Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

PubMed Central

Downey, Luke A.; Loftis, Jennifer M.

2014-01-01

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine.

PubMed

Downey, Luke A; Loftis, Jennifer M

2014-03-15

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. Published by Elsevier B.V.

Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training.

PubMed

Levine, Brian; Schweizer, Tom A; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T; Manly, Tom; Robertson, Ian H

2011-01-01

Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits.

Loss of Neuronal Integrity During Progressive HIV-1 Infection of Humanized Mice

PubMed Central

Dash, Prasanta K.; Gorantla, Santhi; Gendelman, Howard E; Knibbe, Jaclyn; Casale, George P; Makarov, Edward; Epstein, Adrian A; Gelbard, Harris A; Boska, Michael D; Poluektova, Larisa Y

2011-01-01

Neuronal damage induced by ongoing HIV-1 infection was investigated in humanized NOD/scid-IL-2Rgcnull mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4+ T cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity following HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration. PMID:21368026

N-acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis.

PubMed

Trentini, Alessandro; Comabella, Manuel; Tintoré, Mar; Koel-Simmelink, Marleen J A; Killestein, Joep; Roos, Birthe; Rovira, Alex; Korth, Carsten; Ottis, Philipp; Blankenstein, Marinus A; Montalban, Xavier; Bellini, Tiziana; Teunissen, Charlotte E

2014-12-01

Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC). Biomarkers were related to Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) over a long period of follow-up [median (interquartile range) 9 (5.5-12.5) years] in 19 PPMS and 4 SPMS patients, and to T2 lesion load, T1 lesion load, and brain parenchymal fraction at the time of lumbar puncture. Nf light was higher in PPMS (p < 0.005) and Nf heavy was increased in both SPMS and PPMS (p < 0.05 and p < 0.01) compared to NINDC, but were comparable between the two MS subtypes. Nf heavy was a predictor of the ongoing disability measured by MSSS (R(2) = 0.17, β = 0.413; p < 0.05). Conversely, Nf light was the only predictor of the EDSS annual increase (R(2) = 0.195, β = 0.441; p < 0.05). The frequency of abnormal biomarkers did not differ between the two MS progressive subtypes. Our data suggest that PP and SPMS likely share similar mechanisms of axonal damage. Moreover, Nf heavy can be a biomarker of ongoing axonal damage. Conversely, Nf light can be used as a prognostic marker for accumulating disability suggesting it as a good tool for possible treatment monitoring in the progressive MS forms.

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão’s legacy

PubMed Central

Shuttleworth, C William; Kirov, Sergei A; Ayata, Cenk; Hinzman, Jason M; Foreman, Brandon; Andrew, R David; Boutelle, Martyn G; Brennan, KC; Carlson, Andrew P; Dahlem, Markus A; Drenckhahn, Christoph; Dohmen, Christian; Fabricius, Martin; Farkas, Eszter; Feuerstein, Delphine; Graf, Rudolf; Helbok, Raimund; Lauritzen, Martin; Major, Sebastian; Oliveira-Ferreira, Ana I; Richter, Frank; Rosenthal, Eric S; Sakowitz, Oliver W; Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Strong, Anthony J; Urbach, Anja; Westover, M Brandon; Winkler, Maren KL; Witte, Otto W; Woitzik, Johannes; Dreier, Jens P

2016-01-01

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão’s historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage. PMID:27328690

Neuroimmunomodulation and Aging.

PubMed

Gemma, Carmelina

2010-12-01

Inflammation is by definition a protective phase of the immune response. The very first goal of inflammation is destroying and phagocytosing infected or damaged cells to avoid the spread of the pathogen or of the damage to neighboring, healthy, cells. However, we now know that during many chronic neurological disorders, inflammation and degeneration always coexist at certain time points. For example, inflammation comes first in multiple sclerosis, but degeneration follows, while in Alzheimer's or Parkinson's disease degeneration starts and inflammation is secondary. Either way these are the two pathological detectable problems. The central nervous system (CNS) has long been viewed as exempt from the effects of the immune system. The brain has physical barriers for protection, and it is now clear that cells in the nervous system respond to inflammation and injury in unique ways. In recent years, researchers have presented evidence supporting the idea that in the CNS there is an ongoing protective inflammatory mechanism, which involves macrophage, monocytes, T cells, regulatory T-cells, effector T cells and many others; these, in turn, promote repair mechanisms in the brain not only during inflammatory, and degenerative disorders but also in healthy people. This "repair mechanism" can be considered as an intrinsic part of the physiological activities of the brain. It is now well known that the microenvironment of the brain is a crucial player in determining the relative contribution of the two different outcomes. Failure of molecular and cellular mechanisms sustaining the "brain-repair programme" might be, at least in part, a cause of neurological disorders. Today, the neurotoxic and neuroprotective roles of the innate immune reactions in aging, brain injury, ischemia, autoimmune and neurodegenerative disorders of the CNS are widely investigated and highly debated research topics. Nevertheless, several issues remain to be elucidated, notably the earlier cellular events that initiate dysregulation of brain inflammatory pathways. If these inflammatory processes could be identified and harnessed, then cognitive function may be protected during aging and age-related neurodegenerative diseases through early interventions directed against the negative consequences of inflammation. This commentary highlights the major issues/opinions presented by experts on the involvement of the brain immune system in aging and age-related diseases in a special edition of the journal Aging and Disease.

Hemispheric processing of vocal emblem sounds.

PubMed

Neumann-Werth, Yael; Levy, Erika S; Obler, Loraine K

2013-01-01

Vocal emblems, such as shh and brr, are speech sounds that have linguistic and nonlinguistic features; thus, it is unclear how they are processed in the brain. Five adult dextral individuals with left-brain damage and moderate-severe Wernicke's aphasia, five adult dextral individuals with right-brain damage, and five Controls participated in two tasks: (1) matching vocal emblems to photographs ('picture task') and (2) matching vocal emblems to verbal translations ('phrase task'). Cross-group statistical analyses on items on which the Controls performed at ceiling revealed lower accuracy by the group with left-brain damage (than by Controls) on both tasks, and lower accuracy by the group with right-brain damage (than by Controls) on the picture task. Additionally, the group with left-brain damage performed significantly less accurately than the group with right-brain damage on the phrase task only. Findings suggest that comprehension of vocal emblems recruits more left- than right-hemisphere processing.

Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals.

PubMed

Doi, Kunio

2011-01-01

It is not widely known how the developing brain responds to extrinsic damage, although the developing brain is considered to be sensitive to diverse environmental factors including DNA-damaging agents. This paper reviews the mechanisms of neurotoxicity induced in the developing brain of mice and rats by six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide), which cause DNA damage in different ways, especially from the viewpoints of apoptosis and cell cycle arrest in neural progenitor cells. In addition, this paper also reviews the repair process following damage in the developing brain.

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Death revisited: rethinking death and the dead donor rule.

PubMed

Iltis, Ana Smith; Cherry, Mark J

2010-06-01

Traditionally, people were recognized as being dead using cardio-respiratory criteria: individuals who had permanently stopped breathing and whose heart had permanently stopped beating were dead. Technological developments in the middle of the twentieth century and the advent of the intensive care unit made it possible to sustain cardio-respiratory and other functions in patients with severe brain injury who previously would have lost such functions permanently shortly after sustaining a brain injury. What could and should physicians caring for such patients do? Significant advances in human organ transplantation also played direct and indirect roles in discussions regarding the care of such patients. Because successful transplantation requires that organs be removed from cadavers shortly after death to avoid organ damage due to loss of oxygen, there has been keen interest in knowing precisely when people are dead so that organs could be removed. Criteria for declaring death using neurological criteria developed, and today a whole brain definition of death is widely used and recognized by all 50 states in the United States as an acceptable way to determine death. We explore the ongoing debate over definitions of death, particularly over brain death or death determined using neurological criteria, and the relationship between definitions of death and organ transplantation.

Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

PubMed Central

Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

2009-01-01

The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

Catecholamines and cognition after traumatic brain injury

PubMed Central

Jenkins, Peter O.; Mehta, Mitul A.

2016-01-01

Abstract Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

Rehabilitation of Executive Functioning in Patients with Frontal Lobe Brain Damage with Goal Management Training

PubMed Central

Levine, Brian; Schweizer, Tom A.; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T.; Manly, Tom; Robertson, Ian H.

2011-01-01

Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits. PMID:21369362

Emerging insights into barriers to effective brain tumor therapeutics.

PubMed

Woodworth, Graeme F; Dunn, Gavin P; Nance, Elizabeth A; Hanes, Justin; Brem, Henry

2014-01-01

There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM.

Evaluation and Education of Children with Brain Damage.

ERIC Educational Resources Information Center

Bortner, Morton, Ed.

Ten papers consider brain damaged children. Brain damage is considered as an educational category, and the following aspects of evaluation are treated: disorders of oral communication, hearing impairment, psychological deficit, psychiatric factors, and neurological considerations. Educational strategies discussed include the educational methods of…

Interhemispheric and Intrahemispheric Control of Emotion: A Focus on Unilateral Brain Damage.

ERIC Educational Resources Information Center

Borod, Joan C.

1992-01-01

Discusses neocortical contributions to emotional processing. Examines parameters critical to neuropsychological study of emotion: interhemispheric and intrahemispheric factors, processing mode, and communication channel. Describes neuropsychological theories of emotion. Reviews studies of right-brain-damaged, left-brain-damaged, and normal adults,…

Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

PubMed

Bartolomeo, Paolo; Thiebaut de Schotten, Michel

2016-12-01

Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells

PubMed Central

Coufal, Nicole G.; Garcia-Perez, Josè Luis; Peng, Grace E.; Marchetto, Maria C. N.; Muotri, Alysson R.; Mu, Yangling; Carson, Christian T.; Macia, Angela; Moran, John V.; Gage, Fred H.

2011-01-01

Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition. PMID:22159035

Thalamic atrophy in antero-medial and dorsal nuclei correlates with six-month outcome after severe brain injury☆

PubMed Central

Lutkenhoff, Evan S.; McArthur, David L.; Hua, Xue; Thompson, Paul M.; Vespa, Paul M.; Monti, Martin M.

2013-01-01

The primary and secondary damage to neural tissue inflicted by traumatic brain injury is a leading cause of death and disability. The secondary processes, in particular, are of great clinical interest because of their potential susceptibility to intervention. We address the dynamics of tissue degeneration in cortico-subcortical circuits after severe brain injury by assessing volume change in individual thalamic nuclei over the first six-months post-injury in a sample of 25 moderate to severe traumatic brain injury patients. Using tensor-based morphometry, we observed significant localized thalamic atrophy over the six-month period in antero-dorsal limbic nuclei as well as in medio-dorsal association nuclei. Importantly, the degree of atrophy in these nuclei was predictive, even after controlling for full-brain volume change, of behavioral outcome at six-months post-injury. Furthermore, employing a data-driven decision tree model, we found that physiological measures, namely the extent of atrophy in the anterior thalamic nucleus, were the most predictive variables of whether patients had regained consciousness by six-months, followed by behavioral measures. Overall, these findings suggest that the secondary non-mechanical degenerative processes triggered by severe brain injury are still ongoing after the first week post-trauma and target specifically antero-medial and dorsal thalamic nuclei. This result therefore offers a potential window of intervention, and a specific target region, in agreement with the view that specific cortico-thalamo-cortical circuits are crucial to the maintenance of large-scale network neural activity and thereby the restoration of cognitive function after severe brain injury. PMID:24273723

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

Patterns of Post-Stroke Brain Damage that Predict Speech Production Errors in Apraxia of Speech and Aphasia Dissociate

PubMed Central

Basilakos, Alexandra; Rorden, Chris; Bonilha, Leonardo; Moser, Dana; Fridriksson, Julius

2015-01-01

Background and Purpose Acquired apraxia of speech (AOS) is a motor speech disorder caused by brain damage. AOS often co-occurs with aphasia, a language disorder in which patients may also demonstrate speech production errors. The overlap of speech production deficits in both disorders has raised questions regarding if AOS emerges from a unique pattern of brain damage or as a sub-element of the aphasic syndrome. The purpose of this study was to determine whether speech production errors in AOS and aphasia are associated with distinctive patterns of brain injury. Methods Forty-three patients with history of a single left-hemisphere stroke underwent comprehensive speech and language testing. The Apraxia of Speech Rating Scale was used to rate speech errors specific to AOS versus speech errors that can also be associated with AOS and/or aphasia. Localized brain damage was identified using structural MRI, and voxel-based lesion-impairment mapping was used to evaluate the relationship between speech errors specific to AOS, those that can occur in AOS and/or aphasia, and brain damage. Results The pattern of brain damage associated with AOS was most strongly associated with damage to cortical motor regions, with additional involvement of somatosensory areas. Speech production deficits that could be attributed to AOS and/or aphasia were associated with damage to the temporal lobe and the inferior pre-central frontal regions. Conclusion AOS likely occurs in conjunction with aphasia due to the proximity of the brain areas supporting speech and language, but the neurobiological substrate for each disorder differs. PMID:25908457

Patterns of poststroke brain damage that predict speech production errors in apraxia of speech and aphasia dissociate.

PubMed

Basilakos, Alexandra; Rorden, Chris; Bonilha, Leonardo; Moser, Dana; Fridriksson, Julius

2015-06-01

Acquired apraxia of speech (AOS) is a motor speech disorder caused by brain damage. AOS often co-occurs with aphasia, a language disorder in which patients may also demonstrate speech production errors. The overlap of speech production deficits in both disorders has raised questions on whether AOS emerges from a unique pattern of brain damage or as a subelement of the aphasic syndrome. The purpose of this study was to determine whether speech production errors in AOS and aphasia are associated with distinctive patterns of brain injury. Forty-three patients with history of a single left-hemisphere stroke underwent comprehensive speech and language testing. The AOS Rating Scale was used to rate speech errors specific to AOS versus speech errors that can also be associated with both AOS and aphasia. Localized brain damage was identified using structural magnetic resonance imaging, and voxel-based lesion-impairment mapping was used to evaluate the relationship between speech errors specific to AOS, those that can occur in AOS or aphasia, and brain damage. The pattern of brain damage associated with AOS was most strongly associated with damage to cortical motor regions, with additional involvement of somatosensory areas. Speech production deficits that could be attributed to AOS or aphasia were associated with damage to the temporal lobe and the inferior precentral frontal regions. AOS likely occurs in conjunction with aphasia because of the proximity of the brain areas supporting speech and language, but the neurobiological substrate for each disorder differs. © 2015 American Heart Association, Inc.

Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

PubMed

Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

2018-05-01

Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

Sex Differences in the Effects of Unilateral Brain Damage on Intelligence

NASA Astrophysics Data System (ADS)

Inglis, James; Lawson, J. S.

1981-05-01

A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male but not in female patients. This sex difference explains some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked.

Brain damage in fatal non-missile head injury without high intracranial pressure.

PubMed Central

Graham, D I; Lawrence, A E; Adams, J H; Doyle, D; McLellan, D R

1988-01-01

As part of a comprehensive study of brain damage in 635 fatal non-missile head injuries, the type and prevalence of brain damage occurring in the absence of high intracranial pressure were analysed. Of 71 such cases, 53 sustained their injury as a result of a road traffic accident; only 25 experienced a lucid interval. Thirty eight had a fractured skull, a mean total contusion index of 12.9 and diffuse axonal injury in 29: severe to moderate ischaemic damage was present in the cerebral cortex in 25, brain swelling in 13, and acute bacterial meningitis in nine. The prevalence and range of brain damage that may occur in the absence of high intracranial pressure are important to forensic pathologists in the medicolegal interpretation of cases of fatal head injury. PMID:3343378

Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

PubMed Central

Thut, Gregor; Bergmann, Til Ole; Fröhlich, Flavio; Soekadar, Surjo R.; Brittain, John-Stuart; Valero-Cabré, Antoni; Sack, Alexander; Miniussi, Carlo; Antal, Andrea; Siebner, Hartwig Roman; Ziemann, Ulf; Herrmann, Christoph S.

2017-01-01

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges. PMID:28233641

The impact of unilateral brain damage on anticipatory grip force scaling when lifting everyday objects.

PubMed

Eidenmüller, S; Randerath, J; Goldenberg, G; Li, Y; Hermsdörfer, J

2014-08-01

The scaling of our finger forces according to the properties of manipulated objects is an elementary prerequisite of skilled motor behavior. Lesions of the motor-dominant left brain may impair several aspects of motor planning. For example, limb-apraxia, a tool-use disorder after left brain damage is thought to be caused by deficient recall or integration of tool-use knowledge into an action plan. The aim of the present study was to investigate whether left brain damage affects anticipatory force scaling when lifting everyday objects. We examined 26 stroke patients with unilateral brain damage (16 with left brain damage, ten with right brain damage) and 21 healthy control subjects. Limb apraxia was assessed by testing pantomime of familiar tool-use and imitation of meaningless hand postures. Participants grasped and lifted twelve randomly presented everyday objects. Grip force was measured with help of sensors fixed on thumb, index and middle-finger. The maximum rate of grip force was determined to quantify the precision of anticipation of object properties. Regression analysis yielded clear deficits of anticipation in the group of patients with left brain damage, while the comparison of patient with right brain damage with their respective control group did not reveal comparable deficits. Lesion-analyses indicate that brain structures typically associated with a tool-use network in the left hemisphere play an essential role for anticipatory grip force scaling, especially the left inferior frontal gyrus (IFG) and the premotor cortex (PMC). Furthermore, significant correlations of impaired anticipation with limb apraxia scores suggest shared representations. However, the presence of dissociations, implicates also independent processes. Overall, our findings suggest that the left hemisphere is engaged in anticipatory grip force scaling for lifting everyday objects. The underlying neural substrate is not restricted to a single region or stream; instead it may rely on the intact functioning of a left hemisphere network that may overlap with the left hemisphere dominant tool-use network. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Neglect severity after left and right brain damage.

PubMed

Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

2012-05-01

While unilateral spatial neglect after left brain damage is undoubtedly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than -0.086 on the Bells Test and greater than -0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for acute left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

BRAIN DAMAGE IN CHILDREN, THE BIOLOGICAL AND SOCIAL ASPECTS.

ERIC Educational Resources Information Center

BIRCH, HERBERT G., ED.

PAPERS AND DISCUSSION SUMMARIES ARE PRESENTED FROM A CONFERENCE ON THE BIOLOGICAL AND SOCIAL PROBLEMS OF CHILDHOOD BRAIN DAMAGE, HELD AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA IN NOVEMBER 1962. A VARIETY OF DISCIPLINES IS REPRESENTED, AND THE FOLLOWING TOPICS ARE CONSIDERED--(1) "THE PROBLEM OF 'BRAIN DAMAGE' IN CHILDREN" BY HERBERT G. BIRCH, (2)…

Brain and Cognitive-Behavioural Development after Asphyxia at Term Birth

ERIC Educational Resources Information Center

de Haan, Michelle; Wyatt, John S.; Roth, Simon; Vargha-Khadem, Faraneh; Gadian, David; Mishkin, Mortimer

2006-01-01

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has…

Epileptogenesis in experimental models.

PubMed

Pitkänen, Asla; Kharatishvili, Irina; Karhunen, Heli; Lukasiuk, Katarzyna; Immonen, Riikka; Nairismägi, Jaak; Gröhn, Olli; Nissinen, Jari

2007-01-01

Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.

Diabetic aggravation of stroke and animal models

PubMed Central

Rehni, Ashish K.; Liu, Allen; Perez-Pinzon, Miguel A.; Dave, Kunjan R.

2017-01-01

Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia currently being employed to study diabetes-related ischemic brain damage. The rational use of such animal systems in studying the disease condition may better help evaluate novel therapeutic approaches for diabetes related exacerbation of ischemic brain damage. PMID:28274862

Categorization skills and recall in brain damaged children: a multiple case study.

PubMed

Mello, Claudia Berlim de; Muszkat, Mauro; Xavier, Gilberto Fernando; Bueno, Orlando Francisco Amodeo

2009-09-01

During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.

Neurodegenerative changes and apoptosis induced by intrauterine and extrauterine exposure of radiofrequency radiation.

PubMed

Güler, Göknur; Ozgur, Elcin; Keles, Hikmet; Tomruk, Arin; Vural, Sevil Atalay; Seyhan, Nesrin

2016-09-01

Adverse health effects of radiofrequency radiation (RFR) on the ongoing developmental stages of children from conception to childhood are scientifically anticipated subject. This study was performed to identify the effects of global system for mobile communications (GSM) modulated mobile phone like RFR in 1800MHz frequency on oxidative DNA damage and lipid peroxidation beside the apoptotic cell formation, using histopathological and immunohistochemical methods in the brain tissue of 1-month-old male and female New Zealand White rabbits that were exposed to these fields at their mother's womb and after the birth. Oxidative DNA damage and lipid peroxidation levels were investigated by measuring the 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels, respectively. Histopathological changes were observed using by hematoxylin and eosin (HE) staining. Apoptotic cells were detected in the examined organs by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. For both male and female infants; 8-OHdG levels increased in the group exposed to RFR in both intrauterine and extrauterine periods compared to the infants that were never exposed to RFR and the ones were exposed when they reached one month of age (p<0.05). MDA results were different for male and female rabbits. There was no difference between all female infant groups (p>0.05), while only intrauterine exposure significantly causes MDA level increase for the male infants. HE staining revealed mild lessions in neuronal necrobiosis in brain tissues of female rabbits that had only intaruterine exposure and male rabbits had only extrauterine exposure. Gliosis were mildly positive in brain tissues of rabbits that are exposed only intrauterine period, also the group exposed both intrauterine and extrauterine periods. However, there was no apoptotic change detected by TUNEL staining in the brain tissues of all groups. Copyright © 2015 Elsevier B.V. All rights reserved.

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Novel neuroprotective and hepatoprotective effects of citric acid in acute malathion intoxication.

PubMed

Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Yassen, Noha N; Khadrawy, Yasser A; El-Toukhy, Safinaz Ebrahim; Sleem, Amany A

2016-12-01

To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Rats were received intraperitoneal (i.p.) injection of malathion 150 mg/kg along with citric acid (200 or 400 mg/kg, orally), atropine (1 mg/kg, i.p.) or citric acid 200 mg/kg + atropine 1 mg/kg and euthanized 4 h later. Malathion resulted in increased lipid peroxidation (malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase (AChE) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase (iNOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS expression in brain and liver. The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Processing of Basic Speech Acts Following Localized Brain Damage: A New Light on the Neuroanatomy of Language

ERIC Educational Resources Information Center

Soroker, N.; Kasher, A.; Giora, R.; Batori, G.; Corn, C.; Gil, M.; Zaidel, E.

2005-01-01

We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues…

Functional vision in children with perinatal brain damage.

PubMed

Alimović, Sonja; Jurić, Nikolina; Bošnjak, Vlatka Mejaški

2014-09-01

Many authors have discussed the effects of visual stimulations on visual functions, but there is no research about the effects on using vision in everyday activities (i.e. functional vision). Children with perinatal brain damage can develop cerebral visual impairment with preserved visual functions (e.g. visual acuity, contrast sensitivity) but poor functional vision. Our aim was to discuss the importance of assessing and stimulating functional vision in children with perinatal brain damage. We assessed visual functions (grating visual acuity, contrast sensitivity) and functional vision (the ability of maintaining visual attention and using vision in communication) in 99 children with perinatal brain damage and visual impairment. All children were assessed before and after the visual stimulation program. Our first assessment results showed that children with perinatal brain damage had significantly more problems in functional vision than in basic visual functions. During the visual stimulation program both variables of functional vision and contrast sensitivity improved significantly, while grating acuity improved only in 2.7% of children. We also found that improvement of visual attention significantly correlated to improvement on all other functions describing vision. Therefore, functional vision assessment, especially assessment of visual attention is indispensable in early monitoring of child with perinatal brain damage.

Cannabis and Canada’s children and youth

PubMed Central

Bélanger, Richard E

2017-01-01

Abstract Cannabis is the most common illicit drug used worldwide and it is used frequently by Canadian teenagers. Cannabis use during adolescence can cause functional and structural changes to the developing brain, leading to damage. Marijuana use in this age group is strongly linked to: cannabis dependence and other substance use disorders; the initiation and maintenance of tobacco smoking; an increased presence of mental illness, including depression, anxiety and psychosis; impaired neurological development and cognitive decline; and diminished school performance and lifetime achievement. Rates of acute medical care and hospitalization for younger children who have ingested cannabis unintentionally are increasing. Ongoing debate concerning cannabis regulation in Canada makes paying close attention to the evidence for its health effects and ensuring that appropriate safeguards are in place, vital public health priorities. PMID:29480902

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Detection of white matter injury in concussion using high-definition fiber tractography.

PubMed

Shin, Samuel S; Pathak, Sudhir; Presson, Nora; Bird, William; Wagener, Lauren; Schneider, Walter; Okonkwo, David O; Fernandez-Miranda, Juan C

2014-01-01

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients. © 2014 S. Karger AG, Basel.

The influence of victim characteristics on potential jurors' perceptions of brain damage in mild traumatic brain injury.

PubMed

Guilmette, T J; Temple, R O; Kennedy, M L; Weiler, M D; Ruffolo, L F; Dufresne, E

2005-11-01

To determine the influence of victim/plaintiff sex, occupation and intoxication status at the time of injury on potential jurors' judgement about the presence of brain damage in mild traumatic brain injury (MTBI). Survey. One of eight scenarios describing a MTBI from a motor vehicle accident was presented to 460 participants at a Department of Motor Vehicles. Victim sex, occupation (accountant or cafeteria worker) and alcohol intoxication status at the time of injury (sober or intoxicated) were manipulated across eight scenarios. Participants rated whether the victim's complaints at 6 months post-injury were the result of brain damage. Ratings were influenced by victim occupation and intoxication status (chi2>5.3, p<0.03), but not the sex of the victim. The occupational and intoxication status of MTBI victims may influence potential jurors' decision about the presence of brain damage.

The relationship between measured moisture conditions and fungal concentrations in water-damaged building materials.

PubMed

Pasanen, A L; Rautiala, S; Kasanen, J P; Raunio, P; Rantamäki, J; Kalliokoski, P

2000-06-01

We determined the moisture levels, relative humidity (RH) or moisture content (MC) of materials, and concentrations of culturable fungi, actinomycetes and total spores as well as a composition of fungal flora in 122 building material samples collected from 18 moisture problem buildings. The purpose of this work was to clarify if the is any correlation between the moisture parameters and microbial levels or generic composition depending on the type of materials and the time passed after a water damage. The results showed an agreement between the concentrations of total spores and culturable fungi for the wood, wood-based and gypsum board samples (r > 0.47). The concentrations of total spores and/or culturable fungi correlated with RH of materials particularly among the wood and insulation materials (r > 0.79), but not usually with MC (r < 0.45). For the samples collected from ongoing damage, there was a correlation between RH of materials and the concentrations of total spores and culturable fungi (r > 0.51), while such a relationship could not be observed for the samples taken from dry damage. A wide range of fungal species were found in the samples from ongoing damage, whereas Penicillia and in some cases yeasts dominated the fungal flora in the dry samples. This study indicates that fungal contamination can be evaluated on the basis of moisture measurements of constructions in ongoing damage, but the measurements are not solely adequate for estimation of possible microbial growth in dry damage.

Tetanus toxin as a tool for studying epilepsy.

PubMed

Mellanby, J; Hawkins, C; Mellanby, H; Rawlins, J N; Impey, M E

1984-01-01

The use of tetanus toxin, injected into the hippocampus of the rat, to produce an "animal model" of chronic limbic epilepsy is described. This model has yielded information complementary to that derived from other animal models and has several important advantages: while it involves spontaneous seizures, it occurs without gross damage to the brain ; it is eventually reversible in terms of fits and the overall reappearance of the EEG. It can therefore be used to look both at the effects of ongoing epilepsy and also at the long-term changes in brain function induced by previous epilepsy. Evidence is presented that the toxin probably remains localised at the site of injection. The information which has so far been obtained with this model on the relation between epilepsy and abnormal behaviour is summarised. In particular, it appears that the epilepsy produces long-term deficits in the animals' ability to learn and remember of a sort which suggest that an enduring malfunction has been induced in the hippocampus. The significance of the findings for clinical research and for future investigation of the nature of epilepsy are described. It is emphasised that the neurotoxins may be usefully exploited not only for investigating the molecular basis of neuronal mechanisms but also for inducing long-lasting plastic changes in integrated brain function.

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

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

Seibert, Tyler M.; Karunamuni, Roshan; Bartsch, Hauke

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI beforemore » and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.« less

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

PubMed Central

Kalmar, Alain F.; Doorduin, Janine; Struys, Michel M. R. F.; Schoemaker, Regien G.; Absalom, Anthony R.

2018-01-01

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage. PMID:29451906

Traumatic Brain Injury as a Cause of Behavior Disorders.

ERIC Educational Resources Information Center

Nordlund, Marcia R.

There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…

Experience-Dependent Neural Plasticity in the Adult Damaged Brain

ERIC Educational Resources Information Center

Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

2011-01-01

Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

Medical aspects of pediatric rehabilitation after moderate to severe traumatic brain injury.

PubMed

Cantore, Lisa; Norwood, Kenneth; Patrick, Peter

2012-01-01

Recovery from severe traumatic brain injury (TBI) is prolonged, complicated and challenging. Medical rehabilitation is the bridge from acute medical care and stabilization to community reintegration. The process of caring for the recovering brain introduces unknown challenges of neural plasticity with demands to restore and to also move the child and family back to the developmental trajectory they once knew. While the ongoing focus is to maintain and advance medical stability, co- morbid conditions are addressed, and a plan for ongoing health is established. While no one manuscript can cover all of the medical aspects, this article will present in a "systems review" manner the most challenging and demanding medical conditions that children may confront following severe brain injury.

Metyrapone prevents acute glucose hypermetabolism and short-term brain damage induced by intrahippocampal administration of 4-aminopyridine in rats.

PubMed

García-García, Luis; Fernández de la Rosa, Rubén; Delgado, Mercedes; Silván, Ágata; Bascuñana, Pablo; Bankstahl, Jens P; Gomez, Francisca; Pozo, Miguel A

2018-02-01

Intracerebral administration of the potassium channel blocker 4-aminopyridine (4-AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat model of status epilepticus (SE), a single administration of metyrapone, an inhibitor of the 11β-hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i.p.) was also able to prevent eventual changes in the acute brain metabolism and short-term neuronal damage induced by intrahippocampal injection of 4-AP (7 μg/5 μl). To this end, regional brain metabolism was assessed by 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) positron emission tomography (PET) during the ictal period. Three days later, markers of neuronal death and hippocampal integrity and apoptosis (Nissl staining, NeuN and active caspase-3 immunohistochemistry), neurodegeneration (Fluoro-Jade C labeling), astrogliosis (glial fibrillary acidic protein (GFAP) immunohistochemistry) and microglia-mediated neuroinflammation (in vitro [ 18 F]GE180 autoradiography) were evaluated. 4-AP administration acutely triggered marked brain hypermetabolism within and around the site of injection as well as short-term signs of brain damage and inflammation. Most important, metyrapone pretreatment was able to reduce ictal hypermetabolism as well as all the markers of brain damage except microglia-mediated neuroinflammation. Overall, our study corroborates the neuroprotective effects of metyrapone against multiple signs of brain damage caused by seizures triggered by 4-AP. Ultimately, our data add up to the consistent protective effect of metyrapone pretreatment reported in other models of neurological disorders of different etiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.

PubMed

Marsman, Anouk; Mandl, René C W; Klomp, Dennis W J; Bohlken, Marc M; Boer, Vincent O; Andreychenko, Anna; Cahn, Wiepke; Kahn, René S; Luijten, Peter R; Hulshoff Pol, Hilleke E

2014-01-01

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.

ERIC Educational Resources Information Center

Ounce of Prevention Fund.

Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…

Improving visual perception through neurofeedback

PubMed Central

Scharnowski, Frank; Hutton, Chloe; Josephs, Oliver; Weiskopf, Nikolaus; Rees, Geraint

2012-01-01

Perception depends on the interplay of ongoing spontaneous activity and stimulus-evoked activity in sensory cortices. This raises the possibility that training ongoing spontaneous activity alone might be sufficient for enhancing perceptual sensitivity. To test this, we trained human participants to control ongoing spontaneous activity in circumscribed regions of retinotopic visual cortex using real-time functional MRI based neurofeedback. After training, we tested participants using a new and previously untrained visual detection task that was presented at the visual field location corresponding to the trained region of visual cortex. Perceptual sensitivity was significantly enhanced only when participants who had previously learned control over ongoing activity were now exercising control, and only for that region of visual cortex. Our new approach allows us to non-invasively and non-pharmacologically manipulate regionally specific brain activity, and thus provide ‘brain training’ to deliver particular perceptual enhancements. PMID:23223302

Systems approach to the study of brain damage in the very preterm newborn

PubMed Central

Leviton, Alan; Gressens, Pierre; Wolkenhauer, Olaf; Dammann, Olaf

2015-01-01

Background: A systems approach to the study of brain damage in very preterm newborns has been lacking. Methods: In this perspective piece, we offer encephalopathy of prematurity as an example of the complexity and interrelatedness of brain-damaging molecular processes that can be initiated inflammatory phenomena. Results: Using three transcription factors, nuclear factor-kappa B (NF-κB), Notch-1, and nuclear factor erythroid 2 related factor 2 (NRF2), we show the inter-connectedness of signaling pathways activated by some antecedents of encephalopathy of prematurity. Conclusions: We hope that as biomarkers of exposures and processes leading to brain damage in the most immature newborns become more readily available, those who apply a systems approach to the study of neuroscience can be persuaded to study the pathogenesis of brain disorders in the very preterm newborn. PMID:25926780

Lateralization of Egocentric and Allocentric Spatial Processing after Parietal Brain Lesions

ERIC Educational Resources Information Center

Iachini, Tina; Ruggiero, Gennaro; Conson, Massimiliano; Trojano, Luigi

2009-01-01

The purpose of this paper was to verify whether left and right parietal brain lesions may selectively impair egocentric and allocentric processing of spatial information in near/far spaces. Two Right-Brain-Damaged (RBD), 2 Left-Brain-Damaged (LBD) patients (not affected by neglect or language disturbances) and eight normal controls were submitted…

Mapping connectivity damage in the case of Phineas Gage.

PubMed

Van Horn, John Darrell; Irimia, Andrei; Torgerson, Carinna M; Chambers, Micah C; Kikinis, Ron; Toga, Arthur W

2012-01-01

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a "tamping iron" was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25-36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized "average" brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient.

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation

PubMed Central

Kim, Junhwan; Lampe, Joshua W.; Yin, Tai; Shinozaki, Koichiro; Becker, Lance B.

2015-01-01

Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a moderate increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation. PMID:26160279

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Lampe, Joshua W; Yin, Tai; Shinozaki, Koichiro; Becker, Lance B

2015-10-01

Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a substantial increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation.

Right hemisphere damage: Communication processing in adults evaluated by the Brazilian Protocole MEC - Bateria MAC.

PubMed

Fonseca, Rochele Paz; Fachel, Jandyra Maria Guimarães; Chaves, Márcia Lorena Fagundes; Liedtke, Francéia Veiga; Parente, Maria Alice de Mattos Pimenta

2007-01-01

Right-brain-damaged individuals may present discursive, pragmatic, lexical-semantic and/or prosodic disorders. To verify the effect of right hemisphere damage on communication processing evaluated by the Brazilian version of the Protocole Montréal d'Évaluation de la Communication (Montreal Communication Evaluation Battery) - Bateria Montreal de Avaliação da Comunicação, Bateria MAC, in Portuguese. A clinical group of 29 right-brain-damaged participants and a control group of 58 non-brain-damaged adults formed the sample. A questionnaire on sociocultural and health aspects, together with the Brazilian MAC Battery was administered. Significant differences between the clinical and control groups were observed in the following MAC Battery tasks: conversational discourse, unconstrained, semantic and orthographic verbal fluency, linguistic prosody repetition, emotional prosody comprehension, repetition and production. Moreover, the clinical group was less homogeneous than the control group. A right-brain-damage effect was identified directly, on three communication processes: discursive, lexical-semantic and prosodic processes, and indirectly, on pragmatic process.

AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

EPA Science Inventory

Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

ERIC Educational Resources Information Center

Hawley, Theresa

Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

Changes in brain anatomy during the course of PTSD

PubMed Central

Cardenas, Valerie A.; Samuelson, Kristin; Lenoci, Maryann; Studholme, Colin; Neylan, Thomas C.; Marmar, Charles R.; Schuff, Norbert; Weiner, Michael W.

2011-01-01

The goal of this study was to determine whether PTSD was associated with an increase in time-related decline in macrostructural brain volume and whether these changes were associated with accelerated cognitive decline. To quantify brain structure, 3 dimensional T1-weighted MRI scans were performed at baseline and again after a minimum of 24 months in 25 patients with PTSD and 22 controls. Longitudinal changes in brain volume were measured using deformation morphometry. For the group as a whole PTSD+ patients did not show significant ongoing brain atrophy compared to PTSD-. PTSD+ patients were then subgrouped into those with decreasing or increasing symptoms. We found little evidence for brain markers of accelerated atrophy in PTSD+ veterans whose symptoms improved over time, with only a small left parietal region showing greater ongoing tissue loss than PTSD-. PTSD patients whose symptoms increased over time showed accelerated atrophy throughout the brain, particularly brainstem and frontal and temporal lobes. Lastly, for the sample as a whole greater rates of brain atrophy were associated with greater rates of decline in verbal memory and delayed facial recognition. PMID:21683556

Involvement of the anterior cingulate cortex in time-based prospective memory task monitoring: An EEG analysis of brain sources using Independent Component and Measure Projection Analysis

PubMed Central

Burgos, Pablo; Kilborn, Kerry; Evans, Jonathan J.

2017-01-01

Objective Time-based prospective memory (PM), remembering to do something at a particular moment in the future, is considered to depend upon self-initiated strategic monitoring, involving a retrieval mode (sustained maintenance of the intention) plus target checking (intermittent time checks). The present experiment was designed to explore what brain regions and brain activity are associated with these components of strategic monitoring in time-based PM tasks. Method 24 participants were asked to reset a clock every four minutes, while performing a foreground ongoing word categorisation task. EEG activity was recorded and data were decomposed into source-resolved activity using Independent Component Analysis. Common brain regions across participants, associated with retrieval mode and target checking, were found using Measure Projection Analysis. Results Participants decreased their performance on the ongoing task when concurrently performed with the time-based PM task, reflecting an active retrieval mode that relied on withdrawal of limited resources from the ongoing task. Brain activity, with its source in or near the anterior cingulate cortex (ACC), showed changes associated with an active retrieval mode including greater negative ERP deflections, decreased theta synchronization, and increased alpha suppression for events locked to the ongoing task while maintaining a time-based intention. Activity in the ACC was also associated with time-checks and found consistently across participants; however, we did not find an association with time perception processing per se. Conclusion The involvement of the ACC in both aspects of time-based PM monitoring may be related to different functions that have been attributed to it: strategic control of attention during the retrieval mode (distributing attentional resources between the ongoing task and the time-based task) and anticipatory/decision making processing associated with clock-checks. PMID:28863146

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.

Singing ability after right and left sided brain damage. A research note.

PubMed

Kinsella, G; Prior, M R; Murray, G

1988-03-01

Capacity to sing following brain damage was investigated in a series of 15 right sided and 15 left sided lesioned subjects and 15 normal control subjects. All subjects were asked to sing the same well-known song and performance was judged by independent expert musicians using criteria of ability to pitch the melody, accurately produce the rhythm, and overall quality of the production. There was a lack of support for differential effect of right and left cerebral damage on pitch and rhythm aspects of singing, but a generalized effect of brain damage was found.

Brain-Heart Interaction: Cardiac Complications After Stroke.

PubMed

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Gut Microbes and the Brain: Paradigm Shift in Neuroscience

PubMed Central

Knight, Rob; Mazmanian, Sarkis K.; Cryan, John F.; Tillisch, Kirsten

2014-01-01

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. PMID:25392516

Manipulating motor performance and memory through real-time fMRI neurofeedback.

PubMed

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-05-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback

PubMed Central

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-01-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

Objective instrumental memory and performance tests for evaluation of patients with brain damage: a search for a behavioral diagnostic tool.

PubMed

Harness, B Z; Bental, E; Carmon, A

1976-03-01

Cognition and performance of patients with localized and diffuse brain damage was evaluated through the application of objective perceptual testing. A series of visual perceptual and verbal tests, memory tests, as well as reaction time tasks were administered to the patients by logic programming equipment. In order to avoid a bias due to communicative disorders, all responses were motor, and achievement was scored in terms of correct identification and latencies of response. Previously established norms based on a large sample of non-brain-damaged hospitalized patients served to standardize the performance of the brain-damaged patient since preliminary results showed that age and educational level constitute an important variable affecting performance of the control group. The achievement of brain-damaged patients, corrected for these factors, was impaired significantly in all tests with respect to both recognition and speed of performance. Lateralized effects of brain damage were not significantly demonstrated. However, when the performance was analyzed with respect to the locus of visual input, it was found that patients with right hemispheric lesions showed impairment mainly on perception of figurative material, and that this deficit was more apparent in the left visual field. Conversely, patients with left hemispheric lesions tended to show impairment on perception of visually presented verbal material when the input was delivered to the right visual field.

Protective effects of Curcuma longa against neurobehavioral and neurochemical damage caused by cerium chloride in mice.

PubMed

Kadri, Yamina; Nciri, Riadh; Brahmi, Noura; Saidi, Saber; Harrath, Abdel Halim; Alwasel, Saleh; Aldahmash, Waleed; El Feki, Abdelfatteh; Allagui, Mohamed Salah

2018-05-07

Cerium chloride (CeCl 3 ) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl 3 , 20 mg/kg BW) along with Curcuma longa extract, administrated by gavage (100 mg/kg BW), into mice for 60 days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl 3 -treated mice. In addition, CeCl 3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl 3 -treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl 3 -induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl 3 -damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl 3 -induced damage in the brain.

Comprehensive 3D Model of Shock Wave-Brain Interactions in Blast-Induced Traumatic Brain Injuries

DTIC Science & Technology

2009-10-01

waves can cause brain damage by other mechanisms including excess pressure (leading to contusions), excess strain (leading to subdural ... hematomas and/or diffuse axonal injuries), and, in particular, cavitation effects (leading to subcellular damage). This project aims at the development of a

Frequency and Type of Situational Awareness Errors Contributing to Death and Brain Damage: A Closed Claims Analysis.

PubMed

Schulz, Christian M; Burden, Amanda; Posner, Karen L; Mincer, Shawn L; Steadman, Randolph; Wagner, Klaus J; Domino, Karen B

2017-08-01

Situational awareness errors may play an important role in the genesis of patient harm. The authors examined closed anesthesia malpractice claims for death or brain damage to determine the frequency and type of situational awareness errors. Surgical and procedural anesthesia death and brain damage claims in the Anesthesia Closed Claims Project database were analyzed. Situational awareness error was defined as failure to perceive relevant clinical information, failure to comprehend the meaning of available information, or failure to project, anticipate, or plan. Patient and case characteristics, primary damaging events, and anesthesia payments in claims with situational awareness errors were compared to other death and brain damage claims from 2002 to 2013. Anesthesiologist situational awareness errors contributed to death or brain damage in 198 of 266 claims (74%). Respiratory system damaging events were more common in claims with situational awareness errors (56%) than other claims (21%, P < 0.001). The most common specific respiratory events in error claims were inadequate oxygenation or ventilation (24%), difficult intubation (11%), and aspiration (10%). Payments were made in 85% of situational awareness error claims compared to 46% in other claims (P = 0.001), with no significant difference in payment size. Among 198 claims with anesthesia situational awareness error, perception errors were most common (42%), whereas comprehension errors (29%) and projection errors (29%) were relatively less common. Situational awareness error definitions were operationalized for reliable application to real-world anesthesia cases. Situational awareness errors may have contributed to catastrophic outcomes in three quarters of recent anesthesia malpractice claims.Situational awareness errors resulting in death or brain damage remain prevalent causes of malpractice claims in the 21st century.

Impact of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and Positron Emission Tomography/Computed Tomography (PET/CT) in the Diagnosis of Traumatic Brain Injury (TBI): Case Report.

PubMed

Molina-Vicenty, Irma L; Santiago-Sánchez, Michelaldemar; Vélez-Miró, Iván; Motta-Valencia, Keryl

2016-09-01

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external force. TBI, a global leading cause of death and disability, is associated with serious social, economic, and health problems. In cases of mild-to-moderate brain damage, conventional anatomical imaging modalities may or may not detect the cascade of metabolic changes that have occurred or are occurring at the intracellular level. Functional nuclear medicine imaging and neurophysiological parameters can be used to characterize brain damage, as the former provides direct visualization of brain function, even in the absence of overt behavioral manifestations or anatomical findings. We report the case of a 30-year-old Hispanic male veteran who, after 2 traumatic brain injury events, developed cognitive and neuropsychological problems with no clear etiology in the presence of negative computed tomography (CT) findings.

Analysis of brain and spinal cord lesions to occult brain damage in seropositive and seronegative neuromyelitis optica.

PubMed

Sun, Jie; Sun, Xianting; Zhang, Ningnannan; Wang, Qiuhui; Cai, Huanhuan; Qi, Yuan; Li, Ting; Qin, Wen; Yu, Chunshui

2017-09-01

According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (r s =-0.444, P=0.044) and with BLV in the seronegative group (r s =-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (r s =-0.682, P<0.001). Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.

PubMed

Shi, Hong; Wang, Hai-Lian; Pu, Hong-Jian; Shi, Ye-Jie; Zhang, Jia; Zhang, Wen-Ting; Wang, Guo-Hua; Hu, Xiao-Ming; Leak, Rehana K; Chen, Jun; Gao, Yan-Qin

2015-04-01

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed. Ethyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Ethyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage. © 2014 John Wiley & Sons Ltd.

The evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels.

PubMed

Fukuda, Miho; Yamauchi, Hiroshi; Yamamoto, Hitoshi; Aminaka, Masahito; Murakami, Hiroshi; Kamiyama, Noriko; Miyamoto, Yusaku; Koitabashi, Yasushi

2008-02-01

Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearman's rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patient's clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.

Computational Modeling of Resting-State Activity Demonstrates Markers of Normalcy in Children with Prenatal or Perinatal Stroke

PubMed Central

Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R.; Small, Steven L.; Deco, Gustavo

2015-01-01

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere “take over” their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. PMID:26063923

Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

PubMed

Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

2018-05-03

People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

PubMed Central

Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

2011-01-01

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

A neurologist's reflections on boxing. V. Conclude remarks.

PubMed

Unterharnscheidt, F

1995-01-01

Clinical and morphological publications have shown convincingly, that participation in boxing leads to a severe permanent brain damage. The extent of the brain damage is correlated to the number of bouts fought, which correspondents in a certain way how many blows against his head a boxer received and to his weight class. The intensity of a boxing blow of a heavyweight is much more severe than those achieved by boxers of lighter weight classes. The permanent brain damage in a boxer, the amateur and the professional boxer, manifests itself in several clinical syndromes in which the pyramidal, the extrapyramidal and the cerebellar systems are involved. A traumatic Parkinsonism, in its complete or abortive form, develops as the result of the numerous boxing blows a boxer sustains in his boxing career. Especially lateral parts of the substantia nigra are affected and reveal at macroscopical and microscopical examination a severe loss of pigmented neurons. Melanin pigment is visible free in the tissue and/or is phagozytosed in macrophages and glial cells. The traumatic Parkinson syndrome, often only in an abortive form, is combined in a boxer with additional clinical and morphological findings due to traumatic lesions in other areas of the brain. It is not as pure as in a patient with a Parkinson syndrome sui generis. The permanent brain damage in a boxer is diffuse, involving all areas of the brain. Especially involved are the large neurons of different layers of the cerebral cortex, the neurons of the Ammons horn formation, the Purkinje cells of the cerebellum. In place of destroyed and lost neurons, proliferation of glial elements, especially astroglial cells, has occurred. The defects are first replaced by protoplasmatic astroglial elements, and later by fibrillary astroglia. The destroyed neurons are replaced by glial scar tissue, which cannot perform the functions of the lost neurons. It is a process which is called partial necrosis of brain tissue. There is no reparation or restitution of the destroyed neural tissue of the brain. What is destroyed remains so, a restitution ad integrum does not occur. As the result of the diffuse loss of neurons in the brain a cerebral atrophy exists. The septum pellucidum, which consists of two thin lamellae, and is small or very small in a normal brain, forms a Cavum septi pellucidi, which is considerably enlarged. The walls of this structure, especially in its dorsal parts are considerably thinned; they show fenestrations and are, in dorsal parts no longer detectable, so that a direct connection between the two lateral ventricles exists. The clinically and morphologically existing permanent brain damage is the result of the boxing activity. Diagnostically, processes of another origin, such as alcoholism, luetic processes, other forms of dementia, etc. can undoubtedly be excluded. A permanent brain damage develops in professional and amateur boxers. The objection, which are voiced by members of the different Amateur Boxing Association, that such permanent brain damage in amateur boxers today no longer exists, after stricter protective measurements were introduced, is not tenable. Individuals who represent today the opinion, that a permanent brain damage or punch drunkenness in boxers does not occur, are not familiar with the pertinent medical literature. The argument, the injury quotient in boxing is lower than in all other athletic activities is not sound, since the statistics show only the inconsequential injuries of boxers, as lesions of the skin of the face, injuries of the hand, fractures, etc. but not the much more important and severe permanent brain damage, which is not taken into consideration in these so-called statistics. Besides of the permanent brain damage of former boxers as the result of the repeated and numerous blows against their head, severe permanent damage of the eyes and the hearing organ exists.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

PubMed

Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

2008-01-15

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

Cerebellar Degeneration

MedlinePlus

... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ...

The structural basis of moderate disability after traumatic brain damage

PubMed Central

Adams, J; Graham, D; Jennett, B

2001-01-01

The objective was to discover the nature of brain damage in survivors of head injury who are left with moderate disability. Macroscopic and microscopic examination was carried out on the brains of 20 persons who had died long after a head injury that had been treated in a neurosurgical unit. All had become independent but had various disabilities (moderate disability on the Glasgow outcome scale) Most deaths had been sudden, which had led to their referral from forensic pathologists. Post-traumatic epilepsy was a feature in 75%. An intracranial haematoma had been evacuated in 75%, and in 11 of the 15 with epilepsy. Diffuse axonal injury was found in six patients, five of the mildest type (grade 1) and one of grade 2. No patient had diffuse thalamic damage but one had a small focal ischaemic lesion in the thalamus. No patient had severe ischaemic brain damage, but three had moderate lesions which were bilateral in only one. No patient had severe cortical contusions. In conclusion, the dominant lesion was focal damage from an evacuated intracranial haematoma. Severe diffuse damage was not found, with diffuse axonal injury only mild and thalamic damage in only one patient.

 PMID:11561038

Report says Gulf of Mexico oil spill assessment should include ecosystem services approach

NASA Astrophysics Data System (ADS)

Showstack, Randy

2011-11-01

The oil spill in the Gulf of Mexico that resulted from the 20 April 2010 explosion of the Deepwater Horizon (DWH) platform drilling the Macondo well was so massive and affected such a large and deep region of the gulf that the process of determining environmental damage in the region should be more encompassing than a typical habitat and resource equivalency approach, according to a 9 November report by the U.S. National Research Council (NRC). The congressionally requested report calls for an ecosystem services approach to complement ongoing approaches to the damage evaluation for the spill that is being conducted through the ongoing Natural Resources Damage Assessment (NRDA) process triggered by the U.S. Oil Pollution Act (OPA) of 1990.

Right hemisphere damage: Communication processing in adults evaluated by the Brazilian Protocole MEC – Bateria MAC

PubMed Central

Fonseca, Rochele Paz; Fachel, Jandyra Maria Guimarães; Chaves, Márcia Lorena Fagundes; Liedtke, Francéia Veiga; Parente, Maria Alice de Mattos Pimenta

2007-01-01

Right-brain-damaged individuals may present discursive, pragmatic, lexical-semantic and/or prosodic disorders. Objective To verify the effect of right hemisphere damage on communication processing evaluated by the Brazilian version of the Protocole Montréal d’Évaluation de la Communication (Montreal Communication Evaluation Battery) – Bateria Montreal de Avaliação da Comunicação, Bateria MAC, in Portuguese. Methods A clinical group of 29 right-brain-damaged participants and a control group of 58 non-brain-damaged adults formed the sample. A questionnaire on sociocultural and health aspects, together with the Brazilian MAC Battery was administered. Results Significant differences between the clinical and control groups were observed in the following MAC Battery tasks: conversational discourse, unconstrained, semantic and orthographic verbal fluency, linguistic prosody repetition, emotional prosody comprehension, repetition and production. Moreover, the clinical group was less homogeneous than the control group. Conclusions A right-brain-damage effect was identified directly, on three communication processes: discursive, lexical-semantic and prosodic processes, and indirectly, on pragmatic process. PMID:29213400

Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

PubMed

Scott, Gregory; Hellyer, Peter J; Ramlackhansingh, Anil F; Brooks, David J; Matthews, Paul M; Sharp, David J

2015-12-01

Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo. Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage. These findings support a link between axonal damage and persistent inflammation after brain injury.

Laser treatments of deep-seated brain lesions

NASA Astrophysics Data System (ADS)

Ward, Helen A.

1997-06-01

The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

The Use of Computers and Video Games in Brain Damage Therapy.

ERIC Educational Resources Information Center

Lorimer, David

The use of computer assisted therapy (CAT) in the rehabilitation of individuals with brain damage is examined. Hardware considerations are explored, and the variety of software programs available for brain injury rehabilitation is discussed. Structured testing and treatment programs in time measurement, memory, and direction finding are described,…

Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

ERIC Educational Resources Information Center

Ross, Elliott D.; Monnot, Marilee

2008-01-01

Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

Childhood Aphasia and Brain Damage: Volume II, Differential Diagnosis.

ERIC Educational Resources Information Center

Rappaport, Sheldon R., Ed.

Addressing itself to factors leading to the misdiagnosis of the brain damaged child and the aphasic child, the Pathway School's Second Annual Institute considered the differences between the following: the aphasic and the aphasoid child; the sensory aphasic and the deaf child; the psychotic and the psychotic aphasic child; childhood brain damage…

Should Individuals Who Possess Only One Brain Be Allowed To Box?

ERIC Educational Resources Information Center

Brady, Don

This paper questions the acceptance of injuries obtained while participating in sport and in particular, the relationship between participation in boxing and brain injury/damage identified in boxers. A review of the literature indicates research findings support the tenet that brain damage found in boxers is cumulative and is directly related to…

Inferencing Processes after Right Hemisphere Brain Damage: Effects of Contextual Bias

ERIC Educational Resources Information Center

Blake, Margaret Lehman

2009-01-01

Purpose: Comprehension deficits associated with right hemisphere brain damage (RHD) have been attributed to an inability to use context, but there is little direct evidence to support the claim. This study evaluated the effect of varying contextual bias on predictive inferencing by adults with RHD. Method: Fourteen adults with no brain damage…

Embodied Anticipation: A Neurodevelopmental Interpretation

ERIC Educational Resources Information Center

Kinsbourne, Marcel; Jordan, J. Scott

2009-01-01

This article proposes an approach to the brain's role in communication that treats the brain as the vehicle of a multi-scale embodiment of anticipation. Instead of conceptualizing anticipation as something a brain is able to do when circumstances seem to require it, this study proposes that anticipation is continuous and ongoing because to…

Brain MRI fiber-tracking reveals white matter alterations in hypertensive patients without damage at conventional neuroimaging.

PubMed

Carnevale, Lorenzo; D'Angelosante, Valentina; Landolfi, Alessandro; Grillea, Giovanni; Selvetella, Giulio; Storto, Marianna; Lembo, Giuseppe; Carnevale, Daniela

2018-06-12

Hypertension is one of the main risk factor for dementia. The subtle damage provoked by chronic high blood pressure in the brain is usually evidenced by conventional magnetic resonance imaging (MRI), in terms of white matter (WM) hyperintensities or cerebral atrophy. However, it is clear that by the time brain damage is visible, it may be too late hampering neurodegeneration. Aim of this study was to characterize a signature of early brain damage induced by hypertension, before the neurodegenerative injury manifests. This work was conducted on hypertensive and normotensive subjects with no sign of structural damage at conventional neuroimaging and no diagnosis of dementia revealed by neuropsychological assessment. All individuals underwent cardiological clinical examination in order to define the hypertensive status and the related target organ damage. Additionally, patients were subjected to DTI-MRI scan to identify microstructural damage of WM by probabilistic fiber-tracking. To gain insights in the neurocognitive profile of patients a specific battery of tests was administered. As primary outcome of the study we aimed at finding any specific signature of fiber-tracts alterations in hypertensive patients, associated with an impairment of the related cognitive functions. Hypertensive patients showed significant alterations in three specific WM fiber-tracts: the anterior thalamic radiation, the superior longitudinal fasciculus and the forceps minor. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those WM fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and paired associative learning tasks. Overall, WM fiber-tracking on MRI evidenced an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. In perspective, this approach could allow identifying those patients that are in initial stages of brain damage and could benefit of therapies aimed at limiting the transition to dementia and neurodegeneration.

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

PubMed

Shimada, Yoshiaki; Shimura, Hideki; Tanaka, Ryota; Yamashiro, Kazuo; Koike, Masato; Uchiyama, Yasuo; Urabe, Takao; Hattori, Nobutaka

2018-01-01

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.

Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats.

PubMed

He, De-Hua; Zhang, Liang-Min; Lin, Li-Ming; Ning, Ruo-Bing; Wang, Hua-Jun; Xu, Chang-Sheng; Lin, Jin-Xiu

2014-02-01

Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate ⅰ) whether short‑ and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ⅱ) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week‑old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short‑ and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short‑ and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive populations in order to prevent BP-linked brain damage.

Pregnancy Complications: Umbilical Cord Abnormalities

MedlinePlus

... before and during delivery, which may contribute to cerebral palsy and other forms of brain damage References Cruikshank, ... before and during delivery, which may contribute to cerebral palsy and other forms of brain damage References Cruikshank, ...

Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

PubMed

Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

2018-06-01

Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Storying, fiction and philosophy: turning our attention to the traumatised or damaged nurse.

PubMed

Radcliffe, Mark

2016-03-01

The Francis Report, the result of a UK public inquiry into ongoing mistreatment of patients at a large teaching hospital, revealed deep-rooted flaws in care delivery and professional performance. It led to regulatory review, policy initiatives and public outcry. To this point, it has not led to any extended or focused discussion on the sustenance or well-being of nurses so that we might avoid it happening again. This paper emerges from the writing and publication of a novel called Stranger Than Kindness and a subsequent PhD. The novel explored the themes of damaged or hurt healthcare professionals and their attempts at restoration or in one case, redemption. The paper uses the novel as 'data' for an articulation of the emotional world of (some) nurses and imports three theoretical perspectives; McGilchrist's work on the divided brain, Damasio's work on emotion and Merleau-Ponty's phenomenology to support an emerging philosophical position of embodied cognition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis.

PubMed

Orellana, Juan A; Cerpa, Waldo; Carvajal, Maria F; Lerma-Cabrera, José M; Karahanian, Eduardo; Osorio-Fuentealba, Cesar; Quintanilla, Rodrigo A

2017-01-01

Alcohol dependence causes physical, social, and moral harms and currently represents an important public health concern. According to the World Health Organization (WHO), alcoholism is the third leading cause of death worldwide, after tobacco consumption and hypertension. Recent epidemiologic studies have shown a growing trend in alcohol abuse among adolescents, characterized by the consumption of large doses of alcohol over a short time period. Since brain development is an ongoing process during adolescence, short- and long-term brain damage associated with drinking behavior could lead to serious consequences for health and wellbeing. Accumulating evidence indicates that alcohol impairs the function of different components of the melanocortin system, a major player involved in the consolidation of addictive behaviors during adolescence and adulthood. Here, we hypothesize the possible implications of melanocortins and glial cells in the onset and progression of alcohol addiction. In particular, we propose that alcohol-induced decrease in α-MSH levels may trigger a cascade of glial inflammatory pathways that culminate in altered gliotransmission in the ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate dopaminergic drive in the NAc, contributing to increase the vulnerability to alcohol dependence and addiction in the adolescence and adulthood.

Auditory Temporal Processing Deficits in Chronic Stroke: A Comparison of Brain Damage Lateralization Effect.

PubMed

Jafari, Zahra; Esmaili, Mahdiye; Delbari, Ahmad; Mehrpour, Masoud; Mohajerani, Majid H

2016-06-01

There have been a few reports about the effects of chronic stroke on auditory temporal processing abilities and no reports regarding the effects of brain damage lateralization on these abilities. Our study was performed on 2 groups of chronic stroke patients to compare the effects of hemispheric lateralization of brain damage and of age on auditory temporal processing. Seventy persons with normal hearing, including 25 normal controls, 25 stroke patients with damage to the right brain, and 20 stroke patients with damage to the left brain, without aphasia and with an age range of 31-71 years were studied. A gap-in-noise (GIN) test and a duration pattern test (DPT) were conducted for each participant. Significant differences were found between the 3 groups for GIN threshold, overall GIN percent score, and DPT percent score in both ears (P ≤ .001). For all stroke patients, performance in both GIN and DPT was poorer in the ear contralateral to the damaged hemisphere, which was significant in DPT and in 2 measures of GIN (P ≤ .046). Advanced age had a negative relationship with temporal processing abilities for all 3 groups. In cases of confirmed left- or right-side stroke involving auditory cerebrum damage, poorer auditory temporal processing is associated with the ear contralateral to the damaged cerebral hemisphere. Replication of our results and the use of GIN and DPT tests for the early diagnosis of auditory processing deficits and for monitoring the effects of aural rehabilitation interventions are recommended. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Perceptual Asymmetry for Chimeric Stimuli in Children with Early Unilateral Brain Damage

ERIC Educational Resources Information Center

Bava, Sunita; Ballantyne, Angela O.; May, Susanne J.; Trauner, Doris A.

2005-01-01

The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n=46) as compared to typically developing matched controls (n=46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the…

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

PubMed

Adhikari, Mohit H; Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R; Small, Steven L; Deco, Gustavo

2015-06-10

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. Copyright © 2015 the authors 0270-6474/15/358914-11$15.00/0.

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

PubMed Central

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A.; Pappan, Kirk L.; Lampe, Joshua W.; Becker, Lance B.

2014-01-01

Background Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. Method A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. Results After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. Conclusion The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage. PMID:25383962

Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A; Pappan, Kirk L; Lampe, Joshua W; Becker, Lance B

2014-01-01

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.

The oxidative damage and disbalance of calcium homeostasis in brain of chicken induced by selenium deficiency.

PubMed

Xu, Shi-Wen; Yao, Hai-Dong; Zhang, Jian; Zhang, Zi-Wei; Wang, Jin-Tao; Zhang, Jiu-Li; Jiang, Zhi-Hui

2013-02-01

Dietary selenium (Se) deficiency can influence the function of the brain. Our objective was to investigate the effects of Se deficiency on oxidative damage and calcium (Ca) homeostasis in brain of chicken. In the present study, 1-day-old chickens were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 75 days. Then, brain injury biomarkers were examined, including histological analysis, ultrastructure assay, and apoptosis assay. We also examined the effect of Se deficiency on the Se-containing antioxidative enzyme glutathione peroxidase (GSH-Px), the level of glutathione (GSH), and the Ca homeostasis in brain of chicken. The results showed that the levels of Se and GSH and activity of GSH-Px are seriously reduced by 33.8-96 % (P < 0.001), 24.51-27.84 % (P < 0.001), and 20.70-64.24 % (P < 0.01), respectively. In the present study, we also perform histological analysis and ultrastructure assay and find that Se deficiency caused disorganized histological structure, damage to the mitochondria, fusion of nuclear membrane and nucleus shrinkage, higher apoptosis rate (P < 0.001), and increase of Ca homeostasis (P < 0.05 or P < 0.01 or P < 0.001) in the brain of chicken. In conclusion, the results demonstrated that Se deficiency induced oxidative damage and disbalance of Ca homeostasis in the brain of chicken. Similar to mammals, chickens brain is also extremely susceptible to oxidative damage and selenium deficiency.

Processing verbal morphology in patients with congenital left-hemispheric brain lesions.

PubMed

Knecht, Marion; Lidzba, Karen

2016-01-01

The goal of this study was to test whether children, teenagers and adults with congenital left-hemispheric brain lesions master the regularities of German verbal inflectional morphology. Thirteen patients and 35 controls without brain damage participated in three experiments. A grammaticality judgment task, a participle inflection task and a nonce-verb inflection task revealed significant differences between patients and controls. In addition, a main effect of verb type could be observed as patients and controls made more mistakes with irregular than with regular verbs. The findings indicate that the congenitally damaged brain not only has difficulties with complex syntactic structures during language development, as reported by earlier studies, but also has persistent deficits on the morphological level. These observations suggest that the plasticity of the developing brain cannot fully compensate for congenital brain damage which affects regions associated with language functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased reduction in exsanguination rates leaves brain injury as the only major cause of death in blunt trauma.

