational map. Therefore, we released from unfamiliar locations pigeons subjected, when adult, to unilateral ablation of the piriform cortex. After being released, the pigeons lesioned to the right piriform cortex orientated similarly to the intact controls. On the contrary, the left lesioned birds were significantly more scattered than controls, showing a crucial role of the left piriform cortex in processing the olfactory cues needed for determining the direction of displacement. However, both lesioned groups were significantly slower than controls in flying back to the home loft, showing that the integrity of both sides of the piriform cortex is necessary to accomplish the whole homing process.

Does linguistic input play the same role in language learning for children with and without early brain injury?

PubMed

Rowe, Meredith L; Levine, Susan C; Fisher, Joan A; Goldin-Meadow, Susan

2009-01-01

Children with unilateral pre- or perinatal brain injury (BI) show remarkable plasticity for language learning. Previous work highlights the important role that lesion characteristics play in explaining individual variation in plasticity in the language development of children with BI. The current study examines whether the linguistic input that children with BI receive from their caregivers also contributes to this early plasticity, and whether linguistic input plays a similar role in children with BI as it does in typically developing (TD) children. Growth in vocabulary and syntactic production is modeled for 80 children (53 TD, 27 BI) between 14 and 46 months. Findings indicate that caregiver input is an equally potent predictor of vocabulary growth in children with BI and in TD children. In contrast, input is a more potent predictor of syntactic growth for children with BI than for TD children. Controlling for input, lesion characteristics (lesion size, type, seizure history) also affect the language trajectories of children with BI. Thus, findings illustrate how both variability in the environment (linguistic input) and variability in the organism (lesion characteristics) work together to contribute to plasticity in language learning.

Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.

PubMed

Becker, Guillaume; Bahri, Mohamed Ali; Michel, Anne; Hustadt, Fabian; Garraux, Gaëtan; Luxen, André; Lemaire, Christian; Plenevaux, Alain

2017-05-01

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [ 18 F]fluoro-3,4-dihydroxyphenyl-L-alanine ([ 18 F]FDOPA) and 6-[ 18 F]fluoro-L-m-tyrosine ([ 18 F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [ 18 F]FMT and [ 18 F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol-O-methyl transferase inhibitor was also given before [ 18 F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [ 18 F]FMT and [ 18 F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant K c . However, only [ 18 F]FMT K c succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [ 18 F]FMT could be more sensitive, with respect of [ 18 F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo L-aromatic amino acid decarboxylase activity targeting in future investigations on progressive PD models. © 2017 International Society for Neurochemistry.

Analysis of lesions in patients with unilateral tactile agnosia using cytoarchitectonic probabilistic maps.

PubMed

Hömke, Lars; Amunts, Katrin; Bönig, Lutz; Fretz, Christian; Binkofski, Ferdinand; Zilles, Karl; Weder, Bruno

2009-05-01

We propose a novel methodical approach to lesion analyses involving high-resolution MR images in combination with probabilistic cytoarchitectonic maps. 3D-MR images of the whole brain and the manually segmented lesion mask are spatially normalized to the reference brain of a stereotaxic probabilistic cytoarchitectonic atlas using a multiscale registration algorithm based on an elastic model. The procedure is demonstrated in three patients suffering from aperceptive tactile agnosia of the right hand due to chronic infarction of the left parietal cortex. Patient 1 presents a lesion in areas of the postcentral sulcus, Patient 3 in areas of the superior parietal lobule and adjacent intraparietal sulcus, and Patient 2 lesions in both regions. On the basis of neurobehavioral data, we conjectured degradation of sequential elementary sensory information processing within the postcentral gyrus, impeding texture recognition in Patients 1 and 2, and disturbed kinaesthetic information processing in the posterior parietal lobe, causing degraded shape recognition in the patients 2 and 3. The involvement of Brodmann areas 4a, 4p, 3a, 3b, 1, 2, and areas IP1 and IP2 of the intraparietal sulcus was assessed in terms of the voxel overlap between the spatially transformed lesion masks and the 50%-isocontours of the cytoarchitectonic maps. The disruption of the critical cytoarchitectonic areas and the impaired subfunctions, texture and shape recognition, relate as conjectured above. We conclude that the proposed method represents a promising approach to hypothesis-driven lesion analyses, yielding lesion-function correlates based on a cytoarchitectonic model. Finally, the lesion-function correlates are validated by functional imaging reference data. (c) 2008 Wiley-Liss, Inc.

Common Avian Infection Plagued the Tyrant Dinosaurs

PubMed Central

Wolff, Ewan D. S.; Salisbury, Steven W.; Horner, John R.; Varricchio, David J.

2009-01-01

Background Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name ‘Sue’) has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids. Methodology/Principal Findings We conducted an extensive survey of tyrannosaurid specimens and identified ten individuals with full-thickness erosive lesions. These lesions were described, measured and photographed for comparison with one another. We also conducted an extensive survey of related archosaurs for similar lesions. We show here that these lesions are consistent with those caused by an avian parasitic infection called trichomonosis, which causes similar abnormalities on the mandible of modern birds, in particular raptors. Conclusions/Significance This finding represents the first evidence for the ancient evolutionary origin of an avian transmissible disease in non-avian theropod dinosaurs. It also provides a valuable insight into the palaeobiology of these now extinct animals. Based on the frequency with which these lesions occur, we hypothesize that tyrannosaurids were commonly infected by a Trichomonas gallinae-like protozoan. For tyrannosaurid populations, the only non-avian dinosaur group that show trichomonosis-type lesions, it is likely that the disease became endemic and spread as a result of antagonistic intraspecific behavior, consumption of prey infected by a Trichomonas gallinae-like protozoan and possibly even cannibalism. The severity of trichomonosis-related lesions in specimens such as Tyrannosaurus rex FMNH PR2081 and Tyrannosaurus rex MOR 980, strongly suggests that these animals died as a direct result of this disease, mostly likely through starvation. PMID:19789646

[Proven and innovative operative techniques for reanimation of the paralyzed face].

PubMed

Frey, M; Michaelidou, M; Tzou, C-H J; Hold, A; Pona, I; Placheta, E

2010-04-01

This overview on the currently most effective reconstructive techniques for reanimation of the unilaterally or bilaterally paralysed face includes all important techniques of neuromuscular reconstruction as well as of supplementary static procedures, which contribute significantly to the efficiency and quality of the functional overall result. Attention is paid to the best indications at the best time since onset of the facial palsy, depending on the age of the patient, the cause of the lesion, and the compliance of the patient for a long-lasting and complex rehabilitation programme. Immediate neuromuscular reconstruction of mimic function is favourable by nerve suture or nerve grafting of the facial nerve, or by using the contralateral healthy facial nerve via cross-face nerve grafting as long as the time since onset of the irreversible palsy is short enough that the paralysed mimic muscles can still be reinnervated. For the most frequent indication, the unilateral irreversible and complete palsy, a three-stage concept is described including cross-face nerve grafting, free functional gracilis muscle transplantation, and several supplementary procedures. In patients with limited life expectancy, transposition of the masseteric muscles is favoured. Bilateral facial palsy is treated by bilateral free gracilis muscle transplantation with the masseteric nerve branches for motor reinnervation. Functional upgrading in incomplete lesions is achieved by cross-face nerve grafting with distal end-to-side neurorrhaphy or by functional muscle transplantation with ipsilateral facial nerve supply. (c) Georg Thieme Verlag KG Stuttgart-New York.

Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair.

PubMed

Vivekanantham, Sayinthen; Shah, Savan; Dewji, Rizwan; Dewji, Abbas; Khatri, Chetan; Ologunde, Rele

2015-01-01

Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

Exploratory study on the methodology of fast imaging of unilateral stroke lesions by electrical impedance asymmetry in human heads.

PubMed

Ma, Jieshi; Xu, Canhua; Dai, Meng; You, Fusheng; Shi, Xuetao; Dong, Xiuzhen; Fu, Feng

2014-01-01

Stroke has a high mortality and disability rate and should be rapidly diagnosed to improve prognosis. Diagnosing stroke is not a problem for hospitals with CT, MRI, and other imaging devices but is difficult for community hospitals without these devices. Based on the mechanism that the electrical impedance of the two hemispheres of a normal human head is basically symmetrical and a stroke can alter this symmetry, a fast electrical impedance imaging method called symmetrical electrical impedance tomography (SEIT) is proposed. In this technique, electrical impedance tomography (EIT) data measured from the undamaged craniocerebral hemisphere (CCH) is regarded as reference data for the remaining EIT data measured from the other CCH for difference imaging to identify the differences in resistivity distribution between the two CCHs. The results of SEIT imaging based on simulation data from the 2D human head finite element model and that from the physical phantom of human head verified this method in detection of unilateral stroke.

Exploratory Study on the Methodology of Fast Imaging of Unilateral Stroke Lesions by Electrical Impedance Asymmetry in Human Heads

PubMed Central

Xu, Canhua; Dai, Meng; You, Fusheng; Shi, Xuetao

2014-01-01

Stroke has a high mortality and disability rate and should be rapidly diagnosed to improve prognosis. Diagnosing stroke is not a problem for hospitals with CT, MRI, and other imaging devices but is difficult for community hospitals without these devices. Based on the mechanism that the electrical impedance of the two hemispheres of a normal human head is basically symmetrical and a stroke can alter this symmetry, a fast electrical impedance imaging method called symmetrical electrical impedance tomography (SEIT) is proposed. In this technique, electrical impedance tomography (EIT) data measured from the undamaged craniocerebral hemisphere (CCH) is regarded as reference data for the remaining EIT data measured from the other CCH for difference imaging to identify the differences in resistivity distribution between the two CCHs. The results of SEIT imaging based on simulation data from the 2D human head finite element model and that from the physical phantom of human head verified this method in detection of unilateral stroke. PMID:25006594

Stress reactions involving the pars interarticularis in young athletes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, D.W.; Wiltse, L.L.; Dingeman, R.D.

A stress reaction involving the pars interarticularis of the lumbar spine was confirmed in seven young athletes with a positive technetium pyrophosphate bone scan. No pars defects were detectable on their lumbosacral roentgenograms, which included oblique views. The return to normal levels of radioactive uptake on repeat bone scans correlated closely with their clinical course. If the bony reaction is recognized early, it may heal at a subroentgenographic level and prevent the development of lumbar spondylolysis. These early lesions usually show unilateral increased uptake at one lumbar level on the bone scan and, initially, the athlete localizes the pain tomore » the corresponding unilateral lumbar paraspinous area. The ''one-legged hyperextension test'' is positive on the ipsilateral side and aggravates the pain. Treatment consists of avoiding the aggravating activities and resting. The average time for return to pain-free competition was 7.3 months. These developing defects may be the source of considerable prolonged disability in the young athlete, particularly if undiagnosed and untreated.« less

Unilateral external and internal ophthalmoplegia caused by intracranial meningioma in a dog.

PubMed

Larocca, R.D.

2000-01-01

Unilateral internal and external ophthalmoplegia caused by an intracranial meningioma occurred in a 15-year-old Belgian Sheepdog. The dog initially presented with ventro-lateral strabismus of the left eye, and ptosis of the left upper eyelid. Anisocoria was present with the left pupil fixed and dilated. Both eyes were visual. Neuro-ophthalmic evaluation revealed a lesion located in the left oculomotor nerve. Pharmacological testing with dilute pilocarpine (0.1% in artificial tears) revealed evidence of parasympathetic denervation of the left eye. Further evaluation via magnetic resonance imaging (MRI) revealed a well-defined mass to the left of midline and lateral to the sella turcica. An attempt was made to excise/debulk the mass due to worsening conditions and the dog died the following day. Necropsy revealed a mass of randomly arranged bundles and streams of spindle cells. Immunohistochemistry demonstrated a strong avidity for vimentin and a negative response for S-100 protein. These findings suggest a diagnosis of meningioma.

Thalamic Hemorrhagic Stroke in the Term Newborn: A Specific Neonatal Syndrome With Non-uniform Outcome.

PubMed

Merlini, Laura; Hanquinet, Sylviane; Fluss, Joel

2017-07-01

Neonatal thalamic hemorrhagic stroke is related to cerebral sinus venous thrombosis and associated with neurological sequelae. Predicting factors are however lacking. Clinical and radiological findings at onset and on follow-up of 5 neonates with thalamic hemorrhage stroke are described. All neonates presented with abrupt lethargy, ophistotonos, irritability and/or seizures. The thalamic hemorrhagic stroke was most often unilateral (4/5), involving the posterior/entire thalamus in 3 cases and the anterior thalamus in 2. Cerebral venous thrombosis was identified in a single patient. At follow-up, children with unilateral anterior thalamic hemorrhagic stroke demonstrated thalamic atrophy without neurological symptoms, whereas children whose thalamus lesion was extensive exhibit a porencephalic cavity and presented with late-onset epilepsy. Although deep cerebral venous thrombosis is probably the cause of neonatal thalamic hemorrhagic stroke, its radiological evidence is challenging. Outcome seems dependent of the size and location of thalamic hemorrhagic stroke. Epilepsy is a frequent morbidity after thalamic hemorrhagic stroke.

Radiofrequency sensory ablation as a treatment for symptomatic unilateral lumbosacral junction pseudarticulation (Bertolotti's syndrome): a case report.

PubMed

Burnham, Robert

2010-06-01

Describe the clinical presentation, diagnostic evaluation, and successful treatment of a case of symptomatic unilateral lumbosacral junction pseudarticulation using a novel radiofrequency nerve ablation technique. A 56-year-old female patient who had suffered with low back and right upper buttock pain for 16 years experienced incomplete relief with L4/5 facet joint radiofrequency ablation. She was found to have an elongated right L5 transverse process that articulated with the sacral ala (Bertolotti's syndrome). Fluoroscopically guided local anesthetic/corticosteroid injection into the pseudarthrosis eliminated her residual right buttock pain for the duration of the local anesthetic only. Complete pain relief was achieved by injecting local anesthetic circumferentially around the posterior pseudarthrosis articular margin. Accordingly, bipolar radiofrequency strip thermal lesions were created at the same locations. Complete pain relief and full restoration of function was achieved for 16 months postprocedure. This case report describes a novel radiofrequency technique for treating symptomatic lumbosacral junction pseudarticulation that warrants further evaluation.

Alteration of Daily and Circadian Rhythms following Dopamine Depletion in MPTP Treated Non-Human Primates

PubMed Central

Fifel, Karim; Vezoli, Julien; Dzahini, Kwamivi; Claustrat, Bruno; Leviel, Vincent; Kennedy, Henry; Procyk, Emmanuel; Dkhissi-Benyahya, Ouria; Gronfier, Claude; Cooper, Howard M.

2014-01-01

Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([11C]-PE2I) and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed. PMID:24465981

Chronic vocal cord palsy in Thuringia, Germany: a population-based study on epidemiology and outcome.