PubMed

Jochems, D; Leenen, L P H; Hietbrink, F; Houwert, R M; van Wessem, K J P

2018-05-23

Central nervous system (CNS) related injuries and exsanguination have been the most common causes of death in trauma for decades. Despite improvements in haemorrhage control in recent years exsanguination is still a major cause of death. We conducted a prospective database study to investigate the current incidence of haemorrhage related mortality. A prospective database study of all trauma patients admitted to an urban major trauma centre between January 2007 and December 2016 was conducted. All in-hospital trauma deaths were included. Cause of death was reviewed by a panel of trauma surgeons. Patients who were dead on arrival were excluded. Trends in demographics and outcome were analysed per year. Further, 2 time periods (2007-2012 and 2013-2016) were selected representing periods before and after implementation of haemostatic resuscitation and damage control procedures in our hospital to analyse cause of death into detail. 11,553 trauma patients were admitted, 596 patients (5.2%) died. Mean age of deceased patients was 61 years and 61% were male. Mechanism of injury (MOI) was blunt in 98% of cases. Mean ISS was 28 with head injury the most predominant injury (mean AIS head 3.4). There was no statistically significant difference in sex and MOI over time. Even though deceased patients were older in 2016 compared to 2007 (67 vs. 46 years, p < 0.001), mortality was lower in later years (p = 0.02). CNS related injury was the main cause of death in the whole decade; 58% of patients died of CNS in 2007-2012 compared to 76% of patients in 2013-2016 (p = 0.001). In 2007-2012 9% died of exsanguination compared to 3% in 2013-2016 (p = 0.001). In this cohort in a major trauma centre death by exsanguination has decreased to 3% of trauma deaths. The proportion of traumatic brain injury has increased over time and has become the most common cause of death in blunt trauma. Besides on-going prevention of brain injury future studies should focus on treatment strategies preventing secondary damage of the brain once the injury has occurred. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Disorders of emotional control in schizophrenia and unilateral brain damage].

PubMed

Kucharska-Pietura, K; Kopacz, G

2001-01-01

Although, emotions play a crucial role in schizophrenia, the changes in emotional dimension still remain controversial. The aim of our work was: 1) to compare the disorders of emotional control between the examined groups: S--non-chronic schizophrenic patients (n = 50), CS--chronic schizophrenic patients (n = 50), N--healthy controls (n = 50), R--right brain-damaged patients (n = 30), and L--left brain-damaged patients (n = 30), 2) to assess a level of impairment of emotional control, its relation to lateralised hemisphere damage and chronicity of schizophrenic process. All psychiatric subjects were diagnosed as paranoid schizophrenics according to DSM-IV criteria and were scored on the PANSS scale after four weeks of neuroleptic treatment. Brain-damaged patients were included if they experienced single-episode cerebrovascular accidents causing right or left hemisphere damage (confirmed in CT scan reports). The neurological patients were examined at least 3 weeks after the onset of cerebrovascular episode. Emotional control was assessed using Brzeziński Questionnaire of Emotional Control aimed at the evaluation of: 1) control in perception and interpretation of emotive situation, 2) emotional arousal, 3) emotional-rational motivation, and 4) acting caused by emotions. Our results revealed significantly greater impairment of emotional control in schizophrenics (chronic schizophrenics, in particular) compared to healthy volunteers. Chronicity of the schizophrenic process seemed to intensify emotional control impairment. Interestingly, no significant qualitative and quantitative differences in emotional control mechanism between unilateral brain-damaged patients and the control group were found.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.

PubMed

Bisicchia, Elisa; Sasso, Valeria; Catanzaro, Giuseppina; Leuti, Alessandro; Besharat, Zein Mersini; Chiacchiarini, Martina; Molinari, Marco; Ferretti, Elisabetta; Viscomi, Maria Teresa; Chiurchiù, Valerio

2018-01-22

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones.

PubMed

Salford, Leif G; Brun, Arne E; Eberhardt, Jacob L; Malmgren, Lars; Persson, Bertil R R

2003-06-01

The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile phone electromagnetic fields of different strengths. We found highly significant (p< 0.002) evidence for neuronal damage in the cortex, hippocampus, and basal ganglia in the brains of exposed rats.

Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243.

PubMed

Dutca, Laura M; Stasheff, Steven F; Hedberg-Buenz, Adam; Rudd, Danielle S; Batra, Nikhil; Blodi, Frederick R; Yorek, Matthew S; Yin, Terry; Shankar, Malini; Herlein, Judith A; Naidoo, Jacinth; Morlock, Lorraine; Williams, Noelle; Kardon, Randy H; Anderson, Michael G; Pieper, Andrew A; Harper, Matthew M

2014-12-02

Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at an earlier stage when treatments may be more effective in preventing these sequelae. In addition, treatment with the neuroprotective agent P7C3-S243 after TBI protects from visual system dysfunction after TBI. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Early Detection of Subclinical Visual Damage After Blast-Mediated TBI Enables Prevention of Chronic Visual Deficit by Treatment With P7C3-S243

PubMed Central

Dutca, Laura M.; Stasheff, Steven F.; Hedberg-Buenz, Adam; Rudd, Danielle S.; Batra, Nikhil; Blodi, Frederick R.; Yorek, Matthew S.; Yin, Terry; Shankar, Malini; Herlein, Judith A.; Naidoo, Jacinth; Morlock, Lorraine; Williams, Noelle; Kardon, Randy H.; Anderson, Michael G.; Pieper, Andrew A.; Harper, Matthew M.

2014-01-01

Purpose. Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. Methods. Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. Results. We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. Conclusions. Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at an earlier stage when treatments may be more effective in preventing these sequelae. In addition, treatment with the neuroprotective agent P7C3-S243 after TBI protects from visual system dysfunction after TBI. PMID:25468886

Gut microbes and the brain: paradigm shift in neuroscience.

PubMed

Mayer, Emeran A; Knight, Rob; Mazmanian, Sarkis K; Cryan, John F; Tillisch, Kirsten

2014-11-12

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. Copyright © 2014 the authors 0270-6474/14/3415490-07$15.00/0.

TBI Symptoms, Diagnosis, Treatment, Prevention

MedlinePlus

... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury TBI Symptoms, Diagnosis, Treatment, Prevention Past Issues / Fall ... very lucky in my ongoing recovery from the traumatic brain injury I suffered in Iraq." —Bob Woodruff Treatment Immediate ...

CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.

PubMed

Shi, Kaibin; Wang, Zhen; Liu, Yuanchu; Gong, Ye; Fu, Ying; Li, Shaowu; Wood, Kristofer; Hao, Junwei; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping

2016-11-01

A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. Copyright © 2016 by The American Association of Immunologists, Inc.

Systemic Prenatal Insults Disrupt Telencephalon Development

PubMed Central

Robinson, Shenandoah

2006-01-01

Infants born prematurely are prone to chronic neurologic deficits including cerebral palsy (CP), epilepsy, cognitive delay, behavioral problems, and neurosensory impairments. In affected children, imaging and neuropathological findings demonstrate significant damage to white matter. The extent of cortical damage has been less obvious. Advances in the understanding of telencephalon development provide insights into how systemic intrauterine insults affect the developing white matter, subplate and cortex, and lead to multiple neurologic impairments. In addition to white matter oligodendrocytes and axons, other elements at risk for perinatal brain injury include subplate neurons, GABAergic neurons migrating through white matter and subplate, and afferents of maturing neurotransmitter systems. Common insults including hypoxia-ischemia and infection often affect the developing brain differently than the mature brain, and insults precipitate a cascade of damage to multiple neural lineages. Insights from development can identify potential targets for therapies to repair the damaged neonatal brain before it has matured. PMID:16061421

Kawasaki Disease

MedlinePlus

... is to relieve symptoms and prevent long-term damage. Most children who have the rare disease require a hospital ... stay home from school or day care. Some children may need ongoing treatment. This is necessary if they suffer damage or are at risk of health disease. Questions ...

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

PubMed

Klein, H C; Krop-Van Gastel, W; Go, K G; Korf, J

1993-02-01

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

Brain-Dead Donors on Extracorporeal Membrane Oxygenation.

PubMed

Bronchard, Régis; Durand, Louise; Legeai, Camille; Cohen, Johana; Guerrini, Patrice; Bastien, Olivier

2017-10-01

To describe donors after brain death with ongoing extracorporeal membrane oxygenation and to analyze the outcome of organs transplanted from these donors. Retrospective analysis of the national information system run by the French Biomedicine Agency (CRISTAL database). National registry data of all donors after brain death in France and their organ recipients between 2007 and 2013. Donors after brain death and their organ recipients. None. During the study period, there were 22,270 brain-dead patients diagnosed in France, of whom 161 with extracorporeal membrane oxygenation. Among these patients, 64 donors on extracorporeal membrane oxygenation and 10,805 donors without extracorporeal membrane oxygenation had at least one organ retrieved. Donors on extracorporeal membrane oxygenation were significantly younger and had more severe intensive care medical conditions (hemodynamic, biological, renal, and liver insults) than donors without extracorporeal membrane oxygenation. One hundred nine kidneys, 37 livers, seven hearts, and one lung were successfully transplanted from donors on extracorporeal membrane oxygenation. We found no significant difference in 1-year kidney graft survival (p = 0.24) and function between recipients from donors on extracorporeal membrane oxygenation (92.7% [85.9-96.3%]) and matching recipients from donors without extracorporeal membrane oxygenation (95.4% [93.0-97.0%]). We also found no significant difference in 1-year liver recipient survival (p = 0.91): 86.5% (70.5-94.1) from donors on extracorporeal membrane oxygenation versus 80.7% (79.8-81.6) from donors without extracorporeal membrane oxygenation. Brain-dead patients with ongoing extracorporeal membrane oxygenation have more severe medical conditions than those without extracorporeal membrane oxygenation. However, kidney graft survival and function were no different than usual. Brain-dead patients with ongoing extracorporeal membrane oxygenation are suitable for organ procurement.

S100 B: A new concept in neurocritical care

PubMed Central

Rezaei, Omidvar; Pakdaman, Hossein; Gharehgozli, Kurosh; Simani, Leila; Vahedian-Azimi, Amir; Asaadi, Sina; Sahraei, Zahra; Hajiesmaeili, Mohammadreza

2017-01-01

After brain injuries, concentrations of some brain markers such as S100B protein in serum and cerebrospinal fluid (CSF) are correlated with the severity and outcome of brain damage. To perform an updated review of S100B roles in human neurocritical care domain, an electronic literature search was carried among articles published in English prior to March 2017. They were retrieved from PubMed, Scopus, EMBSCO, CINAHL, ISC and the Cochrane Library using keywords including “brain”, “neurobiochemical marker”, “neurocritical care”, and “S100B protein”. The integrative review included 48 studies until March 2017. S100B protein can be considered as a marker for blood brain barrier damage. The marker has an important role in the development and recovery of normal central nervous system (CNS) after injury. In addition to extra cerebral sources of S100B, the marker is principally built in the astroglial and Schwann cells. The neurobiochemical marker, S100B, has a pathognomonic role in the diagnosis of a broad spectrum of brain damage including traumatic brain injury (TBI), brain tumor, and stroke. Moreover, a potential predicting role for the neurobiochemical marker has been presumed in the efficiency of brain damage treatment and prognosis. However further animal and human studies are required before widespread routine clinical introduction of S100 protein. PMID:28761630

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Using Biophysical Models to Understand the Effect of tDCS on Neurorehabilitation: Searching for Optimal Covariates to Enhance Poststroke Recovery

PubMed Central

Malerba, Paola; Straudi, Sofia; Fregni, Felipe; Bazhenov, Maxim; Basaglia, Nino

2017-01-01

Stroke is a leading cause of worldwide disability, and up to 75% of survivors suffer from some degree of arm paresis. Recently, rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). Merging the two approaches is thought to provide outlasting clinical gains, by enhancing synaptic plasticity and motor relearning in the motor cortex primary area. However, this general approach has shown mixed results across the stroke population. In particular, stroke location has been found to correlate with the likelihood of success, which suggests that different patients might require different protocols. Understanding how motor rehabilitation and stimulation interact with ongoing neural dynamics is crucial to optimize rehabilitation strategies, but it requires theoretical and computational models to consider the multiple levels at which this complex phenomenon operate. In this work, we argue that biophysical models of cortical dynamics are uniquely suited to address this problem. Specifically, biophysical models can predict treatment efficacy by introducing explicit variables and dynamics for damaged connections, changes in neural excitability, neurotransmitters, neuromodulators, plasticity mechanisms, and repetitive movement, which together can represent brain state, effect of incoming stimulus, and movement-induced activity. In this work, we hypothesize that effects of tDCS depend on ongoing neural activity and that tDCS effects on plasticity may be also related to enhancing inhibitory processes. We propose a model design for each step of this complex system, and highlight strengths and limitations of the different modeling choices within our approach. Our theoretical framework proposes a change in paradigm, where biophysical models can contribute to the future design of novel protocols, in which combined tDCS and motor rehabilitation strategies are tailored to the ongoing dynamics that they interact with, by considering the known biophysical factors recruited by such protocols and their interaction. PMID:28280482

Assessment of genotoxic effects of flumorph by the comet assay in mice organs.

PubMed

Zhang, T; Zhao, Q; Zhang, Y; Ning, J

2014-03-01

The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice. The DNA damage, measured as comet tail length (µm), was determined using the alkaline comet assay. The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model. Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed. The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight. Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm. Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.

Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

PubMed

Yamakami, I; Yamaura, A; Isobe, K

1993-01-01

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid

PubMed Central

Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R.; Masliah, Eliezer; Lipton, Stuart A.

2015-01-01

Cyanide is a life threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species (ROS). This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain-barrier to upregulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human induced pluripotent stem cell (hiPSC)-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino (NSA) mouse model of cyanide poisoning that simulates damage observed in the human brain. PMID:25692407

Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

PubMed

Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

2018-02-15

Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

PubMed Central

2014-01-01

Background Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. Findings Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction. PMID:24576351

Neural Stability, Sparing, and Behavioral Recovery Following Brain Damage

ERIC Educational Resources Information Center

LeVere, T. E.

1975-01-01

The present article discusses the possibility that behavioral recovery following brain damage is not dependent on the functional reorganization of neural tissue but is rather the result of the continued normal operation of spared neural mechanisms. (Editor)

Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain.

PubMed

Lew, S; Hämäläinen, M S; Okada, Y

2017-12-01

To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs. A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure. The magnetic fields from internal organs and an external noise source were computed for a pregnant woman with a 35-week old fetus. Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain. External interference was reduced by a factor of 1000, sufficient for detecting signals from internal organs when combined with passive and active shielding. The scanner rejects internal interferences better than partial-coverage arrays. It can be used to estimate currents around the uterus. It clearly detects spontaneous activity from the fetal heart and brain without averaging and weaker evoked brain activity at all fetal head positions after averaging. The simulated device will be able to monitor the ongoing activity of the fetal and maternal organs. This type of scanner may become a novel tool in fetal medicine. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

PREDICTING APHASIA TYPE FROM BRAIN DAMAGE MEASURED WITH STRUCTURAL MRI

PubMed Central

Yourganov, Grigori; Smith, Kimberly G.; Fridriksson, Julius; Rorden, Chris

2015-01-01

Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca’s, Wernicke’s, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery. Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients’ aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas. PMID:26465238

Predicting aphasia type from brain damage measured with structural MRI.

PubMed

Yourganov, Grigori; Smith, Kimberly G; Fridriksson, Julius; Rorden, Chris

2015-12-01

Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca's, Wernicke's, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery (WAB). Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients' aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine - SVM) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

PubMed Central

Oscar-Berman, Marlene

2013-01-01

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff’s syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking — the types of information and abilities tapped by intelligence tests — remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

Docosahexaenoic acid Confers Neuroprotection in a Rat Model of Perinatal Hypoxia-ischemia potentiated by E. coli lipopolysaccharide-induced systemic inflammation

PubMed Central

BERMAN, Deborah R; LIU, YiQing; BARKS, John; MOZURKEWICH, Ellen

2010-01-01

Objective Lipopolysaccharide (LPS) pretreatment potentiates HI injury. We hypothesized that docosahexaenoic acid (DHA) pretreatment would improve function and reduce brain damage in this rat model of perinatal brain injury and inflammation. Study Design Seven-day-old Wistar rats were divided into 3 groups. One received intraperitoneal (IP) DHA 1 mg/kg and LPS 0.1mg/kg. The second received 25% Albumin and LPS. The third received normal saline (NS). Injections were given 2.5 hours prior to right carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor testing and brain damage assessment on P14. Results DHA pretreatment improved forepaw placing compared to albumin/LPS. (Mean±SD successes/10 trials: 8.57±1.7 DHA/LPS vs 6.72±2.2 Albumin/LPS, p<.0009). There were no significant differences in brain damage among groups. Conclusions Inflammatory stimulation before HI resulted in poorer function than HI alone. Although DHA pretreatment had no impact on brain damage, it significantly improved function in neonatal rats exposed to LPS and HI. PMID:19254588

[Intrauterine infection and the preterm brain: dimensions of aetiology research].

PubMed

Dammann, O

2006-02-01

Perinatal brain damage has a diverse and complex aetiology. Over the past decades, much progress has been made in this research field. In this article, I offer a discussion of seven dimensions of aetiological perinatal brain damage research: (1) hypoxia-ischaemia vs. inflammation; (2) "classic" vs. "remote" intrauterine infection; (3) focal vs. diffuse white matter damage; (4) maternal vs. foetal inflammatory response; (5) clinical vs. experimental data; (6) bacterial vs. viral infection; and (7) preterm vs. term delivery. Despite these complexities, it is hoped that obstetricians, neonatologists, and neuropaediatricians will agree on a perinatal neuroprotective strategy in the near future.

Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

PubMed

Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

2012-12-21

The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

Bilirubin and its oxidation products damage brain white matter

PubMed Central

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

The 8-oxoguanine DNA glycosylase 1 (ogg1) decreases the vulnerability of the developing brain to DNA damage.

PubMed

Gu, Aihua; Ji, Guixiang; Yan, Lifeng; Zhou, Yong

2013-12-01

The developing brain is particularly vulnerable to oxidative DNA damage, which may be the cause of most major congenital mental anomalies. The repair enzyme ogg1 initiates the highly conserved base-excision repair pathway. However, its function in the embryonic brain is largely unknown. This study is the first to validate the function of ogg1 during brain development using zebrafish embryos. Ogg1 was found to be highly expressed in the brain throughout early embryonic development, with particularly enrichment observed in the midbrain. The lack of ogg1 causes severe brain defects including changes in brain volume and integrity, destruction of the midbrain-hindbrain boundary, and balance and motor impairment, while overexpression of ogg1 can partially rescue these defects. Multiple cellular and molecular events were involved in the manifestation of brain defects due primarily to the lack of ogg1. These included (1) increased apoptosis; (2) decreased proliferation; and (3) aberrant axon distribution and extension from the inner surface towards the outer layers. The results of a microarray analysis showed that the expression of genes involved in cell cycle checkpoint, apoptosis, and neurogenesis were significantly changed in response to ogg1 knockdown. Cmyb was the key downstream gene that responses to DNA damage caused by ogg1 deficiency. Notably, the recruitment of ogg1 mRNA can alleviate the effects on the brain due to neural DNA damage. In summary, we introduce here that ogg1 is fundamentally required for protecting the developing brain, which may be helpful in understanding the aetiology of congenital brain deficits. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

PubMed

Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen

2015-01-01

Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The Brain As a Mixer, I. Preliminary Literature Review: Auditory Integration. Studies in Language and Language Behavior, Progress Report Number VII.

ERIC Educational Resources Information Center

Semmel, Melvyn I.; And Others

Methods to evaluate central hearing deficiencies and to localize brain damage are reviewed beginning with Bocca who showed that patients with temporal lobe tumors made significantly lower discrimination scores in the ear opposite the tumor when speech signals were distorted. Tests were devised to attempt to pinpoint brain damage on the basis of…

Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

PubMed

Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

2017-01-01

Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Co-speech hand movements during narrations: What is the impact of right vs. left hemisphere brain damage?

PubMed

Hogrefe, Katharina; Rein, Robert; Skomroch, Harald; Lausberg, Hedda

2016-12-01

Persons with brain damage show deviant patterns of co-speech hand movement behaviour in comparison to healthy speakers. It has been claimed by several authors that gesture and speech rely on a single production mechanism that depends on the same neurological substrate while others claim that both modalities are closely related but separate production channels. Thus, findings so far are contradictory and there is a lack of studies that systematically analyse the full range of hand movements that accompany speech in the condition of brain damage. In the present study, we aimed to fill this gap by comparing hand movement behaviour in persons with unilateral brain damage to the left and the right hemisphere and a matched control group of healthy persons. For hand movement coding, we applied Module I of NEUROGES, an objective and reliable analysis system that enables to analyse the full repertoire of hand movements independent of speech, which makes it specifically suited for the examination of persons with aphasia. The main results of our study show a decreased use of communicative conceptual gestures in persons with damage to the right hemisphere and an increased use of these gestures in persons with left brain damage and aphasia. These results not only suggest that the production of gesture and speech do not rely on the same neurological substrate but also underline the important role of right hemisphere functioning for gesture production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model.

PubMed

Berman, Deborah R; Mozurkewich, Ellen; Liu, Yiqing; Shangguan, Yu; Barks, John D; Silverstein, Faye S

2013-01-01

In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI. Copyright © 2013 S. Karger AG, Basel.

Methamphetamine- and Trauma-Induced Brain Injuries: Comparative Cellular and Molecular Neurobiological Substrates

PubMed Central

Gold, Mark S.; Kobeissy, Firas H.; Wang, Kevin K.W.; Merlo, Lisa J.; Bruijnzeel, Adriaan W.; Krasnova, Irina N.; Cadet, Jean Lud

2009-01-01

The use of methamphetamine (METH) is a growing public health problem because its abuse is associated with long-term biochemical and structural effects on the human brain. Neurodegeneration is often observed in humans as a result of mechanical injuries (e.g. traumatic brain injury, TBI) and ischemic damage (strokes). In this review, we discuss recent findings documenting the fact that the psychostimulant drug, METH, can cause neuronal damage in several brain regions. The accumulated evidence from our laboratories and those of other investigators indicates that acute administration of METH leads to activation of calpain and caspase proteolytic systems. These systems are also involved in causing neuronal damage secondary to traumatic and ischemic brain injuries. Protease activation is accompanied by proteolysis of endogenous neuronal structural proteins (αII-spectrin and MAP-tau protein) evidenced by the appearance of their breakdown products after these injuries. When taken together, these observations suggest that METH exposure, like TBI, can cause substantial damage to the brain by causing both apoptotic and necrotic cell death in the brains of METH addicts who use large doses of the drug during their lifetimes. Finally, because METH abuse is accompanied by functional and structural changes in the brain similar to those in TBI, METH addicts might experience greater benefit if their treatment involved greater emphasis on rehabilitation in conjunction with the use of potential neuroprotective pharmacological agents such as calpain and caspase inhibitors similar to those used in TBI. PMID:19345341

Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats.

PubMed

Shiha, Ahmed A; de la Rosa, Rubén Fernández; Delgado, Mercedes; Pozo, Miguel A; García-García, Luis

2017-01-01

Epilepsy is a central disorder associated with neuronal damage and brain hypometabolism. It has been reported that antidepressant drugs show anticonvulsant and neuroprotective effects in different animal models of seizures and epilepsy. The purpose of this study was to investigate the eventual short-term brain impairment induced by a single low convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP) and the eventual neuroprotective effects exerted by fluoxetine, a prototypical selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and several histological assessments were carried out in adult male rats after i.p. administration of 3 mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage. We also evaluated the effects of a short-term fluoxetine treatment (10 mg/kg, i.p. for 7 days) in this seizure model. [18F]FDG PET analysis revealed no changes in the regional brain metabolism on day 3 after 4-AP injection. The histological assessments revealed signs of damage in the hippocampus, a brain area usually affected by seizures. Thus, reactive gliosis and a significant increase in the expression of caspase-9 were found in the aforementioned brain area. By contrast, we observed no signs of neurodegeneration or neuronal death. Regarding the effects of fluoxetine, this SSRI showed beneficial neurologic effects, since it significantly increased the seizure latency time and reduced the abovementioned 4-AP-induced hippocampal damage markers. Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective agents against convulsant-induced hippocampal damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: A meta-analysis in human pathological specimens.

PubMed

Zabel, Matthew; Nackenoff, Alex; Kirsch, Wolff M; Harrison, Fiona E; Perry, George; Schrag, Matthew

2018-02-01

Oxidative stress and decreased cellular responsiveness to oxidative stress are thought to influence brain aging and Alzheimer's disease, but the specific patterns of oxidative damage and the underlying mechanism leading to this damage are not definitively known. The objective of this study was to define the pattern of changes in oxidative-stress related markers by brain region in human Alzheimer's disease and mild cognitive impairment brain tissue. Observational case-control studies were identified from systematic queries of PubMed, ISI Web of Science and Scopus databases and studies were evaluated with appropriate quality measures. The data was used to construct a region-by-region meta-analysis of malondialdehyde, 4-hydroxynonenal, protein carbonylation, 8-hydroxyguanine levels and superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase activities. We also evaluated ascorbic acid, tocopherol, uric acid and glutathione levels. The analysis was complicated in several cases by publication bias and/or outlier data. We found that malondialdehyde levels were slightly increased in the temporal and occipital lobes and hippocampus, but this analysis was significantly impacted by publication bias. 4-hydroxynonenal levels were unchanged in every brain region. There was no change in 8-hydroxyguanine level in any brain region and protein carbonylation levels were unchanged except for a slight increase in the occipital lobe. Superoxide dismutase, glutathione peroxidase and reductase and catalase activities were not decreased in any brain region. There was limited data reporting non-enzymatic antioxidant levels in Alzheimer's disease brain, although glutathione and tocopherol levels appear to be unchanged. Minimal quantitative data is available from brain tissue from patients with mild cognitive impairment. While there is modest evidence supporting minor regional changes in markers of oxidative damage, this analysis fails to identify a consistent pattern of pro-oxidative changes and accumulation of oxidative damage in bulk tissue analysis in the setting of Alzheimer's disease, as has been widely reported. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

PubMed

Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

2012-05-02

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

PubMed

Andersen, Monica L; Ribeiro, Daniel A; Alvarenga, Tathiana A; Silva, Andressa; Araujo, Paula; Zager, Adriano; Tenorio, Neuli M; Tufik, Sergio

2010-02-01

The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. Copyright 2009 Elsevier Inc. All rights reserved.

Concepts and strategies for clinical management of blast-induced traumatic brain injury and posttraumatic stress disorder.

PubMed

Chen, Yun; Huang, Wei; Constantini, Shlomi

2013-01-01

After exposure of the human body to blast, kinetic energy of the blast shock waves might be transferred into hydraulic energy in the cardiovascular system to cause a rapid physical movement or displacement of blood (a volumetric blood surge). The volumetric blood surge moves through blood vessels from the high-pressure body cavity to the low-pressure cranial cavity, causing damage to tiny cerebral blood vessels and the blood-brain barrier (BBB). Large-scale cerebrovascular insults and BBB damage that occur globally throughout the brain may be the main causes of non-impact, blast-induced brain injuries, including the spectrum of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). The volumetric blood surge may be a major contributor not only to blast-induced brain injuries resulting from physical trauma, but may also be the trigger to psychiatric disorders resulting from emotional and psychological trauma. Clinical imaging technologies, which are able to detect tiny cerebrovascular insults, changes in blood flow, and cerebral edema, may help diagnose both TBI and PTSD in the victims exposed to blasts. Potentially, prompt medical treatment aiming at prevention of secondary neuronal damage may slow down or even block the cascade of events that lead to progressive neuronal damage and subsequent long-term neurological and psychiatric impairment.

Performance of brain-damaged and non-brain-damaged institutionalized children on the Minnesota Percepto-Diagnostic Test.

PubMed

Holland, J M; Fuller, G B; Barth, C E

1982-01-01

Examined the performance of 64 children on the Minnesota Percepto-Diagnostic test (MPD) who were diagnosed as either Brain-Damaged (BD) or emotionally impaired Non-Brain-Damaged (NBD). There were 31 children in the NBD group and 33 in the BD group. The MPD T-score and Actuarial Table significantly differentiated between the two groups. Seventy-four percent of the combined BD-NBD groups were identified correctly. Additional discriminant analysis on this sample yielded combined BD-NBD groups classification rates that ranged from 77% with the MPD variables Separation of Circle-Diamond (SPCD), Distortion of Circle-Diamond (DCD) and Distortion of Dots (DD) to 83% with the WISC-R three IQ scores plus the MPD T-score, SPCD and DD. The MPD T-score and Actuarial Table (MPD Two-Step Diagnosis) appeared to generalize to other populations more readily than discriminant analysis formulae, which tend to be sensitive to the samples from which they are derived.

Car Accident Reconstruction and Head Injury Correlation

NASA Astrophysics Data System (ADS)

Chawla, A.; Grover, V.; Mukherjee, S.; Hassan, A. M.

2013-04-01

Estimation of brain damage remains an elusive issue and controlled tests leading to brain damage cannot be carried out on volunteers. This study reconstructs real-world car accidents to estimate the kinematics of the head impact. This data is to be used to estimate the head injury measures through computer simulations and then correlate reported skull as well as brain damage to impact measures; whence validating the head FE model (Willinger, IJCrash 8:605-617, 2003). In this study, two crash cases were reconstructed. Injury correlation was successful in one of these cases in that the injuries to the brain of one of the car drivers could be correlated in terms of type, location and severity when compared with the tolerance limits of relevant injury parameters (Willinger, IJCrash 8:605-617, 2003).

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

PubMed

Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

2017-03-17

Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration did not result in a net rescue of axons in late lesion stages of experimental autoimmune encephalomyelitis. Our data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss.

A Case Study on the Professional Development of Elementary Teachers Related to Brain Research and the Strategies Used to Help Struggling Readers

ERIC Educational Resources Information Center

Denton, Valerie R.

2010-01-01

This case study examined the impact of classroom interventions for struggling readers as changed/improved by teachers who participated in ongoing professional development on brain research studies. It investigated how teachers' knowledge of brain research impacted their instruction and the interventions they implemented in elementary classrooms.…

Spatio-Temporal Features of Visual Exploration in Unilaterally Brain-Damaged Subjects with or without Neglect: Results from a Touchscreen Test

PubMed Central

Rabuffetti, Marco; Farina, Elisabetta; Alberoni, Margherita; Pellegatta, Daniele; Appollonio, Ildebrando; Affanni, Paola; Forni, Marco; Ferrarin, Maurizio

2012-01-01

Cognitive assessment in a clinical setting is generally made by pencil-and-paper tests, while computer-based tests enable the measurement and the extraction of additional performance indexes. Previous studies have demonstrated that in a research context exploration deficits occur also in patients without evidence of unilateral neglect at pencil-and-paper tests. The objective of this study is to apply a touchscreen-based cancellation test, feasible also in a clinical context, to large groups of control subjects and unilaterally brain-damaged patients, with and without unilateral spatial neglect (USN), in order to assess disturbances of the exploratory skills. A computerized cancellation test on a touchscreen interface was used for assessing the performance of 119 neurologically unimpaired control subjects and 193 patients with unilateral right or left hemispheric brain damage, either with or without USN. A set of performance indexes were defined including Latency, Proximity, Crossings and their spatial lateral gradients, and Preferred Search Direction. Classic outcome scores were computed as well. Results show statistically significant differences among groups (assumed p<0.05). Right-brain-damaged patients with USN were significantly slower (median latency per detected item was 1.18 s) and less efficient (about 13 search-path crossings) in the search than controls (median latency 0.64 s; about 3 crossings). Their preferred search direction (53.6% downward, 36.7% leftward) was different from the one in control patients (88.2% downward, 2.1% leftward). Right-brain-damaged patients without USN showed a significantly abnormal behavior (median latency 0.84 s, about 5 crossings, 83.3% downward and 9.1% leftward direction) situated half way between controls and right-brain-damaged patients with USN. Left-brain-damaged patients without USN were significantly slower and less efficient than controls (latency 1.19 s, about 7 crossings), preserving a normal preferred search direction (93.7% downward). Therefore, the proposed touchscreen-based assessment had evidenced disorders in spatial exploration also in patients without clinically diagnosed USN. PMID:22347489

[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany].

PubMed

Walter, U; Noachtar, S; Hinrichs, H

2018-02-01

The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.

Judo as a possible cause of anoxic brain damage. A case report.

PubMed

Owens, R G; Ghadiali, E J

1991-12-01

The rules of judo provide for strangulation techniques in which the blood supply to the brain is blocked by pressure on the carotid arteries; such techniques produce anoxia and possible unconsciousness if the victim fails to submit. A case is presented of a patient with signs of anoxic brain damage, with psychometric investigation showing memory disturbance consistent with a left temporal lobe lesion. This patient had been frequently strangled during his career as a judo player; it is suggested that such frequent strangulation was the cause of the damage. Such an observation indicates the need for caution in the use of such techniques.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain Malformations

MedlinePlus

Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

Effects of global warming on fish reproductive endocrine axis, with special emphasis in pejerrey Odontesthes bonariensis.