PubMed

Djugai, S; Boeger, D; Buentzel, J; Esser, D; Hoffmann, K; Jecker, P; Mueller, A; Radtke, G; Bohne, S; Finkensieper, M; Volk, G F; Guntinas-Lichius, O

2014-02-01

Although surgical treatment of patients with chronic vocal cord palsy (VCP) is an integral part of clinical routine of otorhinolaryngologists, there is nearly no population-based data published on incidence and efficiency of this surgery country-wide or nation-wide. 1430 patients with chronic VCP were treated in a department of otorhinolaryngology between 2005 and 2010 in Thuringia, Germany. VCP was unilateral and bilateral in 63 and 18%, respectively. The affected side was not documented in 20%. Iatrogenic lesions of the recurrent nerve (42%) and neoplastic infiltration (27%) were the leading etiologies. 192 patients (13%) received surgical treatment. 31% of patient needed more than one surgery. The rate of surgeries was higher for bilateral VCP (p < 0.0001). Vocal cord augmentation was the most frequent surgery for unilateral VCP and posterior cordectomy for bilateral VCP. The complication rate was high (16%), but not different between unilateral and bilateral VCP (p = 0.108). The risk for tracheostomy was higher in the bilateral VCP group (p < 0.0001). Voice improvement was better after treatment of unilateral VCP (p < 0.0001). Breathing improvement was more frequent after bilateral VCP (p = 0.028). Dysphagia did not improve significantly. The rate of better voice, breathing, and swallowing function was higher in patients treated surgically than without surgery (all p < 0.0001). The rate of patients admitted for treatment of vocal fold palsy was 9.9/100,000 habitants. The surgical rate of VCP was 1.38/100,000 habitants. This population-based analysis shows that surgery for VCP is performed with higher incidence than expected effectively, but with relevant risks in daily routine of otorhinolaryngologists.

Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke

PubMed Central

Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Fayyaz, Tabbassum; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

2014-01-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into three groups: vagus nerve stimulation during rehab, vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), pre-lesion training, post-lesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed one week of recovery before post-lesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All seventeen trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to pre-lesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to pre-lesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared to rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

Three-dimensional vascular mapping of the breast by using contrast-enhanced MRI: association of unilateral increased vascularity with ipsilateral breast cancer.

PubMed

Orgüç, Şebnem; Başara, Işıl; Coşkun, Teoman; Pekindil, Gökhan

2012-01-01

We aimed to retrospectively compare three-dimensional vascular maps of both breasts obtained by dynamic magnetic resonance imaging (MRI) and determine the association of one-sided vascular prominence with ipsilateral breast cancer. MRI was performed using gadolinium in 194 cases. Two readers scored vascular density using maximum intensity projections (MIPs). Dynamic fat-saturated T1-weighted gradientecho MIPs were acquired. Two readers evaluated the MIPs, and vessels greater than 2 mm in diameter and longer than 3 cm were counted. The difference in vessel numbers detected in the two breasts determined the score. A total of 54 patients had malignant lesions (prevalence, 28%), including invasive ductal carcinoma (n=40), invasive mixed ductal-lobular carcinoma (n=5), invasive lobular carcinoma (n=3), ductal carcinoma in situ (n=3), mucinous carcinoma (n=1), medullary carcinoma (n=1), and leukemic metastasis (n=1). In 62 patients, there were benign lesions (fibroadenomas, fibrocysts), and four patients had inflammation (granulomatous mastitis in two patients, breast tuberculosis in two patients). There were 78 normal cases. When a difference of at least two vessels was scored as vascular asymmetry, the sensitivity, specificity, positive likelihood ratio (+LR), and negative (-LR) of unilaterally increased vascularity associated with ipsilateral malignancy were 69%, 92%, 8.72, and 0.34, respectively. When four infection and three post-operative cases with vascular asymmetry were excluded; prevalence, specificity, and +LR increased to 29%, 97%, and 22.8, respectively, with the same sensitivity and -LR. Differences in mean vascularity scores were evaluated with regard to tumor size. T1 and T2 tumors were not significantly different from each other. The mean score of T3 tumors differed significantly from T1 and T2 tumors. MRI vascular mapping is an effective method for determining breast tissue vascularization. Ipsilateral increased vascularity was commonly associated with malignant breast lesions.

Case Report: Nodule Development From Subcapsular Aldosterone-Producing Cell Clusters Causes Hyperaldosteronism.

PubMed

Nishimoto, Koshiro; Seki, Tsugio; Kurihara, Isao; Yokota, Kenichi; Omura, Masao; Nishikawa, Tetsuo; Shibata, Hirotaka; Kosaka, Takeo; Oya, Mototsugu; Suematsu, Makoto; Mukai, Kuniaki

2016-01-01

We previously reported that the human adrenal cortex remodels to form subcapsular aldosterone-producing cell clusters (APCCs). Some APCCs were recently found to carry aldosterone-producing adenoma (APA)-associated somatic mutations in ion channel/pump genes, which implied that APCCs produce aldosterone autonomously and are an origin of APA. However, there has been no report describing an APCC-to-APA transitional lesion. A histological examination revealed unilateral multiple adrenocortical micronodules in the adrenals of two patients with primary aldosteronism (PA). Based on immunohistochemistry for aldosterone synthase, some of the micronodules were identified as possible APCC-to-APA transitional lesions (pAATLs; a tentative term used in this manuscript), which consisted of a subcapsular APCC-like portion and an inner micro-APA-like (mAPA-like) portion without an apparent histological border. Genomic DNA samples prepared from pAATL histological sections were analyzed by next-generation sequencing for the known APA-associated mutations. The mAPA-like portions from two of the three large pAATLs examined harbored mutations (KCNJ5 [p.G151R] in pAATL 3 and ATP1A1 [p.L337M] in pAATL 7), whereas their corresponding APCC-like portions did not, suggesting their role in the formation of mAPA. Another lesion carried novel mutations in ATP1A1 (p.Ile322_Ile325del and p.Ile327Ser) in both the mAPA-like and APCC-like portions, thereby supporting these portions having a clonal origin. A novel aldosterone-producing pathology, pAATL that causes unilateral PA, was detected in the adrenals of two patients. Next-generation sequencing analyses of the large pAATLs suggested that the introduction of APA-associated mutations in the ion channel/pump genes may be involved in the development of mAPA from existing APCCs.

Outcomes of laparoscopic adrenalectomy. Clinical experience with 68 patients.

PubMed

Pugliese, Raffaele; Boniardi, Marco; Sansonna, Fabio; Maggioni, Dario; De Carli, Stefano; Costanzi, Andrea; Scandroglio, Ildo; Ferrari, Giovanni Carlo; Di Lernia, Stefano; Magistro, Carmelo; Loli, Paola; Grossrubatscher, Erika

2008-07-01

The aim of this study was to analyze feasibility and outcomes of laparoscopic adrenalectomy (LA). Pathology, size and bilateral site of lesions were considered. Between December 1998 and May 2007 in our institution a total of 68 patients of mean age of 53 years underwent unilateral (n=57) or bilateral (n=11) LA. Adrenal masses averaged 5.4cm in size (range 1.2-13cm) and 56.7g in weight (range 10-265) including 71 benign and 8 malignant lesions. A total of 79 adrenal glands were resected, 44 right sided and 35 left sided. Removal was complete in 77 cases and partial (sparing adrenalectomy) in 1 patient affected by bilateral pheochomocytoma. Three left adrenalectomies for pheochromocytoma were robot-assisted. The transperitoneal lateral approach was preferred and the posterior retroperitoneal approach was adopted in 5 patients. The mean duration of surgery for each LA was 138+/-90min and 3.8 trocar were used on average (range 3-6). Conversion was needed in 3 cases owing to difficult dissection of large masses. Estimated mean blood loss for each LA was 95+/-30ml and it was greater for bilateral LA. Mortality was nil and morbidity was 5.8%. The average length of hospital stay (LOS) in surgical unit was 4+/-2.4 days (range 2-8). Patients affected by hormone secreting or bilateral lesions, by unilateral or bilateral pheochromocytoma and by bilateral Cushing's disease were transferred to the endocrinological ward so that their overall hospital stay was prolonged to 9+/-2.8 days on average (range 7-17). Mean duration of follow-up of patients was 38 months (range 2-100) and demonstrated acceptable endocrine results. Three primary cortical carcinomas were discovered as chance findings on histologic examination. While long-term results after LA for cortical carcinomas were poor and LA is not recommended in such cases, long-term results after LA for adrenal metastases were encouraging.

Functional lesional neurosurgery for tremor-a protocol for a systematic review and meta-analysis.

PubMed

Schreglmann, Sebastian R; Krauss, Joachim K; Chang, Jin Woo; Bhatia, Kailash P; Kägi, Georg

2017-05-09

The recent introduction of incision-less lesional neurosurgery using Gamma Knife and MRI-guided focused ultrasound has revived interest in lesional treatment options for tremor disorders. Preliminary literature researches reveal that the consistency of treatment effects after lesional neurosurgery for tremor has not formally been assessed yet. Similarly, the efficacy of different targets for lesional treatment and incidence of persistent side effects of lesional neurosurgical interventions has not been comprehensively assessed. This work therefore aims to describe a suitable process how to review the existing literature on efficacy and persistent side effects of lesional neurosurgical treatment for tremor due to Parkinson's disease, essential tremor, multiple sclerosis and midbrain/rubral tremor. We will search electronic databases (Medline, Cochrane) and reference lists of included articles for studies reporting lesional interventions for tremor in cohorts homogeneous for tremor aetiology and intervention (technique and target). We will include cohorts with a minimum number of five subjects and follow-up of 2 months. One investigator will perform the initial literature search and two investigators then independently decide which references to include for final efficacy and safety analysis. After settling of disagreement, data will be extracted from articles using a standardised template. We will perform a random-effect meta-analysis calculating standardised mean differences (Hedge's g) for comparison in Forest plots and subgroup analysis after assessment of heterogeneity using I 2 statistics. This study will summarise the available evidence on the efficacy of lesional interventions for the most frequent tremor disorders, as well as for the incidence rate of persisting side effects after unilateral lesional treatment. This data will be useful to guide future work on incision-less lesional interventions for tremor. This study has been registered with the PROSPERO database (no. CRD42016048049). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat.

PubMed

Kauppila, T; Kontinen, V K; Pertovaara, A

1998-01-01

Effect of weight bearing of the hindlimbs on the assessment of mechanically-induced hindlimb withdrawal threshold was determined in intact rats and in rats with various pathophysiological conditions causing allodynia or hyperalgesia. Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments to the plantar or the dorsal surface of the paw. During testing the rat was either in a restraint tube with hindlimbs hanging semi-extended without weight bearing or it was standing on a metal grid (bearing its own weight). In intact rats, the withdrawal thresholds were significantly lower when the stimulus site was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds were significantly lower when the hindlimbs were not bearing weight. Following carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve cut there was a marked threshold decrease to test stimuli applied to plantar or dorsal paw, respectively, ipsilateral to the pathological condition in standing rats. However, when the hindlimbs were not weight bearing the unilateral threshold decrease was markedly attenuated (carrageenan-treated rats) or completely abolished (tibial cut). In contrast, in rats with a unilateral spinal nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly significant independent of the weight bearing of the hindlimbs. The results indicate that weight bearing of hindlimbs is an important confounding factor in the assessment of tactile allodynia in rats.

Increased expression of glutamic acid decarboxylase mRNA in rat substantia nigra after an ibotenic acid lesion in the caudate-putamen.

PubMed

Lindefors, N; Brené, S; Persson, H

1990-04-01

In situ hybridization histochemistry and RNA blots were used to study expression of glutamic acid decarboxylase (GAD) mRNA in rat caudate-nucleus and substantia nigra. In situ hybridization combined with computerized image analysis revealed that in the intact substantia nigra reticulata the cross-section area of GAD mRNA positive neurons were 25% larger in the dorsolateral part as compared with the ventromedial part. A unilateral ibotenic acid injection in caudate-putamen lesioned neurons, some of which project to the ipsilateral substantia nigra. An increased level of GAD mRNA was observed in substantia nigra ipsilateral to the lesion. Computerized image analysis of sections from in situ hybridization revealed an increase in the number of silver grains over GAD mRNA positive neurons in the dorsolateral substantia nigra reticulata ipsilateral to the lesion. However, no change was observed in the ventromedial part suggesting that GAD mRNA expression in this part of the nigra is less sensitive to inhibition by caudate-putamen afferents. In agreement with in situ experiments, RNA blots showed a 2-fold increased level of GAD mRNA in substantia nigra ipsilateral to the lesion. The increased GAD mRNA expression in the deafferented substantia nigra suggests a disinhibition of nigral GABA neurons, resulting in an increased utilization of GABA in these substantia nigra neurons.

The posterior parietal cortex in recognition memory: a neuropsychological study.

PubMed

Haramati, Sharon; Soroker, Nachum; Dudai, Yadin; Levy, Daniel A

2008-01-01

Several recent functional neuroimaging studies have reported robust bilateral activation (L>R) in lateral posterior parietal cortex and precuneus during recognition memory retrieval tasks. It has not yet been determined what cognitive processes are represented by those activations. In order to examine whether parietal lobe-based processes are necessary for basic episodic recognition abilities, we tested a group of 17 first-incident CVA patients whose cortical damage included (but was not limited to) extensive unilateral posterior parietal lesions. These patients performed a series of tasks that yielded parietal activations in previous fMRI studies: yes/no recognition judgments on visual words and on colored object pictures and identifiable environmental sounds. We found that patients with left hemisphere lesions were not impaired compared to controls in any of the tasks. Patients with right hemisphere lesions were not significantly impaired in memory for visual words, but were impaired in recognition of object pictures and sounds. Two lesion--behavior analyses--area-based correlations and voxel-based lesion symptom mapping (VLSM)---indicate that these impairments resulted from extra-parietal damage, specifically to frontal and lateral temporal areas. These findings suggest that extensive parietal damage does not impair recognition performance. We suggest that parietal activations recorded during recognition memory tasks might reflect peri-retrieval processes, such as the storage of retrieved memoranda in a working memory buffer for further cognitive processing.

Skeletal abnormalities in humpback whales Megaptera novaeangliae stranded in the Brazilian breeding ground.

PubMed

Groch, Kátia R; Marcondes, Milton C C; Colosio, Adriana C; Catão-Dias, José Luiz

2012-11-08

Skeletal tissues of 49 humpback whales Megaptera novaeangliae that stranded between 2002 and 2011 along the Abrolhos Bank seashore and its adjacent waters in Brazil were studied. Twelve (24.5%) animals presented pathological changes in one or more bones. Degenerative changes and developmental malformations were most frequent (10.2% each), followed by inflammatory/infectious and traumatic lesions (8.2% each). Infectious diseases led to severe lesions of the caudal vertebrae of 2 whales. In one of these individuals, the lesions involved 6 caudal vertebrae, leading to ankylosis of 3 vertebrae. Degenerative changes were observed in the vertebral columns of 3 animals, involving the joints of 13 ribs of 1 individual, and in the humerus of 1 whale. Traumatic lesions, such as osseous callus in the ribs, were observed in 4 animals. In 1 whale, the rib showed severe osteomyelitis, possibly resulting from the infection of multiple fractures. Developmental abnormalities such as spina bifida on 3 cervical vertebrae of 1 whale, fusion of spinal processes on thoracic vertebrae of 1 individual and fusion of the first 2 ribs unilaterally or bilaterally in 4 animals were found. Chronic infectious conditions found in the axial skeleton may have restrained spinal mobility and had detrimental effects on the general health of the animals, contributing to stranding and death. To our knowledge, this is the first systematic study on skeletal lesions in stranded humpback whales.

Cortical Auditory Deafferentation Induces Long-Term Plasticity in the Inferior Colliculus of Adult Rats: Microarray and qPCR Analysis

PubMed Central

Clarkson, Cheryl; Herrero-Turrión, M. Javier; Merchán, Miguel A.

2012-01-01

The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs. PMID:23233834

Lesion site patterns in severe, nonverbal aphasia to predict outcome with a computer-assisted treatment program.

PubMed

Naeser, M A; Baker, E H; Palumbo, C L; Nicholas, M; Alexander, M P; Samaraweera, R; Prete, M N; Hodge, S M; Weissman, T

1998-11-01

To test whether lesion site patterns in patients with chronic, severe aphasia who have no meaningful spontaneous speech are predictive of outcome following treatment with a nonverbal, icon-based computer-assisted visual communication (C-ViC) program. Retrospective study in which computed tomographic scans performed 3 months after onset of stroke and aphasia test scores obtained before C-ViC therapy were reviewed for patients after receiving C-ViC treatment. A neurology department and speech pathology service of a Department of Veterans Affairs medical center and a university aphasia research center. Seventeen patients with stroke and severe aphasia who began treatment with C-ViC from 3 months to 10 years after onset of stroke. Level of ability to use C-ViC on a personal computer to communicate. All patients with bilateral lesions failed to learn C-ViC. For patients with unilateral left hemisphere lesion sites, statistical analyses accurately discriminated between those who could initiate communication with C-ViC from those who were only able to answer directed questions. The critical lesion areas involved temporal lobe structures (Wernicke cortical area and the subcortical temporal isthmus), supraventricular frontal lobe structures (supplementary motor area or cingulate gyrus 24), and the subcortical medial subcallosal fasciculus, deep to the Broca area. Specific lesion sites were also identified for appropriate candidacy for C-ViC. Lesion site patterns on computed tomographic scans are helpful to define candidacy for C-ViC training, and to predict outcome level. A practical method is presented for clinical application of these lesion site results in combination with aphasia test scores.

Central nervous system integration of sensorimotor signals in oral and pharyngeal structures: oropharyngeal kinematics response to recurrent laryngeal nerve lesion.

PubMed

Gould, Francois D H; Ohlemacher, Jocelyn; Lammers, Andrew R; Gross, Andrew; Ballester, Ashley; Fraley, Luke; German, Rebecca Z

2016-03-01

Safe, efficient liquid feeding in infant mammals requires the central coordination of oropharyngeal structures innervated by multiple cranial and spinal nerves. The importance of laryngeal sensation and central sensorimotor integration in this system is poorly understood. Recurrent laryngeal nerve lesion (RLN) results in increased aspiration, though the mechanism for this is unclear. This study aimed to determine the effect of unilateral RLN lesion on the motor coordination of infant liquid feeding. We hypothesized that 1) RLN lesion results in modified swallow kinematics, 2) postlesion oropharyngeal kinematics of unsafe swallows differ from those of safe swallows, and 3) nonswallowing phases of the feeding cycle show changed kinematics postlesion. We implanted radio opaque markers in infant pigs and filmed them pre- and postlesion with high-speed videofluoroscopy. Markers locations were digitized, and swallows were assessed for airway protection. RLN lesion resulted in modified kinematics of the tongue relative to the epiglottis in safe swallows. In lesioned animals, safe swallow kinematics differed from unsafe swallows. Unsafe swallow postlesion kinematics resembled prelesion safe swallows. The movement of the tongue was reduced in oral transport postlesion. Between different regions of the tongue, response to lesion was similar, and relative timing within the tongue was unchanged. RLN lesion has a pervasive effect on infant feeding kinematics, related to the efficiency of airway protection. The timing of tongue and hyolaryngeal kinematics in swallows is a crucial locus for swallow disruption. Laryngeal sensation is essential for the central coordination in feeding of oropharyngeal structures receiving motor inputs from different cranial nerves. Copyright © 2016 the American Physiological Society.

Neuroprotection and Functional Recovery Associated with Decreased Microglial Activation Following Selective Activation of mGluR2/3 Receptors in a Rodent Model of Parkinson's Disease

PubMed Central

Chan, Hugh; Paur, Helen; Vernon, Anthony C.; Zabarsky, Virginia; Datla, Krishna P.; Croucher, Martin J.; Dexter, David T.

2010-01-01

Clinical trials have demonstrated positive proof of efficacy of dual metabotropic glutamate receptor 2/3 (mGluR2/3) agonists in both anxiety and schizophrenia. Importantly, evidence suggests that these drugs may also be neuroprotective against glutamate excitotoxicity, implicated in the pathogenesis of Parkinson's disease (PD). However, whether this neuroprotection also translates into functional recovery is unclear. In the current study, we examined the neuroprotective efficacy of the dual mGluR2/3 agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), and whether this is accompanied by behavioral recovery in a rodent 6-hydroxydopamine (6-OHDA) model of PD. We now report that delayed post lesion treatment with 2R,4R-APDC (10 nmol), results in robust neuroprotection of the nigrostriatal system, which translated into functional recovery as measured by improved forelimb use asymmetry and reduced (+)-amphetamine-induced rotation compared to vehicle treated animals. Interestingly, these beneficial effects were associated with a decrease in microglial markers in the SNc, which may suggest an antiinflammatory action of this drug. PMID:20948891

Different subcellular localization of neurotensin-receptor and neurotensin-acceptor sites in the rat brain dopaminergic system.

PubMed

Schotte, A; Rostène, W; Laduron, P M

1988-04-01

The subcellular localization of neurotensin-receptor sites (NT2 sites) and neurotensin-acceptor sites (NT1 sites) was studied in rat caudate-putamen by isopycnic centrifugation in sucrose density gradients. [3H]Neurotensin binding to NT2 sites occurred as a major peak at higher sucrose densities, colocalized with [3H]dopamine uptake, and as a small peak at a lower density; whereas binding to NT1 sites occurred as a single large peak at an intermediate density. 6-Hydroxydopamine lesions of the median forebrain bundle resulted in a total loss of NT2 sites in the caudate-putamen but did not affect NT2 sites in the nucleus accumbens and the olfactory tubercle. NT1 sites were not affected. Kainic acid injections into the rat caudate-putamen led to a partial decrease of NT1 sites in this region 5 days later. After a few weeks they returned to normal. Therefore NT2 sites are probably associated with presynaptic nigrostriatal dopaminergic terminals in the caudate-putamen but not in the nucleus accumbens and the olfactory tubercle. A possible association of NT1 sites with glial cells is suggested.

A New Variant of Connective Tissue Nevus with Elastorrhexis and Predilection for the Upper Chest.

PubMed

Chu, Derek H; Goldbach, Hayley; Wanat, Karolyn A; Rubin, Adam I; Yan, Albert C; Treat, James R

2015-01-01

Localized changes in cutaneous elastic tissue often manifest with flesh-colored, hypopigmented, or yellow papules, plaques, and nodules. We present five children with clinically similar cobblestone plaques composed of multiple hypopigmented, nonfollicular, pinpoint papules located unilaterally over the upper chest. All lesions first appeared at birth or during early infancy. No associated extracutaneous abnormalities have been identified. Histopathology was remarkable for many, thick elastic fibers with elastorrhexis. We believe that these cases represent a distinct and unique variant of connective tissue nevi. © 2014 Wiley Periodicals, Inc.

Clinical image: MRI during migraine with aura

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNeal, A.C.

1996-03-01

Migraine refers to severe headaches that are usually unilateral, throbbing, and associated with nausea, vomiting, photophobia, and phonophobia. Migraine with aura (formerly called {open_quotes}classic migraine{close_quotes}) consists of the headache preceded or accompanied by neurological dysfunction. This dysfunction (aura) usually involves visual and sensory symptoms. The patient described herein experienced migraine with aura. MRI during and after the attack showed a reversible abnormality of the right posterior cerebral artery, with no parenchymal lesions. This appears to be the first report of abnormal MR vascular imaging during migraine with aura. 10 refs., 2 figs.

Evaluation of expert criteria for preoperative magnetic resonance imaging of newly diagnosed breast cancer.

PubMed

Behrendt, Carolyn E; Tumyan, Lusine; Gonser, Laura; Shaw, Sara L; Vora, Lalit; Paz, I Benjamin; Ellenhorn, Joshua D I; Yim, John H

2014-08-01

Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women (n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57-5.91 (p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genital herpes simplex virus infections: clinical manifestations, course, and complications.

PubMed

Corey, L; Adams, H G; Brown, Z A; Holmes, K K

1983-06-01

The clinical course and complications of 268 patients with first episodes and 362 with recurrent episodes of genital herpes infection were reviewed. Symptoms of genital herpes were more severe in women than in men. Primary first-episode genital herpes was accompanied by systemic symptoms (67%), local pain and itching (98%), dysuria (63%), and tender adenopathy (80%). Patients presented with several bilaterally distributed postular ulcerative lesions that lasted a mean of 19.0 days. Herpes simplex virus was isolated from the urethra, cervix, and pharynx of 82%, 88%, and 13% of women with first-episode primary genital herpes, and the urethra and pharynx of 28% and 7% of men. Complications included aseptic meningitis (8%), sacral autonomic nervous system dysfunction (2%), development of extragenital lesions (20%), and secondary yeast infections (11%). Recurrent episodes were characterized by small vesicular or ulcerative unilaterally distributed lesions that lasted a mean of 10.1 days. Systemic symptoms were uncommon and 25% of recurrent episodes were asymptomatic. The major concerns of patients were the frequency of recurrences and fear of transmitting infection to partners or infants.

Narrative discourse in children with early focal brain injury.

PubMed

Reilly, J S; Bates, E A; Marchman, V A

1998-02-15

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

Tyrosine - Effects on catecholamine release

NASA Technical Reports Server (NTRS)

Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

1988-01-01

Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

"Parkinson-dementia" diseases: a comparison by double tracer SPECT studies.

PubMed

Rossi, Carlo; Volterrani, Duccio; Nicoletti, Valentina; Manca, Gianpiero; Frosini, Daniela; Kiferle, Lorenzo; Unti, Elisa; De Feo, Paola; Bonuccelli, Ubaldo; Ceravolo, Roberto

2009-12-01

We performed 123I-FP-CIT/SPECT and ECD/SPECT in 30 patients with Parkinson's disease with dementia (PDD) and 30 patients with dementia with Lewy bodies (DLB) to evaluate whether presynaptic nigro-striatal function and/or cerebral perfusional pattern is different in these diseases. The striatal uptake of DAT tracer was statistically significantly lower in PDD and DLB with respect to control data (p < 0.0005), however no significant difference was found between PDD and DLB. Patients with PDD and DLB showed a significant reduction of rCBF (p < 0.001) in parieto-occipital and frontal areas, with respect to controls, but the comparison between the two groups did not result in any significant difference by SPM analysis. Finally no correlation was found between any regional perfusional changes and nigro-striatal dysfunction. We conclude that neither studies with 123I-FP-CIT nor ECD/SPECT were able to discriminate between DLB and PDD in vivo.

Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatt, M.H.; Snow, B.J.; Martin, W.R.

1991-06-01

The authors performed sequential positron emission tomography scans with 6-(18F)fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). They infer that the usual rate of lossmore » of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.« less

Cannabinoid–dopamine interactions in the physiology and physiopathology of the basal ganglia

PubMed Central

García, Concepción; Palomo‐Garo, Cristina; Gómez‐Gálvez, Yolanda

2015-01-01

Endocannabinoids and their receptors play a modulatory role in the control of dopamine transmission in the basal ganglia. However, this influence is generally indirect and exerted through the modulation of GABA and glutamate inputs received by nigrostriatal dopaminergic neurons, which lack cannabinoid CB1 receptors although they may produce endocannabinoids. Additional evidence suggests that CB2 receptors may be located in nigrostriatal dopaminergic neurons, and that certain eicosanoid‐related cannabinoids may directly activate TRPV1 receptors, which have been found in nigrostriatal dopaminergic neurons, thus allowing in both cases a direct regulation of dopamine transmission by specific cannabinoids. In addition, CB1 receptors form heteromers with dopaminergic receptors which provide another pathway to direct interactions between both systems, in this case at the postsynaptic level. Through these direct mechanisms or through indirect mechanisms involving GABA or glutamate neurons, cannabinoids may interact with dopaminergic transmission in the basal ganglia and this is likely to have important effects on dopamine‐related functions in these structures (i.e. control of movement) and, particularly, on different pathologies affecting these processes, in particular, Parkinson's disease, but also dyskinesia, dystonia and other pathological conditions. The present review will address the current literature supporting these cannabinoid–dopamine interactions at the basal ganglia, with emphasis on aspects dealing with the physiopathological consequences of these interactions. Linked Articles This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc PMID:26059564

Neuroprotective role of chrysin in attenuating loss of dopaminergic neurons and improving motor, learning and memory functions in rats.

PubMed

Ahmed, Muhammad Rashid; Shaikh, Masood Ahmed; Ul Haq, Syed Hafiz Imran; Nazir, Shakila

2018-01-01

Selective degeneration of dopaminergic neurons is the pathological hallmark of Parkinson disease (PD). Enhanced oxidative stress, lipid peroxidation and susceptibility of dopaminergic neurons to apoptotic cellular death are the leading pathogenetic mechanisms. Chrysin is an active flavonoid. Its neuroprotective effects have been reported. This study examined the neuroprotective effects of chrysin in ameliorating the dopaminergic neuronal degeneration and motor behavioral changes in rotenone model of PD. Thirty Sprague-Dawley rats were assigned into three groups: Control, rotenone-treated, and rotenone+chrysin treated groups. Rotenone was given at a dose of 3 mg/kg daily intraperitoneally, and chrysin was given at a dose of 50 mg/kg daily intraperitoneally for 4 weeks. Using five neurobehavioral assessment tests, evaluation was done weekly to record the motor behavioral changes. After 4 weeks, animals were sacrificed, brains were removed, and section from striatum and substantia nigra were stained using hematoxylin and eosin and cresyl violet stains. Immunohistochemical sections were also prepared using anti-tyrosine hydroxylase (TH) antibody. Rotenone-induced Parkinson like changes were evident from deteriorating motor behavior. These animals showed extensive loss of dopaminergic neurons, decreased immunoreactivity against anti-TH antibodies and number of TH positive dopaminergic neurons in the nigrostriatal region. Chrysin treated animals showed a significant reduction in motor behavioral changes, degeneration and loss of nigrostriatal dopaminergic neurons and increased immunoreactivity to anti-TH antibody. This study concludes that chrysin confers neuroprotection in rat model of PD. It attenuates the degeneration of the nigrostriatal dopaminergic neurons and motor behavioral abnormalities.

Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.

PubMed

Abdallah, Luna; Bonasera, Stephen J; Hopf, F Woodward; O'Dell, Laura; Giorgetti, Marco; Jongsma, Minke; Carra, Scott; Pierucci, Massimo; Di Giovanni, Giuseppe; Esposito, Ennio; Parsons, Loren H; Bonci, Antonello; Tecott, Laurence H

2009-06-24

The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT(2C)R) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT(2C)Rs produces marked alterations in the activity and functional output of this pathway. 5-HT(2C)R mutant mice displayed increased activity of substantia nigra pars compacta (SNc) dopaminergic neurons, elevated baseline extracellular dopamine concentrations in the dorsal striatum (DSt), alterations in grooming behavior, and enhanced sensitivity to the stereotypic behavioral effects of d-amphetamine and GBR 12909. These psychostimulant responses occurred in the absence of phenotypic differences in drug-induced extracellular dopamine concentration, suggesting a phenotypic alteration in behavioral responses to released dopamine. This was further suggested by enhanced behavioral responses of mutant mice to the D(1) receptor agonist SKF 81297. Differences in DSt D(1) or D(2) receptor expression were not found, nor were differences in medium spiny neuron firing patterns or intrinsic membrane properties following dopamine stimulation. We conclude that 5-HT(2C)Rs regulate nigrostriatal dopaminergic activity and function both at SNc dopaminergic neurons and at a locus downstream of the DSt.