PubMed

Miranda, Leandro Andrés; Chalde, Tomás; Elisio, Mariano; Strüssmann, Carlos Augusto

2013-10-01

The ongoing of global warming trend has led to an increase in temperature of several water bodies. Reproduction in fish, compared with other physiological processes, only occurs in a bounded temperature range; therefore, small changes in water temperature could significantly affect this process. This review provides evidence that fish reproduction may be directly affected by further global warming and that abnormal high water temperature impairs the expression of important genes throughout the brain-pituitary-gonad axis. In all fishes studied, gonads seem to be the organ more readily damaged by heat treatments through the inhibition of the gene expression and subsequent synthesis of different gonadal steroidogenic enzymes. In view of the feedback role of sex steroids upon the synthesis and release of GnRH and GtHs in fish, it is possible that the inhibition observed at brain and pituitary levels in treated fish is consequence of the sharp decrease in plasma steroids levels. Results of in vitro studies on the inhibition of pejerrey gonad aromatase expression by high temperature corroborate that ovary functions are directly disrupted by high temperature independently of the brain-pituitary axis. For the reproductive responses obtained in laboratory fish studies, it is plausible to predict changes in the timing and magnitude of reproductive activity or even the total failure of spawning season may occur in warm years, reducing annual reproductive output and affecting future populations. Copyright © 2013 Elsevier Inc. All rights reserved.

Coping with brain damage

NASA Technical Reports Server (NTRS)

Waring, W.

1974-01-01

Two neurological disorders, cerebral palsy, and traumatic brain damage as from an accident, are considered. The discussion covers the incidence of disabilities, their characteristics, and what is now being done to deal with them, particularly in reference to areas in which the capabilities of the engineer can be effectively applied.

Brain hemorrhage after electrical burn injury: Case report and probable mechanism.

PubMed

Axayacalt, Gutierrez Aceves Guillermo; Alejandro, Ceja Espinosa; Marcos, Rios Alanis; Inocencio, Ruiz Flores Milton; Alfredo, Herrera Gonzalez Jose

2016-01-01

High-voltage electric injury may induce lesion in different organs. In addition to the local tissue damage, electrical injuries may lead to neurological deficits, musculoskeletal damage, and cardiovascular injury. Severe vascular damage may occur making the blood vessels involved prone to thrombosis and spontaneous rupture. Here, we present the case of a 39-year-old male who suffered an electrical burn with high tension wire causing intracranial bleeding. He presented with an electrical burn in the parietal area (entry zone) and the left forearm (exit zone). The head tomography scan revealed an intraparenchimatous bleeding in the left parietal area. In this case, the electric way was the scalp, cranial bone, blood vessels and brain, upper limb muscle, and skin. The damage was different according to the dielectric property in each tissue. The injury was in the scalp, cerebral blood vessel, skeletal muscle, and upper limb skin. The main damage was in brain's blood vessels because of the dielectric and geometric features that lead to bleeding, high temperature, and gas delivering. This is a report of a patient with an electric brain injury that can be useful to elucidate the behavior of the high voltage electrical current flow into the nervous system.

Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication.

PubMed

Ruban, Angela; Mohar, Boaz; Jona, Ghil; Teichberg, Vivian I

2014-02-01

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication

PubMed Central

Ruban, Angela; Mohar, Boaz; Jona, Ghil; Teichberg, Vivian I

2014-01-01

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure. PMID:24149933

Is the Brain a Quantum Computer?

ERIC Educational Resources Information Center

Litt, Abninder; Eliasmith, Chris; Kroon, Frederick W.; Weinstein, Steven; Thagard, Paul

2006-01-01

We argue that computation via quantum mechanical processes is irrelevant to explaining how brains produce thought, contrary to the ongoing speculations of many theorists. First, quantum effects do not have the temporal properties required for neural information processing. Second, there are substantial physical obstacles to any organic…

The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer’s disease

PubMed Central

2013-01-01

Background The pathological features of the common neurodegenerative conditions, Alzheimer’s disease (AD), Parkinson’s disease and multiple sclerosis are all known to be associated with iron dysregulation in regions of the brain where the specific pathology is most highly expressed. Iron accumulates in cortical plaques and neurofibrillary tangles in AD where it participates in redox cycling and causes oxidative damage to neurons. To understand these abnormalities in the distribution of iron the expression of proteins that maintain systemic iron balance was investigated in human AD brains and in the APP-transgenic (APP-tg) mouse. Results Protein levels of hepcidin, the iron-homeostatic peptide, and ferroportin, the iron exporter, were significantly reduced in hippocampal lysates from AD brains. By histochemistry, hepcidin and ferroportin were widely distributed in the normal human brain and co-localised in neurons and astrocytes suggesting a role in regulating iron release. In AD brains, hepcidin expression was reduced and restricted to the neuropil, blood vessels and damaged neurons. In the APP-tg mouse immunoreactivity for ferritin light-chain, the iron storage isoform, was initially distributed throughout the brain and as the disease progressed accumulated in the core of amyloid plaques. In human and mouse tissues, extensive AD pathology with amyloid plaques and severe vascular damage with loss of pericytes and endothelial disruption was seen. In AD brains, hepcidin and ferroportin were associated with haem-positive granular deposits in the region of damaged blood vessels. Conclusion Our results suggest that the reduction in ferroportin levels are likely associated with cerebral ischaemia, inflammation, the loss of neurons due to the well-characterised protein misfolding, senile plaque formation and possibly the ageing process itself. The reasons for the reduction in hepcidin levels are less clear but future investigation could examine circulating levels of the peptide in AD and a possible reduction in the passage of hepcidin across damaged vascular endothelium. Imbalance in the levels and distribution of ferritin light-chain further indicate a failure to utilize and release iron by damaged and degenerating neurons. PMID:24252754

Challenges associated with post-deployment screening for mild traumatic brain injury in military personnel.

PubMed

Iverson, Grant L; Langlois, Jean A; McCrea, Michael A; Kelly, James P

2009-11-01

There is ongoing debate regarding the epidemiology of mild traumatic brain injury (MTBI) in military personnel. Accurate and timely estimates of the incidence of brain injury and the prevalence of long-term problems associated with brain injuries among active duty service members and veterans are essential for (a) operational planning, and (b) to allocate sufficient resources for rehabilitation and ongoing services and supports. The purpose of this article is to discuss challenges associated with post-deployment screening for MTBI. Multiple screening methods have been used in military, Veterans Affairs, and independent studies, which complicate cross-study comparisons of the resulting epidemiological data. We believe that post-deployment screening is important and necessary--but no screening methodology will be flawless, and false positives and false negatives are inevitable. Additional research is necessary to refine the sequential screening methodology, with the goal of minimizing false negatives during initial post-deployment screening and minimizing false positives during follow-up evaluations.

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

Fluorescent Pressure Response of Protein-Nanocluster Polymer Composites

DTIC Science & Technology

2016-05-01

composites as pressure sensitive indicators of brain damage. The PNC composites are made up of protein coated gold nanoclusters and a styrene- ethylene ...styrene- ethylene /butylene-styrene (SEBS):mineral oil composites that were developed as a brain tissue surrogate at ARL. Finally, we would like to...allowing us to use solid samples and create a model for brain damage. To this end, we used styrene- ethylene /butylene-styrene (SEBS) as the matrix to

Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production.

PubMed

Rosenblum, William I

2015-03-01

Traumatic brain injury may result in immediate long-lasting coma. Much attention has been given to predicting this outcome from the initial examination because these predictions can guide future treatment and interactions with the patient's family. Reports of diffuse axonal injury in these cases have ascribed the coma to widespread damage in the deep white matter that disconnects the hemispheres from the ascending arousal system (AAS). However, brainstem lesions are also present in such cases, and the AAS may be interrupted at the brainstem level. This review examines autopsy and imaging literature that assesses the presence, extent, and predictive value of lesions in both sites. The evidence suggests that diffuse injury to the deep white matter is not the usual cause of immediate long-lasting posttraumatic coma. Instead, brainstem lesions in the rostral pons or midbrain are almost always the cause but only if the lesions are bilateral. Moreover, recovery is possible if critical brainstem inputs to the AAS are spared. The precise localization of the latter is subject to ongoing investigation with advanced imaging techniques using magnets of very high magnetic gradients. Limited availability of this equipment plus the need to verify the findings continue to require meticulous autopsy examination.

Traumatic Brain Injury: Effects on the Endocrine System

MedlinePlus

Fact Sheet BTrarainumInajutircy: Effects on the Endocrine System What is traumatic brain injury? Traumatic brain injury, also called TBI, is sudden damage to the brain. It happens when the head hits ...

Traumatic Brain Injury

MedlinePlus

Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...

Can Herpes Simplex Virus Encephalitis Cause Aphasia?

ERIC Educational Resources Information Center

Naude, H.; Pretorius, E.

2003-01-01

Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical…

Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

ERIC Educational Resources Information Center

Blake, Margaret Lehman

2006-01-01

Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

Perspectives on Treatment for Communication Deficits Associated with Right Hemisphere Brain Damage

ERIC Educational Resources Information Center

Blake, Margaret Lehman

2007-01-01

Purpose: To describe the current treatment research for communication (prosodic, discourse, and pragmatic) deficits associated with right hemisphere brain damage and to provide suggestions for treatment selection given the paucity of evidence specifically for this population. Method: The discussion covers (a) clinical decision processes and…

Cognitive Development in Children with Brain Damage.

ERIC Educational Resources Information Center

Bortner, Morton

Presented is a report on a cross-sectional and longitudinal study concerned with the course of intellectual development in 210 children (6-12 years old) educationally designated as brain damaged (learning disabled and/or behavior problems) and assigned to special school placement. The report is divided into four sections which focus on…

Conversation after Right Hemisphere Brain Damage: Motivations for Applying Conversation Analysis

ERIC Educational Resources Information Center

Barnes, Scott; Armstrong, Elizabeth

2010-01-01

Despite the well documented pragmatic deficits that can arise subsequent to Right Hemisphere Brain Damage (RHBD), few researchers have directly studied everyday conversations involving people with RHBD. In recent years, researchers have begun applying Conversation Analysis (CA) to the everyday talk of people with aphasia. This research programme…

Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages.

PubMed

He, Xiao-Fei; Lan, Yue; Zhang, Qun; Liu, Dong-Xu; Wang, Qinmei; Liang, Feng-Ying; Zeng, Jin-Sheng; Xu, Guang-Qing; Pei, Zhong

2016-08-01

Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine (DFX), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57BL6 and Thy-1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two-photon laser irradiation. DFX (100 mg/kg) was administered 6 h after microhemorrhage induction, followed by every 12 h for three consecutive days. The water maze task was conducted 7 days after induction of microhemorrhages, followed by measurement of blood-brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser-induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX, supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment. Irons accumulation after intracranial hemorrhage induced a serious secondary damage to the brain. We proposed that irons accumulation after parietal microhemorrhages impaired spatial cognition. After parietal multiple microhemorrhages, increased irons and ferritin contents induced blood-brain barrier disruption, microglial activation, and further induced dendrites loss, eventually impaired the water maze, deferoxamine treatment protected from these damages. © 2016 International Society for Neurochemistry.

Are the consequences of neonatal hypoxia-ischemia dependent on animals' sex and brain lateralization?

PubMed

Sanches, E F; Arteni, N S; Scherer, E B; Kolling, J; Nicola, F; Willborn, S; Wyse, A T S; Netto, C A

2013-04-24

Hypoxia-ischemia on 3-day-old rats (HIP3) allows the investigation of HI damage in the immature brain. HIP3 is characterized for neurological disabilities caused by white matter injury. This study investigates the relationship between animals' sex and injured hemisphere on HIP3 consequences. Male and female Wistar rats had their right or left common carotid artery occluded under halotane anesthesia and exposed to 8% O2 for 1.5 h. Control rats received sham surgery and exposure to 1.5 h of room air in isolation of their mothers. Sex and injured hemisphere influence in Na+/K+ -ATPase activity 24h after lesion: females and the right brain hemispheres showed decreased enzymatic activity after HIP3. Cognitive impairment was observed in step-down inhibitory avoidance, in which females HIP3 left injured were the most damaged. Histological analysis showed a trend to white matter damage in females left injured without hemispherical nor hippocampal volume decrease in HIP3 rats at postnatal day 21. However, at PND90, hemisphere and sex effects were noted in hemispherical volume and myelination: left brain hemisphere and the females evidenced higher histological damage. Our results points to an increased resistance of male rats and right brain hemisphere to support the impairment caused in Na+/K+ -ATPase activity early after HIP3, and evidencing more discrete behavioral impairments and histological damage at adulthood. Present data adds new evidence of distinct effects of brain lateralization and sex vulnerability on biochemical, behavioral and histological parameters after hypoxia-ischemia. Copyright © 2013 Elsevier B.V. All rights reserved.

Composite Characterization Using Ultrasonic Wavefield Techniques

NASA Technical Reports Server (NTRS)

Leckey, Cara A. C.; Juarez, Peter D.; Seebo, Jeffrey P.

2016-01-01

The large-scale use of composite components in aerospace applications is expected to continue due to the benefits of composite materials, such as reduced weight, increased strength, and tailorability. NASA's Advanced Composites Project (ACP) has the goals of reducing the timeline for certification of composite materials and enabling the expanded use of advanced composite materials. A key technical challenge area for accomplishing these goals is the need for nondestructive evaluation and materials characterization techniques that are optimized for rapid inspection and detailed defect/damage characterization in composite materials. This presentation will discuss ongoing research investigating the use of ultrasonic wavefield techniques for the characterization of defects such as fiber waviness and delamination damage. Ongoing work includes the development of realistic ultrasonic simulation tools for use in predicting the inspectability of composites and optimizing inspection methodologies. Recent studies on detecting/characterizing delamination damage and fiber waviness via wavefield methods will be described.

Pulsed Out of Awareness: EEG Alpha Oscillations Represent a Pulsed-Inhibition of Ongoing Cortical Processing

PubMed Central

Mathewson, Kyle E.; Lleras, Alejandro; Beck, Diane M.; Fabiani, Monica; Ro, Tony; Gratton, Gabriele

2011-01-01

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and we propose that alpha exerts its inhibitory role through alternating microstates of inhibition and excitation. Finally, we discuss evidence that this pulsed-inhibition can be entrained to rhythmic stimuli in the environment, such that preferential processing occurs for stimuli at predictable moments. The entrainment of preferential phase may provide a mechanism for temporal attention in the brain. This pulsed inhibitory account of alpha has important implications for many common cognitive phenomena, such as the attentional blink, and seems to indicate that our visual experience may at least some times be coming through in waves. PMID:21779257

Relationship between orientation to a blast and pressure wave propagation inside the rat brain.

PubMed

Chavko, Mikulas; Watanabe, Tomas; Adeeb, Saleena; Lankasky, Jason; Ahlers, Stephen T; McCarron, Richard M

2011-01-30

Exposure to a blast wave generated during an explosion may result in brain damage and related neurological impairments. Several mechanisms by which the primary blast wave can damage the brain have been proposed, including: (1) a direct effect of the shock wave on the brain causing tissue damage by skull flexure and propagation of stress and shear forces; and (2) an indirect transfer of kinetic energy from the blast, through large blood vessels and cerebrospinal fluid (CSF), to the central nervous system. To address a basic question related to the mechanisms of blast brain injury, pressure was measured inside the brains of rats exposed to a low level of blast (~35kPa), while positioned in three different orientations with respect to the primary blast wave; head facing blast, right side exposed to blast and head facing away from blast. Data show different patterns and durations of the pressure traces inside the brain, depending on the rat orientation to blast. Frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration, suggesting direct transmission and reflection of the pressure inside the brain (dynamic pressure transfer). The pattern of the pressure wave inside the brain in the head facing away from blast exposures assumes contribution of the static pressure, similar to hydrodynamic pressure to the pressure wave inside the brain. Published by Elsevier B.V.

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

PubMed

Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

2011-09-01

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

PubMed Central

Orellana, Juan A.; Cerpa, Waldo; Carvajal, Maria F.; Lerma-Cabrera, José M.; Karahanian, Eduardo; Osorio-Fuentealba, Cesar; Quintanilla, Rodrigo A.

2017-01-01

Alcohol dependence causes physical, social, and moral harms and currently represents an important public health concern. According to the World Health Organization (WHO), alcoholism is the third leading cause of death worldwide, after tobacco consumption and hypertension. Recent epidemiologic studies have shown a growing trend in alcohol abuse among adolescents, characterized by the consumption of large doses of alcohol over a short time period. Since brain development is an ongoing process during adolescence, short- and long-term brain damage associated with drinking behavior could lead to serious consequences for health and wellbeing. Accumulating evidence indicates that alcohol impairs the function of different components of the melanocortin system, a major player involved in the consolidation of addictive behaviors during adolescence and adulthood. Here, we hypothesize the possible implications of melanocortins and glial cells in the onset and progression of alcohol addiction. In particular, we propose that alcohol-induced decrease in α-MSH levels may trigger a cascade of glial inflammatory pathways that culminate in altered gliotransmission in the ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate dopaminergic drive in the NAc, contributing to increase the vulnerability to alcohol dependence and addiction in the adolescence and adulthood. PMID:28424592

Mechanisms of chemoresistance to alkylating agents in malignant glioma.

PubMed

Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

2008-05-15

Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

Brain and cognitive-behavioural development after asphyxia at term birth.

PubMed

de Haan, Michelle; Wyatt, John S; Roth, Simon; Vargha-Khadem, Faraneh; Gadian, David; Mishkin, Mortimer

2006-07-01

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has been implicated in two different long-term outcomes, cognitive memory impairment and the psychiatric disorder schizophrenia. Factors in addition to the acute episode of asphyxia likely contribute to these specific outcomes, making prediction difficult. Future studies that better document long-term cognitive-behavioural outcome, quantitatively identify patterns of brain injury over development and consider additional variables that may modulate the impact of asphyxia on cognitive and behavioural function will forward the goals of predicting long-term outcome and understanding the mechanisms by which it unfolds.

Impaired behavior on real-world tasks following damage to the ventromedial prefrontal cortex.

PubMed

Tranel, Daniel; Hathaway-Nepple, Julie; Anderson, Steven W

2007-04-01

Patients with damage to the ventromedial prefrontal cortices (VMPC) commonly manifest blatant behavioral navigation defects in the real world, but it has been difficult to measure these impairments in the clinic or laboratory. Using a set of "strategy application" tasks, which were designed by Shallice and Burgess (1991) to be ecologically valid for detecting executive dysfunction, we investigated the hypothesis that VMPC damage would be associated with defective performance on such tasks, whereas damage outside the VMPC region would not. A group of 9 patients with bilateral VMPC damage was contrasted with comparison groups of participants with (a) prefrontal brain damage outside the VMPC region (n = 8); (b) nonprefrontal brain damage (n = 17); and (c) no brain damage (n = 20). We found support for the hypothesis: VMPC patients had more impaired performances on the strategy application tasks, especially on a Multiple Errands Test that required patients to execute a series of unstructured tasks in a real-world setting (shopping mall). The results are consistent with the notion that efficacious behavioral navigation is dependent on the VMPC region. However, the strategy application tasks were relatively time consuming and effortful, and their diagnostic yield over and above conventional executive functioning tests may not be sufficient to warrant their inclusion in standard clinical assessment.

Impaired behavior on real-world tasks following damage to the ventromedial prefrontal cortex

PubMed Central

Tranel, Daniel; Hathaway-Nepple, Julie; Anderson, Steven W.

2008-01-01

Patients with damage to the ventromedial prefrontal cortices (VMPC) commonly manifest blatant behavioral navigation defects in the real world, but it has been difficult to measure these impairments in the clinic or laboratory. Using a set of “strategy application” tasks, which were designed by Shallice and Burgess (1991) to be ecologically valid for detecting executive dysfunction, we investigated the hypothesis that VMPC damage would be associated with defective performance on such tasks, whereas damage outside the VMPC region would not. A group of 9 patients with bilateral VMPC damage was contrasted with comparison groups of participants with (a) prefrontal brain damage outside the VMPC region (n=8); (b) nonprefrontal brain damage (n=17); and (c) no brain damage (n=20). We found support for the hypothesis: VMPC patients had more impaired performances on the strategy application tasks, especially on a Multiple Errands Test that required patients to execute a series of unstructured tasks in a real-world setting (shopping mall). The results are consistent with the notion that efficacious behavioral navigation is dependent on the VMPC region. However, the strategy application tasks were relatively time consuming and effortful, and their diagnostic yield over and above conventional executive functioning tests may not be sufficient to warrant their inclusion in standard clinical assessment. PMID:17454352

Moderate ethanol preconditioning of rat brain cultures engenders neuroprotection against dementia-inducing neuroinflammatory proteins: possible signaling mechanisms.

PubMed

Collins, Michael A; Neafsey, Edward J; Wang, Kewei; Achille, Nicholas J; Mitchell, Robert M; Sivaswamy, Sreevidya

2010-06-01

There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol "preconditioning" phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20-30 mM ethanol) of rat brain cultures prevents neurodegeneration due to beta-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic protein-evoked initial increases in [Ca(+2)](i) and proinflammatory mediators--e.g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor --> transducer --> effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in "effector" heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyl-d-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning-like suppression of ongoing neuroinflammation related to amyloidogenic protein accumulation.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population.

PubMed

Amen, Daniel G; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A

2016-04-25

National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

PubMed Central

Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.

2016-01-01

Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players. PMID:27128374

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

PubMed Central

Milleit, Berko; Smesny, Stefan; Rothermundt, Matthias; Preul, Christoph; Schroeter, Matthias L.; von Eiff, Christof; Ponath, Gerald; Milleit, Christine; Sauer, Heinrich; Gaser, Christian

2016-01-01

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. PMID:27013967

Nutrition and the brain: what advice should we give?

PubMed

Cooper, James K

2014-09-01

The knowledge base of nutrition and the brain is steadily expanding. Much of the research is aimed at ways to protect the brain from damage. In adults, the major causes of brain damage are aging and dementia. The most prominent dementia, and the condition that grabs the most public attention, is Alzheimer's disease. The assumption in the field is that possibly some change in nutrition could protect the brain and prevent, delay, or minimize Alzheimer's disease damage. Presented here is a framework for understanding the implications of this research. There is a gap between publishing research results and change in public nutrition behavior. Several influencing elements intervene. These include regulatory agencies and all the organizations and people who advise the public, all with their own perspectives. In considering what advice to give, advisors may consider effectiveness, research model, persuasiveness, and risks, among other factors. Advice about nutrition and Alzheimer's disease today requires several caveats. Copyright © 2014 Elsevier Inc. All rights reserved.

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

[Developmental neurotoxicity of industrial chemicals].

PubMed

Labie, Dominique

2007-10-01

"A Silent Pandemic : Industrial Chemicals Are Impairing the Brain Development of Children Worldwide" Fetal and early childhood exposures to industrial chemicals in the environment can damage the developing brain and can lead to neurodevelopmental disorders (NDDs)--autism, attention deficit disorder (ADHD), and mental retardation. In a new review study, published in The Lancet, Philip Grandjean and Philip Landrigan from the Harvard School of Public Health systematically examined publicly available data on chemical toxicity in order to identify the industrial chemicals that are the most likely to damage the developing brain. The researchers found that 202 industrial chemicals have the capacity to damage the human brain, and they conclude that chemical pollution may have harmed the brains of millions of children worldwide. The authors conclude further that the toxic effects of industrial chemicals on children have generally been overlooked. In North Amercia, the commission for environmental cooperation, and in European Union the DEVNERTOX projects had reached to the same conclusions. We analyse this review and discuss these rather pessimistic conclusions.

Time, Memory, and Consciousness a View from the Brain

NASA Astrophysics Data System (ADS)

Markowitsch, Hans J.

2005-10-01

Memory can be defined as mental time traveling. Seen in this way, memory provides the glue which combines different time episodes and leads to a coherent view of one's own person. The importance of time becomes apparent in a neuroscientific comparison of animals and human beings. All kinds of animals have biorhythms -- times when they sleep, prefer or avoid sex, or move to warmer places. Mammalian brains have a number of time sensitive structures damage to which alters a subject's behavior to his or her environment. For human beings, damage to certain brain regions may alter the sense of time and consciousness of time in quite different ways. Furthermore, brain damage, drugs, or psychiatric disturbances may lead to an impaired perception of time, sometimes leading to major positive or negative accelerations in time perception. An impaired time perception alters consciousness and awareness of oneself. A proper synchronized action of time perception, brain activation, memory processing, and autonoetic (self-aware) consciousness provides the bases of an integrated personality.

Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

PubMed

Sokolowska, P; Passemard, S; Mok, A; Schwendimann, L; Gozes, I; Gressens, P

2011-01-26

Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Self-amplification of nigral degeneration in Parkinson's disease: a hypothesis.

PubMed

Ionov, Ilya D

2008-12-01

This review analyzes current evidence regarding possible mechanisms of nigral damage in idiopathic Parkinson's disease (iPD). In normal brain, a specific interplay among the blood-brain barrier (BBB), substantia nigra (SN), and locus coeruleus (LC) creates the condition for a self-accelerating damage to the SN. Three vicious circles involving SN-BBB, LC-SN-BBB, and histamine-BBB-SN interactions are described. In iPD, a self-accelerating loss of nigral cells can be triggered by brain hypoperfusion and by an increased blood histamine level. iPD-associated factors such as decreased CSF levels of substance P, somatostatin, and glutamate can aggravate the vicious-circle-induced damage to the SN.

Brain Damage in School Age Children.

ERIC Educational Resources Information Center

Haywood, H. Carl, Ed.

The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

The Effects of Brain Damage on Visual Functioning in Children.

ERIC Educational Resources Information Center

Alexander, P. K.

1990-01-01

The review of research concluded that, although brain damage affects visual functioning, the prognosis for good functional vision after remedial intervention is better than previously thought. Although electrodiagnostic testing was found to be valuable, use of a combination of tests is recommended to obtain the most complete picture of brain…

Neuroscience in Schools

ERIC Educational Resources Information Center

Schachter, Ron

2012-01-01

For generations, teachers in the early elementary years have urged their young pupils to use their brains. They're still offering the same encouragement, but nowadays they can know even more about what they're talking about. Recent advances in neuroscience--from detailed scans of the brain to ongoing research on teaching methods that increase…

What next for Fukushima?

NASA Astrophysics Data System (ADS)

Drinkwater, Bruce; Malkin, Rob

2018-01-01

Nearly seven years after a powerful tsunami caused catastrophic damage to Japan's Fukushima Daiichi nuclear-power plant, the clean-up and recovery is still ongoing. Bruce Drinkwater and Rob Malkin recently visited the disaster site and the undamaged Tsuruga plant to see if they can pinpoint the true extent of the damage in the dangerously radioactive reactors

Right-sided representational neglect after left brain damage in a case without visuospatial working memory deficits.

PubMed

van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Fias, Wim

2013-10-01

Brain damaged patients suffering from representational neglect (RN) fail to report, orient to, or verbally describe contra-lesional elements of imagined environments or objects. So far this disorder has only been reported after right brain damage, leading to the idea that only the right hemisphere is involved in this deficit. A widely accepted account attributes RN to a lateralized impairment in the visuospatial component of working memory. So far, however, this hypothesis has not been tested in detail. In the present paper, we describe, for the first time, the case of a left brain damaged patient suffering from right-sided RN while imagining both known and new environments and objects. An in-depth evaluation of her visuospatial working memory abilities, with special focus on the presence of a lateralized deficit, did not reveal any abnormality. In sharp contrast, her ability to memorize visual information was severely compromised. The implications of these results are discussed in the light of recent insights in the neglect syndrome. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sensitivity of the Halstead and Wechsler Test Batteries to brain damage: Evidence from Reitan's original validation sample.

PubMed

Loring, David W; Larrabee, Glenn J

2006-06-01

The Halstead-Reitan Battery has been instrumental in the development of neuropsychological practice in the United States. Although Reitan administered both the Wechsler-Bellevue Intelligence Scale and Halstead's test battery when evaluating Halstead's theory of biologic intelligence, the relative sensitivity of each test battery to brain damage continues to be an area of controversy. Because Reitan did not perform direct parametric analysis to contrast group performances, we reanalyze Reitan's original validation data from both Halstead (Reitan, 1955) and Wechsler batteries (Reitan, 1959a) and calculate effect sizes and probability levels using traditional parametric approaches. Eight of the 10 tests comprising Halstead's original Impairment Index, as well as the Impairment Index itself, statistically differentiated patients with unequivocal brain damage from controls. In addition, 13 of 14 Wechsler measures including Full-Scale IQ also differed statistically between groups (Brain Damage Full-Scale IQ = 96.2; Control Group Full Scale IQ = 112.6). We suggest that differences in the statistical properties of each battery (e.g., raw scores vs. standardized scores) likely contribute to classification characteristics including test sensitivity and specificity.

Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

PubMed Central

Rabinowicz, Noa; Mangala, Lingegowda S.; Brown, Kevin R.; Checa-Rodriguez, Cintia; Castiel, Asher; Moskovich, Oren; Zarfati, Giulia; Trakhtenbrot, Luba; Levy-Barda, Adva; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Pradeep, Sunila; van Praag, Yael; Lopez-Berestein, Gabriel; David, Ahuvit; Novikov, Ilya; Huertas, Pablo; Rottapel, Robert; Sood, Anil K.; Izraeli, Shai

2017-01-01

Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer. PMID:28423708

Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer.

PubMed

Rabinowicz, Noa; Mangala, Lingegowda S; Brown, Kevin R; Checa-Rodriguez, Cintia; Castiel, Asher; Moskovich, Oren; Zarfati, Giulia; Trakhtenbrot, Luba; Levy-Barda, Adva; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Pradeep, Sunila; van Praag, Yael; Lopez-Berestein, Gabriel; David, Ahuvit; Novikov, Ilya; Huertas, Pablo; Rottapel, Robert; Sood, Anil K; Izraeli, Shai

2017-04-18

Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer.

No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.

PubMed

Blennow, K; Jonsson, M; Andreasen, N; Rosengren, L; Wallin, A; Hellström, P A; Zetterberg, H

2011-04-01

Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons. © 2010 John Wiley & Sons A/S.

The ELGAN study of the brain and related disorders in extremely low gestational age newborns.

PubMed

O'Shea, T M; Allred, E N; Dammann, O; Hirtz, D; Kuban, K C K; Paneth, N; Leviton, A

2009-11-01

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. To identify factors that contribute to brain damage in ELGANs. Multi-center cohort study. We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots. Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.

Zingiber zerumbet L. (Smith) extract alleviates the ethanol-induced brain damage via its antioxidant activity.

PubMed

Hamid, Asmah; Ibrahim, Farah Wahida; Ming, Teoh Hooi; Nasrom, Mohd Nazir; Eusoff, Norelina; Husain, Khairana; Abdul Latif, Mazlyzam

2018-03-20

Zingiber zerumbet (L.) Smith belongs to the Zingiberaceae family that is widely distributed throughout the tropics, particularly in Southeast Asia. It is locally known as 'Lempoyang' and traditionally used to treat fever, constipation and to relieve pain. It is also known to possess antioxidant and anti-inflammatory activities. Based on these antioxidant and anti-inflammatory activities, this study was conducted to investigate the effects of ethyl-acetate extract of Z. zerumbet rhizomes against ethanol-induced brain damage in male Wistar rats. Twenty-four male Wistar rats were divided into four groups which consist of normal, 1.8 g/kg ethanol (40% v/v), 200 mg/kg Z. zerumbet extract plus ethanol and 400 mg/kg Z. zerumbet plus ethanol. The extract of Z. zerumbet was given once daily by oral gavage, 30 min prior to ethanol exposure via intraperitoneal route for 14 consecutive days. The rats were then sacrificed. Blood and brain homogenate were subjected to biochemical tests and part of the brain tissue was sectioned for histological analysis. Treatment with ethyl-acetate Z. zerumbet extract at 200 mg/kg and 400 mg/kg significantly reduced the level of malondialdehyde (MDA) and protein carbonyl (p < 0.05) in the brain homogenate. Both doses of extracts also significantly increased the level of serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities as well as glutathione (GSH) level (p < 0.05). However, administration of ethyl-acetate Z. zerumbet extract at 400 mg/kg showed better protective effects on the ethanol-induced brain damage as shown with higher levels of SOD, CAT, GPx and GSH in the brain homogenate as compared to 200 mg/kg dose. Histological observation of the cerebellum and cerebral cortex showed that the extract prevented the loss of Purkinje cells and retained the number and the shape of the cells. Ethyl-acetate extract of Z. zerumbet has protective effects against ethanol-induced brain damage and this is mediated through its antioxidant properties. Z. zerumbet extract protects against ethanol-induced brain damage via its antioxidant properties.

Discourse Impairments Following Right Hemisphere Brain Damage: A Critical Review

PubMed Central

Johns, Clinton L.; Tooley, Kristen M.; Traxler, Matthew J.

2015-01-01

Right hemisphere brain damage (RHD) rarely causes aphasias marked by clear and widespread failures of comprehension or extreme difficulty producing fluent speech. Nonetheless, subtle language comprehension deficits can occur following unilateral RHD. In this article, we review the empirical record on discourse function following right hemisphere damage, as well as relevant work on non-brain damaged individuals that focuses on right hemisphere function. The review is divided into four sections that focus on discourse processing, inferencing, humor, and non-literal language. While the exact role that the right hemisphere plays in language processing, and the exact way that the two cerebral hemispheres coordinate their linguistic processes are still open to debate, our review suggests that the right hemisphere plays a critical role in managing inferred or implied information by maintaining relevant information and/or suppressing irrelevant information. Deficits in one or both of these mechanisms may account for discourse deficits following RHD. PMID:26085839

Potential effects of environmental contaminants on P450 aromatase activity and DNA damage in swallows from the Rio Grande and Somerville, Texas

USGS Publications Warehouse

Sitzlar, M.A.; Mora, M.A.; Fleming, J.G.W.; Bazer, F.W.; Bickham, J.W.; Matson, C.W.

2009-01-01

Cliff swallows (Petrochelidon pyrrhonota) and cave swallows (P. fulva) were sampled during the breeding season at several locations in the Rio Grande, Texas, to evaluate the potential effects of environmental contaminants on P450 aromatase activity in brain and gonads and DNA damage in blood cells. The tritiated water-release aromatase assay was used to measure aromatase activity and flow cytometry was used to measure DNA damage in nucleated blood cells. There were no significant differences in brain and gonadal aromatase activities or in estimates of DNA damage (HPCV values) among cave swallow colonies from the Lower Rio Grande Valley (LRGV) and Somerville. However, both brain and gonadal aromatase activities were significantly higher (P < 0.05) in male cliff swallows from Laredo than in those from Somerville. Also, DNA damage estimates were significantly higher (P < 0.05) in cliff swallows (males and females combined) from Laredo than in those from Somerville. Contaminants of current high use in the LRGV, such as atrazine, and some of the highly persistent organochlorines, such as toxaphene and DDE, could be potentially associated with modulation of aromatase activity in avian tissues. Previous studies have indicated possible DNA damage in cliff swallows. We did not observe any differences in aromatase activity or DNA damage in cave swallows that could be associated with contaminant exposure. Also, the differences in aromatase activity and DNA damage between male cliff swallows from Laredo and Somerville could not be explained by contaminants measured at each site in previous studies. Our study provides baseline information on brain and gonadal aromatase activity in swallows that could be useful in future studies. ?? 2008 Springer Science+Business Media, LLC.

Development of In Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2015-02-01

distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain...who have sustained multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently, there are no methods to...repetitive concussive TBI in mice has been optimal. Ongoing efforts include development of more sensitive methods to detect tau, and combinations of

DNA damage in the oligodendrocyte lineage and its role in brain aging.

PubMed

Tse, Kai-Hei; Herrup, Karl

2017-01-01

Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain. As in neurons, unrepaired DNA damage accumulates in the postmitotic oligodendrocyte genome during normal aging, and indeed may be one of the upstream causes of cellular aging - a fact well illustrated by myelin co-morbidity in premature aging syndromes arising from deficits in DNA repair enzymes. The clinical and experimental evidence from Alzheimer's disease, progeroid syndromes, ataxia-telangiectasia and other conditions strongly suggest that oligodendrocytes may in fact be uniquely vulnerable to oxidative DNA damage. If this damage remains unrepaired, as is increasingly true in the aging brain, myelin gene transcription and oligodendrocyte differentiation is impaired. Delineating the relationships between early myelin loss and DNA damage in brain aging will offer an additional dimension outside the neurocentric view of neurodegenerative disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

PubMed

Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

2018-06-01

The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Identifying functional reorganization of spelling networks: an individual peak probability comparison approach

PubMed Central

Purcell, Jeremy J.; Rapp, Brenda

2013-01-01

Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981

Driving safety after brain damage: follow-up of twenty-two patients with matched controls.

PubMed

Katz, R T; Golden, R S; Butter, J; Tepper, D; Rothke, S; Holmes, J; Sahgal, V

1990-02-01

Driving after brain damage is a vital issue, considering the large number of patients who suffer from cerebrovascular and traumatic encephalopathy. The ability to operate a motor vehicle is an integral part of independence for most adults and so should be preserved whenever possible. The physician may estimate a patient's ability to drive safely based on his own examination, the evaluation of a neuropsychologist, and a comprehensive driving evaluation--testing, driving simulation, behind-the-wheel observation--with a driving specialist. This study sought to evaluate the ability of brain-damaged individuals to operate a motor vehicle safely at follow-up. These patients had been evaluated (by a physician, a neuropsychologist, and a driving specialist) and were judged able to operate a motor vehicle safely after their cognitive insult. Twenty-two brain-damaged patients who were evaluated at our institution were successfully followed up to five years (mean interval of 2.67 years). Patients were interviewed by telephone. Their driving safely was compared with a control group consisting of a close friend or spouse of each patient. Statistical analysis revealed no difference between patient and control groups in the type of driving, the incidence of speeding tickets, near accidents, and accidents, and the cost of vehicle damage when accidents occurred. The patient group was further divided into those who had, and those who had not experienced driving difficulties so that initial neuropsychologic testing could be compared. No significant differences were noted in any aspect of the neuropsychologic test battery. We conclude that selected brain-damaged patients who have passed a comprehensive driving assessment as outlined were as fit to drive as were their normal matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Postural abnormalities and contraversive pushing following right hemisphere brain damage.

PubMed

Lafosse, C; Kerckhofs, E; Vereeck, L; Troch, M; Van Hoydonck, G; Moeremans, M; Sneyers, C; Broeckx, J; Dereymaeker, L

2007-06-01

We investigated the presence of postural abnormalities in a consecutive sample of stroke patients, with either left or right brain damage, in relation to their perceived body position in space. The presence or absence of posture-related symptoms was judged by two trained therapists and subsequently analysed by hierarchical classes analysis (HICLAS). The subject classes resulting from the HICLAS model were further validated with respect to posture-related measurements, such as centre of gravity position and head position, as well as measurements related to the postural body scheme, such as the perception of postural and visual verticality. The results of the classification analysis clearly demonstrated a relation between the presence of right brain damage and abnormalities in body geometry. The HICLAS model revealed three classes of subjects: The first class contained almost all the patients without neglect and without any signs of contraversive pushing. They were mainly characterised by a normal body axis in any position. The second class were all neglect patients but predominantly without any contraversive pushing. The third class contained right brain damaged patients, all showing neglect and mostly exhibiting contraversive pushing. The patients in the third class showed a clear resistance to bringing the weight over to the ipsilesional side when the therapist attempted to make the subject achieve a vertical posture across the midline. The clear correspondence between abnormalities of the observed body geometry and the tilt of the subjective postural and visual vertical suggests that a patient's postural body geometry is characterised by leaning towards the side of space where he/she feels aligned with an altered postural body scheme. The presence of contraversive pushing after right brain damage points in to a spatial higher-order processing deficit underlying the higher frequency and severity of the axial postural abnormalities found after right brain lesions.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats.

PubMed

Tenorio, Neuli M; Ribeiro, Daniel A; Alvarenga, Tathiana A; Fracalossi, Ana Carolina C; Carlin, Viviane; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica L

2013-01-01

The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

MRI-Guided Focused Ultrasound Surgery

PubMed Central

Jolesz, Ferenc A.

2014-01-01

MRI-guided focused ultrasound (MRgFUS) surgery is a noninvasive thermal ablation method that uses magnetic resonance imaging (MRI) for target definition, treatment planning, and closed-loop control of energy deposition. Integrating FUS and MRI as a therapy delivery system allows us to localize, target, and monitor in real time, and thus to ablate targeted tissue without damaging normal structures. This precision makes MRgFUS an attractive alternative to surgical resection or radiation therapy of benign and malignant tumors. Already approved for the treatment of uterine fibroids, MRgFUS is in ongoing clinical trials for the treatment of breast, liver, prostate, and brain cancer and for the palliation of pain in bone metastasis. In addition to thermal ablation, FUS, with or without the use of microbubbles, can temporarily change vascular or cell membrane permeability and release or activate various compounds for targeted drug delivery or gene therapy. A disruptive technology, MRgFUS provides new therapeutic approaches and may cause major changes in patient management and several medical disciplines. PMID:19630579

Ammonia toxicity and its prevention in inherited defects of the urea cycle.

PubMed

Walker, V

2009-09-01

The urea cycle is the final pathway for removal of surplus nitrogen from the body, and the major route in humans for detoxification of ammonia. The full complement of enzymes is expressed only in liver. Inherited deficiencies of urea cycle enzymes lead to hyperammonaemia, which causes brain damage. Severe defects present with hyperammonaemic crises in neonates. Equally devastating episodes may occur in previously asymptomatic adults with mild defects, most often X-linked ornithine transcarbamylase (OTC) deficiency. Several mechanisms probably contribute to pathogenesis. Treatment aims to reduce plasma ammonia quickly, reduce production of waste nitrogen, dispose of waste nitrogen using alternative pathways to the urea cycle and replace arginine. These therapies have increased survival and probably improve the neurological outcome. Arginine, sodium benzoate, sodium phenylbutyrate and, less often, sodium phenylacetate are used. Long-term correction is achieved by liver transplantation. Gene therapy for OTC deficiency is effective in animals, and work is ongoing to improve persistence and safety.

Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

PubMed

Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

2014-07-01

Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased understanding of mechanisms underlying delayed microvascular damage following TBI could provide novel insights into chronic pathological responses to TBI and potential common mechanisms underlying TBI and neurodegenerative diseases.

An Evidence-Based Systematic Review on Communication Treatments for Individuals with Right Hemisphere Brain Damage

ERIC Educational Resources Information Center

Blake, Margaret Lehman; Frymark, Tobi; Venedictov, Rebecca

2013-01-01

Purpose: The purpose of this review is to evaluate and summarize the research evidence related to the treatment of individuals with right hemisphere communication disorders. Method: A comprehensive search of the literature using key words related to right hemisphere brain damage and communication treatment was conducted in 27 databases (e.g.,…

Inference Generation during Text Comprehension by Adults with Right Hemisphere Brain Damage: Activation Failure Versus Multiple Activation.

ERIC Educational Resources Information Center

Tompkins, Connie A.; Fassbinder, Wiltrud; Blake, Margaret Lehman; Baumgaertner, Annette; Jayaram, Nandini

2004-01-01

ourse comprehensionEvidence conflicts as to whether adults with right hemisphere brain damage (RHD) generate inferences during text comprehension. M. Beeman (1993) reported that adults with RHD fail to activate the lexical-semantic bases of routine bridging inferences, which are necessary for comprehension. But other evidence indicates that adults…

Perception of Lexical Stress by Brain-Damaged Individuals: Effects on Lexical-Semantic Activation

ERIC Educational Resources Information Center

Shah, Amee P.; Baum, Shari R.

2006-01-01

A semantic priming, lexical-decision study was conducted to examine the ability of left- and right-brain damaged individuals to perceive lexical-stress cues and map them onto lexical-semantic representations. Correctly and incorrectly stressed primes were paired with related and unrelated target words to tap implicit processing of lexical prosody.…

Testing the Language of German Cerebral Palsy Patients with Right Hemispheric Language Organization after Early Left Hemispheric Damage

ERIC Educational Resources Information Center

Schwilling, Eleonore; Krageloh-Mann, Ingeborg; Konietzko, Andreas; Winkler, Susanne; Lidzba, Karen

2012-01-01

Language functions are generally represented in the left cerebral hemisphere. After early (prenatally acquired or perinatally acquired) left hemispheric brain damage language functions may be salvaged by reorganization into the right hemisphere. This is different from brain lesions acquired in adulthood which normally lead to aphasia. Right…

Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

ERIC Educational Resources Information Center

Kleim, Jeffrey A.; Jones, Theresa A.

2008-01-01

Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance

PubMed Central

Chavan, Camille F.; Manuel, Aurelie L.; Mouthon, Michael; Spierer, Lucas

2013-01-01

Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms. PMID:23761747

Alterations in brain temperatures as a possible cause of migraine headache.

PubMed

Horváth, Csilla

2014-05-01

Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased serotonin content, and dural "inflammation" including vasodilation and brainstem activation. The hypothesis postulates that a migraine attack serves to restore the brain temperature. Abnormally low temperatures in the brain can also result in headache. Surprisingly, no systematic examination of brain temperature changes in migraineurs has been published. Certain case reports support the present hypothesis. Various noninvasive technologies (e.g. MR) capable of monitoring brain temperature are available. If a systematic examination of local brain temperature revealed abnormalities in structures presumed to be involved in migraine, that would increase our understanding of the disease and trigger the development of improved treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

The pathological role of NLRs and AIM2 inflammasome-mediated pyroptosis in damaged blood-brain barrier after traumatic brain injury.

PubMed

Ge, Xintong; Li, Wenzhu; Huang, Shan; Yin, Zhenyu; Xu, Xin; Chen, Fanglian; Kong, Xiaodong; Wang, Haichen; Zhang, Jianning; Lei, Ping

2018-06-07

Pyroptosis is a highly specific type of inflammatory programmed cell death that different from necrosis or apoptosis. It is initiated by cellular detection of acute damage via recognizing pathogen-associated molecular patterns (PAMPs) by NOD-like receptors (NLRs) or AIM2-like receptor (AIM2). NLRs and AIM2 could trigger the formation of a multi-protein complex, known as inflammasome. It also contains apoptotic speck-containing protein (ASC) and pro-Caspase-1, and could process the signals to induce a cascade of inflammatory response. Recently, growing evidence showed that inflammasome-mediated pyroptosis is involved in the pathogenesis of traumatic brain injury (TBI). However, less attention has been paid to their particular roles in regulating blood-brain barrier (BBB) damage, the central pathological change in secondary brain damage of TBI. Thus, we designed this research to explore the impact and mechanism of NLRs and AIM2 inflammasome-mediated pyroptosis in BBB after TBI. We employed the controlled cortical impact (CCI) mice model and manipulated the severity of pyroptosis in BBB using Caspase-1 inhibitor, Ac-YVAD-cmk. We found that TBI led to NLRs and AIM2 inflammasome-mediated pyroptosis in brain microvascular endothelial cells (BMVECs) from injured cerebral cortex. Ac-YVAD-cmk treatment inhibited pyroptosis in injured BMVECs by suppressing the expression of essential inflammasome subunit - Caspase-1 and pivotal downstream pro-inflammatory cytokines (IL-1β and IL-18), as well as hindering GSDMD cleavage and ASC oligomerization. In addition, inhibiting pyroptosis could alleviate TBI-induced BBB leakage, brain edema, loss of tight junction proteins, and the inflammatory response in injured BMVECs. These effects contributed to improving the neurological outcome of CCI mice. In conclusion, NLRs and AIM2 inflammasome-mediated pyroptosis could aggravate BBB damage after TBI. Targeting and controlling pyroptosis in injured BBB would be a promising therapeutic strategy for TBI in the future. Copyright © 2018. Published by Elsevier B.V.

Low-level light therapy of the eye and brain.

PubMed

Rojas, Julio C; Gonzalez-Lima, F

2011-01-01

Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.

Low-level light therapy of the eye and brain

PubMed Central

Rojas, Julio C; Gonzalez-Lima, F

2011-01-01

Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain. PMID:28539775

Blast induced mild traumatic brain injury/concussion: A physical analysis

NASA Astrophysics Data System (ADS)

Kucherov, Yan; Hubler, Graham K.; DePalma, Ralph G.

2012-11-01

Currently, a consensus exists that low intensity non-impact blast wave exposure leads to mild traumatic brain injury (mTBI). Considerable interest in this "invisible injury" has developed in the past few years but a disconnect remains between the biomedical outcomes and possible physical mechanisms causing mTBI. Here, we show that a shock wave travelling through the brain excites a phonon continuum that decays into specific acoustic waves with intensity exceeding brain tissue strength. Damage may occur within the period of the phonon wave, measured in tens to hundreds of nanometers, which makes the damage difficult to detect using conventional modalities.

Protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion.

PubMed

Zhai, S-Q; Guo, W; Hu, Y-Y; Yu, N; Chen, Q; Wang, J-Z; Fan, M; Yang, W-Y

2011-05-01

To explore the protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion. Recombinant adenovirus brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and artificial perilymph were prepared. Guinea pigs with audiometric auditory brainstem response thresholds of more than 75 dB SPL, measured seven days after four hours of noise exposure at 135 dB SPL, were divided into three groups. Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and perilymph were infused into the cochleae of the three groups, variously. Eight weeks later, the cochleae were stained immunohistochemically and the spiral ganglion cells counted. The auditory brainstem response threshold recorded before and seven days after noise exposure did not differ significantly between the three groups. However, eight weeks after cochlear perfusion, the group receiving brain-derived neurotrophic factor had a significantly decreased auditory brainstem response threshold and increased spiral ganglion cell count, compared with the adenovirus LacZ and perilymph groups. When administered via cochlear infusion following noise damage, brain-derived neurotrophic factor appears to improve the auditory threshold, and to have a protective effect on the spiral ganglion cells.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Bacterial Cytolysin during Meningitis Disrupts the Regulation of Glutamate in the Brain, Leading to Synaptic Damage

PubMed Central

Wippel, Carolin; Maurer, Jana; Förtsch, Christina; Hupp, Sabrina; Bohl, Alexandra; Ma, Jiangtao; Mitchell, Timothy J.; Bunkowski, Stephanie; Brück, Wolfgang; Nau, Roland; Iliev, Asparouh I.

2013-01-01

Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage. PMID:23785278

Alterations of Hippocampal Myelin Sheath and Axon Sprouting by Status Convulsion and Regulating Lingo-1 Expression with RNA Interference in Immature and Adult Rats.

PubMed

Song, Xiao-Jie; Han, Wei; He, Rong; Li, Tian-Yi; Xie, Ling-Ling; Cheng, Li; Chen, Heng-Sheng; Jiang, Li

2018-03-01

Seizure-induced brain damage is age-dependent, as evidenced by the different alterations of neural physiopathology in developing and mature brains. However, little is known about the age-dependent characteristics of myelinated fiber injury induced by seizures. Considering the critical functions of oligodendrocyte progenitor cells (OPCs) in myelination and Lingo-1 signaling in regulating OPCs' differentiation, the present study aimed to explore the effects of Lingo-1 on myelin and axon in immature and adult rats after status convulsion (SC) induced by lithium-pilocarpine, and the differences between immature and adult brains. Dynamic variations in electrophysiological activity and spontaneous recurrent seizures were recorded by electroencephalogram monitoring after SC. The impaired microstructures of myelin sheaths and decrease in myelin basic protein caused by SC were observed through transmission electron microscopy and western blot analysis respectively, which became more severe in adult rats, but improved gradually in immature rats. Aberrant axon sprouting occurred in adult rats, which was more prominent than in immature rats, as shown by a Timm stain. This damage was improved or negatively affected after down or upregulating Lingo-1 expression. These results demonstrated that in both immature and adult brains, Lingo-1 signaling plays important roles in seizure-induced damage to myelin sheaths and axon growth. The plasticity of the developing brain may provide a potential window of opportunity to prevent the brain from damage.

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2010-01-01

Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…

Opaque for the Reader but Transparent for the Brain: Neural Signatures of Morphological Complexity

ERIC Educational Resources Information Center

Meinzer, Marcus; Lahiri, Aditi; Flaisch, Tobias; Hannemann, Ronny; Eulitz, Carsten

2009-01-01

Within linguistics, words with a complex internal structure are commonly assumed to be decomposed into their constituent morphemes (e.g., un-help-ful). Nevertheless, an ongoing debate concerns the brain structures that subserve this process. Using functional magnetic resonance imaging, the present study varied the internal complexity of derived…

Incorporating virtual reality graphics with brain imaging for assessment of sport-related concussions.

PubMed

Slobounov, Semyon; Sebastianelli, Wayne; Newell, Karl M

2011-01-01

There is a growing concern that traditional neuropsychological (NP) testing tools are not sensitive to detecting residual brain dysfunctions in subjects suffering from mild traumatic brain injuries (MTBI). Moreover, most MTBI patients are asymptomatic based on anatomical brain imaging (CT, MRI), neurological examinations and patients' subjective reports within 10 days post-injury. Our ongoing research has documented that residual balance and visual-kinesthetic dysfunctions along with its underlying alterations of neural substrates may be detected in "asymptomatic subjects" by means of Virtual Reality (VR) graphics incorporated with brain imaging (EEG) techniques.

Cortisol Excess and the Brain.

PubMed

Resmini, Eugenia; Santos, Alicia; Webb, Susan M

2016-01-01

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

Swimming training attenuates oxidative damage and increases enzymatic but not non-enzymatic antioxidant defenses in the rat brain.

PubMed

Nonato, L F; Rocha-Vieira, E; Tossige-Gomes, R; Soares, A A; Soares, B A; Freitas, D A; Oliveira, M X; Mendonça, V A; Lacerda, A C; Massensini, A R; Leite, H R

2016-09-29

Although it is well known that physical training ameliorates brain oxidative function after injuries by enhancing the levels of neurotrophic factors and oxidative status, there is little evidence addressing the influence of exercise training itself on brain oxidative damage and data is conflicting. This study investigated the effect of well-established swimming training protocol on lipid peroxidation and components of antioxidant system in the rat brain. Male Wistar rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8) and non-trained (n=7) groups. Forty-eight hours after the last session of exercise, animals were euthanized and the brain was collected for oxidative stress analysis. Swimming training decreased thiobarbituric acid reactive substances (TBARS) levels (P<0.05) and increased the activity of the antioxidant enzyme superoxide dismutase (SOD) (P<0.05) with no effect on brain non-enzymatic total antioxidant capacity, estimated by FRAP (ferric-reducing antioxidant power) assay (P>0.05). Moreover, the swimming training promoted metabolic adaptations, such as increased maximal workload capacity (P<0.05) and maintenance of body weight. In this context, the reduced TBARS content and increased SOD antioxidant activity induced by 8 weeks of swimming training are key factors in promoting brain resistance. In conclusion, swimming training attenuated oxidative damage and increased enzymatic antioxidant but not non-enzymatic status in the rat brain.

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2015-02-01

Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and...11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17...To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing efforts include

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2016-02-01

14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive...pugilistica 3, 11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain...Progress to date: To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing

Using Brain–Computer Interfaces and Brain-State Dependent Stimulation as Tools in Cognitive Neuroscience

PubMed Central

Jensen, Ole; Bahramisharif, Ali; Oostenveld, Robert; Klanke, Stefan; Hadjipapas, Avgis; Okazaki, Yuka O.; van Gerven, Marcel A. J.

2011-01-01

Large efforts are currently being made to develop and improve online analysis of brain activity which can be used, e.g., for brain–computer interfacing (BCI). A BCI allows a subject to control a device by willfully changing his/her own brain activity. BCI therefore holds the promise as a tool for aiding the disabled and for augmenting human performance. While technical developments obviously are important, we will here argue that new insight gained from cognitive neuroscience can be used to identify signatures of neural activation which reliably can be modulated by the subject at will. This review will focus mainly on oscillatory activity in the alpha band which is strongly modulated by changes in covert attention. Besides developing BCIs for their traditional purpose, they might also be used as a research tool for cognitive neuroscience. There is currently a strong interest in how brain-state fluctuations impact cognition. These state fluctuations are partly reflected by ongoing oscillatory activity. The functional role of the brain state can be investigated by introducing stimuli in real-time to subjects depending on the actual state of the brain. This principle of brain-state dependent stimulation may also be used as a practical tool for augmenting human behavior. In conclusion, new approaches based on online analysis of ongoing brain activity are currently in rapid development. These approaches are amongst others informed by new insight gained from electroencephalography/magnetoencephalography studies in cognitive neuroscience and hold the promise of providing new ways for investigating the brain at work. PMID:21687463

Investigation of dental alginate and agar impression materials as a brain simulant for ballistic testing.

PubMed

Falland-Cheung, Lisa; Piccione, Neil; Zhao, Tianqi; Lazarjan, Milad Soltanipour; Hanlin, Suzanne; Jermy, Mark; Waddell, J Neil

2016-06-01

Routine forensic research into in vitro skin/skull/brain ballistic blood backspatter behavior has traditionally used gelatin at a 1:10 Water:Powder (W:P) ratio by volume as a brain simulant. A limitation of gelatin is its high elasticity compared to brain tissue. Therefore this study investigated the use of dental alginate and agar impression materials as a brain simulant for ballistic testing. Fresh deer brain, alginate (W:P ratio 91.5:8.5) and agar (W:P ratio 81:19) specimens (n=10) (11×22×33mm) were placed in transparent Perspex boxes of the same internal dimensions prior to shooting with a 0.22inch caliber high velocity air gun. Quantitative analysis to establish kinetic energy loss, vertical displacement elastic behavior and qualitative analysis to establish elasticity behavior was done via high-speed camera footage (SA5, Photron, Japan) using Photron Fastcam Viewer software (Version 3.5.1, Photron, Japan) and visual observation. Damage mechanisms and behavior were qualitatively established by observation of the materials during and after shooting. The qualitative analysis found that of the two simulant materials tested, agar behaved more like brain in terms of damage and showed similar mechanical response to brain during the passage of the projectile, in terms of energy absorption and vertical velocity displacement. In conclusion agar showed a mechanical and subsequent damage response that was similar to brain compared to alginate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neurosurgical patties: adhesion and damage mitigation.

PubMed

Stratton-Powell, Ashley A; Anderson, Ian A; Timothy, Jake; Kapur, Nikil; Culmer, Peter

2015-07-01

Neurosurgical patties are textile pads used during most neurosurgical operations to protect tissues, manage the fluid environment, control hemostasis, and aid tissue manipulation. Recent research has suggested that, contrary to their aim, patties adhere to brain tissue and cause damage during removal. This study aimed to characterize and quantify the degree of and consequences resulting from adhesion between neurosurgical patties and brain tissue. Using a customized peel apparatus, the authors performed 90° peel tests on 5 patty products: Policot, Telfa, Americot, Delicot, and Ray-Cot (n = 247) from American Surgical Company. They tested 4 conditions: wet patty on glass (control), wet patty on wet brain peeled at 5 mm/sec (wet), dry patty on wet brain peeled at 5 mm/sec (dry), and wet patty on wet brain peeled at 20 mm/sec (speed). The interaction between patty and tissue was analyzed using peel-force traces and pre-peel histological analysis. Adhesion strength differed between patty products (p < 0.001) and conditions (p < 0.001). Adhesion strength was greatest for Delicot patties under wet (2.22 mN/mm) and dry (9.88 mN/mm) conditions. For all patties, damage at the patty-tissue interface was proportional to the degree of fiber contact. When patties were irrigated, mechanical adhesion was reduced by up to 550% compared with dry usage. For all patty products, mechanical (destructive) and liquid-mediated (nondestructive) adhesion caused damage to neural tissue. The greatest adhesion occurred with Delicot patties. To mitigate patty adhesion and neural tissue damage, surgeons should consider regular irrigation to be essential during neurosurgical procedures.

Canceled connections: Lesion-derived network mapping helps explain differences in performance on a complex decision-making task

PubMed Central

Sutterer, Matthew J.; Bruss, Joel; Boes, Aaron D.; Voss, Michelle W.; Bechara, Antoine; Tranel, Daniel

2016-01-01

Studies of patients with brain damage have highlighted a broad neural network of limbic and prefrontal areas as important for adaptive decision-making. However, some patients with damage outside these regions have impaired decision-making behavior, and the behavioral impairments observed in these cases are often attributed to the general variability in behavior following brain damage, rather than a deficit in a specific brain-behavior relationship. A novel approach, lesion-derived network mapping, uses healthy subject resting-state functional connectivity (RSFC) data to infer the areas that would be connected with each patient’s lesion area in healthy adults. Here, we used this approach to investigate whether there was a systematic pattern of connectivity associated with decision-making performance in patients with focal damage in areas not classically associated with decision-making. These patients were categorized a priori into “impaired” or “unimpaired” groups based on their performance on the Iowa Gambling Task (IGT). Lesion-derived network maps based on the impaired patients showed overlap in somatosensory, motor and insula cortices, to a greater extent than patients who showed unimpaired IGT performance. Akin to the classic concept of “diaschisis” (von Monakow, 1914), this focus on the remote effects that focal damage can have on large-scale distributed brain networks has the potential to inform not only differences in decision-making behavior, but also other cognitive functions or neurological syndromes where a distinct phenotype has eluded neuroanatomical classification and brain-behavior relationships appear highly heterogeneous. PMID:26994344

Targeting Microglia to Prevent Post-Traumatic Epilepsy

DTIC Science & Technology

2012-07-01

long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation. Eur J Neurosci 22 :317-330...attenuating damaging effects of hyperexcitability in the brain induced by inflammation resulting from glial cell immune responses to trauma. We are...damaging effects of hyperexcitability in the brain induced by inflammation resulting from glial cell immune responses to trauma. We are exploring two

Poor Hand-Pointing to Sounds in Right Brain-Damaged Patients: Not Just a Problem of Spatial-Hearing

ERIC Educational Resources Information Center

Pavani, Francesco; Farne, Alessandro; Ladavas, Elisabetta

2005-01-01

We asked 22 right brain-damaged (RBD) patients and 11 elderly healthy controls to perform hand-pointing movements to free-field unseen sounds, while modulating two non-auditory variables: the initial position of the responding hand (left, centre or right) and the presence or absence of task-irrelevant ambient vision. RBD patients suffering from…

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

PubMed

Kaur, Shamsherjit; Singh, Satinderpal; Chahal, Karan Singh; Prakash, Atish

2014-11-01

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment

PubMed Central

Krynetskiy, Evgeny; Krynetskaia, Natalia; Rihawi, Diana; Wieczerzak, Katarzyna; Ciummo, Victoria; Walker, Ellen

2013-01-01

Aims Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al. 2008). Main methods Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24 h and weighed every 24 h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay). Key findings We detected significant differences (p<0.0001) for all DNA damage characteristics (DNA “comet” tail shape, migration pattern, tail moment and Olive moments) between control mice cohort and 5FU-treated mice cohort: tail length – 119 vs. 153; tail moment – 101 vs. 136; olive moment – 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r=0.52, p<0.05) and increased rate of errors (r=0.51, p<0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r=−0.75, p<0.02). Significance Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy. PMID:23567806

The right hemisphere in esthetic perception.

PubMed

Bromberger, Bianca; Sternschein, Rebecca; Widick, Page; Smith, William; Chatterjee, Anjan

2011-01-01

Little about the neuropsychology of art perception and evaluation is known. Most neuropsychological approaches to art have focused on art production and have been anecdotal and qualitative. The field is in desperate need of quantitative methods if it is to advance. Here, we combine a quantitative approach to the assessment of art with modern voxel-lesion-symptom-mapping methods to determine brain-behavior relationships in art perception. We hypothesized that perception of different attributes of art are likely to be disrupted by damage to different regions of the brain. Twenty participants with right hemisphere damage were given the Assessment of Art Attributes, which is designed to quantify judgments of descriptive attributes of visual art. Each participant rated 24 paintings on 6 conceptual attributes (depictive accuracy, abstractness, emotion, symbolism, realism, and animacy) and 6 perceptual attributes (depth, color temperature, color saturation, balance, stroke, and simplicity) and their interest in and preference for these paintings. Deviation scores were obtained for each brain-damaged participant for each attribute based on correlations with group average ratings from 30 age-matched healthy participants. Right hemisphere damage affected participants' judgments of abstractness, accuracy, and stroke quality. Damage to areas within different parts of the frontal parietal and lateral temporal cortices produced deviation in judgments in four of six conceptual attributes (abstractness, symbolism, realism, and animacy). Of the formal attributes, only depth was affected by inferior prefrontal damage. No areas of brain damage were associated with deviations in interestingness or preference judgments. The perception of conceptual and formal attributes in artwork may in part dissociate from each other and from evaluative judgments. More generally, this approach demonstrates the feasibility of quantitative approaches to the neuropsychology of art.

Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment.

PubMed

Krynetskiy, Evgeny; Krynetskaia, Natalia; Rihawi, Diana; Wieczerzak, Katarzyna; Ciummo, Victoria; Walker, Ellen

2013-10-17

Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al., 2008). Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24h and weighed every 24h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and the retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay). We detected significant differences (p<0.0001) for all DNA damage characteristics (DNA "comet" tail shape, migration pattern, tail moment and olive moments) between control mice cohort and 5FU-treated mice cohort: tail length - 119 vs. 153; tail moment - 101 vs. 136; olive moment - 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r=0.52, p<0.05) and increased rate of errors (r=0.51, p<0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r=-0.75, p<0.02). Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

The Lateralizer: A Tool for Students to Explore the Divided Brain

ERIC Educational Resources Information Center

Motz, Benjamin A.; James, Karin H.; Busey, Thomas A.