Neurotrophic factors as a therapeutic target for Parkinson's disease.

PubMed

Evans, Jonathan R; Barker, Roger A

2008-04-01

The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered. In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data. Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised. NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.

Exposure to the Polybrominated Diphenyl Ether Mixture DE-71 Damages the Nigrostriatal Dopamine System: Role of Dopamine Handling in Neurotoxicity

PubMed Central

Bradner, Joshua M.; Suragh, Tiffany A.; Wilson, W. Wyatt; Lazo, Carlos R.; Stout, Kristen A.; Kim, Hye Mi; Wang, Min Z.; Walker, Douglas I.; Pennell, Kurt D.; Richardson, Jason R.; Miller, Gary W.; Caudle, W. Michael

2013-01-01

In the last several decades polybrominated diphenyl ethers (PBDEs) have replaced the previously banned polychlorinated biphenyls (PCBs) in multiple flame retardant utilities. As epidemiological and laboratory studies have suggested PCBs as a risk factor for Parkinson’s disease (PD), the similarities between PBDEs and PCBs suggest that PBDEs have the potential to be neurotoxic to the dopamine system. The purpose of this study was to evaluate the neurotoxic effects of the PBDE mixture, DE-71, on the nigrostriatal dopamine system and address the role of altered dopamine handling in mediating this neurotoxicity. Using an in vitro model system we found DE-71 effectively caused cell death in a dopaminergic cell line as well as reducing the number of TH+ neurons isolated from VMAT2 WT and LO animals. Assessment of DE-71 neurotoxicity in vivo demonstrated significant deposition of PBDE congeners in the brains of mice, leading to reductions in striatal dopamine and dopamine handling, as well as reductions in the striatal dopamine transporter (DAT) and VMAT2. Additionally, DE-71 elicited a significant locomotor deficit in the VMAT2 WT and LO mice. However, no change was seen in TH expression in dopamine terminal or in the number of dopamine neurons in the substantia nigra pars compacta (SNpc). To date, these are the first data to demonstrate that exposure to PBDEs disrupts the nigrostriatal dopamine system. Given their similarities to PCBs, additional laboratory and epidemiological research should be considered to assess PBDEs as a potential risk factor for PD and other neurological disorders. PMID:23287494

Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

PubMed

Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

2018-07-16

Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

PubMed

Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

2016-07-01

Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.

Local oxidative stress in interdigital tinea pedis.

PubMed

Ozturk, Perihan; Arican, Ozer; Kurutas, Ergul B; Karakas, Tugba; Gungor, Meltem

2013-02-01

Several skin diseases are believed to be associated with oxidative stress. Tinea pedis is an infection of the feet caused by fungi. The infectious diseases caused by dermatophytes are mainly related to the enzymes produced by these fungi. The cutaneous oxidative stress status of tinea pedis has not been demonstrated in the published work up to now. The aim of the present study was to evaluate the role of oxidative stress in affected skin areas in a group of patients with interdigital tinea pedis. Thirty-one consecutive patients with a diagnosis of unilateral interdigital tinea pedis were enrolled. The samples were obtained by scraping the skin surface. Oxidative stress biomarkers such as superoxide dismutase, catalase and malondialdehyde levels were measured spectrophotometrically. The activities of superoxide dismutase and catalase and the levels of malondialdehyde were significantly higher on the lesional area than the non-lesional area (P < 0.001). According to sex and fungal subtypes, there was no significant difference in the levels of oxidative stress biomarkers in patients with tinea pedis (P > 0.05). Our results suggested that antioxidant defense of lesional skin surface was higher compared to non-lesional skin. This is possibly due to a compensatory response to various fungal infections and thereby protects the cells against oxidative damage. © 2012 Japanese Dermatological Association.

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

PubMed Central

Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

PubMed

Arnt, J

1985-08-26

The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

PubMed

Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

2010-04-01

The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

Clinical Features of Ocular Toxocariasis in Adult Korean Patients.

PubMed

Jee, Donghyun; Kim, Kyu Seop; Lee, Won Ki; Kim, Wungjae; Jeon, Sohee

2016-01-01

To investigate the clinical characteristics and treatment results of adult patients with ocular toxocariasis. A total of 54 consecutive patients who were clinically and serologically diagnosed with ocular toxocariasis were retrospectively reviewed. Among patients, 66.7 and 77.3% showed increases in eosinophil cationic protein (ECP) and total Ig E in serum, respectively. Four eyes (7.2%) initially presented as neuroretinitis with subsequent motile retinal lesion. The recurrence rates in the combination treatment group with albendazole and corticosteroids were significantly lower than those in the steroid-alone group during the mean follow-up of 27.6 months (p = 0.001). The adjunctive test of serum total IgE level may be helpful for the diagnosis of ocular toxocariasis. Ocular toxocariasis should be considered in the differential diagnosis of unilateral neuroretinitis with subsequent motile retinal lesion. Combined treatment with albendazole and corticosteroids appeared to be effective for reducing the recurrence of intraocular inflammation.

An unusual case of episodic SUNCT responding to high doses of topiramate.

PubMed

Khalil, Modar; Maniyar, Farooq; Ahmed, Fayyaz

2014-01-01

Trigeminal autonomic cephalalgias (TAC) are rare. Cluster headaches comprise the majority, with short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) being the rarest and shortest in duration. The majority of SUNCT are primary with a few cases occurring secondary to posterior fossa or pituitary lesions. Although activities like exercise or blowing of the nose can trigger SUNCT, onset during orgasm has not been described. Short-lasting aura has been described in TACs including SUNCT, but persistence of focal symptoms and signs without an underlying structural lesion have not been described. Lastly, treatment of SUNCT is difficult, with lamotrigine being the most common effective reported. We report a case of episodic SUNCT with symptoms suggestive of brainstem stroke that completely resolved spontaneously for which no underlying structural cause was found. The onset of first attack occurred during orgasm, and the patient responded to a high dose of topiramate. © 2014 American Headache Society.

[Motor neglect of thalamic origin: report on two cases (author's transl)].

PubMed

Laplane, D; Escourolle, R; Degos, J D; Sauron, B; Massiou, H

1982-01-01

Two cases of thalamic lesions with motor neglect are presented. The syndrome of motor neglect was complete in those cases with a) underutilization of left limbs, but good utilization upon verbal orders, b) loss of placement reaction, c) weakness of movement when hand was approaching the target, d) weakness of motor reaction to nociceptive stimuli. Those cases confirm that motor neglect exists after thalamic lesions and bring pathologic clues for topographic discussion. Motor neglect seems to be a particular case of partial unilateral neglect throwing some doubt on the hypothesis of a global trouble of hemispheric activation. Prevalence of left motor neglects suggests some linkage between propositional motility and language. One may suppose that in the right hemisphere language is able to have a vicarious action when spontaneous activation is lost; at the opposite, in the left hemisphere language and motility would be too linked to let this dissociation be generally possible.

Otic Langerhans' Cell Histiocytosis in an Adult: A Case Report and Review of the Literature

PubMed Central

Gungadeen, Anil; Kullar, Peter; Yates, Philip

2013-01-01

Objective. To present a case of otic Langerhans' cell histiocytosis in an adult. Also included the diagnosis and management of the condition and a review of the relevant literature. Case Report. We report a case of a 41-year-old man with a history of persistent unilateral ear discharge associated with an aural polyp. Radiological imaging showed bony lesions of the skull and a soft-tissue mass within the middle ear. Histological analysis of the polyp demonstrated Langerhans' cell histiocytosis. His otological symptoms were completely resolved with the systemic therapy. Conclusions. Otic Langerhans' cell histiocytosis can present in adults. Persistent ear symptoms along with evidence of soft-tissue masses within the ear and bony lesions of the skull or elsewhere should prompt the otolaryngologists to include Langerhans' cell histiocytosis in their differential diagnosis. Management should be with systemic therapy rather than local surgical treatment. PMID:23762704

Pathological Laughter as a Symptom of Midbrain Infarction

PubMed Central

Dabby, Ron; Watemberg, Nathan; Lampl, Yair; Eilam, Anda; Rapaport, Abraham; Sadeh, Menachem

2004-01-01

Pathological laughter is an uncommon symptom usually caused by bilateral, diffuse cerebral lesions. It has rarely been reported in association with isolated cerebral lesions. Midbrain involvement causing pathological laughter is extremely unusual. We describe three patients who developed pathological laughter after midbrain and pontine-midbrain infarction. In two patients a small infarction in the left paramedian midbrain was detected, whereas the third one sustained a massive bilateral pontine infarction extending to the midbrain. Laughter heralded stroke by one day in one patient and occurred as a delayed phenomenon three months after stroke in another. Pathological laughter ceased within a few days in two patients and was still present at a two year follow-up in the patient with delayed-onset laughter. Pathological laughter can herald midbrain infarction or follow stroke either shortly after onset of symptoms or as a delayed phenomenon. Furthermore, small unilateral midbrain infarctions can cause this rare complication. PMID:15706050

Tonic cervical influences on eye nystagmus following hemilabyrinthectomy: immediate and plastic effects.

PubMed

Pettorossi, V E; Petrosini, L

1984-12-17

In intact guinea pigs a passive horizontal rotation of the body about the fixed head induces compensatory ocular movements (cervico-ocular reflex). When the static neck deviation is maintained, a significant ocular displacement is observed. In acutely hemilabyrinthectomized animals, static body deviation towards the lesion side tonically alters eye nystagmus. It affects slow phase eye velocity and quick phase amplitude and frequency causing the eye to reach a less eccentric orbital position. Apart from such immediate influences, a plastic effect on eye nystagmus abatement is induced. In the animals restrained with no body-on-head deviation, abatement of nystagmus is delayed with respect to the animals restrained with 35 degrees body deviation towards the lesion side. Thus the head position signal is not only a contributing factor for the correction of postural deficits but also influences the time course of the ocular balancing process following unilateral vestibular damage.

Roth Spots in Ocular Toxoplasmosis.

PubMed

Furtado, João M; Toscano, Marcelo; Castro, Vinicius; Rodrigues, Murilo W

2016-10-01

To report a case with unilateral preexisting ocular toxoplasmosis (OT) and newly occurred active retinochoroidal inflammation associated with white-centered retinal hemorrhages (Roth spots) in the healthy eye. Case report. A 20 year-old man presented with a decrease of visual acuity in his right eye associated with 2+ cells in the anterior chamber. Ophthalmoscopy revealed an active retinochoroidal lesion on the upper nasal border of the optic disc associated with local hemorrhage and vitritis. The posterior pole presented white-centered flame-shaped retinal hemorrhages. Toxoplasmosis serology showed an IgG titer >300IU/ml and a negative IgM titer. A complete blood count revealed no abnormalities; other serologies were negative. After 2 weeks of treatment with sulfadiazine, pyrimethamine, folinic acid and prednisone, although the peripapillary lesion was still active, the Roth spots disappeared. OT may be one differential diagnosis of patients suffering Roth spots in association with retinochoroidal inflammation.

Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

PubMed

Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

2014-08-01

This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. © 2014 British Small Animal Veterinary Association.

Antiphospholipid syndrome complicated by unilateral pleural effusion.

PubMed

Mitamura, Yasutaka; Takahara, Masakazu; Ito, Takamichi; Nakano, Misa; Moroi, Yoichi; Furue, Masutaka

2013-05-01

Antiphospholipid syndrome (APS) with pleural effusion is extremely rare. A 75-year-old man was admitted to our hospital for spreading erythema on his trunk and extremities, as well as dyspnea. One year before admission, he had visited us with a 1-year history of erythema and purpura on his legs and occasional fever. Given the diagnosis of APS, we initiated a combination therapy of aspirin and warfarin, but the skin lesions had gradually worsened. A biopsy specimen revealed marked thrombosis in the dermal and subcutaneous small vessels. In addition, chest X-ray and computed tomography demonstrated a large pleural effusion in the left lung. He underwent repeated drainage of the pleural effusion but the effusion recurred. We added oral prednisolone 30 mg daily to his prior anticoagulant therapy. The skin lesions and pleural effusion rapidly improved and disappeared without any complication. Corticosteroids might be a choice of treatment for intractable pleural effusion in APS patients.

Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors.

PubMed

Suda, Yukari; Kuzumaki, Naoko; Narita, Michiko; Hamada, Yusuke; Shibasaki, Masahiro; Tanaka, Kenichi; Tamura, Hideki; Kawamura, Takashi; Kondo, Takashige; Yamanaka, Akihiro; Narita, Minoru

2018-02-19

Ghrelin plays roles in a wide range of central functions by activating the growth hormone secretagogue receptor (GHSR). This receptor has recently been found in the substantia nigra (SN) to control dopamine (DA)-related physiological functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the consequent depletion of striatal DA are known to underlie the motor deficits observed in Parkinson's disease (PD). In the present study, we further investigated the role of the SN-ghrelin system in motor function under the stereotaxic injection of AAV-CMV-FLEX-diphtheria toxin A (DTA) into the SN of dopamine transporter (DAT)-Cre (DAT SN ::DTA) mice to expunge DA neurons of the SNc. First, we confirmed the dominant expression of GHSR1a, which is a functional GHSR, in tyrosine hydroxylase (TH)-positive DA neurons in the SNc of control mice. In DAT SN ::DTA mice, we clearly observed motor dysfunction using several behavioral tests. An immunohistochemical study revealed a dramatic loss of TH-positive DA neurons in the SNc and DAT-labeled axon terminals in the striatum, and an absence of mRNAs for TH and DAT in the SN of DAT SN ::DTA mice. The mRNA level of GHSR1a was drastically decreased in the SN of these mice. In normal mice, we also found the mRNA expression of GHSR1a within GABAergic neurons in the SN pars reticulata (SNr). Under these conditions, a single injection of ghrelin into the SN failed to improve the motor deficits caused by ablation of the nigrostriatal DA network using DAT SN ::DTA mice, whereas intra-SN injection of ghrelin suppressed the motor dysfunction caused by the administration of haloperidol, which is associated with the transient inhibition of DA transmission. These findings suggest that phasic activation of the SNc-ghrelin system could improve the dysregulation of nigrostriatal DA transmission related to the initial stage of PD, but not the motor deficits under the depletion of nigrostriatal DA. Although GHSRs are found in non-DA cells of the SNr, GHSRs on DA neurons in the SNc may play a crucial role in motor function. Copyright © 2018. Published by Elsevier Inc.

Advanced age, cardiovascular risk burden, and timed up and go test performance in Parkinson disease.

PubMed

Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M; Koeppe, Robert A; Studenski, Stephanie; Frey, Kirk A; Bohnen, Nicolaas I

2014-12-01

Cardiovascular comorbidities are a known risk factor for impaired mobility in elderly individuals. Motor impairments in Parkinson disease are conventionally ascribed to nigrostriatal dopaminergic denervation although progressive gait and balance impairments become more common with aging and often show limited response to dopaminergic replacement therapies. We explored the association between elevated cardiovascular risk factors and performance on the Timed Up and Go test in cross-sectional of Parkinson disease subjects (n = 83). Cardiovascular risk factor status was estimated using the Framingham General Cardiovascular Disease risk-scoring algorithm in order to dichotomize the cohort into those with and without elevated modifiable cardiovascular risk compared with normative scores for age and gender. All subjects underwent clinical and neuroimaging evaluations including a 3-m Timed Up and Go test, [(11)C]dihydrotetrabenazine positron emission tomography imaging to estimate nigrostriatal dopamine terminal loss, and an magnetic resonance imaging assessment of leukoaraiosis. A similar analysis was performed in 49 healthy controls. After adjusting for disease duration, leukoaraiosis, and nigrostriatal dopaminergic denervation, Parkinson disease subjects with elevated Framingham risk scores (n = 61) displayed slower Timed Up and Go test performance (β = 1.86, t = 2.41, p = .018) compared with subjects with normal range Framingham risk scores (n = 22). When age ≥65 was added to the model in a post hoc analysis, the strength of effect seen with older age (β = 1.51, t = 2.44, p = .017) was similar to that of elevated Framingham risk scoring (β = 1.87, t = 2.51, p = .014). In a multivariable regression model studying the healthy control population, advanced age (t = 2.15, p = .037) was a significant predictor of Timed Up and Go speed though striatal [(11)C]dihydrotetrabenazine (t = -1.30, p = .19) and elevated Framingham risk scores (t = 1.32, p = .19) were not. Modifiable cardiovascular risk factors and older age may independently exacerbate balance-related disability in Parkinson disease and may exert additive or synergistic pathological effects. The pathophysiology of these impairments cannot be explained completely by nigrostriatal dopaminergic denervation or leukoaraiosis burden and may relate to systemic factors seen with accelerated aging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations

PubMed Central

2017-01-01

Midbrain dopamine neurons recorded in vivo pause their firing in response to reward omission and aversive stimuli. While the initiation of pauses typically involves synaptic or modulatory input, intrinsic membrane properties may also enhance or limit hyperpolarization, raising the question of how intrinsic conductances shape pauses in dopamine neurons. Using retrograde labeling and electrophysiological techniques combined with computational modeling, we examined the intrinsic conductances that shape pauses evoked by current injections and synaptic stimulation in subpopulations of dopamine neurons grouped according to their axonal projections to the nucleus accumbens or dorsal striatum in mice. Testing across a range of conditions and pulse durations, we found that mesoaccumbal and nigrostriatal neurons differ substantially in rebound properties with mesoaccumbal neurons displaying significantly longer delays to spiking following hyperpolarization. The underlying mechanism involves an inactivating potassium (IA) current with decay time constants of up to 225 ms, and small-amplitude hyperpolarization-activated currents (IH), characteristics that were most often observed in mesoaccumbal neurons. Pharmacological block of IA completely abolished rebound delays and, importantly, shortened synaptically evoked inhibitory pauses, thereby demonstrating the involvement of A-type potassium channels in prolonging pauses evoked by GABAergic inhibition. Therefore, these results show that mesoaccumbal and nigrostriatal neurons display differential responses to hyperpolarizing inhibitory stimuli that favors a higher sensitivity to inhibition in mesoaccumbal neurons. These findings may explain, in part, observations from in vivo experiments that ventral tegmental area neurons tend to exhibit longer aversive pauses relative to SNc neurons. SIGNIFICANCE STATEMENT Our study examines rebound, postburst, and synaptically evoked inhibitory pauses in subpopulations of midbrain dopamine neurons. We show that pauses in dopamine neuron firing, evoked by either stimulation of GABAergic inputs or hyperpolarizing current injections, are enhanced by a subclass of potassium conductances that are recruited at voltages below spike threshold. Importantly, A-type potassium currents recorded in mesoaccumbal neurons displayed substantially slower inactivation kinetics, which, combined with weaker expression of hyperpolarization-activated currents, lengthened hyperpolarization-induced delays in spiking relative to nigrostriatal neurons. These results suggest that input integration differs among dopamine neurons favoring higher sensitivity to inhibition in mesoaccumbal neurons and may partially explain in vivo observations that ventral tegmental area neurons exhibit longer aversive pauses relative to SNc neurons. PMID:28219982

Effects of CDP-choline on striatal dopamine level and behavior in rats.

PubMed

Shibuya, M; Kageyama, N; Taniguchi, T; Hidaka, H; Fujiwara, M

1981-02-01

To further assess the effects of CDP (cytidine diphosphate)-choline on Parkinsonian symptoms, striatal dopamine (DA) was measured fluorometrically in rats after injection of CDP-choline. CDP-choline (300 mg/kg, i.p.) increased the DA content in the striatum (p less than 0.05) one hour after injection. The behavioral effect of CDP-choline was then tested in rats in which the unilateral nigro-striatal DA neurons had degenerated following an intranigral injection of 6-hydroxydopamine (6-OHDA). CDP-choline alone did not produce behavioral changes in these rats. However, pretreatment with a single dose of CDP-choline (900 mg/kg, i.p.) suppressed both the apomorphine-induced contralateral and the d-amphetamine-induced ipsilateral circling. The same dose of CDP-choline suppressed the number of treadmill revolutions in mice. On the other hand, a 7-day consecutive treatment with 300 mg/kg of CDP-choline enhanced the apomorphine-induced contralateral circling (by 42%, p less than 0.05). The same treatment with CDP-choline raised the striatal DA content by 29% (p less than 0.05) on the intact side, but not on the 6-OHDA injected side. These results indicate that CDP-choline has either a direct nor an indirect DA agonistic effect. The increase in DA content, decrease in locomotion and enhancement of the effect of apomorphine can be explained on the hypothesis that CDP-choline may act as an antagonist on the DA neurons and receptors. The validity of this apparently paradoxical use of CDP-choline with antagonistic effect on DA neurons in the treatment of Parkinson's disease is discussed.

Severe traumatic head injury: prognostic value of brain stem injuries detected at MRI.

PubMed

Hilario, A; Ramos, A; Millan, J M; Salvador, E; Gomez, P A; Cicuendez, M; Diez-Lobato, R; Lagares, A

2012-11-01

Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P < .05). Posterior location showed the best discriminatory capability in terms of outcome (OR 6.8, P < .05) and disability (OR 4.8, P < .01). The addition of nonhemorrhagic and anterior lesions or unilateral injuries showed the highest odds and best discriminatory capacity for good outcome. The prognosis worsens in direct relationship to the extent of traumatic injury. Posterior and bilateral brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

Neuropsychology of Aesthetic Judgment of Ambiguous and Non-Ambiguous Artworks

PubMed Central

Boccia, Maddalena; Barbetti, Sonia; Piccardi, Laura; Guariglia, Cecilia; Giannini, Anna Maria

2017-01-01

Several affective and cognitive processes have been found to be pivotal in affecting aesthetic experience of artworks and both neuropsychological as well as psychiatric symptoms have been found to affect artistic production. However, there is a paucity of studies directly investigating effects of brain lesions on aesthetic judgment. Here, we assessed the effects of unilateral brain damage on aesthetic judgment of artworks showing part/whole ambiguity. We asked 19 unilaterally brain-damaged patients (10 left and 9 right brain damaged patients, respectively LBDP and RBDP) and 20 age- and education-matched healthy individuals (controls, C) to rate 10 Arcimboldo’s ambiguous portraits (AP), 10 realistic Renaissance portraits (RP), 10 still life paintings (SL), and 10 Arcimboldo’s modified portraits where only objects/parts are detectable (AO). They were also administered a Navon task, a facial recognition test, and evaluated on visuo-perceptual and visuo-constructional abilities. Patients included in the study did not show any deficits that could affect the capability to explore and enjoy artworks. SL and RP was not affected by brain damage regardless of its laterality. On the other hand, we found that RBDP liked AP more than the C participants. Furthermore, we found a positive correlation between aesthetic judgment of AP and visuo-perceptual skills even if the single case analyses failed to find a systematic association between neuropsychological deficits and aesthetic judgment of AP. On the whole, the present data suggest that a right hemisphere lesion may affect aesthetic judgment of ambiguous artworks, even in the absence of exploration or constructional deficits. PMID:28335460

Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

PubMed

Carmel, Jason B; Kimura, Hiroki; Martin, John H

2014-01-08

Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

Apraxia.

PubMed

Goldenberg, Georg

2013-09-01

The term apraxia refers to 'higher level' disorders of motor control. Apraxia differs from other motor symptoms of unilateral brain damage by the bilaterality of symptoms following unilateral lesions. Lesions causing apraxia are located predominantly in the left hemisphere and apraxia is frequently, although not invariably, associated with aphasia. Examination for apraxia traditionally assesses imitation of gestures, performance of communicative gestures on command, and use of tools and objects. It has, however, been amply demonstrated that these three domains can be affected more or less independently from each other. This review discusses current topics of research and controversy from each of these domains concentrating on questions that are relevant for determining the border between motor and cognitive mechanisms underlying apraxic errors. For imitation, the proposal of a direct link from perception to motor execution is confronted with the hypothesis that body part coding is interpolated between perception and motor replication of gestures. Discussion of communicative gestures concentrates on pantomime of tool use and argues that pantomime is not equivalent to reproduction of the motor programs of actual tool use but that pantomimes are created by selection and combination of distinctive features of the object and its use. For tool use the boundary between visuo-motor coordination and knowledge about tool use is addressed by discussion of the selection of grips for use or for transport of tools. WIREs Cogn Sci 2013, 4:453-462. doi: 10.1002/wcs.1241 For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article. © 2013 John Wiley & Sons, Ltd.

Visuomotor training improves stroke-related ipsilesional upper extremity impairments.

PubMed

Quaney, Barbara M; He, Jianghua; Timberlake, George; Dodd, Kevin; Carr, Caitlin

2010-01-01

Unilateral middle cerebral artery infarction has been reported to impair bilateral hand grasp. Individuals (5 males and 5 females; age 33-86 years) with chronic unilateral middle cerebral artery stroke (4 right lesions and 6 left lesions) repeatedly lifted a 260-g object. Participants were then trained to lift the object using visuomotor feedback via an oscilloscope that displayed their actual grip force (GF) and a target GF, which roughly matched the physical properties of the object. The subjects failed to accurately modulate the predictive GF when relying on somatosensory information from the previous lifts. Instead, for all the lifts, they programmed excessive GF equivalent to the force used for the first lift. The predictive GF was lowered for lifts following the removal of the visual feedback. The mean difference in predictive GF between the lifts before and after visual training was significant (4.35 +/- 0.027 N; P

Hemodynamic Signal Changes Accompanying Execution and Imagery of Swallowing in Patients with Dysphagia: A Multiple Single-Case Near-Infrared Spectroscopy Study

PubMed Central

Kober, Silvia Erika; Bauernfeind, Günther; Woller, Carina; Sampl, Magdalena; Grieshofer, Peter; Neuper, Christa; Wood, Guilherme

2015-01-01

In the present multiple case study, we examined hemodynamic changes in the brain in response to motor execution (ME) and motor imagery (MI) of swallowing in dysphagia patients compared to healthy matched controls using near-infrared spectroscopy (NIRS). Two stroke patients with cerebral lesions in the right hemisphere, two stroke patients with lesions in the brainstem, and two neurologically healthy control subjects actively swallowed saliva (ME) and mentally imagined to swallow saliva (MI) in a randomized order while changes in concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) were assessed. In line with recent findings in healthy young adults, MI and ME of swallowing led to the strongest NIRS signal change in the inferior frontal gyrus in stroke patients as well as in healthy elderly. We found differences in the topographical distribution and time course of the hemodynamic response in dependence on lesion location. Dysphagia patients with lesions in the brainstem showed bilateral hemodynamic signal changes in the inferior frontal gyrus during active swallowing comparable to healthy controls. In contrast, dysphagia patients with cerebral lesions in the right hemisphere showed more unilateral activation patterns during swallowing. Furthermore, patients with cerebral lesions showed a prolonged time course of the hemodynamic response during MI and ME of swallowing compared to healthy controls and patients with brainstem lesions. Brain activation patterns associated with ME and MI of swallowing were largely comparable, especially for changes in deoxy-Hb. Hence, the present results provide new evidence regarding timing and topographical distribution of the hemodynamic response during ME and MI of swallowing in dysphagia patients and may have practical impact on future dysphagia treatment. PMID:26217298

Reactive fibroblastic and myofibroblastic proliferation of the vulva (Cyclist's Nodule): A hitherto poorly described vulval lesion occurring in cyclists.

PubMed

McCluggage, W Glenn; Smith, John H F

2011-01-01

Perineal nodules occurring in male cyclists are reported in the literature, although the histologic features are not extensively documented. There has been little description of similar lesions in the female population. We describe 4 cases in which a vulval nodule or swelling developed in competitive female cyclists aged 15 to 45 years. The lesions were unilateral and occurred on the right or left labium majus (2 cases each). The histologic features were similar in all cases and consisted of a haphazard admixture of adipose tissue, variably cellular hyalinized tissue containing bland spindle-shaped fibroblasts, blood vessels, and nerve fibers. In some areas, thick cords of fibrous tissue imparted a keloid-like appearance. Other histologic features included plump mesenchymal cells with round or ovoid nuclei and abundant eosinophilic cytoplasm resulting in an epithelioid, plasmacytoid, or ganglion-like appearance (2 cases), a lymphocytic infiltrate around blood vessels (3 cases), foci of fat necrosis (1 case), and collections of elastic fibers (2 cases). One case recurred, the histologic features of the recurrent lesion being identical to the original. The overall morphologic appearances, especially in the cases with plump mesenchymal cells, bore some resemblance to proliferative fasciitis. Immunohistochemically, the cells were estrogen receptor positive and the plump mesenchymal cells were smooth muscle actin positive, in keeping with myofibroblasts. Desmin, S100, CD34, and HMGA2 were negative. Pathologists should be aware of this pseudoneoplastic lesion occurring on the vulva, which arises in a specific clinical setting and has the potential to be misdiagnosed as a variety of other mesenchymal lesions. We term this lesion as reactive fibroblastic and myofibroblastic proliferation of the vulva or "cyclist's nodule."

Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place scene memory

PubMed Central

Wilson, Charles R E; Gaffan, David; Mitchell, Anna S; Baxter, Mark G

2007-01-01

Disconnection of the frontal lobe from the inferotemporal cortex produces deficits in a number of cognitive tasks that require the application of memory-dependent rules to visual stimuli. The specific regions of frontal cortex that interact with the temporal lobe in performance of these tasks remain undefined. One capacity that is impaired by frontal–temporal disconnection is rapid learning of new object-in-place scene problems, in which visual discriminations between two small typographic characters are learned in the context of different visually complex scenes. In the present study, we examined whether neurotoxic lesions of ventrolateral prefrontal cortex in one hemisphere, combined with ablation of inferior temporal cortex in the contralateral hemisphere, would impair learning of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new object-in-place problems in each daily test session. Unilateral neurotoxic lesions of ventrolateral prefrontal cortex produced by multiple injections of a mixture of ibotenate and N-methyl-d-aspartate did not affect performance. However, when disconnection from inferotemporal cortex was completed by ablating this region contralateral to the neurotoxic prefrontal lesion, new learning was substantially impaired. Sham disconnection (injecting saline instead of neurotoxin contralateral to the inferotemporal lesion) did not affect performance. These findings support two conclusions: first, that the ventrolateral prefrontal cortex is a critical area within the frontal lobe for scene memory; and second, the effects of ablations of prefrontal cortex can be confidently attributed to the loss of cell bodies within the prefrontal cortex rather than to interruption of fibres of passage through the lesioned area. PMID:17445247

Ultra-wide-field fundus autofluorescence in multiple evanescent white dot syndrome.