2012-01-01

Despite a profusion of popular misinformation about the left brain and right brain, there are functional differences between the left and right cerebral hemispheres in humans. Evidence from split-brain patients, individuals with unilateral brain damage, and neuroimaging studies suggest that each hemisphere may be specialized for certain cognitive…

Mangiferin decreases inflammation and oxidative damage in rat brain after stress.

PubMed

Márquez, Lucía; García-Bueno, Borja; Madrigal, José L M; Leza, Juan C

2012-09-01

Stress exposure elicits neuroinflammation and oxidative damage in brain, and stress-related neurological and neuropsychiatric diseases have been associated with cell damage and death. Mangiferin (MAG) is a polyphenolic compound abundant in the stem bark of Mangifera indica L. with antioxidant and anti-inflammatory properties in different experimental settings. In this study, the capacity of MAG to prevent neuroinflammation and brain oxidative damage induced by stress exposure was investigated. Young-adult male Wistar rats immobilized during 6 h were administered by oral gavage with increasing doses of MAG (15, 30, and 60 mg/Kg), respectively, 7 days before stress. Prior treatment with MAG prevented all of the following stress-induced effects: (1) increase in glucocorticoids (GCs) and interleukin-1β (IL-1β) plasma levels, (2) loss of redox balance and reduction in catalase brain levels, (3) increase in pro-inflammatory mediators, such as tumor necrosis factor alpha TNF-α and its receptor TNF-R1, nuclear factor-kappa B (NF-κB) and synthesis enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation. These multifaceted protective effects suggest that MAG administration could be a new therapeutic strategy in neurological/neuropsychiatric pathologies in which hypothalamic/pituitary/adrenal (HPA) stress axis dysregulation, neuroinflammation, and oxidative damage take place in their pathophysiology.

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

PubMed

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats

PubMed Central

Deshmukh, Pravin Suryakantrao; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Chandna, Sudhir; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar

2013-01-01

Background: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. Objective: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. Materials and Methods: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10−4 W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10−4 W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10−4 W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. Results: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. Conclusion: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue. PMID:23833433

Cellular senescence in honey bee brain is largely independent of chronological age

PubMed Central

Seehuus, Siri-Christine; Krekling, Trygve; Amdam, Gro V.

2008-01-01

Accumulation of oxidative stress-induced damage in brain tissue plays an important role in the pathogenesis of normal aging and neurodegenerative diseases. Neuronal oxidative damage typically increases with age in humans, and also in the invertebrate and vertebrate model species most commonly used in aging research. By use of quantitative immunohistochemistry and Western blot, we show that this aspect of brain senescence is largely decoupled from chronological age in the honey bee (Apis mellifera). The bee is a eusocial insect characterized by the presence of a reproductive queen caste and a caste of functionally sterile female workers that performs various alloparental tasks such as nursing and foraging. We studied patterns of oxidative nitration and carbonylation damage in the brain of worker bees that performed nurse tasks as 8- and 200-day-olds and foraging tasks as 20- and 200-day-olds. In addition, we examined 180-day-old diutinus bees, a stress-resistant temporal worker form that survives unfavorable periods. Our results indicate that nitration damage occurs only at low levels in vivo, but that a 60-kDa protein from honey bee brain is selectively nitrated by peroxynitrite in vitro. Oxidative carbonylation is present at varying levels in the visual and chemosensory neuropiles of worker bees, and this inter-individual variation is better explained by social role than by chronological age. PMID:17052880

Creativity, brain, and art: biological and neurological considerations.

PubMed

Zaidel, Dahlia W

2014-01-01

Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity's neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). The verb "to create" has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson's), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals.

Creativity, brain, and art: biological and neurological considerations

PubMed Central

Zaidel, Dahlia W.

2014-01-01

Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity’s neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). The verb “to create” has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson’s), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals. PMID:24917807

Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

PubMed Central

Lee, Chao Yu; Wang, Liang-Fei; Wu, Chun-Hu; Ke, Chia-Hua; Chen, Szu-Fu

2014-01-01

Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg−1) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect. PMID:25546475

Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

PubMed

Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

2015-02-05

Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhalants

MedlinePlus

... brain problems) brain damage (from cut-off oxygen flow to the brain) In addition, because nitrites are misused for sexual pleasure and performance, they can lead to unsafe sexual practices or other risky behavior. This increases the chance of getting or spreading ...

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

A construction trailer damaged by Hurricane Matthew is seen in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

An ice dispenser damaged by Hurricane Matthew is seen in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

In situ FTIR microspectroscopy of extravasated blood-damaged brain tissue

NASA Astrophysics Data System (ADS)

Wetzel, David L.; Le Vine, Steven M.

1994-01-01

Fourier transform infrared (FT-IR) microspectroscopy enables the collection of infrared spectra from microscopic regions of tissue sections. The objectives of this study were to utilize FT-IR microspectroscopy to analyze the spatial distribution of chemical changes that result from the extravasation of blood into the brain and to determine if products of free radical damage are associated with the damaged areas. An animal model that involves the injection of blood into the white matter of rat brains was used. Maps depicting the relative concentrations of chemical functional groups of lesioned sites and surrounding areas were made. Significant decreases were observed for CH2, C equals O, P equals O, and HO-C-H functional groups at the lesioned site and penumbra regions compared to the neighboring normal tissue areas.

The osmotic/calcium stress theory of brain damage: are free radicals involved?

PubMed

Pazdernik, T L; Layton, M; Nelson, S R; Samson, F E

1992-01-01

This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx of calcium (i.e., calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.

Interpreting and Utilising Intersubject Variability in Brain Function.

PubMed

Seghier, Mohamed L; Price, Cathy J

2018-06-01

We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone.

PubMed

Harazin, András; Bocsik, Alexandra; Barna, Lilla; Kincses, András; Váradi, Judit; Fenyvesi, Ferenc; Tubak, Vilmos; Deli, Maria A; Vecsernyés, Miklós

2018-01-01

The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.

The influence of damage distribution on serious brain injury in occupants in frontal motor vehicle crashes.

PubMed

Coimbra, Raul; Conroy, Carol; Hoyt, David B; Pacyna, Sharon; May, MarSue; Erwin, Steve; Tominaga, Gail; Kennedy, Frank; Sise, Michael; Velky, Tom

2008-07-01

In spite of improvements in motor vehicle safety systems and crashworthiness, motor vehicle crashes remain one of the leading causes of brain injury. The purpose of this study was to determine if the damage distribution across the frontal plane affected brain injury severity of occupants in frontal impacts. Occupants in "head on" frontal impacts with a Principal Direction of Force (PDOF) equal to 11, 12, or 1o'clock who sustained serious brain injury were identified using the Crash Injury Research Engineering Network (CIREN) database. Impacts were further classified based on the damage distribution across the frontal plane as distributed, offset, and extreme offset (corner). Overall, there was no significant difference for brain injury severity (based on Glasgow Coma Scale<9, or brain injury AIS>2) comparing occupants in the different impact categories. For occupants in distributed frontal impacts, safety belt use was protective (odds ratio (OR)=0.61) and intrusion at the occupant's seat position was four times more likely to result in severe (Glasgow Coma Scale (GCS)<9) brain injury (OR=4.35). For occupants in offset frontal impacts, again safety belt use was protective against severe brain injury (OR=0.25). Possibly due to the small number of brain-injured occupants in corner impacts, safety belts did not significantly protect against increased brain injury severity during corner impacts. This study supports the importance of safety belt use to decrease brain injury severity for occupants in distributed and offset frontal crashes. It also illustrates how studying "real world" crashes may provide useful information on occupant injuries under impact circumstances not currently covered by crash testing.

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone

PubMed Central

Barna, Lilla; Kincses, András; Váradi, Judit; Fenyvesi, Ferenc; Tubak, Vilmos

2018-01-01

The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB. PMID:29780671

Brain Hemispheric Consensus and the Quality of Investment Decisions.

ERIC Educational Resources Information Center

Boyd, Michael

This on-going study explores the hypothesis that stock fund managers who underperform do so because they make bad decisions, and examines whether their choices can be improved by using a decision model that invokes principles of brain hemispheric consensus. The study, begun in fall 1999, involves two groups of business students: the control group…

"She Was a Little Social Butterfly": A Qualitative Analysis of Parent Perception of Social Functioning in Adolescent and Young Adult Brain Tumor Survivors.

PubMed

Wilford, Justin; Buchbinder, David; Fortier, Michelle A; Osann, Kathryn; Shen, Violet; Torno, Lilibeth; Sender, Leonard S; Parsons, Susan K; Wenzel, Lari

Psychosocial sequelae of diagnosis and treatment for childhood brain tumor survivors are significant, yet little is known about their impact on adolescent and young adult (AYA) brain tumor survivors. Interviews were conducted with parents of AYA brain tumor survivors with a focus on social functioning. Semistructured interviews were conducted with English- and Spanish-speaking parents of AYA brain tumor survivors ≥10 years of age who were >2 years postdiagnosis, and analyzed using emergent themes theoretically integrated with a social neuroscience model of social competence. Twenty parents representing 19 survivors with a survivor mean age 15.7 ± 3.3 years and 10.1 ± 4.8 years postdiagnosis were interviewed. Several themes relevant to the social neuroscience social competence model emerged. First, parents' perceptions of their children's impaired social functioning corroborated the model, particularly with regard to poor social adjustment, social withdrawal, impaired social information processing, and developmentally inappropriate peer communication. Second, ongoing physical and emotional sequelae of central nervous system insults were seen by parents as adversely affecting social functioning among survivors. Third, a disrupted family environment and ongoing parent psychosocial distress were experienced as salient features of daily life. We document that the aforementioned framework is useful for understanding the social impact of diagnosis and treatment on AYA brain tumor survivorship. Moreover, the framework highlights areas of intervention that may enhance social functioning for AYA brain tumor survivors.

Influence of hesperidin and vitamin C on glycemic parameters, lipid profile, and DNA damage in rats treated with sucrose overload.

PubMed

Franke, Silvia I R; Molz, Patrícia; Mai, Camila; Ellwanger, Joel H; Zenkner, Fernanda F; Horta, Jorge A; Prá, Daniel

2018-04-16

We evaluated the influence of hesperidin and vitamin C (VitC) on glycemic parameters, lipid profile, and DNA damage in male Wistar rats treated with sucrose overload. Rats were divided into six experimental groups: I-water control; II-sucrose control; III-hesperidin control; IV-VitC control; V-co-treatment of sucrose plus hesperidin; VI-co-treatment of sucrose plus VitC. We measured the levels of triglycerides, total cholesterol, HDL-c, LDL-c, fasting glucose, and glycated hemoglobin (A1C). DNA damage was evaluated in blood and brain cells using the comet assay and the micronucleus test was used to evaluate chromosomal damages in the rat bone marrow. Co-treatment with VitC, but not with hesperidin, normalized the serum glucose. No effect of co-treatments was observed on A1C. The co-treatment with VitC or hesperidin did not influence the lipid profile (p>0.05). Rats co-treated with hesperidin had a significantly lower DNA damage level in blood (p<0.05) and brain (p<0.05). Rats treated with VitC only, but not those co-treated with VitC plus sucrose, had significantly higher DNA damage in brain (p<0.05). No significant differences were observed in the results of micronucleus test (p>0.05). Hesperidin and VitC showed different effects on sucrose and DNA damage levels. While VitC lowered the serum glucose, hesperidin reduced the DNA damage.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice.

PubMed

Yamamoto, Hiro-aki; Mohanan, Parayanthala V

2003-07-20

The effects of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA (mtDNA) damage and seizures induced by kainic acid were examined both in vivo and in vitro. An intraperitoneal (ip) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. The seizures were abolished when alpha-ketoglutarate (2 g/kg) or oxaloacetate (1 g/kg) was injected intraperitoneally in the animals 1 min before kainic acid administration. In addition, the administration of kainic acid caused damage to mtDNA in brain frontal and middle cortex of mice. These effects were completely abolished by the ip preinjection of alpha-ketoglutarate (2 g/kg) or oxaloacetate (1 g/kg). In vitro exposure of kainic acid (0.25, 0.5 or 1.0 mM) to brain homogenate inflicted damage to mtDNA in a concentration-dependent manner. The damage of mtDNA induced by 1.0 mM kainic acid was attenuated by the co-treatment with alpha-ketoglutarate (2.5 or 5.0 mM) or oxaloacetate (0.75 or 1.0 mM). Furthermore, in vivo and in vitro exposure of kainic acid elicited an increase in lipid peroxidation. However, the increased lipid peroxidation was completely inhibited by cotreatment of alpha-ketoglutarate or oxaloacetate. These results suggest that alpha-keto acids such as alpha-ketoglutarate and oxaloacetate play a role in the inhibition of seizures and subsequent mtDNA damage induced by the excitotoxic/neurotoxic agent, kainic acid.

[Physical activity: positive impact on brain plasticity].

PubMed

Achiron, Anat; Kalron, Alon

2008-03-01

The central nervous system has a unique capability of plasticity that enables a single neuron or a group of neurons to undergo functional and constructional changes that are important to learning processes and for compensation of brain damage. The current review aims to summarize recent data related to the effects of physical activity on brain plasticity. In the last decade it was reported that physical activity can affect and manipulate neuronal connections, synaptic activity and adaptation to new neuronal environment following brain injury. One of the most significant neurotrophic factors that is critical for synaptic re-organization and is influenced by physical activity is brain-derived neurotrophic factor (BDNF). The frequency of physical activity and the intensity of exercises are of importance to brain remodeling, support neuronal survival and positively affect rehabilitation therapy. Physical activity should be employed as a tool to improve neural function in healthy subjects and in patients suffering from neurological damage.

Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

PubMed

Kril, Jillian J; Harper, Clive G

2012-06-01

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain.

PubMed

Wu, Yuan-Ting; Adnan, Ashfaq

2017-07-13

The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain's perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain's extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

Emotion Recognition in Stroke Patients with Left and Right Hemispheric Lesion: Results with a New Instrument-The Feel Test

ERIC Educational Resources Information Center

Braun, M.; Traue, H.C.; Frisch, S.; Deighton, R.M.; Kessler, H.

2005-01-01

The aim of this study was to investigate the effect of a stroke event on people's ability to recognize basic emotions. In particular, the hypothesis that right brain-damaged (RBD) patients would show less of emotion recognition ability compared with left brain-damaged (LBD) patients and healthy controls, was tested. To investigate this the FEEL…

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

PubMed Central

Joh, Daniel Y.; Sun, Lova; Stangl, Melissa; Al Zaki, Ajlan; Murty, Surya; Santoiemma, Phillip P.; Davis, James J.; Baumann, Brian C.; Alonso-Basanta, Michelle; Bhang, Dongha; Kao, Gary D.; Tsourkas, Andrew; Dorsey, Jay F.

2013-01-01

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature. PMID:23638079

Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma

PubMed Central

Lötsch, Jörn; Ultsch, Alfred; Eckhardt, Maren; Huart, Caroline; Rombaux, Philippe; Hummel, Thomas

2016-01-01

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time. PMID:26937377

Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress.

PubMed

Özevren, Hüseyin; İrtegün, Sevgi; Deveci, Engin; Aşır, Fırat; Pektanç, Gülsüm; Deveci, Şenay

2017-10-01

Traumatic brain injury causes tissue damage, breakdown of cerebral blood flow and metabolic regulation. This study aims to investigate the protective influence of antioxidant Ganoderma lucidum ( G. lucidum ) polysaccharides (GLPs) on brain injury in brain-traumatized rats. Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g weight from 1 m height. Groups were categorized as control, G. lucidum , trauma, trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were dissected from anesthetized rats 7 days after injury. For biochemical analysis, malondialdehyde, glutathione and myeloperoxidase values were measured. In histopathological examination, neuronal damage in brain cortex and changes in blood brain barrier were observed. In the analysis of immunohistochemical and western blot, p38 mitogen-activated protein kinase, vascular endothelial growth factor and cluster of differentiation 68 expression levels were shown. These analyzes demonstrated the beneficial effects of GLPs on brain injury. We propose that GLPs treatment after brain injury could be an alternative treatment to decraseing inflammation and edema, preventing neuronal and glial cells degeneration if given in appropriate dosage and in particular time intervals.

C-fiber-related EEG-oscillations induced by laser radiant heat stimulation of capsaicin-treated skin

PubMed Central

Domnick, Claudia; Hauck, Michael; Casey, Kenneth L; Engel, Andreas K; Lorenz, Jürgen

2009-01-01

Nociceptive input reaches the brain via two different types of nerve fibers, moderately fast A-delta and slowly conducting C-fibers, respectively. To explore their distinct roles in normal and inflammatory pain we used laser stimulation of normal and capsaicin treated skin at proximal and distal arm sites in combination with time frequency transformation of electroencephalography (EEG) data. Comparison of phase-locked (evoked) and non-phase-locked (total) EEG to laser stimuli revealed three significant pain-related oscillatory responses. First, an evoked response in the delta-theta band, mediated by A-fibers, was reduced by topical capsaicin treatment. Second, a decrease of total power in the alpha-to-gamma band reflected both an A- and C-nociceptor-mediated response with only the latter being reduced by capsaicin treatment. Finally, an enhancement of total power in the upper beta band was mediated exclusively by C-nociceptors and appeared strongly augmented by capsaicin treatment. These findings suggest that phase-locking of brain activity to stimulus onset is a critical feature of A-delta nociceptive input, allowing rapid orientation to salient and potentially threatening events. In contrast, the subsequent C-nociceptive input exhibits clearly less phase coupling to the stimulus. It may primarily signal the tissue status allowing more long-term behavioral adaptations during ongoing inflammatory events that accompany tissue damage. PMID:21197293

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

PubMed

Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

2005-08-01

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

Scientific progress - wireless phones and brain cancer: current state of the science.

PubMed

Carlo, G L; Jenrow, R S

2000-07-11

The current science is not definitive about health risks from wireless phones; however, the legitimate questions about safety that have arisen from recent studies make claims of absolute safety no longer supportable. The objective of this paper is to outline for primary care providers the results of the most current research on the possible impact of wireless phone use on human health. Presented are study results from Wireless Technology Research (WTR) program, the 7-year, $27 million effort funded by the wireless industry in the United States, that represents the world's most comprehensive research effort addressing this issue to date. Science-based recommendations for consumer interventions and future research are presented. Original studies performed under the WTR program as well as other relevant research from around the world. This article presents a synopsis of the peer-reviewed in vitro and in vivo laboratory research, and the peer-reviewed epidemiology studies supported by the WTR, as well as a summary of other relevant work. Only peer-reviewed scientific studies are presented, primarily WTR-sponsored research. In addition, results of the WTR literature surveillance program, which identified other relevant toxicology and epidemiology studies on an ongoing basis, are presented. These studies are presented in the context of their usefulness in providing intervention recommendations for consumers. Following a qualitative synthesis of specific relevant non-WTR research and a critical assessment of the WTR results, the following represents the current state of scientific understanding relevant to the public health impact of wireless phones: laboratory studies appear to have confirmed that radio frequency radiation from wireless phone antennas is insufficient to cause DNA breakage; however, this same radiation appears to cause genetic damage in human blood as measured through the formation of micronuclei. An increase in the rate of brain cancer mortality among hand-held cellular phone users as compared to car phone users, though not statistically significant, was observed in the WTR cohort study. A statistically significant increase in the risk of neuro-epithelial brain tumors was observed among cellular phone users in another case-control study. As new data emerge, our understanding of this complex problem will improve; however, at present there is a critical need for ongoing and open evaluation of the public health impact of new science, and communication of this science and derivative intervention options to those who are potentially affected.

Role of inter-hemispheric transfer in generating visual evoked potentials in V1-damaged brain hemispheres

PubMed Central

Kavcic, Voyko; Triplett, Regina L.; Das, Anasuya; Martin, Tim; Huxlin, Krystel R.

2015-01-01

Partial cortical blindness is a visual deficit caused by unilateral damage to the primary visual cortex, a condition previously considered beyond hopes of rehabilitation. However, recent data demonstrate that patients may recover both simple and global motion discrimination following intensive training in their blind field. The present experiments characterized motion-induced neural activity of cortically blind (CB) subjects prior to the onset of visual rehabilitation. This was done to provide information about visual processing capabilities available to mediate training-induced visual improvements. Visual Evoked Potentials (VEPs) were recorded from two experimental groups consisting of 9 CB subjects and 9 age-matched, visually-intact controls. VEPs were collected following lateralized stimulus presentation to each of the 4 visual field quadrants. VEP waveforms were examined for both stimulus-onset (SO) and motion-onset (MO) related components in postero-lateral electrodes. While stimulus presentation to intact regions of the visual field elicited normal SO-P1, SO-N1, SO-P2 and MO-N2 amplitudes and latencies in contralateral brain regions of CB subjects, these components were not observed contralateral to stimulus presentation in blind quadrants of the visual field. In damaged brain hemispheres, SO-VEPs were only recorded following stimulus presentation to intact visual field quadrants, via inter-hemispheric transfer. MO-VEPs were only recorded from damaged left brain hemispheres, possibly reflecting a native left/right asymmetry in inter-hemispheric connections. The present findings suggest that damaged brain hemispheres contain areas capable of responding to visual stimulation. However, in the absence of training or rehabilitation, these areas only generate detectable VEPs in response to stimulation of the intact hemifield of vision. PMID:25575450

Near Real-Time Applications of Earth Remote Sensing for Response to Meteorological Disasters

NASA Technical Reports Server (NTRS)

Molthan, Andrew L.; Burks, Jason E.; McGrath, Kevin M.; Bell, Jordan R.

2013-01-01

Numerous on-orbit satellites provide a wide range of spatial, spectral, and temporal resolutions supporting the use of their resulting imagery in assessments of disasters that are meteorological in nature. This presentation will provide an overview of recent use of Earth remote sensing by NASA's Short-term Prediction Research and Transition (SPoRT) Center in response to disaster activities in 2012 and 2013, along with case studies supporting ongoing research and development. The SPoRT Center, with support from NASA's Applied Sciences Program, has explored a variety of new applications of Earth-observing sensors to support disaster response. In May 2013, the SPoRT Center developed unique power outage composites representing the first clear sky view of damage inflicted upon Moore and Oklahoma City, Oklahoma following the devastating EF-5 tornado that occurred on May 20. Subsequent ASTER, MODIS, Landsat-7 and Landsat-8 imagery help to identify the damaged area. Higher resolution imagery of Moore, Oklahoma were provided by commercial satellites and the recently available International Space Station (ISS) SERVIR Environmental Research and Visualization System (ISERV) instrument. New techniques are being explored by the SPoRT team in order to better identify damage visible in high resolution imagery, and to monitor ongoing recovery for Moore, Oklahoma. Other applications are being developed to refine light source detections with the VIIRS day-night band and to map hail during the growing season through combination of available satellite and radar imagery. The aforementioned products and support are not useful unless they are distributed in a timely manner and within an appropriate decision support system. This presentation will provide an update on ongoing activities to support inclusion of these data sets within the NOAA National Weather Service Damage Assessment Toolkit, which allows meteorologists in the field to consult available satellite imagery while performing their damage assessment.

Near Real-­Time Applications of Earth Remote Sensing for Response to Meteorological Disasters

NASA Technical Reports Server (NTRS)

Molthan, Andrew L.; Burks, Jason E.; McGrath, Kevin M.; Bell, Jordan R.

2013-01-01

Numerous on-orbit satellites provide a wide range of spatial, spectral, and temporal resolutions supporting the use of their resulting imagery in assessments of disasters that are meteorological in nature. This presentation will provide an overview of recent use of Earth remote sensing by NASA's Short-term Prediction Research and Transition (SPoRT) Center in response to disaster activities in 2012 and 2013, along with case studies supporting ongoing research and development. The SPoRT Center, with support from NASA's Applied Sciences Program, has explored a variety of new applications of Earth-observing sensors to support disaster response. In May 2013, the SPoRT Center developed unique power outage composites representing the first clear sky view of damage inflicted upon Moore and Oklahoma City, Oklahoma following the devastating EF-5 tornado that occurred on May 20. Subsequent ASTER, MODIS, Landsat-7 and Landsat-8 imagery help to identify the damaged area. Higher resolution imagery of Moore, Oklahoma were provided by commercial satellites and the recently available International Space Station (ISS) SERVIR Environmental Research and Visualization System (ISERV) instrument. New techniques are being explored by the SPoRT team in order to better identify damage visible in high resolution imagery, and to monitor ongoing recovery for Moore, Oklahoma. Other applications are being developed to refine light source detections with the VIIRS day-night band and to map hail during the growing season through combination of available satellite and radar imagery. The aforementioned products and support are not useful unless they are distributed in a timely manner and within an appropriate decision support system. This presentation will provide an update on ongoing activities to support inclusion of these data sets within the NOAA National Weather Service Damage Assessment Toolkit, which allows meteorologists in the field to consult available satellite imagery while performing their damage assessment.

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

PubMed

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan; Skovgaard, Lene Theil; Moos, Torben

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

PubMed

Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

2014-08-21

Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Cerebrospinal fluid levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in subacute sclerosing panencephalitis.

PubMed

Ichiyama, Takashi; Matsushige, Takeshi; Siba, Peter; Suarkia, Dagwin; Takasu, Toshiaki; Miki, Kenji; Furukawa, Susumu

2008-05-01

To investigate the brain inflammation and damage in subacute sclerosing panencephalitis (SSPE), the cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined in SSPE patients. CSF MMP-9 and TIMP-1 levels were measured in 23 patients with SSPE in Papua New Guinea by ELISA. CSF MMP-9 levels and MMP-9/TIMP-1 ratios of SSPE patients were significantly higher than controls (p<0.001 and p=0.005, respectively). There were no significant differences in CSF TIMP-1 levels between SSPE patients and controls. Previous studies suggested that CSF MMP-9 levels reflect inflammatory damage to the brain. Our findings suggest that the MMP-9 level in CSF is an indicator of inflammatory damage to the brain in SSPE.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

PubMed

Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2018-01-01

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice

PubMed Central

Ghosh, Somnath; Canugovi, Chandrika; Yoon, Jeong Seon; Wilson, David M.; Croteau, Deborah L.; Mattson, Mark P.; Bohr, Vilhelm A.

2017-01-01

Oxidative DNA damage is mainly repaired by base excision repair (BER). Previously, our lab showed that mice lacking the BER glycosylases Ogg1 or Neil1 recover more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model was used to investigate whether loss of one of the two alleles of Xrcc1, which encodes a non-enzymatic scaffold protein required for BER, alters recovery from stroke. Ischemia and reperfusion caused higher brain damage and lower functional recovery in Xrcc1+/− mice than in wild-type mice. Additionally, a greater percentage of Xrcc1+/− mice died as a result of the stroke. Brain samples from human individuals who died of stroke and individuals who died of non-neurological causes were assayed for various steps of BER. Significant losses of thymine glycol incision, abasic endonuclease incision and single nucleotide incorporation activities were identified, as well as lower expression of XRCC1 and NEIL1 proteins in stroke brains compared to controls. Together, these results suggest that impaired BER is a risk factor in ischemic brain injury and contributes to its recovery. PMID:25971543

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

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

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.« less

Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain

PubMed Central

MIYATAKE, Shin-Ichi; NONOGUCHI, Noasuke; FURUSE, Motomasa; YORITSUNE, Erina; MIYATA, Tomo; KAWABATA, Shinji; KUROIWA, Toshihiko

2015-01-01

New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain. PMID:25744350

Vocal emotion of humanoid robots: a study from brain mechanism.

PubMed

Wang, Youhui; Hu, Xiaohua; Dai, Weihui; Zhou, Jie; Kuo, Taitzong

2014-01-01

Driven by rapid ongoing advances in humanoid robot, increasing attention has been shifted into the issue of emotion intelligence of AI robots to facilitate the communication between man-machines and human beings, especially for the vocal emotion in interactive system of future humanoid robots. This paper explored the brain mechanism of vocal emotion by studying previous researches and developed an experiment to observe the brain response by fMRI, to analyze vocal emotion of human beings. Findings in this paper provided a new approach to design and evaluate the vocal emotion of humanoid robots based on brain mechanism of human beings.

High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).

PubMed

Ilic, S; Drmic, D; Zarkovic, K; Kolenc, D; Coric, M; Brcic, L; Klicek, R; Radic, B; Sever, M; Djuzel, V; Ivica, M; Boban Blagaic, A; Zoricic, Z; Anic, T; Zoricic, I; Djidic, S; Romic, Z; Seiwerth, S; Sikiric, P

2010-04-01

We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.

The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

PubMed

Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

2016-09-01

We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Temporal Dynamics of Late Second Language Acquisition: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

Steinhauer, Karsten; White, Erin J.; Drury, John E.

2009-01-01

The ways in which age of acquisition (AoA) may affect (morpho)syntax in second language acquisition (SLA) are discussed. We suggest that event-related brain potentials (ERPs) provide an appropriate online measure to test some such effects. ERP findings of the past decade are reviewed with a focus on recent and ongoing research. It is concluded…

Natural and accelerated recovery from brain damage: experimental and theoretical approaches.

PubMed

Andersen, Richard A; Schieber, Marc H; Thakor, Nitish; Loeb, Gerald E

2012-03-01

The goal of the Caltech group is to gain insight into the processes that occur within the primate nervous system during dexterous reaching and grasping and to see whether natural recovery from local brain damage can be accelerated by artificial means. We will create computational models of the nervous system embodying this insight and explain a variety of clinically observed neurological deficits in human subjects using these models.

Evidence for Separate Tonal and Segmental Tiers in the Lexical Specification of Words: A Case Study of a Brain-Damaged Chinese Speaker

ERIC Educational Resources Information Center

Liang, Jie; van Heuven, Vincent J.

2004-01-01

We present an acoustic study of segmental and prosodic properties of words produced by a female speaker of Chinese with left-hemisphere brain damage. We measured the location of the point vowels /a, e, @?, i, y, o, u/ and determined their separation in the vowel plane, and their perceptual distinctivity. Similarly, the acoustic properties of the…

Blockade and knock-out of CALHM1 channels attenuate ischemic brain damage.

PubMed

Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Ruiz, Asier; Chara, Juan C; Pérez-Samartín, Alberto; Marambaud, Philippe; Matute, Carlos

2018-06-01

Overactivation of purinergic receptors during cerebral ischemia results in a massive release of neurotransmitters, including adenosine triphosphate (ATP), to the extracellular space which leads to cell death. Some hypothetical pathways of ATP release are large ion channels, such as calcium homeostasis modulator 1 (CALHM1), a membrane ion channel that can permeate ATP. Since this transmitter contributes to postischemic brain damage, we hypothesized that CALHM1 activation may be a relevant target to attenuate stroke injury. Here, we analyzed the contribution of CALHM1 to postanoxic depolarization after ischemia in cultured neurons and in cortical slices. We observed that the onset of postanoxic currents in neurons in those preparations was delayed after its blockade with ruthenium red or silencing of Calhm1 gene by short hairpin RNA, as well as in slices from CALHM1 knockout mice. Subsequently, we used transient middle cerebral artery occlusion and found that ruthenium red, a blocker of CALHM1, or the lack of CALHM1, substantially attenuated the motor symptoms and reduced significantly the infarct volume. These results show that CALHM1 channels mediate postanoxic depolarization in neurons and brain damage after ischemia. Therefore, targeting CALHM1 may have a high therapeutic potential for treating brain damage after ischemia.

Magnolol protects against ischemic-reperfusion brain damage following oxygen-glucose deprivation and transient focal cerebral ischemia.

PubMed

Huang, Sheng-Yang; Tai, Shih-Huang; Chang, Che-Chao; Tu, Yi-Fang; Chang, Chih-Han; Lee, E-Jian

2018-04-01

In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin‑6, tumor necrosis factor‑a and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygen‑glucose deprivation‑induced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult. In a rat model of stable ischemia, compared with a vehicle‑treated ischemic control, pretreatment with magnolol (0.01‑1 mg/kg, intravenously) significantly reduced brain infarction following ischemic stroke, and post‑treatment with magnolol (1 mg/kg) remained effective and significantly reduced infarction when administered 2 h following the onset of ischemia. Additionally, magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide anions at the border zones of infarction and reduced oxidative damage in the ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the immunoreactions of 8‑hydroxy‑2'‑deoxyguanosine and 4‑hydroxynonenal. Thus, magnolol was revealed to protect against ischemia‑reperfusion brain damage. This may be partly attributed to its antioxidant, radical scavenging and anti‑inflammatory effects.

Use of the Progressive Figures Test in evaluating brain-damaged children, children with academic problems, and normal controls.