PubMed

Hashimoto, Hideaki; Kishi, Shoji

2015-04-01

To observe the progression of affected lesions using ultra-wide-field fundus autofluorescence (FAF) in multiple evanescent white dot syndrome. Retrospective, observational case series. setting: Institutional. 14 eyes of 13 patients (mean age, 35.8 years) with acute disease unilaterally. Patients underwent ultra-wide-field FAF, spectral-domain optical coherence tomography (SD OCT), multifocal electroretinography (mfERG), and Goldmann or automated perimetry; the best-corrected visual acuity (BCVA) and refractive error were measured. Ability of ultra-wide-field FAF to detect lesions with greater sensitivity compared with color fundus photography. Ultra-wide-field FAF imaging enabled improved visualization of the affected lesions and showed that the core lesion was in the posterior fundus involving the peripapillary retina and posterior pole and surrounded by hyper-autofluorescent spots outside the vascular arcade. The posterior lesions expanded rapidly and peripheral spots spread farther peripherally and reached a maximal extent during the acute stage. During follow-up, the peripheral hyper-autofluorescent spots resolved and then hyper-autofluorescence of the posterior fundus gradually faded. SD OCT showed diffuse disruption of the photoreceptor inner segment/outer segment junction (IS/OS) in the posterior fundus during the acute stage. The correlation between the IS/OS abnormality and hyper-autofluorescent areas was unclear. The disrupted IS/OS was restored with normalization of the FAF. Ultra-wide-field FAF showed that the lesions arise from the peripapillary retina and the posterior pole and spread peripherally in a centrifugal manner during the acute stage. The hyper-autofluorescent spots faded from the periphery in a centripetal manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Imaging of VMAT2 binding sites in the brain by (18)F-AV-133: the effect of a pseudo-carrier.

PubMed

Zhu, Lin; Qiao, Hongwen; Lieberman, Brian P; Wu, Jingxiao; Liu, Yajing; Pan, Zhongyun; Ploessl, Karl; Choi, Seok Rye; Chan, Piu; Kung, Hank F

2012-10-01

Recently, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of (18)F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using (18)F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative (18)F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. The radiochemical purity of the (18)F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250 μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of (18)F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). The pseudo-carrier, AV-149, did not affect the (18)F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable (18)F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses. Copyright © 2012 Elsevier Inc. All rights reserved.

Visuo-spatial memory deficits following medial temporal lobe damage: A comparison of three patient groups.

PubMed

Esfahani-Bayerl, Nazli; Finke, Carsten; Braun, Mischa; Düzel, Emrah; Heekeren, Hauke R; Holtkamp, Martin; Hasper, Dietrich; Storm, Christian; Ploner, Christoph J

2016-01-29

The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in non-associative memory tasks likely reflect damage of regions outside the MTL. Importantly, the choice of a patient model in human lesion studies of the MTL significantly influences overall performance patterns in visuo-spatial memory tasks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility and Efficacy of Intra‐Arterial Administration of Mesenchymal Stem Cells in an Animal Model of Double Toxin‐Induced Multiple System Atrophy

PubMed Central

Na Kim, Ha; Yeol Kim, Dong; Hee Oh, Se; Sook Kim, Hyung; Suk Kim, Kyung

2017-01-01

Abstract Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra‐arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 107 MSCs) and efficacy test using a ×0.2, ×2, and ×20 of the standard dose. An ultrasonic flow meter and magnetic resonance imaging (MRI) showed that no cerebral ischemic lesions with patent ICA blood flow was were observed in animals receiving a ×10 of the standard dose of MSCs. However, no MSA animals receiving a ×50 of the standard dose survived. In efficacy test, animals injected with a ×2 of the standard dose increased nigrostriatal neuronal survival relative to a ×0.2 or ×20 of the standard dose. MSA animals receiving MSCs at ×0.2 and ×2 concentrations of the standard dose exhibited a significant reduction in rotation behavior relative to ×20 of the standard dose of MSCs. Cerebral ischemic lesions on MRI were only observed in MSA animals receiving a ×20 of the standard dose. The present study revealed that if their concentration is appropriate, intra‐arterial injection of MSCs is safe and exerts a neuroprotective effect on striatal and nigral neurons with a coincidental improvement in motor behavior. Stem Cells Translational Medicine 2017;6:1424–1433 PMID:28296268

The effect of unilateral electrostimulation of the subthalamic nucleus on respiratory/phonatory subsystems of speech production in Parkinson's disease--a preliminary report.

PubMed

Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

2003-01-01

This paper reports findings on the respiratory/phonatory subsystems from an on-going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinson's disease (PD). Speech recordings were made in the medication-off state at baseline, three months post surgery with stimulation-on, and with stimulation-off, in six right-handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) obtained under the same conditions. Results showed that stimulation-on improved UPDRS-III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation-on condition, three subjects received left-STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.

Recognition and identification of famous faces in patients with unilateral temporal lobe epilepsy.

PubMed

Seidenberg, Michael; Griffith, Randall; Sabsevitz, David; Moran, Maria; Haltiner, Alan; Bell, Brian; Swanson, Sara; Hammeke, Thomas; Hermann, Bruce

2002-01-01

We examined the performance of 21 patients with unilateral temporal lobe epilepsy (TLE) and hippocampal damage (10 lefts, and 11 rights) and 10 age-matched controls on the recognition and identification (name and occupation) of well-known faces. Famous face stimuli were selected from four time periods; 1970s, 1980s, 1990-1994, and 1995-1996. Differential patterns of performance were observed for the left and right TLE group across distinct face processing components. The left TLE group showed a selective impairment in naming famous faces while they performed similar to the controls in face recognition and semantic identification (i.e. occupation). In contrast, the right TLE group was impaired across all components of face memory; face recognition, semantic identification, and face naming. Face naming impairment in the left TLE group was characterized by a temporal gradient with better naming performance for famous faces from more distant time periods. Findings are discussed in terms of the role of the temporal lobe system for the acquisition, retention, and retrieval of face semantic networks, and the differential effects of lateralized temporal lobe lesions in this process.

Sudden unexpected death owing to unilateral medial medullary infarction with early involvement of the respiratory center.

PubMed

Hata, Yukiko; Yoshida, Koji; Kinoshita, Koshi; Nishida, Naoki

2014-05-01

A 64-year-old woman was found dead in her home. At autopsy, although relatively fresh bruises were found on her body, no lethal injury was observed in an internal observation. Mild edematous swelling of the right half of the medulla oblongata was observed. There was acute medial medullary infarction (MMI), which mainly involved the nucleus hypoglossi, medial lemniscus, hypoglossal root, inferior olivary nucleus, and pyramidal tract. Subacute infarction of the lower part of the cerebellum was also found, and severe atherosclerosis of the right vertebral artery containing thrombi was found as the culprit lesion. Immunohistochemistry using amyloid precursor protein (APP) was positive in neuronal tissue in the nucleus ambiguus, despite not showing coagulative necrosis in the nucleus. Therefore, acute ischemic necrosis of the nucleus ambiguus, which is considered to be a component of the dorsal respiratory group, may be a significant finding for her expected death. Immunohistochemistry of APP may be useful for confirming the precise extent of acute ischemia in brain stem infarction, such as unilateral MMI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilts, R.P.; Kalivas, P.W.

The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbicmore » dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.« less

Prism adaptation improves ego-centered but not allocentric neglect in early rehabilitation patients.

PubMed

Gossmann, Anja; Kastrup, Andreas; Kerkhoff, Georg; López-Herrero, Carmen; Hildebrandt, Helmut

2013-01-01

Unilateral neglect due to parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, and prism adaptation (PA) enhances recovery from neglect. However, it is unclear if this effect holds also in severely impaired patients and/or in the postacute phase of rehabilitation. Moreover, it is not known whether PA affects all aspects of neglect recovery or ego-centered spatial orientation only. Sixteen patients in a postacute stage (on average 36 days after a large right cerebrovascular stroke) were entered into a series of single case design studies with 4 measurements: 2 before and 2 after 1 week of PA treatment. All patients had severe neglect (showing trunk, head, and eye deviation; canceling less than 20% of targets in a visual cancellation test). Lesions were transferred to a standard brain to analyze size and location. Patients improved in cued body orientation and in the cancellation task, that is, in ego-centered neglect. However, none of the measures used to evaluate neglect of left side of objects irrespective of their position on the right or left side of the patient (allocentric neglect) showed an improvement. Treatment effects were not influenced by total lesion size, but lesions including the postcentral cortex were related to smaller recovery gains. PA is helpful in treating severely impaired patients in the postacute phase, but the effect is restricted to ego-centered neglect. Lesions in the postcentral cortex (middle occipito-temporal, middle temporal, and posterior parietal areas) seem to limit the effect of PA.

Constructional ability in two- versus three-dimensions: relationship to spatial vision and locus of cerebrovascular lesion.

PubMed

Capruso, Daniel X; Hamsher, Kerry deS

2011-06-01

Clinical evaluation and research on constructional ability have come to rely almost exclusively on two-dimensional tasks such as graphomotor copying or mosaic Block Design (BD). A return to the inclusion of a third dimension in constructional tests may increase the spatial demands of the task, and improve understanding of the relationship between visual perception and constructional ability in patients with cerebral disease. Subjects were patients (n=43) with focal or multifocal cerebrovascular lesions as determined by CT or MRI. Tests of temporal orientation, verbal intelligence, language, object vision and spatial vision were used to determine which factors were predictive of performance on two-dimensional BD and Three-Dimensional Block Construction (3-DBC) tasks. Stepwise linear regression indicated that spatial vision predicted BD performance, and was even more strongly predictive of 3-DBC. Other cognitive domains did not account for significant additional variance in performance of either BD or 3-DBC. Bilateral cerebral lesions produced more severe deficits on BD than did unilateral cerebral lesions. The presence of a posterior cerebral lesion was the significant factor in producing deficits in 3-DBC. The spatial aspect of a constructional task is enhanced when the patient is required to assemble an object in all three dimensions of space. In the typical patient with cerebrovascular disease, constructional deficits typically occur in the context of a wider syndrome of deficits in spatial vision. Copyright © 2010 Elsevier Srl. All rights reserved.

Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit.

PubMed

Gaal, Botond; Jóhannesson, Einar Örn; Dattani, Amit; Magyar, Agnes; Wéber, Ildikó; Matesz, Clara

2015-09-01

We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrinthectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestibular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tenascin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.

Bilaterally Abnormal Head Impulse Tests Indicate a Large Cerebellopontine Angle Tumor.

PubMed

Kim, Hyo Jung; Park, Seong Ho; Kim, Ji Soo; Koo, Ja Won; Kim, Chae Yong; Kim, Young Hoon; Han, Jung Ho

2016-01-01

Tumors involving the cerebellopontine angle (CPA) pose a diagnostic challenge due to their diverse manifestations. Head impulse tests (HITs) have been used to evaluate vestibular function, but few studies have explored the head impulse gain of the vestibulo-ocular reflex (VOR) in patients with a vestibular schwannoma. This study tested whether the head impulse gain of the VOR is an indicator of the size of a unilateral CPA tumor. Twenty-eight patients (21 women; age=64±12 years, mean±SD) with a unilateral CPA tumor underwent a recording of the HITs using a magnetic search coil technique. Patients were classified into non-compressing (T1-T3) and compressing (T4) groups according to the Hannover classification. Most (23/28, 82%) of the patients showed abnormal HITs for the semicircular canals on the lesion side. The bilateral abnormality in HITs was more common in the compressing group than the non-compressing group (80% vs. 8%, Pearson's chi-square test: p<0.001). The tumor size was inversely correlated with the head impulse gain of the VOR in either direction. Bilaterally abnormal HITs indicate that a patient has a large unilateral CPA tumor. The abnormal HITs in the contralesional direction may be explained either by adaptation or by compression and resultant dysfunction of the cerebellar and brainstem structures. The serial evaluation of HITs may provide information on tumor growth, and thereby reduce the number of costly brain scans required when following up patients with CPA tumors.

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

PubMed Central

Akundi, Ravi S.; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D.; Zhi, Lianteng; Cass, Wayne A.; Sullivan, Patrick G.; Büeler, Hansruedi

2011-01-01

Background PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca2+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1−/− mice. Methods and Findings Purified brain mitochondria of Pink1−/− mice showed impaired Ca2+ storage capacity, resulting in increased Ca2+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1−/− mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1−/− mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1−/− mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Conclusions Increased mitochondrial Ca2+ sensitivity and JNK activity are early defects in Pink1−/− mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1−/− mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1−/− mice to inflammation and injury-induced cell death. PMID:21249202

Right unilateral agraphia following callosal infarction in a left-hander.

PubMed

Tei, H; Soma, Y; Maruyama, S

1994-01-01

A left-handed Japanese man is reported who presented right-hand agraphia and tactile anomia following callosal infarction. Magnetic resonance imaging revealed an ischemic lesion extending from the posterior half of the trunk to the splenium of the corpus callosum. In his right handwriting, the 'Kana' (phonogram) was more severely impaired than the 'Kanji' (ideogram), and the most frequent typewriting error was morphological followed by neographism. His visuoconstructional ability was also more impaired in the right hand than in the left. Right-hand agraphia in our case is readily explained by the right hemisphere dominance both for language and visuoconstructional ability.

Influence of the extraocular muscle proprioceptors on the orientation of the vestibulo-ocular reflex.

PubMed

Pettorossi, V E; Errico, P; Ferraresi, A; Manni, E

1996-03-01

In the intact brain lamb, unilateral electrolytic lesion of the medial dorso-lateral portion of the semilunar ganglion containing the first order neurons of the eye muscle proprioception induced modifications of the horizontal and vertical vestibulo-ocular reflex (HVOR and VVOR) which consisted in marked alterations of the trajectories of the quick phases, while the slow phases were scarcely affected. Similar results were observed after section of the branches described by Winckler in the retrobulbar region along the extraocular muscle proprioceptive information travels. These findings extend those of previous investigations carried out in decorticate animals.

Femorofemoral bypass grafting in high-risk patients.

PubMed

Deruyter, L; Caes, F; Van den Brande, P; Cham, B; Welch, W

1986-01-01

A total of 37 extra-anatomic femorofemoral bypasses were inserted for severe unilateral iliac artery stenosis or a thrombosed graft limb of an aorto-bifemoral bifurcation graft. All patients were severely debilitated and at high risk for direct aorto-iliac reconstruction. 30% suffered severe claudication; 70% had ischemic restpain or trophic lesions. 43% died during a mean follow-up period of 17 months. This study demonstrates that the extra-anatomic femoro-femoral bypass procedure is an effective alternative therapeutic modality for high-risk patients with an acceptable operative mortality (5.4%) and morbidity to improve the quality of life.