PubMed

Reitan, Ralph M; Wolfson, Deborah

2004-03-01

This study explores the use of the Progressive Figures Test as an instrument for broad initial screening of children in the 6- through 8-year age range with respect to the possible need for more definitive neuropsychological evaluation. Considering earlier results obtained in comparison of brain-damaged and control children [Clinical Neuropsychology: Current Applications, Hemisphere Publishing Corp., Washington, DC, 1974, p. 53; Proceedings of the Conference on Minimal Brain Dysfunction, New York Academy of Sciences, New York, 1973, p. 65], the Progressive Figures Test seemed potentially useful as a first step in determining whether a comprehensive neuropsychological evaluation is indicated. In this investigation, three groups were studied: (1) children with definitive evidence of brain damage or disease who, when compared with normal controls, help to establish the limits of neuropsychological functioning, (2) a group of children who had normal neurological examinations but also had academic problems of significant concern to both parents and teachers, and (3) a normal control group. Statistically significant differences were present in comparing each pair of groups, with the brain-damaged children performing most poorly and the controls performing best. Score distributions for the three groups make it possible to identify a score-range that represented a borderline or "gray" area and to suggest a cutting score that identified children whose academic problems might have a neurological basis and for whom additional neuropsychological evaluation appeared to be indicated.

Brain Pressure Monitoring

NASA Technical Reports Server (NTRS)

1977-01-01

A transducer originally used to measure air pressure in aircraft wind tunnel tests is the basis for a development important in diagnosis and treatment of certain types of brain damage. A totally implantable device, tbe intracranial pressure monitor measures and reports brain pressure by telemetry.

[Quantitative evaluation of visual gnosis in children with focal brain lesions].

PubMed

Pencheva, S; Zaprianova, L

1983-01-01

Bearing in mind the opinion of many authors on a great plasticity and interchangeability of the brain cortical functional systems in children the authors have carried out an experiment with 40 children with focal damages of the brain hemispheres, in 20 of whom the right, and in the other 20 the left hemisphere was affected. Use was made of the method of visual gnosis quantitative assessment in the modification of Pencheva and Mavlov (1975). In the children with the focal damages, more or less marked disturbances of the visual gnosis were revealed, however, no statistically significant relationship between the disturbances and the brain side were disclosed. The agnostic disorders were equally frequent in the children of both groups.

Hydrocephalus

MedlinePlus

... support and help with the care of a child with hydrocephalus who has serious brain damage. ... such as meningitis or encephalitis Intellectual impairment Nerve damage (decrease in movement, sensation, function) Physical disabilities

[Memory and brain--neurobiological correlates of memory disturbances].

PubMed

Calabrese, P; Markowitsch, H J

2003-04-01

A differentiation of memory is possible on the basis of chronological and contents-related aspects. Furthermore, it is possible to make process-specific subdivisions (encoding, transfer, consolidation, retrieval). The time-related division on the one hand refers to the general differentiation into short-term and long-term memory, and, on the other, to that between anterograde and retrograde memory ("new" and "old memory"; measured from a given time point, usually that when brain damage occurred). Anterograde memory means the successful encoding and storing of new information; retrograde the ability to retrieve successfully acquired and/or stored information. On the contents-based level, memory can be divided into five basic long-term systems--episodic memory, the knowledge system, perceptual, procedural and the priming form of memory. Neural correlates for these divisions are discussed with special emphasis of the episodic and the knowledge systems, based both on normal individuals and brain-damaged subjects. It is argued that structures of the limbic system are important for encoding of information and for its transfer into long-term memory. For this, two independent, but interacting memory circuits are proposed--one of them controlling and integrating primarily the emotional, and the other primarily the cognitive components of newly incoming information. For information storage principally neocortical structures are regarded as important and for the recall of information from the episodic and semantic memory systems the combined action of portions of prefrontal and anterior temporal regions is regarded as essential. Within this fronto-temporal agglomerate, a moderate hemispheric-specificity is assumed to exist with the right-hemispheric combination being mainly engaged in episodic memory retrieval and the left-hemispheric in that of semantic information. Evidence for this specialization comes from the results from focally brain-damaged patients as well as from that functional brain imaging in normal human subjects. Comparing results from imaging studies in memory disturbed patients with brain damage and from patients with a psychiatric diagnosis (e. g., psychogenic amnesia) revealed that both patient groups demonstrate comparable metabolic changes on the brain level. It can therefore be concluded that in neurological patients distinct, identifiable tissue damage is existent, while in psychiatric patients changes in the brain's biochemistry (release of stress hormones, and transmitters) constitute the physiological bases for the memory disturbances.

Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

PubMed Central

Christie, Kimberly J.; Turnley, Ann M.

2012-01-01

Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

PubMed Central

Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

2016-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

Nucleus accumbens invulnerability to methamphetamine neurotoxicity.

PubMed

Kuhn, Donald M; Angoa-Pérez, Mariana; Thomas, David M

2011-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

A construction trailer damaged by Hurricane Matthew is seen in front of the Mobile Launcher within the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

Siding damage caused by Hurricane Matthew is seen inside a support building in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

Ceiling and furniture damage caused by Hurricane Matthew is seen inside a support building in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

Distinct effects of acute and chronic sleep loss on DNA damage in rats.

PubMed

Andersen, M L; Ribeiro, D A; Bergamaschi, C T; Alvarenga, T A; Silva, A; Zager, A; Campos, R R; Tufik, S

2009-04-30

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

Breathing as a Fundamental Rhythm of Brain Function.

PubMed

Heck, Detlef H; McAfee, Samuel S; Liu, Yu; Babajani-Feremi, Abbas; Rezaie, Roozbeh; Freeman, Walter J; Wheless, James W; Papanicolaou, Andrew C; Ruszinkó, Miklós; Sokolov, Yury; Kozma, Robert

2016-01-01

Ongoing fluctuations of neuronal activity have long been considered intrinsic noise that introduces unavoidable and unwanted variability into neuronal processing, which the brain eliminates by averaging across population activity (Georgopoulos et al., 1986; Lee et al., 1988; Shadlen and Newsome, 1994; Maynard et al., 1999). It is now understood, that the seemingly random fluctuations of cortical activity form highly structured patterns, including oscillations at various frequencies, that modulate evoked neuronal responses (Arieli et al., 1996; Poulet and Petersen, 2008; He, 2013) and affect sensory perception (Linkenkaer-Hansen et al., 2004; Boly et al., 2007; Sadaghiani et al., 2009; Vinnik et al., 2012; Palva et al., 2013). Ongoing cortical activity is driven by proprioceptive and interoceptive inputs. In addition, it is partially intrinsically generated in which case it may be related to mental processes (Fox and Raichle, 2007; Deco et al., 2011). Here we argue that respiration, via multiple sensory pathways, contributes a rhythmic component to the ongoing cortical activity. We suggest that this rhythmic activity modulates the temporal organization of cortical neurodynamics, thereby linking higher cortical functions to the process of breathing.

Sirtuin 5 as a novel target to blunt blood-brain barrier damage induced by cerebral ischemia/reperfusion injury.

PubMed

Diaz-Cañestro, Candela; Merlini, Mario; Bonetti, Nicole R; Liberale, Luca; Wüst, Patricia; Briand-Schumacher, Sylvie; Klohs, Jan; Costantino, Sara; Miranda, Melroy; Schoedon-Geiser, Gabriele; Kullak-Ublick, Gerd A; Akhmedov, Alexander; Paneni, Francesco; Beer, Jürg H; Lüscher, Thomas F; Camici, Giovanni G

2018-06-01

In acute ischemic stroke (AIS) patients, impaired blood-brain barrier (BBB) integrity is associated with hemorrhagic transformation and worsened outcome. Yet, the mechanisms underlying these relationships are poorly understood and consequently therapeutic strategies are lacking. This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury. SIRT5 knockout (SIRT5 -/- ) and wild type (WT) mice underwent transient middle cerebral artery (MCA) occlusion (tMCAO) followed by 48h of reperfusion. Genetic deletion of SIRT5 decreased infarct size, improved neurological function and blunted systemic inflammation following stroke. Similar effects were also achieved by in vivo SIRT5 silencing. Immunohistochemical analysis revealed decreased BBB leakage and degradation of the tight junction protein occludin in SIRT5 -/- mice exposed to tMCAO as compared to WT. In primary human brain microvascular endothelial cells (HBMVECs) exposed to hypoxia/reoxygenation (H/R), SIRT5 silencing decreased endothelial permeability and upregulated occludin and claudin-5; this effect was prevented by the PI3K inhibitor wortmannin. Lastly, SIRT5 gene expression was increased in peripheral blood monocytes (PBMCs) of AIS patients at 6h after onset of stroke compared to sex- and age-matched healthy controls. SIRT5 is upregulated in PBMCs of AIS patients and in the MCA of WT mice exposed to tMCAO; SIRT5 mediates I/R-induced brain damage by increasing BBB permeability through degradation of occludin. This effect was reproduced in HBMVECs exposed to H/R, mediated by the PI3K/Akt pathway. Our findings shed new light on the mechanisms of I/R-dependent brain damage and suggest SIRT5 as a novel therapeutic target. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

PubMed

Song, Y; Zhong, M; Cai, F-C

2018-01-01

Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (p<0.05). OXC administration causes histological changes of neurocytes. OXC 281.25 mg/kg or more concentration significantly decreased neurocytes counts and increased TUNEL-staining positive neurocytes compared to Control group (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased caspase 3 activity compared to Control group in P5 rats (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased Bax, Bax/Bcl-2 ratio and cytochrome C release in frontal lobes compared to Control group in P5 rats (p<0.05). Oxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

PubMed

Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

2015-06-01

Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

The Effect of Early Intervention and Rehabilitation in the Expression of Aquaporin-4; and Ultrastructure Changes on Rat's Offspring's Damaged Brain Caused by Intrauterine Infection

PubMed Central

Rajesh, Kumar; Xiangying, Kong

2015-01-01

Objective To study the effect of early intervention and rehabilitation in the expression of aquaporin-4 and ultrastructure changes on cerebral palsy pups model induced by intrauterine infection. Methods 20 pregnant Wistar rats were consecutively injected with lipopolysaccharide intraperitoneally. 60 Pups born from lipopolysaccharide group were randomly divided into intervention group (n=30) and non-intervention group (n=30); intervention group further divided into early intervention and rehabilitation group (n=10), acupuncture group (n=10) and consolidate group (n=10). Another 5 pregnant rats were injected with normal saline intraperitoneally; 30 pups born from the normal saline group were taken as control group. The intervention group received early intervention, rehabilitation and acupuncture treatment. The motor functions of all pups were assessed via suspension test and modified BBB locomotor score. Aquaporin-4 expression in brain tissue was studied through immunohistochemical and western-blot analysis. Ultrastructure changes in damaged brain and control group were studied electron-microscopically. Results The scores of suspension test and modified BBB locomotor test were significantly higher in the control group than the intervention and non intervention group (p<0.01); higher in the intervention group than the non-intervention group (p<0.01). The expression of Aquaporin-4 was lower in intervention and non intervention group than in the control group (p<0.01); also lower in non-intervention group than the intervention group (p<0.01). Marked changes were observed in ultrastructure of cortex and hippocampus CAI in brain damaged group. Conclusion Early intervention and rehabilitation training can improve the motor function in offspring with brain injury and reduce the expression of aquaporin-4 in damaged brain. PMID:26279808

Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

PubMed

Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

2004-09-15

Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

Increased frequency of brain pathology in inmates of a high-security forensic institution: a qualitative CT and MRI scan study.

PubMed

Witzel, Joachim G; Bogerts, Bernhard; Schiltz, Kolja

2016-09-01

This study aimed to assess whether brain pathology might be more abundant in forensic inpatients in a high-security setting than in non-criminal individuals. By using a previously used reliable approach, we explored the frequency and extent of brain pathology in a large group of institutionalized offenders who had not previously been considered to be suffering from structural brain damage and compare it to healthy, non-offending subjects. MRI and CT brain scans from 148 male inpatients of a high-security mental health institution (offense type: 51 sex, 80 violent, 9 arson, and 8 nonviolent) that were obtained due to headache, vertigo, or psychological complaints during imprisonment were assessed and compared to 52 non-criminal healthy controls. Brain scans were assessed qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1), or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex, and medial temporal structures bilaterally as well as third ventricle. Forensic inpatients displayed signs of brain damage to a significantly higher degree than healthy controls (p < 0.001). Even after adjustment for age, in the patients, being younger than the controls (p < 0.05), every offender type group displayed a higher proportion of subjects with brain regions categorized as definitely abnormal than the non-criminal controls. Within the forensic inpatients, offense type groups did not significantly differ in brain pathology. The astonishingly high prevalence of brain pathology in institutionalized inmates of a high-security mental health institution who previously had not been considered to be suffering from an organic brain syndrome raises questions on whether such neuroradiological assessment might be considered as a routine procedure in newly admitted patients. Furthermore, it highlights that organic changes, detectable under clinical routine conditions, may play a role in the development of legally relevant behavioral disturbances which might be underestimated.

A damage tolerance comparison of IM7/8551 and IM8G/8553 carbon/epoxy composites

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1991-01-01

A damage tolerance study of two new toughened carbon fiber/epoxy resin systems was undertaken as a continuation of ongoing work into screening new opposites for resistance to foreign object impact. This report is intended to be a supplement to NASA TP 3029 in which four new fiber/resin systems were tested for damage tolerance. Instrumented drop weight impact testing was used to inflict damage to 16-ply quasi-isotropic specimens. Instrumented output data and cross-sectional examinations of the damage zone were utilized to quantify the damage. It was found that the two fiber/resin systems tested in this study were much more impact resistant than an untoughened composite such as T300/934, but were not as impact resistant as other materials previously studied.

Ledipasvir and Sofosbuvir

MedlinePlus

... Ribasphere, others) to treat certain types of chronic hepatitis C (an ongoing viral infection that damages the liver) ... also used to treat certain types of chronic hepatitis C in children 12 years of age and older ...

Daclatasvir

MedlinePlus

... Solvadi]) to treat a certain type of chronic hepatitis C (an ongoing viral infection that damages the liver). ... is in a class of antiviral medications called hepatitis C virus (HCV) NS5A inhibitors. It works by stopping ...

Sofosbuvir and Velpatasvir

MedlinePlus

... to treat chronic hepatitis C (an ongoing viral infection that damages the liver). Sofosbuvir is in a class of antiviral medications called nucleotide hepatitis C virus (HCV) NS5B polymerase inhibitors. Velpatasvir is in a ...

Relating Brain Damage to Brain Plasticity in Patients With Multiple Sclerosis

PubMed Central

Tomassini, Valentina; Johansen-Berg, Heidi; Jbabdi, Saad; Wise, Richard G.; Pozzilli, Carlo; Palace, Jacqueline; Matthews, Paul M.

2013-01-01

Background Failure of adaptive plasticity with increasing pathology is suggested to contribute to progression of disability in multiple sclerosis (MS). However, functional impairments can be reduced with practice, suggesting that brain plasticity is preserved even in patients with substantial damage. Objective Here, functional magnetic resonance imaging (fMRI) was used to probe systems-level mechanisms of brain plasticity associated with improvements in visuomotor performance in MS patients and related to measures of microstructural damage. Methods 23 MS patients and 12 healthy controls underwent brain fMRI during the first practice session of a visuomotor task (short-term practice) and after 2 weeks of daily practice with the same task (longer-term practice). Participants also underwent a structural brain MRI scan. Results Patients performed more poorly than controls at baseline. Nonetheless, with practice, patients showed performance improvements similar to controls and independent of the extent of MRI measures of brain pathology. Different relationships between performance improvements and activations were found between groups: greater short-term improvements were associated with lower activation in the sensorimotor, posterior cingulate, and parahippocampal cortices for patients, whereas greater long-term improvements correlated with smaller activation reductions in the visual cortex of controls. Conclusions Brain plasticity for visuomotor practice is preserved in MS patients despite a high burden of cerebral pathology. Cognitive systems different from those acting in controls contribute to this plasticity in patients. These findings challenge the notion that increasing pathology is accompanied by an outright failure of adaptive plasticity, supporting a neuroscientific rationale for recovery-oriented strategies even in chronically disabled patients. PMID:22328685

Attenuation of brain edema and spatial learning deficits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats.

PubMed

Song, Si-Xin; Gao, Jun-Ling; Wang, Kai-Jie; Li, Ran; Tian, Yan-Xia; Wei, Jian-Qiang; Cui, Jian-Zhong

2013-01-01

Diffuse brain injury (DBI) is a leading cause of mortality and disability among young individuals and adults worldwide. In specific cases, DBI is associated with permanent spatial learning dysfunction and motor deficits due to primary and secondary brain damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a major complex that produces reactive oxygen species (ROS) during the ischemic period. The complex aggravates brain damage and cell death following ischemia/reperfusion injury; however, its role in DBI remains unclear. The present study aimed to investigate the hypothesis that levels of NOX2 (a catalytic subunit of NOX) protein expression and the activation of NOX are enhanced following DBI induction in rats and are involved in aggravating secondary brain damage. A rat model of DBI was created using a modified weight-drop device. Our results demonstrated that NOX2 protein expression and NOX activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h following DBI induction. Treatment with apocynin (50 mg/kg body weight), a specific inhibitor of NOX, injected intraperitoneally 30 min prior to DBI significantly attenuated NOX2 protein expression and NOX activation. Moreover, treatment with apocynin reduced brain edema and improved spatial learning function assessed using the Morris water maze. These results reveal that treatment with apocynin may provide a new neuroprotective therapeutic strategy against DBI by diminishing the upregulation of NOX2 protein and NOX activity.

40 plus or minus 10, a new magical number: reply to Russell.

PubMed

Larrabee, Glenn J; Millis, Scott R; Meyers, John E

2009-07-01

Russell (2009 this issue) has criticized our recently published investigation (Larrabee, Millis, & Meyers, 2008) comparing the diagnostic discrimination of an ability-focused neuropsychological battery (AFB) to that of the Halstead Reitan Battery (HRB). He contended that our symptom validity test (SVT) screening excluding 43% of brain dysfunction and 15% of control patients using computations based on Digit Span inappropriately excluded patients with brain damage, due to the correlation of Digit Span with the Average Index Score (AIS). Our exclusion of 43% of brain dysfunction participants matches the frequency of invalid neuropsychological data of 40-50% or more reported by numerous studies for a wide range of settings with external incentive. Moreover, our study was not an investigation of malingering; rather, we screened our data to insure that only valid data remained, for the most meaningful comparison of the AFB to the HRB. Russell's argument that Digit Span is correlated with brain damage confounds the criterion, AIS (a composite cognitive score), with the predictor, Digit Span (another cognitive score), rather than employing a truly independent neurologic criterion. The fact that Digit Span is notoriously insensitive to brain dysfunction underscores the robustness of our findings, for if we inappropriately excluded brain-damaged patients for low Digit Span, as Russell claimed, this resulted in our sample reflecting more subtle degree of brain dysfunction, and the superiority of the AFB over the HRB was demonstrated under the most challenging of discriminative conditions.

Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, "protective" glial stem cells and stromal ependymal cells.

PubMed

Hauwel, Mathieu; Furon, Emeline; Canova, Cecile; Griffiths, Mark; Neal, Jim; Gasque, Philippe

2005-04-01

In invertebrates and primitive vertebrates, the brain contains large numbers of "professional" macrophages associated with neurones, ependymal tanycytes and radial glia to promote robust regenerative capacity. In higher vertebrates, hematogenous cells are largely excluded from the brain, and innate immune molecules and receptors produced by the resident "amateur" macrophages (microglia, astrocytes and ependymal cells) control pathogen infiltration and clearance of toxic cell debris. However, there is minimal capacity for regeneration. The transfer of function from hematogenous cells to macroglia and microglia is associated with the sophistication of a yet poorly-characterized neurone-glia network. This evolutionary pattern may have been necessary to reduce the risk of autoimmune attack while preserving the neuronal web but the ability to repair central nervous system damage may have been sacrificed in the process. We herein argue that it may be possible to re-educate and stimulate the resident phagocytes to promote clearance of pathogens (e.g., Prion), toxic cell debris (e.g., amyloid fibrils and myelin) and apoptotic cells. Moreover, as part of this greater division of labour between cell types in vertebrate brains, it may be possible to harness the newly described properties of glial stem cells in neuronal protection (revitalization) rather than replacement, and to control brain inflammation. We will also highlight the emerging roles of stromal ependymal cells in controlling stem cell production and migration into areas of brain damage. Understanding the mechanisms involved in the nurturing of damaged neurons by protective glial stem cells with the safe clearance of cell debris could lead to remedial strategies for chronic brain diseases.

Nanobubbles, cavitation, shock waves and traumatic brain injury.

PubMed

Adhikari, Upendra; Goliaei, Ardeshir; Berkowitz, Max L

2016-12-07

Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the impinging pressure wave produces a jet of particles moving in the direction of the wave. If there is a surface nearby, the high-speed jet particles hit it, and as a result damage to the surface is produced. This cavitation effect is well known and intensely studied in case of microscopic sized bubbles. It can be quite damaging to materials, including biological tissues, but it can also be beneficial when controlled, like in case of sonoporation of biological membranes for the purpose of drug delivery. Here we consider recent simulation work performed to study collapse of nanobubbles exposed to shock waves, in order to understand the detailed mechanism of the cavitation induced damage to soft materials, such as biological membranes. We also discuss the connection of the cavitation effect with the traumatic brain injury caused by blasts. Specifically, we consider possible damage to model membranes containing lipid bilayers, bilayers with embedded ion channel proteins like the ones found in neural cells and also protein assemblies found in the tight junction of the blood brain barrier.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

PubMed

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

PubMed Central

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E.; Cohen, Leonardo G.; Birbaumer, Niels; Soekadar, Surjo R.

2016-01-01

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796

Genomic integrity and the ageing brain.

PubMed

Chow, Hei-man; Herrup, Karl

2015-11-01

DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

Brain damage and the moral significance of consciousness.

PubMed

Kahane, Guy; Savulescu, Julian

2009-02-01

Neuroimaging studies of brain-damaged patients diagnosed as in the vegetative state suggest that the patients might be conscious. This might seem to raise no new ethical questions given that in related disputes both sides agree that evidence for consciousness gives strong reason to preserve life. We question this assumption. We clarify the widely held but obscure principle that consciousness is morally significant. It is hard to apply this principle to difficult cases given that philosophers of mind distinguish between a range of notions of consciousness and that is unclear which of these is assumed by the principle. We suggest that the morally relevant notion is that of phenomenal consciousness and then use our analysis to interpret cases of brain damage. We argue that enjoyment of consciousness might actually give stronger moral reasons not to preserve a patient's life and, indeed, that these might be stronger when patients retain significant cognitive function.

Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

PubMed

Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori

2014-10-01

Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.

Epileptic encephalopathy in children with risk factors for brain damage.

PubMed

Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J; Barrera-Reséndiz, Jesús E; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

2012-01-01

In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-12-01

response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

[Depersonalization syndrome after acquired brain damage. Overview based on 3 case reports and the literature and discussion of etiological models].

PubMed

Paulig, M; Böttger, S; Sommer, M; Prosiegel, M

1998-12-01

Depersonalization after brain damage is still only rarely reported and poorly understood. We describe three patients between the ages of 21 and 25 who experienced depersonalization and derealization for periods of 6 weeks to 4 months, two after traumatic brain injury, the third after surgical and radiation treatment of a pineocytoma. Each one believed to be living in a nightmare and thought about committing suicide in order to wake up. One patient developed symptoms as described in Cotard delusion. Aspects of neuroanatomy, psychodynamics, and anthropology are discussed with reference to the literature. Frontal and temporal lesions seem only to play a facilitating role but not to be a necessary condition. There is evidence for additional influence of psychological and premorbid personality factors. Summarizing the current state of information we consider depersonalization with the experience of being in a dream or being dead as a heuristic reaction to brain damage. Similar models have already been discussed in neuropsychological disorders as for instance reduplicative paramnesias, neglect, and anosognosia.

Earliest Cranio-Encephalic Trauma from the Levantine Middle Palaeolithic: 3D Reappraisal of the Qafzeh 11 Skull, Consequences of Pediatric Brain Damage on Individual Life Condition and Social Care

PubMed Central

Coqueugniot, Hélène; Dutour, Olivier; Arensburg, Baruch; Duday, Henri; Vandermeersch, Bernard; Tillier, Anne-marie

2014-01-01

The Qafzeh site (Lower Galilee, Israel) has yielded the largest Levantine hominin collection from Middle Palaeolithic layers which were dated to circa 90–100 kyrs BP or to marine isotope stage 5b–c. Within the hominin sample, Qafzeh 11, circa 12–13 yrs old at death, presents a skull lesion previously attributed to a healed trauma. Three dimensional imaging methods allowed us to better explore this lesion which appeared as being a frontal bone depressed fracture, associated with brain damage. Furthermore the endocranial volume, smaller than expected for dental age, supports the hypothesis of a growth delay due to traumatic brain injury. This trauma did not affect the typical human brain morphology pattern of the right frontal and left occipital petalia. It is highly probable that this young individual suffered from personality and neurological troubles directly related to focal cerebral damage. Interestingly this young individual benefited of a unique funerary practice among the south-western Asian burials dated to Middle Palaeolithic. PMID:25054798

Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices

PubMed Central

Khalsa, Sahib S.; Damasio, Antonio; Tranel, Daniel; Landini, Gregory; Williford, Kenneth

2012-01-01

It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his “autobiographical self”, the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices. PMID:22927899

Traumatic brain injury impairs small-world topology

PubMed Central

Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

2013-01-01

Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

Pipe degradation investigations for optimization of flow-accelerated corrosion inspection location selection

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

Chandra, S.; Habicht, P.; Chexal, B.

1995-12-01

A large amount of piping in a typical nuclear power plant is susceptible to Flow-Accelerated Corrosion (FAC) wall thinning to varying degrees. A typical PAC monitoring program includes the wall thickness measurement of a select number of components in order to judge the structural integrity of entire systems. In order to appropriately allocate resources and maintain an adequate FAC program, it is necessary to optimize the selection of components for inspection by focusing on those components which provide the best indication of system susceptibility to FAC. A better understanding of system FAC predictability and the types of FAC damage encounteredmore » can provide some of the insight needed to better focus and optimize the inspection plan for an upcoming refueling outage. Laboratory examination of FAC damaged components removed from service at Northeast Utilities` (NU) nuclear power plants provides a better understanding of the damage mechanisms involved and contributing causes. Selected results of this ongoing study are presented with specific conclusions which will help NU to better focus inspections and thus optimize the ongoing FAC inspection program.« less

Increased miR-21-3p in injured brain microvascular endothelial cells following traumatic brain injury aggravates blood-brain barrier damage by promoting cellular apoptosis and inflammation through targeting MAT2B.

PubMed

Ge, Xintong; Li, Wenzhu; Huang, Shan; Yin, Zhenyu; Yang, Mengchen; Han, Zhenying; Han, Zhaoli; Chen, Fanglian; Wang, Haichen; Lei, Ping; Zhang, Jian-Ning

2018-04-26

Our recent papers have reported that increased miR-21-5p in brain following traumatic brain injury (TBI) could improve the neurological outcome through alleviating blood-brain barrier (BBB) damage. miR-21-3p is another mature miRNA derived from pre-miR-21 after Dicer Procession other than miR-21-5p. Its roles in various diseases, such as tumors and myocardial disease aroused great interest for research in recent years. To further explore the function and underlying mechanism of miR-21, especially miR-21-3p in regulating the pathological development of BBB damage after TBI, we designed this research and focused on studying the impact of miR-21-3p on apoptosis and inflammation in brain microvascular endothelial cells (BMVECs), the major cellular component of BBB. We performed controlled cortical impact on mouse brain, and employed the oxygen glucose deprivation/reoxygenation (OGD)-treated bEnd.3 cells injury model. We found that miR-21-3p level in BMVECs from injured cerebral cortex of controlled cortical impact (CCI) mice, and bEnd.3 cells with OGD treatment were both increased after injury. For in-vitro experiments, downregulation on miR-21-3p level by transfecting miR-21-3p antagomir in cultured cells alleviated OGD-induced BBB damage, characterized by decreased BBB leakage and increased expression of tight junction proteins. Besides, miR-21-3p antagomir could suppress cell death by anti-apoptosis, and control inflammatory response by inhibiting the activity of NF-κB signaling. Using luciferase reporter assay and a MAT2B-silenced shRNA vector, we further proved that miR-21-3p exerted above functions through targeting MAT2B. In addition, in-vivo experiments also confirmed that intracerebroventricular infusion of miR-21-3p antagomir could alleviate BBB leakage after TBI. It reduced Evans Blue extravasation and promoted the expression of tight junction proteins, thus contributed to improve the neurological outcome of CCI mice. Taken together, increased miR-21-3p in BMVECs after TBI was bad for restoration of injured BBB. Downregulation on miR-21-3p level in injured brain could be a promising therapeutic strategy for BBB damage after TBI.

NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

PubMed

Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

2017-11-14

Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.

PubMed

Amen, Daniel G; Wu, Joseph C; Taylor, Derek; Willeumier, Kristen

2011-01-01

Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.

New perspectives on central and peripheral immune responses to acute traumatic brain injury

PubMed Central

2012-01-01

Traumatic injury to the brain (TBI) results in a complex set of responses involving various symptoms and long-term consequences. TBI of any form can cause cognitive, behavioral and immunologic changes in later life, which underscores the problem of underdiagnosis of mild TBI that can cause long-term neurological deficits. TBI disrupts the blood–brain barrier (BBB) leading to infiltration of immune cells into the brain and subsequent inflammation and neurodegeneration. TBI-induced peripheral immune responses can also result in multiorgan damage. Despite worldwide research efforts, the methods of diagnosis, monitoring and treatment for TBI are still relatively ineffective. In this review, we delve into the mechanism of how TBI-induced central and peripheral immune responses affect the disease outcome and discuss recent developments in the continuing effort to combat the consequences of TBI and new ways to enhance repair of the damaged brain. PMID:23061919

Mechanical Evaluation of the Skeletal Structure and Tissue of the Woodpecker and Its Shock Absorbing System

NASA Astrophysics Data System (ADS)

Oda, Juhachi; Sakamoto, Jiro; Sakano, Kenichi

A woodpecker strikes its beak toward a tree repeatedly. But, the damage of brain or the brain concussion doesn’t occur by this action. Human cannot strike strongly the head without the damage of a brain. Therefore, it is predicted that the brain of a woodpecker is protected from the shock by some methods and that the woodpecker has the original mechanism to absorb a shock. In this study, the endoskeltal structure, especially head part structure of woodpecker is dissected and the impact-proof system is analyzed by FEM and model experiment. From the results, it is obvious that the woodpecker has the original impact-proof system as the unique states of hyoid bone, skull, tissue and brain. Moreover it is considered that woodpecker has the advanced impact-proof system relating with not only the head part but also with the whole body.

[Neuroendocrine dysfunction and brain damage. A consensus statement].

PubMed

Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

2009-01-01

This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

RAPD Profiling, DNA Fragmentation, and Histomorphometric Examination in Brains of Wistar Rats Exposed to Indoor 2.5 Ghz Wi-Fi Devices Radiation.

PubMed

Ibitayo, A O; Afolabi, O B; Akinyemi, A J; Ojiezeh, T I; Adekoya, K O; Ojewunmi, O O

2017-01-01

The advent of Wi-Fi connected high technology devices in executing day-to-day activities is fast evolving especially in developing countries of the world and hence the need to assess its safety among others. The present study was conducted to investigate the injurious effect of radiofrequency emissions from installed Wi-Fi devices in brains of young male rats. Animals were divided into four equal groups; group 1 served as control while groups 2, 3, and 4 were exposed to 2.5 Ghz at intervals of 30, 45, and 60 consecutive days with free access to food and water ad libitum. Alterations in harvested brain tissues were confirmed by histopathological analyses which showed vascular congestion and DNA damage in the brain was assayed using agarose gel electrophoresis. Histomorphometry analyses of their brain tissues showed perivascular congestion and tissue damage as well.

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Concussion Awareness: Getting School Psychologists into the Game

ERIC Educational Resources Information Center

Davies, Susan C.

2011-01-01

A concussion is a serious injury--a mild traumatic brain injury (TBI)--that induces physiological disruption of brain function. A concussion is caused by a bump, blow, or jolt to the head or body. The sudden movement causes stretching and tearing of brain cells; cells become damaged and chemical changes occur within the brain. Concussions can lead…

Research in seismology and earthquake engineering in Venezuela

USGS Publications Warehouse

Urbina, L.; Grases, J.