The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study

PubMed Central

Moen, Kent Gøran; Skandsen, Toril; Kvistad, Kjell Arne; Laureys, Steven; Håberg, Asta; Vik, Anne

2018-01-01

Abstract The aim of this study was to investigate how traumatic axonal injury (TAI) lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic resonance imaging (MRI) are associated with level of consciousness in the acute phase in patients with moderate to severe traumatic brain injury (TBI). There were 158 patients with moderate to severe TBI (7–70 years) with early 1.5T MRI (median 7 days, range 0–35) without mass lesion included prospectively. Glasgow Coma Scale (GCS) scores were registered before intubation or at admission. The TAI lesions were identified in T2*gradient echo, fluid attenuated inversion recovery, and diffusion weighted imaging scans. In addition to registering TAI lesions in hemispheric white matter and the corpus callosum, TAI lesions in the thalamus, basal ganglia, and brainstem were classified as uni- or bilateral. Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26 bilateral lesions in the thalamus or brainstem was found on computed tomography. The GCS scores were lower in patients with bilateral lesions in the thalamus (median four) and brainstem (median five) than in those with corresponding unilateral lesions (median six and eight, p = 0.002 and 0.022). The TAI locations most associated with low GCS scores in univariable ordinal regression analyses were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence interval [CI: 10.5−121.8], p < 0.001), followed by bilateral lesions in basal ganglia (OR 13.1 [CI: 2.0–88.2], p = 0.008) and bilateral lesions in the brainstem (OR 11.4 [CI: 4.0–32.2], p < 0.001). This Trondheim TBI study showed that patients with bilateral TAI lesions in the thalamus, basal ganglia, or brainstem had particularly low consciousness at admission. We suggest these bilateral lesions should be evaluated further as possible biomarkers in a new TAI-MRI classification as a worst grade, because they could explain low consciousness in patients without mass lesions. PMID:29334825

Microglia-Derived Cytokines/Chemokines Are Involved in the Enhancement of LPS-Induced Loss of Nigrostriatal Dopaminergic Neurons in DJ-1 Knockout Mice

PubMed Central

Chien, Chia-Hung; Lee, Ming-Jen; Liou, Houng-Chi; Liou, Horng-Huei; Fu, Wen-Mei

2016-01-01

Mutation of DJ-1 (PARK7) has been linked to the development of early-onset Parkinson’s disease (PD). However, the underlying molecular mechanism is still unclear. This study is aimed to compare the sensitivity of nigrostriatal dopaminergic neurons to lipopolysaccharide (LPS) challenge between DJ-1 knockout (KO) and wild-type (WT) mice, and explore the underlying cellular and molecular mechanisms. Our results found that the basal levels of interferon (IFN)-γ (the hub cytokine) and interferon-inducible T-cell alpha chemoattractant (I-TAC) (a downstream mediator) were elevated in the substantia nigra of DJ-1 KO mice and in microglia cells with DJ-1 deficiency, and the release of cytokine/chemokine was greatly enhanced following LPS administration in the DJ-1 deficient conditions. In addition, direct intranigral LPS challenge caused a greater loss of nigrostriatal dopaminergic neurons and striatal dopamine content in DJ-1 KO mice than in WT mice. Furthermore, the sensitization of microglia cells to LPS challenge to release IFN-γ and I-TAC was via the enhancement of NF-κB signaling, which was antagonized by NF-κB inhibitors. LPS-induced increase in neuronal death in the neuron-glia co-culture was enhanced by DJ-1 deficiency in microglia, which was antagonized by the neutralizing antibodies against IFN-γ or I-TAC. These results indicate that DJ-1 deficiency sensitizes microglia cells to release IFN-γ and I-TAC and causes inflammatory damage to dopaminergic neurons. The interaction between the genetic defect (i.e. DJ-1) and inflammatory factors (e.g. LPS) may contribute to the development of PD. PMID:26982707

Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function

PubMed Central

Ciron, C.; Lengacher, S.; Dusonchet, J.; Aebischer, P.; Schneider, B.L.

2012-01-01

Mitochondrial dysfunction and oxidative stress have been implicated in the etiology of Parkinson's disease. Therefore, pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets. Here, we explore the neuronal response to prolonged overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional regulator of mitochondrial function, both in vitro and in vivo. In neuronal primary cultures from the ventral midbrain, PGC-1α induces mitochondrial biogenesis and increases basal respiration. Over time, we observe an increasing proportion of the oxygen consumed by neurons which are dedicated to adenosine triphosphate production. In parallel to enhanced oxidative phosphorylation, PGC-1α progressively leads to a decrease in mitochondrial polarization. In the adult rat nigrostriatal system, adeno-associated virus (AAV)-mediated overexpression of PGC-1α induces the selective loss of dopaminergic markers and increases dopamine (DA) catabolism, leading to a reduction in striatal DA content. In addition, PGC-1α prevents the labeling of nigral neurons following striatal injection of the fluorogold retrograde tracer. When PGC-1α is expressed at higher levels following intranigral AAV injection, it leads to overt degeneration of dopaminergic neurons. Finally, PGC-1α overexpression does not prevent nigrostriatal degeneration in pathologic conditions induced by α-synuclein overexpression. Overall, we find that lasting overexpression of PGC-1α leads to major alterations in the metabolic activity of neuronal cells which dramatically impair dopaminergic function in vivo. These results highlight the central role of PGC-1α in the function and survival of dopaminergic neurons and the critical need for maintaining physiological levels of PGC-1α activity. PMID:22246294

Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia.

PubMed

Sabogal, Angélica María; Arango, César Augusto; Cardona, Gloria Patricia; Céspedes, Ángel Enrique

2014-01-01

Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.

Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

PubMed

Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

2014-05-01

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter. © Georg Thieme Verlag KG Stuttgart · New York.

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

Reduced TH expression and α-synuclein accumulation contribute towards nigrostriatal dysfunction in experimental hepatic encephalopathy.

PubMed

Suárez, Isabel; Bodega, Guillermo; Rubio, Miguel; Fernández, Benjamín

2017-01-01

The present work examines α-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and α-synuclein expression were sought. Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), α-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub). In the control rats, TH immunoreactivity was detected in the neuronal cell bodies and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH-positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of α-synuclein-immunoreactive neurons in the SNc; some of the TH-positive neurons also showed α-synuclein immunoreactivity. In addition, α-synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas α-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure. α-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation.

Different interactions of prolyl oligopeptidase and neurotensin in dopaminergic function of the rat nigrostriatal and mesolimbic pathways.

PubMed

Peltonen, I; Myöhänen, T T; Männistö, P T

2012-09-01

Prolyl oligopeptidase (PREP) is an intracellular enzyme digesting small proline-containing peptides. Since PREP resides the same brain areas as neurotensin in the nigrostriatal and mesolimbic dopaminergic pathways, we were interested to study if there is an intracellular interaction between them. A colocalization of PREP with neurotensin and neurotensin receptor 1 (NTS1) in the rat striatum, nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) was studied with immunofluorescence. From the same brain areas, the levels of dopamine and its metabolites were measured 1 h after the injection of saline, NTS1 ligands (JMV-449; 5 μg) or antagonist (SR142948; 5 μg) to the rat striatum or NAcc. We also studied whether an intraperitoneal injection of a PREP inhibitor (KYP-2047; 5 mg/kg) affects the levels of dopamine and its metabolites alone or modifies the effects of the NTS1 ligands. PREP was highly colocalized with neurotensin and NTS1 in the VTA, and with NTS1 in the SN. Colocalization was moderate or low in other brain areas. When injected to the striatum, JMV-449 had a tendency to increase dopamine (p = 0.052) and metabolite levels in the striatum and SN, whereas SR142948 did not. After the injection to the NAcc, JMV-449 but not SR142948, increased dopamine levels in the VTA and dopamine metabolite levels in the NAcc and VTA. KYP-2047 decreased the dopamine levels in the striatum, but increased dopamine metabolite levels in the NAcc and VTA. Our results suggest a novel role for PREP in the modulation of dopaminergic transmission, which may be different in nigrostriatal and mesolimbic pathways.

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson’s Disease Stages?

PubMed Central

Hopes, Lucie; Grolez, Guillaume; Moreau, Caroline; Lopes, Renaud; Ryckewaert, Gilles; Carrière, Nicolas; Auger, Florent; Laloux, Charlotte; Petrault, Maud; Devedjian, Jean-Christophe; Bordet, Regis; Defebvre, Luc; Jissendi, Patrice; Delmaire, Christine; Devos, David

2016-01-01

Introduction Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Methods Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. Results The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Conclusion Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease. PMID:27035571

Varus deformity of the left lower extremity causing degenerative lesion of the posterior horn of the left medial meniscus in a patient with Paget's disease of bone.

PubMed

Al Kaissi, Ali; Ganger, Rudolf; Mindler, Gabriel; Klaushofer, Klaus; Grill, Franz

2014-01-01

We report on a 42-year-old woman who presented with persistent pain in her left knee with no history of trauma. Sagittal T1-weighted MRI of the left knee showed discontinuity between the anterior and posterior horns of the left medial meniscus, causing effectively the development of degenerative lesion of the posterior horn. The latter was correlated to varus deformity of the left lower extremity associated with subsequent narrowing of the medial knee joint. The unusual craniofacial contour of the patient, the skeletal survey and the elevated serum alkaline phosphatase were compatible with the diagnosis of Paget's disease of the bone. To alleviate the adverse effect of the mal-alignment of the left femur onto the left knee, corrective osteotomy of the left femoral diaphysis by means of fixators was performed. To the best of our knowledge this is the first clinical report describing the management and the pathological correlation of a unilateral varus deformity of the femoral shaft and degenerative lesions of the left knee in a patient with Paget's disease of the bone.

Incidence and clinical characteristics in a Colombian cohort of ocular toxoplasmosis.

PubMed

de-la-Torre, A; López-Castillo, C A; Gómez-Marín, J E

2009-05-01

To evaluate the incidence and clinical features of patients with ocular toxoplasmosis in a Colombian cohort. We collected prospectively the clinical features of patients with ocular toxoplasmosis seen at the 'Universidad del Quindio' health centre between September 2005 and September 2007 (24 months). Seventy patients were included in the analysis (95 affected eyes). The median age at the first episode was 21 years (range: 1-54 years). Thirty-two patients had active lesions (45.7%), one of them had active lesions in both eyes. The acquisition of infection was determined in 14 patients as congenital (20%), in seven as an acquired postnatal infection (10%), and in 49 as undetermined (70%). Bilateral involvement was found in 25 cases (35.7%). Unilateral legal blindness (<20/200) was found in 14 of 37 inactive cases (37.8%). The most frequent complication was strabismus (n: 12; 13.4%). There is a high incidence of cases of ocular toxoplasmosis in Quindio region (three new episodes by 100,000 inhabitants by year). Clinical features of ocular toxoplasmosis in Colombia are similar to those reported in other regions but there are no comparative data about the size and number of lesions.

Feeding-produced subchronic high plasma levels of uric acid improve behavioral dysfunction in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

PubMed

Nakashima, Akio; Yamauchi, Atsushi; Matsumoto, Junichi; Dohgu, Shinya; Takata, Fuyuko; Koga, Mitsuhisa; Fukae, Jiro; Tsuboi, Yoshio; Kataoka, Yasufumi

2018-05-25

The development of Parkinson's disease (PD) involves the degeneration of dopaminergic neurons caused by oxidative stress. Accumulating clinical evidence indicates that high blood levels of uric acid (UA), an intrinsic antioxidative substance, are associated with reduced risk of PD. However, this hypothesis has not been confirmed by in-vivo experiments. The present study investigated the effects of UA on behavioral abnormalities in the development of PD. We used unilateral 6-hydroxydopamine-lesioned mice, which were fed on a diet containing 1% UA and 2.5% potassium oxonate (an uricase inhibitor) to induce hyperuricemia. A significant elevation in UA levels was found in groups that were fed a UA diet. The 6-hydroxydopamine-lesioned mice showed impaired rotarod performance and increased apomorphine-induced contralateral rotations. These behavioral abnormalities were significantly reversed by feeding a UA diet for 1 week before and 5 weeks after surgery (subchronic hyperuricemia). These behavioral improvements occurred in parallel with recovery of tyrosine hydroxylase protein levels in the lesioned striatal side. The present study with a dietary hyperuricemia mice model confirms that UA exerts a neuroprotective effect on dopaminergic neuronal loss, improving motor dysfunction and ameliorating PD development.

Varus deformity of the left lower extremity causing degenerative lesion of the posterior horn of the left medial meniscus in a patient with Paget’s disease of bone

PubMed Central

Al Kaissi, Ali; Ganger, Rudolf; Mindler, Gabriel; Klaushofer, Klaus; Grill, Franz

2014-01-01

We report on a 42-year-old woman who presented with persistent pain in her left knee with no history of trauma. Sagittal T1-weighted MRI of the left knee showed discontinuity between the anterior and posterior horns of the left medial meniscus, causing effectively the development of degenerative lesion of the posterior horn. The latter was correlated to varus deformity of the left lower extremity associated with subsequent narrowing of the medial knee joint. The unusual craniofacial contour of the patient, the skeletal survey and the elevated serum alkaline phosphatase were compatible with the diagnosis of Paget’s disease of the bone. To alleviate the adverse effect of the mal-alignment of the left femur onto the left knee, corrective osteotomy of the left femoral diaphysis by means of fixators was performed. To the best of our knowledge this is the first clinical report describing the management and the pathological correlation of a unilateral varus deformity of the femoral shaft and degenerative lesions of the left knee in a patient with Paget’s disease of the bone. PMID:25276115

Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration

PubMed Central

Mor, Danielle E.; Tsika, Elpida; Mazzulli, Joseph R.; Gould, Neal S.; Kim, Hanna; Daniels, Malcolm J.; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L.; Tan, Victor X.; Kalb, Robert G.; Caldwell, Kim A.; Caldwell, Guy A.; Wolfe, John H.; Ischiropoulos, Harry

2018-01-01

Parkinson’s disease is defined by the loss of dopaminergic neurons in the substantia nigra and formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated dopamine levels in addition to α-synuclein expression. Nigra-targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine without damaging neurons in non-transgenic mice. In contrast, raising dopamine in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable C. elegans models expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. The data suggest a unique mechanism linking two cardinal features of Parkinson’s disease, dopaminergic cell death and α-synuclein aggregation. PMID:28920936

Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

PubMed

Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

2017-11-01

Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

PubMed

Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

1986-01-01

In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

PubMed

Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

2017-04-01

Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

Analysis of clinical value of CT in the diagnosis of pediatric pneumonia and mycoplasma pneumonia.

PubMed

Gong, Liang; Zhang, Chong-Lin; Zhen, Qing

2016-04-01

Pneumonia is an infectious disease of the lung causing mortality. Mycoplasma pneumonia (MP) is an atypical bacterial pneumonia that damages several organs. Lung computed tomography (CT) has been utilized in its identification. The aim of the present study was to examine the value of computed tomography diagnosis for pediatric MP. The present study prospectively analyzed the clinical and imaging data of 1,280 cases of pediatric MP in the out- and inpatient departments from March, 2010 to March, 2014; analyzed the morphology and distribution of the pneumonic lesion in the lungs; and summarized the value of CT diagnosis for pediatric MP. In the included children, there were 688 cases of lesions in the unilateral lobe, 592 cases of lesions in the bilateral lobes, 1,101 cases of extensive patchy opacity, 496 cases of mottled opacity, 432 cases of increased lung marking, 256 cases of streak opacity, 192 cases of ground-glass opacity, 992 cases of thickened bronchial wall in the lesions, 128 cases of lymphadenopathy in the hilar lymph nodes and mediastinal lymph nodes, and the lung CT showed 32 cases of pulmonary cavity and 144 cases of pleural effusion. In conclusion, the CT signals of pediatric MP had several types with some children exhibiting complicated changes. The child's clinical manifestation and symptoms should thus be considered in the diagnosis to improve the diagnostic rate.

Re-assessing acalculia: Distinguishing spatial and purely arithmetical deficits in right-hemisphere damaged patients.

PubMed

Benavides-Varela, S; Piva, D; Burgio, F; Passarini, L; Rolma, G; Meneghello, F; Semenza, C

2017-03-01

Arithmetical deficits in right-hemisphere damaged patients have been traditionally considered secondary to visuo-spatial impairments, although the exact relationship between the two deficits has rarely been assessed. The present study implemented a voxelwise lesion analysis among 30 right-hemisphere damaged patients and a controlled, matched-sample, cross-sectional analysis with 35 cognitively normal controls regressing three composite cognitive measures on standardized numerical measures. The results showed that patients and controls significantly differ in Number comprehension, Transcoding, and Written operations, particularly subtractions and multiplications. The percentage of patients performing below the cutoffs ranged between 27% and 47% across these tasks. Spatial errors were associated with extensive lesions in fronto-temporo-parietal regions -which frequently lead to neglect- whereas pure arithmetical errors appeared related to more confined lesions in the right angular gyrus and its proximity. Stepwise regression models consistently revealed that spatial errors were primarily predicted by composite measures of visuo-spatial attention/neglect and representational abilities. Conversely, specific errors of arithmetic nature linked to representational abilities only. Crucially, the proportion of arithmetical errors (ranging from 65% to 100% across tasks) was higher than that of spatial ones. These findings thus suggest that unilateral right hemisphere lesions can directly affect core numerical/arithmetical processes, and that right-hemisphere acalculia is not only ascribable to visuo-spatial deficits as traditionally thought. Copyright © 2017 Elsevier Ltd. All rights reserved.

Caudal Zona Incerta/VOP Radiofrequency Lesioning Guided by Combined Stereotactic MRI and Microelectrode Recording for Posttraumatic Midbrain Resting-Kinetic Tremor.

PubMed

Contreras Lopez, William Omar; Azevedo, Angelo R; Cury, Rubens G; Alencar, Francisco; Neville, Iuri S; Reis, Paul R; Navarro, Jessie; Monaco, Bernardo; da Silva, Fabio E Fernandes; Teixeira, Manoel J; Fonoff, Erich T

2016-02-01

Reporting the outcome of two patients who underwent unilateral ablative stereotactic surgery to treat pharmacologic resistant posttraumatic tremor (PTT). We present two patients (31 and 47 years old) with refractory PTT severely affecting their quality of life. Under stereotactic guidance, refined by T2-weighted magnetic resonance imaging and double-channel multiunit microelectrode recording (MER), three sequential radiofrequency lesions were performed in the caudal zona incerta (cZi) up to the base of thalamus (VOP). Effects of cZi/VOP lesion were prospectively rated with a tremor rating scale. Both patients demonstrated intraoperative tremor suppression with sustained results up to 18 months follow-up, with improvement of 92% and 84%, respectively, on the tremor rating scale. Tremor improvement was associated with enhancement functionality and quality of life for the patients. The patients returned to their work after the procedure. No adverse effects were observed up to the last follow-up. Radiofrequency lesion of the cZi/VOP target was effective for posttraumatic tremor in both cases. The use of T2-weighted images and MER was found helpful in increasing the precision and safety of the procedure, because it leads the RF probe by relying on neighbor structures based on thalamus and subthalamic nucleus. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroprotective effect of the methanolic extract of Hibiscus asper leaves in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

PubMed

Hritcu, Lucian; Foyet, Harquin Simplice; Stefan, Marius; Mihasan, Marius; Asongalem, Acha Emmanuel; Kamtchouing, Pierre

2011-09-01

While the Hibiscus asper Hook.f. (Malvaceae) is a traditional herb largely used in tropical region of the Africa as vegetable, potent sedative, tonic and restorative, anti-inflammatory and antidepressive drug, there is very little scientific data concerning the efficacy of this. The antioxidant and antiapoptotic activities of the methanolic extract of Hibiscus asper leaves (50 and 100 mg/kg) were assessed using superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) specific activities, total glutathione (GSH) content, malondialdehyde (MDA) level (lipid peroxidation) and DNA fragmentation assays in male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion. In 6-OHDA-lesioned rats, methanolic extract of Hibiscus asper leaves showed potent antioxidant and antiapoptotic activities. Chronic administration of the methanolic extract (50 and 100 mg/kg, i.p., daily, for 7 days) significantly increased antioxidant enzyme activities (SOD, GPX and CAT), total GSH content and reduced lipid peroxidation (MDA level) in rat temporal lobe homogenates, suggesting antioxidant activity. Also, DNA cleavage patterns were absent in the 6-OHDA-lesioned rats treated with methanolic extract of Hibiscus asper leaves, suggesting antiapoptotic activity. Taken together, our results suggest that the methanolic extract of Hibiscus asper leaves possesses neuroprotective activity against 6-OHDA-induced toxicity through antioxidant and antiapoptotic activities in Parkinson's disease model. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Localization of Impaired Kinesthetic Processing Post-stroke.

PubMed

Kenzie, Jeffrey M; Semrau, Jennifer A; Findlater, Sonja E; Yu, Amy Y; Desai, Jamsheed A; Herter, Troy M; Hill, Michael D; Scott, Stephen H; Dukelow, Sean P

2016-01-01

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects ( N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

Localization of Impaired Kinesthetic Processing Post-stroke

PubMed Central

Kenzie, Jeffrey M.; Semrau, Jennifer A.; Findlater, Sonja E.; Yu, Amy Y.; Desai, Jamsheed A.; Herter, Troy M.; Hill, Michael D.; Scott, Stephen H.; Dukelow, Sean P.

2016-01-01

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network. PMID:27799902

Expression of dopamine D2 receptor and choline acetyltransferase mRNA in the dopamine deafferented rat caudate-putamen.

PubMed

Brené, S; Lindefors, N; Herrera-Marschitz, M; Persson, H

1990-01-01

In situ hybridization was used to study dopamine D2 receptor (D2R) and choline acetyltransferase (ChAT) mRNA expression in neurons of the rat forebrain, both on control animals and after a unilateral 6-hydroxydopamine (6-OHDA) lesion of midbrain dopamine neurons. D2R mRNA expressing neurons were seen in regions which are known to be heavily innervated by midbrain dopamine fibers such as caudate-putamen, nucleus accumbens and olfactory tubercle. ChAT mRNA expressing neurons were seen in caudate-putamen, nucleus accumbens and septal regions including vertical limb of the diagonal band. In caudate-putamen, approximately 55% of the medium sized neurons, which is the predominating neuronal cell-size in this region, were specifically labeled with the D2R probe. In addition, approximately 95% of the large size neurons in caudate-putamen were specifically labeled with both the D2R and ChAT probes, suggesting that most cholinergic neurons in the caudate-putamen express D2R mRNA. After a unilateral lesion of midbrain dopamine neurons, no change in the level of either D2R or ChAT mRNA were seen in the large size intrinsic cholinergic neurons in caudate-putamen. Similarly, no evidence was obtained for altered levels of D2R mRNA in medium size neurons in medial caudate-putamen, or nucleus accumbens. However, an increase in the number of medium size neurons expressing D2R mRNA was observed in the lateral part of the dopamine deafferented caudate-putamen. Thus, it appears that midbrain dopamine deafferentation causes an increase in D2R mRNA expression in a subpopulation of medium size neurons in the lateral caudate-putamen.

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

PubMed

Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

2018-01-01

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs

PubMed Central

Michel, Anne; Downey, Patrick; Van Damme, Xavier; De Wolf, Catherine; Schwarting, Rainer; Scheller, Dieter

2015-01-01

In Parkinson’s disease (PD), dopaminergic therapies are often associated with the development of motor complications. Attention has therefore been focused on the use of non-dopaminergic drugs. This study developed a new behavioural method capable of demonstrating the added value of combining adenosinergic and glutamatergic receptor antagonists in unilateral 6-OHDA lesioned rats. Rats were dosed orally with Tozadenant, a selective A2A receptor antagonist, and three different doses of Radiprodil, an NR2B-selective NMDA receptor antagonist. The drugs were given alone or in combination and rats were placed in an open-field for behavioural monitoring. Video recordings were automatically analysed. Five different behaviours were scored: distance traveled, ipsi- and contraversive turns, body position, and space occupancy. The results show that A2A or NR2B receptor antagonists given alone or in combination did not produce enhanced turning as observed with an active dose of L-Dopa/benserazide. Instead the treated rats maintained a straight body position, were able to shift from one direction to the other and occupied a significantly larger space in the arena. The highest “Tozadenant/Radiprodil” dose combination significantly increased all five behavioural parameters recorded compared to rats treated with vehicle or the same doses of the drugs alone. Our data suggest that the A2A/NR2B antagonist combination may be able to stimulate motor activity to a similar level as that achieved by L-Dopa but in the absence of the side-effects that are associated with dopaminergic hyperstimulation. If these results translate into the clinic, this combination could represent an alternative symptomatic treatment option for PD. PMID:26322641

Alterations in regional shape on ipsilateral and contralateral cortex contrast in children with unilateral cerebral palsy and are predictive of multiple outcomes.

PubMed

Pagnozzi, Alex M; Dowson, Nicholas; Fiori, Simona; Doecke, James; Bradley, Andrew P; Boyd, Roslyn N; Rose, Stephen

2016-10-01

Congenital brain lesions result in a wide range of cerebral tissue alterations observed in children with cerebral palsy (CP) that are associated with a range of functional impairments. The relationship between injury severity and functional outcomes, however, remains poorly understood. This research investigates the differences in cortical shape between children with congenital brain lesions and typically developing children (TDC) and investigates the correlations between cortical shape and functional outcome in a large cohort of patients diagnosed with unilateral CP. Using 139 structural magnetic resonance images, including 95 patients with clinically diagnosed CP and 44 TDC, cortical segmentations were obtained using a modified expectation maximization algorithm. Three shape characteristics (cortical thickness, curvature, and sulcal depth) were computed within a number of cortical regions. Significant differences in these shape measures compared to the TDC were observed on both the injured hemisphere of children with CP (P < 0.004), as well as on the apparently uninjured hemisphere, illustrating potential compensatory mechanisms in these children. Furthermore, these shape measures were significantly correlated with several functional outcomes, including motor, cognition, vision, and communication (P < 0.012), with three out of these four models performing well on test set validation. This study highlights that cortical neuroplastic effects may be quantified using MR imaging, allowing morphological changes to be studied longitudinally, including any influence of treatment. Ultimately, such approaches could be used for the long term prediction of outcomes and the tailoring of treatment to individuals. Hum Brain Mapp 37:3588-3603, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions

PubMed Central

Scheck, Simon M.; Pannek, Kerstin; Raffelt, David A.; Fiori, Simona; Boyd, Roslyn N.; Rose, Stephen E.

2015-01-01

In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC–precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC–superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = −0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function. PMID:26640762

Diffusion-Weighted Magnetic Resonance Imaging Characterization of White Matter Injury Produced by Axon-Sparing Demyelination and Severe Contusion Spinal Cord Injury in Rats

PubMed Central

Nout-Lomas, Yvette S.; Wendland, Michael F.; Mukherjee, Pratik; Huie, J. Russell; Hess, Christopher P.; Mabray, Marc C.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2016-01-01

Abstract Alterations in magnetic resonance imaging (MRI)–derived measurements of water diffusion parallel (D∥) and perpendicular (D⊥) to white matter tracts have been specifically attributed to pathology of axons and myelin, respectively. We test the hypothesis that directional diffusion measurements can distinguish between axon-sparing chemical demyelination and severe contusion spinal cord white matter injury. Adult rats received either unilateral ethidium bromide (EB) microinjections (chemical demyelination) into the lateral funiculus of the spinal cord at C5 or were subjected to unilateral severe contusion spinal cord injury (SCI). Diffusion MRI metrics in the lateral funiculus were analyzed at early and late time-points following injury and correlated with histology. Early EB-demyelination resulted in a significant elevation in D⊥ and significant reduction in D∥ at the injury epicenter, with histological evidence of uniform axon preservation. Alterations in D⊥ and D∥ at the epicenter of early EB-demyelination were not significantly different from those observed with severe contusion at the epicenter, where histology demonstrated severe combined axonal and myelin injury. Diffusion abnormalities away from the injury epicenter were seen with contusion injury, but not with EB-demyelination. Chronic EB lesions underwent endogenous remyelination with normalization of diffusion metrics, whereas chronic contusion resulted in persistently altered diffusivities. In the early setting, directional diffusion measurements at the injury epicenter associated with chemical demyelination are indistinguishable from those seen with severe contusive SCI, despite dramatic pathologic differences between injury models. Caution is advised in interpretation of diffusion metrics with respect to specific white matter structural alterations. Diffusion analysis should not be limited to the epicenter of focal spinal lesions as alterations marginal to the epicenter are useful for assessing the nature of focal white matter injury. PMID:26483094

Expression of mRNAs encoding dopamine receptors in striatal regions is differentially regulated by midbrain and hippocampal neurons.

PubMed

Brené, S; Herrera-Marschitz, M; Persson, H; Lindefors, N

1994-02-01

The glutamate analogue kainic acid was injected into the hippocampus of intact or 6-hydroxydopamine deafferented rats to investigate the influence of hippocampal neurons on the expression of dopamine D1 and D2 receptor mRNAs in subregions of the striatal complex and possible modulation by dopaminergic neurons. Quantitative in situ hybridization using 35S-labeled oligonucleotide probes specific for dopamine D1 and D2 receptor mRNAs, respectively, were used. It was found that an injection of kainic acid into the hippocampal formation had alone no significant effect on dopamine D1 or D2 receptor mRNA levels in any of the analyzed striatal subregions in animals analyzed 4 h after the injections. Kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion produced an increase in D1 receptor mRNA levels in the ipsilateral medial caudate-putamen, and a bilateral increase in core and shell of nucleus accumbens (ventral striatal limbic regions). A unilateral 6-hydroxydopamine lesion alone caused an increase in D2 receptor mRNA in the lateral caudate-putamen (dorsal striatal motor region) ipsilateral to the lesion and an increase in D1 receptor mRNA in the accumbens core ipsilateral to the lesion. However, in dopamine-lesioned animals, dopamine D1 receptor mRNA levels were increased bilaterally in nucleus accumbens core and shell and in the ipsilateral medial caudate-putamen following kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion. These results indicate a differential regulation of the expression of dopamine D1 and D2 receptor mRNAs by midbrain and hippocampal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)