1983-01-01

After the July 29, 1967, damaging earthquake (with a moderate magnitude of 6.3) caused widespread damage to the northern coastal area of Venezuela and to the Caracas Valley, the Venezuelan Government decided to establish a Presidential Earthquake Commission. This commission undertook the task of coordinating the efforts to study the after-effects of the earthquake. The July 1967 earthquake claimed numerous lives and caused extensive damage to the capital of Venezuela. In 1968, the U.S Geological Survey conducted a seismological field study in the northern coastal area and in the Caracas Valley of Venezuela. the objective was to study the area that sustained severe, moderate, and no damage to structures. A reported entitled Ground Amplification Studies in Earthquake Damage Areas: The Caracas Earthquake of 1967 documented, for the first time, short-period seismic wave ground-motion amplifications in the Caracas Valley. Figure 1 shows the area of severe damage in the Los Palos Grantes suburb and the correlation with depth of alluvium and the arabic numbers denote the ground amplification factor at each site in the area. the Venezuelan Government initiated many programs to study in detail the damage sustained and to investigate the ongoing construction practices. These actions motivated professionals in the academic, private, and Government sectors to develops further capabilities and self-sufficiency in the fields of engineering and seismology. Allocation of funds was made to assist in training professionals and technicians and in developing new seismological stations and new programs at the national level in earthquake engineering and seismology. A brief description of the ongoing programs in Venezuela is listed below. these programs are being performed by FUNVISIS and by other national organizations listed at the end of this article.   

[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder].

PubMed

Kubo, S; Orihara, Y; Gotohda, T; Tokunaga, I; Tsuda, R; Ikematsu, K; Kitamura, O; Yamamoto, A; Nakasono, I

1998-12-01

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death.

Quantitation of heavy ion damage to the mammalian brain - Some preliminary findings

NASA Technical Reports Server (NTRS)

Cox, A. B.; Kraft, L. M.

1984-01-01

For several years, studies have been conducted regarding late effects of particulate radiations in mammalian tissues, taking into account the brains of rodents and lagomorphs. Recently, it has become feasible to quantify pathological damage and morpho-physiologic alterations accurately in large numbers of histological specimens. New investigative procedures make use of computer-assisted automated image analysis systems. Details regarding the employed methodology are discussed along with the results of the information. The radiations of high linear energy transfer (LET) cause apparently earlier and more dramatic shrinkage of olfactory glomeruli in exposed rabbit brains than comparable doses of Co-60 gamma photons.

Inferential stereomorphology of human brain lesions

NASA Astrophysics Data System (ADS)

Gedye, John L.

1980-07-01

I very much appreciated the invitation to contribute a paper to this Symposium on Applications of Human Biostereometrics, as it provides a valuable opportunity for me to take a fresh look at a problemâ€""the cerebral localisation of psychological function"â€"in which I have been interested for many years. This interest grew out of considerations of the clinically important problem of how we should go about the task of relating the form of the changes in human behavior consequent upon damage to the human brain following, say, head injury, to the form of the changes in brain morphology which constitute that damage, and related issues.

Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve

PubMed Central

Barulli, Daniel; Stern, Yaakov

2013-01-01

Cognitive reserve (CR) is a concept meant to account for the frequent discrepancy between an individual’s measured level of brain pathology and her expected cognitive performance. It is particularly important within the context of aging and dementia, but has wider applicability to all forms of brain damage. As such, it has intimate links to related compensatory and neuroprotective concepts, as well as to the related notion of brain reserve. In this article, we introduce the concept of cognitive reserve and explicate its potential cognitive neural implementation. We conclude that cognitive reserve is compatible and complementary with many related concepts, but that each much draw sharper conceptual boundaries in order to truly explain preserved cognitive function in the face of aging or brain damage. PMID:24018144

The Effect of Cannabis on the Brain: Can it cause brain anomalies that lead to increased risk for Schizophrenia?

PubMed Central

DeLisi, Lynn E.

2015-01-01

Purpose of This Review This review explores what is known about cannabis’s association with schizophrenia, cannabis’s effects on the brain, and whether the brain changes known to be present in schizophrenia could be caused by cannabis and thus lead to a psychosis. Recent Findings The heavy use of cannabis is known to be associated with some adverse consequences, such as the occurrence of acute psychotic episodes and the development of chronic schizophrenia in some people even after its use has terminated. Recent studies have produced controversy about whether cannabis in heavy use can cause irreversible brain damage, particularly to adolescents and thus, whether a chronic psychosis could be a result of brain changes caused by cannabis. Summary From the evidence that exists, it appears that the above view is unlikely and that cannabis may even have benign effects on brain structure, not producing deleterious damage. However, its neurochemical interactions with the dopaminergic pathway may, particularly in genetically vulnerable individuals, have adverse consequences. PMID:18332661

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

PubMed

Steele, C A; Powell, J L; Kemp, G J; Halford, J C G; Wilding, J P; Harrold, J A; Kumar, S V D; Cuthbertson, D J; Cross, A A; Javadpour, M; MacFarlane, I A; Stancak, A A; Daousi, C

2015-09-01

Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

PubMed

Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

2006-02-16

Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

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

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Cognitive neuroscience 2.0: building a cumulative science of human brain function

PubMed Central

Yarkoni, Tal; Poldrack, Russell A.; Van Essen, David C.; Wager, Tor D.

2010-01-01

Cognitive neuroscientists increasingly recognize that continued progress in understanding human brain function will require not only the acquisition of new data, but also the synthesis and integration of data across studies and laboratories. Here we review ongoing efforts to develop a more cumulative science of human brain function. We discuss the rationale for an increased focus on formal synthesis of the cognitive neuroscience literature, provide an overview of recently developed tools and platforms designed to facilitate the sharing and integration of neuroimaging data, and conclude with a discussion of several emerging developments that hold even greater promise in advancing the study of human brain function. PMID:20884276

Vocal Emotion of Humanoid Robots: A Study from Brain Mechanism

PubMed Central

Wang, Youhui; Hu, Xiaohua; Zhou, Jie; Kuo, Taitzong

2014-01-01

Driven by rapid ongoing advances in humanoid robot, increasing attention has been shifted into the issue of emotion intelligence of AI robots to facilitate the communication between man-machines and human beings, especially for the vocal emotion in interactive system of future humanoid robots. This paper explored the brain mechanism of vocal emotion by studying previous researches and developed an experiment to observe the brain response by fMRI, to analyze vocal emotion of human beings. Findings in this paper provided a new approach to design and evaluate the vocal emotion of humanoid robots based on brain mechanism of human beings. PMID:24587712

An Integrated MRI and MRS Approach to Evaluation of Multiple Sclerosis with Cognitive Impairment

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Li, Lihong; Lu, Hongbing; Huang, Wei; Tudorica, Alina; Krupp, Lauren

Magnetic resonance imaging and spectroscopy (MRI/MRS) plays a unique role in multiple sclerosis (MS) evaluation, because of its ability to provide both high image contrast and significant chemical change among brain tissues. The image contrast renders the possibility of quantifying the tissue volumetric and texture variations, e.g., cerebral atrophy and progressing speed, reflecting the ongoing destructive pathologic processes. Any chemical change reflects an early sign of pathological alteration, e.g., decreased N-acetyl aspartate (NAA) in lesions and normal appearing white matter, related to axonal damage or dysfunction. Both MRI and MRS encounter partial volume (PV) effect, which compromises the quantitative capability, especially for MRS. This work aims to develop a statistical framework to segment the tissue mixtures inside each image element, eliminating theoretically the PV effect, and apply the framework to the evaluation of MS with cognitive impairment. The quantitative measures from MRI/MRS neuroimaging are strongly correlated with the qualitative neuropsychological scores of Brief Repeatable Battery (BRB) test on cognitive impairment, demonstrating the usefulness of the PV image segmentation framework in this clinically significant problem.

Baicalin Attenuates Subarachnoid Hemorrhagic Brain Injury by Modulating Blood-Brain Barrier Disruption, Inflammation, and Oxidative Damage in Mice

PubMed Central

Fu, Yongjian; Zhang, SongSong; Ding, Hao; Chen, Jin

2017-01-01

In subarachnoid hemorrhagic brain injury, the early crucial events are edema formation due to inflammatory responses and blood-brain barrier disruption. Baicalin, a flavone glycoside, has antineuroinflammatory and antioxidant properties. We examined the effect of baicalin in subarachnoid hemorrhagic brain injury. Subarachnoid hemorrhage was induced through filament perforation and either baicalin or vehicle was administered 30 min prior to surgery. Brain tissues were collected 24 hours after surgery after evaluation of neurological scores. Brain tissues were processed for water content, real-time PCR, and immunoblot analyses. Baicalin improved neurological score and brain water content. Decreased levels of tight junction proteins (occludin, claudin-5, ZO-1, and collagen IV) required for blood-brain barrier function were restored to normal level by baicalin. Real-time PCR data demonstrated that baicalin attenuated increased proinflammatory cytokine (IL-1β, IL-6, and CXCL-3) production in subarachnoid hemorrhage mice. In addition to that, baicalin attenuated microglial cell secretion of IL-1β and IL-6 induced by lipopolysaccharide (100 ng/ml) dose dependently. Finally, baicalin attenuated induction of NOS-2 and NOX-2 in SAH mice at the mRNA and protein level. Thus, we demonstrated that baicalin inhibited microglial cell activation and reduced inflammation, oxidative damage, and brain edema. PMID:28912935

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish.

PubMed

Cacialli, Pietro; Palladino, Antonio; Lucini, Carla

2018-06-01

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Meningococcal ACWY Vaccines (MenACWY and MPSV4)

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts.Meningococcal ACWY vaccines can help prevent meningococcal disease caused by serogroups ...

The Neurotrophic Substances and Behavioral Recovery from Brain Damage.

DTIC Science & Technology

1984-11-01

neurotrophic substances that facilitate synthesis may be partially responsible for the com- neuronal regeneration" 12 pensatory effects of the NGF in...1962. Facilitation of simultaneous discrimination learning with strychnine sulphate. Psychopharmacologia 3: 166-172. 21. MEANS, E. D., AND D. K...34 ’- ,P ’% --- SALINE EFFECT 1071 28. SIESJO, B. K. 1981. Cell damage in the brain. A speculative synthesis . J. Cereb. Blood’ Flow Meiab. t: s155-slS5. 29

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

DTIC Science & Technology

2010-01-01

mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

Psychotherapy of the child with true brain damage.

PubMed

Christ, Adolph E

1978-07-01

Psychotherapy of the child with true brain damage presents special problems and requires special approaches. Those who are cognitively primitive--at the sensorimotor or preoperational stage of development--require a crisis approach; those at the concrete or formal operational stage can be treated with a modified insight-oriented approach. Development of a therapeutic alliance, establishment of workable defense mechanisms, identification and clarification of unalterable cognitive defects and issues of termination unique to this special population are discussed.

Oxidative Damage in the Guinea Pig Hippocampal Slice

DTIC Science & Technology

1989-01-01

Original Contribution OXIDATIVE DAMAGE IN THE GUINEA PIG HIPPOCAMPAL SLICE TIRRY C. Pnt.N1.iAR’ and KATIlRNN L. Nt-t-t- Physiology Department. Armed Forces...responses in the hippocampal slice isolated from the brains of guinea pigs . Electrical stim- ulation of afferents to neurons of the CA I region of...from the brains be secreted by the microglia invading a region of in- of euthanized male Hartley guinea pigs as previously Jury. ’ Another possible

Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.

PubMed

McDannold, Nathan; Arvanitis, Costas D; Vykhodtseva, Natalia; Livingstone, Margaret S

2012-07-15

The blood-brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method.

Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

NASA Astrophysics Data System (ADS)

Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

2015-04-01

The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

Imitation and matching of meaningless gestures: distinct involvement from motor and visual imagery.

PubMed

Lesourd, Mathieu; Navarro, Jordan; Baumard, Josselin; Jarry, Christophe; Le Gall, Didier; Osiurak, François

2017-05-01

The aim of the present study was to understand the underlying cognitive processes of imitation and matching of meaningless gestures. Neuropsychological evidence obtained in brain damaged patients, has shown that distinct cognitive processes supported imitation and matching of meaningless gestures. Left-brain damaged (LBD) patients failed to imitate while right-brain damaged (RBD) patients failed to match meaningless gestures. Moreover, other studies with brain damaged patients showed that LBD patients were impaired in motor imagery while RBD patients were impaired in visual imagery. Thus, we hypothesize that imitation of meaningless gestures might rely on motor imagery, whereas matching of meaningless gestures might be based on visual imagery. In a first experiment, using a correlational design, we demonstrated that posture imitation relies on motor imagery but not on visual imagery (Experiment 1a) and that posture matching relies on visual imagery but not on motor imagery (Experiment 1b). In a second experiment, by manipulating directly the body posture of the participants, we demonstrated that such manipulation evokes a difference only in imitation task but not in matching task. In conclusion, the present study provides direct evidence that the way we imitate or we have to compare postures depends on motor imagery or visual imagery, respectively. Our results are discussed in the light of recent findings about underlying mechanisms of meaningful and meaningless gestures.

Oxidative damage and brain concentrations of free amino acid in chicks exposed to high ambient temperature.

PubMed

Chowdhury, Vishwajit S; Tomonaga, Shozo; Ikegami, Taro; Erwan, Edi; Ito, Kentaro; Cockrem, John F; Furuse, Mitsuhiro

2014-03-01

High ambient temperatures (HT) reduce food intake and body weight in young chickens, and HT can cause increased expression of hypothalamic neuropeptides. The mechanisms by which HT act, and the effects of HT on cellular homeostasis in the brain, are however not well understood. In the current study lipid peroxidation and amino acid metabolism were measured in the brains of 14 d old chicks exposed to HT (35 °C for 24- or 48-h) or to control thermoneutral temperature (CT; 30 °C). Malondialdehyde (MDA) was measured in the brain to determine the degree of oxidative damage. HT increased body temperature and reduced food intake and body weight gain. HT also increased diencephalic oxidative damage after 48 h, and altered some free amino acid concentrations in the diencephalon. Diencephalic MDA concentrations were increased by HT and time, with the effect of HT more prominent with increasing time. HT altered cystathionine, serine, tyrosine and isoleucine concentrations. Cystathionine was lower in HT birds compared with CT birds at 24h, whilst serine, tyrosine and isoleucine were higher at 48 h in HT birds. An increase in oxidative damage and alterations in amino acid concentrations in the diencephalon may contribute to the physiological, behavioral and thermoregulatory responses of heat-exposed chicks. Copyright © 2013 Elsevier Inc. All rights reserved.

What You Need to Know about Drugs: Methamphetamines

MedlinePlus

... the body and brain, especially with repeated use. Long-term use of methamphetamines can cause brain damage that causes problems with memory and body movement, mood swings, and violent behavior. ...

Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses.

PubMed

Lima, Jean Pierre Mendes; Rayêe, Danielle; Silva-Rodrigues, Thaia; Pereira, Paula Ribeiro Paes; Mendonca, Ana Paula Miranda; Rodrigues-Ferreira, Clara; Szczupak, Diego; Fonseca, Anna; Oliveira, Marcus F; Lima, Flavia Regina Souza; Lent, Roberto; Galina, Antonio; Uziel, Daniela

2018-03-26

Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses' brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

PubMed

Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

2017-09-01

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

Opposing Effects of Pigment Epithelium-Derived Factor on Breast Cancer Cell versus Neuronal Survival: Implication for Brain Metastasis and Metastasis-Induced Brain Damage

PubMed Central

Fitzgerald, Daniel P.; Subramanian, Preeti; Deshpande, Monika; Graves, Christian; Gordon, Ira; Qian, Yongzhen; Snitkovsky, Yeva; Liewehr, David J.; Steinberg, Seth M.; Paltán-Ortiz, José D.; Herman, Mary M.; Camphausen, Kevin; Palmieri, Diane; Becerra, S. Patricia; Steeg, Patricia S.

2011-01-01

Brain metastases are a significant cause of cancer patient morbidity and mortality, yet preventative and therapeutic options remain an unmet need. The cytokine PEDF is downregulated in resected human brain metastases of breast cancer compared to primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression, as supported by in vitro analyses as well as direct intracranial implantation. Notably, the suppressive effects of PEDF were not only rapid but independent of the effects of this factor on angiogenesis. Paralleling its cytotoxic effects on breast cancer cells, PEDF also exerted a pro-survival effect on neurons that shielded the brain from tumor-induced damage, as indicated by a relative 3.5-fold reduction in the number of dying neurons adjacent to tumors expressing PEDF. Our findings establish that PEDF as both a metastatic suppressor and a neuroprotectant in the the brain, highlighting its role as a double agent in limiting brain metastasis and its local consequences. PMID:22215693

Nanobiotechnology-based strategies for crossing the blood-brain barrier.

PubMed

Jain, Kewal K

2012-08-01

The blood-brain barrier (BBB) is meant to protect the brain from noxious agents; however, it also significantly hinders the delivery of therapeutics to the brain. Several strategies have been employed to deliver drugs across this barrier and some of these may do structural damage to the BBB by forcibly opening it to allow the uncontrolled passage of drugs. The ideal method for transporting drugs across the BBB should be controlled and should not damage the barrier. Among the various approaches that are available, nanobiotechnology-based delivery methods provide the best prospects for achieving this ideal. This review describes various nanoparticle (NP)-based methods used for drug delivery to the brain and the known underlying mechanisms. Some strategies require multifunctional NPs combining controlled passage across the BBB with targeted delivery of the therapeutic cargo to the intended site of action in the brain. An important application of nanobiotechnology is to facilitate the delivery of drugs and biological therapeutics for brain tumors across the BBB. Although there are currently some limitations and concerns for the potential neurotoxicity of NPs, the future prospects for NP-based therapeutic delivery to the brain are excellent.

DNA damage in an animal model of maple syrup urine disease.

PubMed

Scaini, Giselli; Jeremias, Isabela C; Morais, Meline O S; Borges, Gabriela D; Munhoz, Bruna P; Leffa, Daniela D; Andrade, Vanessa M; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

2012-06-01

Maple syrup urine disease is an inborn error of metabolism caused by a severe deficiency of the branched chain alpha-ketoacid dehydrogenase complex. Neurological dysfunction is a common finding in patients with maple syrup urine disease. However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly understood. In this study, we investigated whether acute or chronic administration of a branched chain amino acid pool (leucine, isoleucine and valine) causes transient DNA damage, as determined by the alkaline comet assay, in the brain and blood of rats during development and whether antioxidant treatment prevented the alterations induced by branched chain amino acids. Our results showed that the acute administration of branched chain amino acids increased the DNA damage frequency and damage index in the hippocampus. However, the chronic administration of branched chain amino acids increased the DNA damage frequency and damage index in both the hippocampus and the striatum, and the antioxidant treatment was able to prevent DNA damage in the hippocampus and striatum. The present study demonstrated that metabolite accumulation in MSUD induces DNA damage in the hippocampus and striatum and that it may be implicated in the neuropathology observed in the affected patients. We demonstrated that the effect of antioxidant treatment (N-acetylcysteine plus deferoxamine) prevented DNA damage, suggesting the involvement of oxidative stress in DNA damage. Copyright © 2012 Elsevier Inc. All rights reserved.

[Comatose states: etiopathogenesis, experimental studies, treatment of hepatic coma].

PubMed

Strekalova, O S; Uchaĭkin, V F; Ipatova, O M; Torkhovskaia, T I; Medvedeva, N V; Storozhakov, G I; Archakov, A I

2009-01-01

The review presents the modern concepts on biochemical mechanisms of processes, that result in comatose states (CS), with emphasis on the search of new therapeutic approaches. CS of various origin causes severe suppression of brain cells functioning and stable unconsciousness. Numerous reasons of various CS are classified into two main groups: primary brain damages (ischemia, tumor, trauma) and secondary damages originating from system injuries in the body (endocrine, toxic e. c.). The most often primary CS is the hypoxic-ischemic one, as result of corresponding encephalopathy. Its mechanism is the brain cells "energy crisis"--because of decreased blood supply or its deficiency by energy substrates or/and by oxygen. Among secondary CS the substantial place takes hepatic coma as a consequence of hepatic encephalopathy in severe liver diseases--cirrhosis, acute liver failure, sharp intoxication. Its main reason is associated with exess of ammonia entering the brain tissue (it accumulates in blood because of lack of its removing by damaged hepatocytes). Ammonia reacts with glutamate in brain astrocytes and the product of this reaction, glutamine, induced osmotic imbalance, that results in change of form and functions of these important brain cells. It induces, in turn, neurons functions damages, changes in neurotransmission and cerebral blood flow and all these may give rise CS. The most of CS studies are carried out in human. Experimental models ofhepatic CS are reproduced mainly in rats, the most often by surgery methods. Other models included administration of thioacetamide or D-galactosamine, sometimes in combination with lipopolysaccharide. In earlier studies ammonia administration together with liver damages by ligation or by CCl4 was used. The main principles of hepatic coma treatment include the care of encephalopathy, detoxification, and liver treatment. Elaboration of new nanodrugs with increased penetration into tissues and cells, in particular, on the base of phospholipid nanoparticles, may increase substantially the therapeuti efficiency. One of such drug is thought to be a new hepatoprotective preparation phosphogliv--nanoparticles of soy phosphatidylcholine with glycyrrhizic acid. It is supposed, that the further development of phospholipid nanoforms, with minimal particle sizes, may reveal the more action in CS treatment.

N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain

PubMed Central

Chen, Sujuan; Ren, Qian; Zhang, Jinfei; Ye, Yangjing; Zhang, Zhen; Xu, Yijiao; Guo, Min; Ji, Haiyan; Xu, Chong; Gu, Chenjian; Gao, Wei; Huang, Shile; Chen, Long

2014-01-01

Aims This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd). Methods NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR) signaling pathway in brain neurons were assessed. To verify the role of mTOR activation in Cd-induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days. Results Chronic exposure of mice to Cd induced brain damage or neuronal cell death, due to ROS induction. Co-administration of NAC significantly reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd-induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd-induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC. Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity. Conclusions NAC protects against Cd-induced neuronal apoptosis in mouse brain partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of Cd-induced neurodegenerative diseases. PMID:24299490

Glutamate as a neurotransmitter in the brain: review of physiology and pathology.

PubMed

Meldrum, B S

2000-04-01

Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.

Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy.

PubMed

Blair, Laura J; Frauen, Haley D; Zhang, Bo; Nordhues, Bryce A; Bijan, Sara; Lin, Yen-Chi; Zamudio, Frank; Hernandez, Lidice D; Sabbagh, Jonathan J; Selenica, Maj-Linda B; Dickey, Chad A

2015-01-31

The blood-brain barrier (BBB) is damaged in tauopathies, including progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is thought to contribute to pathogenesis later in the disease course. In AD, BBB dysfunction has been associated with amyloid beta (Aß) pathology, but the role of tau in this process is not well characterized. Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage. Longitudinal evaluation of brain tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model showed progressive IgG, T cell and red blood cell infiltration. The Evans blue (EB) dye that is excluded from the brain when the BBB is intact also permeated the brains of rTg4510 mice following peripheral administration, indicative of a bonafide BBB defect, but this was only evident later in life. Thus, despite the marked brain atrophy and inflammation that occurs earlier in this model, BBB integrity is maintained. Interestingly, BBB dysfunction emerged at the same time that perivascular tau emerged around major hippocampal blood vessels. However, when tau expression was suppressed using doxycycline, BBB integrity was preserved, suggesting that the BBB can be stabilized in a tauopathic brain by reducing tau levels. For the first time, these data demonstrate that tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation. Moreover, the BBB can recover integrity when tau levels are reduced. Thus, late stage interventions targeting tau may slow the vascular contributions to cognitive impairment and dementia that occur in tauopathies.

White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

ERIC Educational Resources Information Center

Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

2011-01-01

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

PubMed

Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2016-01-01

A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

PubMed

Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

2014-06-01

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

Stroke Rehabilitation

MedlinePlus

A stroke can cause lasting brain damage. People who survive a stroke need to relearn skills they lost because of ... them relearn those skills. The effects of a stroke depend on which area of the brain was ...

Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?

PubMed

Korzeniewski, Steven J; Soto-Rivera, Carmen L; Fichorova, Raina N; Allred, Elizabeth N; Kuban, Karl C K; O'Shea, T Michael; Paneth, Nigel; Agus, Michael; Dammann, Olaf; Leviton, Alan

2014-11-01

We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage. We measured the concentrations of thyroid-stimulating hormone (TSH) on day 14 and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on 2 separate days a week apart during the first 2 postnatal weeks. We first assessed the risk of brain damage indicators by comparing 1) neonates who had HTT to those without (regardless of ISSI) and 2) neonates with HTT only, ISSI only, or HTT+ISSI to those who were exposed to neither HTT nor ISSI. In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (ORs) 2-6], whereas those with HTT only were at significantly reduced risk of a hypoechoic lesion (ORs 0.2-0.4). Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis (ORs 1.6-2.4). Elevated risk of a very low mental development score was associated with both ISSI only and HTT+ISSI, whereas a very low motor development score and microcephaly were associated with HTT+ISSI. The association of HTT with increased or decreased risk of indicators of brain damage depends on the presence or absence of ISSI.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

A damaged construction trailer and several pieces of associated debris, aftermath of Hurricane Matthew, are seen in front of the Mobile Launcher in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

A damaged construction trailer and several pieces of associated debris, aftermath of Hurricane Matthew, are seen near the Mobile Launcher in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-18

Damaged construction trailers and several pieces of associated debris, aftermath of Hurricane Matthew, are seen in front of the Mobile Launcher in the Launch Complex 39 area at NASA's Kennedy Space Center in Florida. Assessments and repairs are in progress at various structures and facilities across the spaceport, part of the ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Mouse Sperm Cryopreservation Using Cryoprotectant Containing l-Glutamine.

PubMed

Takeo, Toru; Nakagata, Naomi

2018-06-01

Efforts to advance sperm cryopreservation are ongoing and include modifications in the cryoprotective agents. The addition of l-glutamine maintains post-thaw motility and reduces plasma membrane damage to sperm. © 2018 Cold Spring Harbor Laboratory Press.

[Complex application 2-ethyl-6-methyl-3-hydroxypyridine-succinate and vinpocetine in cerebrovascular disorder.

PubMed

Solovyeva, E Yu; Karneev, A N; Chekanov, A V; Baranova, O A; Choi, I V

Developing brain ischemia due to cerebral vascularization leads to disruption of brain metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of some types of dementia. Early use of antioxidants such as ethyl ether apovincamine acid (vinpocetine) and 2-ethyl-6-methyl-3-hydroxypyridine-succinate in the treatment of this pathology is seen as a real pathogenetically based method of correction of cerebral metabolism with cerebral vascular disorders, demonstrating the increase in cerebral blood flow and also neuroprotective effects. Clinical studies and studies on biological models show that the main mechanisms of action of vinpocetine and 2-ethyl-6-methyl-3-hydroxypyridine-succinate, although have a similar focus, but implementing neuroprotective and nootropic effects via various links in the pathogenesis of ischemic brain damage.

The effects of vitamin E on brain derived neurotrophic factor, tissues oxidative damage and learning and memory of juvenile hypothyroid rats.

PubMed

Baghcheghi, Yousef; Beheshti, Farimah; Shafei, Mohammad Naser; Salmani, Hossein; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Anaeigoudari, Akbar; Hosseini, Mahmoud

2018-06-01

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition

PubMed Central

Song, Juhyun; Yoon, So Ra

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor-α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases. PMID:28680530

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

PubMed

Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

[Neuroprotective activity of the proline-containing dipeptide noopept on the model of brain ischemia induced by the middle cerebral artery occlusion].

PubMed

Gavrilova, S A; Us, K S; Ostrovskaia, R U; Koshelev, V B

2006-01-01

The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on the extent of ischemic cortical stroke was investigated in experiments on white mongrel male rats with ischemia induced by a combination of the middle cerebral artery occlusion with ipsilateral common carotid artery ligation. Animals were treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15 min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h after occlusion, brains were extracted and frozen, and thin brain slices were stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and processed using Auc 1 computer program, which estimates the percentage of damaged area relative to that of the whole ipsilateral hemisphere. The conditions of coagulation the distal segment of middle cerebral artery were selected, which caused necrosis localized in the fronto-parietal and dorso-lateral regions of the brain cortex without any damage of subcortical structures. The extent of the brain damage in control group (treated by saline) was 18.6%, while that in the group treated with noopept was 12.2%, thus demonstrating a decrease in the infarction area by 34.5% (p < 05). The data on noopept efficacy on the model of the extensive ischemic injury of brain cortex show that this drug has good prospects for use in the neuroprotective treatment of stroke.

Inhibition of Inducible Nitric Oxide Controls Pathogen Load and Brain Damage by Enhancing Phagocytosis of Escherichia coli K1 in Neonatal Meningitis

PubMed Central

Mittal, Rahul; Gonzalez-Gomez, Ignacio; Goth, Kerstin A.; Prasadarao, Nemani V.

2010-01-01

Escherichia coli K1 is a leading cause of neonatal meningitis in humans. In this study, we sought to determine the pathophysiologic relevance of inducible nitric oxide (iNOS) in experimental E. coli K1 meningitis. By using a newborn mouse model of meningitis, we demonstrate that E. coli infection triggered the expression of iNOS in the brains of mice. Additionally, iNOS−/− mice were resistant to E. coli K1 infection, displaying normal brain histology, no bacteremia, no disruption of the blood–brain barrier, and reduced inflammatory response. Treatment with an iNOS specific inhibitor, aminoguanidine (AG), of wild-type animals before infection prevented the development of bacteremia and the occurrence of meningitis. The infected animals treated with AG after the development of bacteremia also completely cleared the pathogen from circulation and prevented brain damage. Histopathological and micro-CT analysis of brains revealed significant damage in E. coli K1–infected mice, which was completely abrogated by AG administration. Peritoneal macrophages and polymorphonuclear leukocytes isolated from iNOS−/− mice or pretreated with AG demonstrated enhanced uptake and killing of the bacteria compared with macrophages and polymorphonuclear leukocytes from wild-type mice in which E. coli K1 survive and multiply. Thus, NO produced by iNOS may be beneficial for E. coli to survive inside the macrophages, and prevention of iNOS could be a therapeutic strategy to treat neonatal E. coli meningitis. PMID:20093483

Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

PubMed Central

Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

2013-01-01

Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

Inhibition of inducible nitric oxide controls pathogen load and brain damage by enhancing phagocytosis of Escherichia coli K1 in neonatal meningitis.

PubMed

Mittal, Rahul; Gonzalez-Gomez, Ignacio; Goth, Kerstin A; Prasadarao, Nemani V

2010-03-01

Escherichia coli K1 is a leading cause of neonatal meningitis in humans. In this study, we sought to determine the pathophysiologic relevance of inducible nitric oxide (iNOS) in experimental E. coli K1 meningitis. By using a newborn mouse model of meningitis, we demonstrate that E. coli infection triggered the expression of iNOS in the brains of mice. Additionally, iNOS-/- mice were resistant to E. coli K1 infection, displaying normal brain histology, no bacteremia, no disruption of the blood-brain barrier, and reduced inflammatory response. Treatment with an iNOS specific inhibitor, aminoguanidine (AG), of wild-type animals before infection prevented the development of bacteremia and the occurrence of meningitis. The infected animals treated with AG after the development of bacteremia also completely cleared the pathogen from circulation and prevented brain damage. Histopathological and micro-CT analysis of brains revealed significant damage in E. coli K1-infected mice, which was completely abrogated by AG administration. Peritoneal macrophages and polymorphonuclear leukocytes isolated from iNOS-/- mice or pretreated with AG demonstrated enhanced uptake and killing of the bacteria compared with macrophages and polymorphonuclear leukocytes from wild-type mice in which E. coli K1 survive and multiply. Thus, NO produced by iNOS may be beneficial for E. coli to survive inside the macrophages, and prevention of iNOS could be a therapeutic strategy to treat neonatal E. coli meningitis.

Involvement of brain-gut axis in treatment of cerebral infarction by β-asaron and paeonol.

PubMed

He, Xiaogang; Cai, Qiufang; Li, Jianxiang; Guo, Weifeng

2018-02-14

Cerebral infarction (CI) causes severe brain damage with high incidence. This study aimed to investigate the involvement of brain-gut axis in the treatment of CI by combined administration of β-asaron and paeonol. Rat middle cerebral artery occlusion (MCAO) model was established, the interleukin-1beta (IL-1β) and tumor necrosis factor α (TNF-α) in the rat peripheral blood were determined by ELISA assay, and brain tissue damage was evaluated by TUNNEL assay. The correlation of cholecystokinin (CCK) and nuclear factor-kappaB (NF-κB) signaling components between intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol were analyzed by quantitative RT-PCR and western blotting. In vitro transwell co-culture was performed to confirm the correlated expression. The expression of CCK and NF-κB signaling components were closely correlated between the intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol. The combined administration also regulates the IL-1β and TNF-α in the MCAO rat peripheral blood and ameliorate the brain damage in MCAO rats. Elevated expression of related genes was observed in the cortical neurons co-cultured with intestinal mucosal epithelial cells treated by β-asaron and paeonol. The brain-gut axis mediates the therapeutic effect of β-asaron and paeonol for cerebral infarction through CCK and NF-κB signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

[Intelligence and creativity changes induced by pathological growth of space-occupying cerebral lesion].

PubMed

Perfil'ev, A M; Razumnikova, O M; Stupak, V V

2013-01-01

Creativity and intelligence changes depending on tumor localization in frontal or parietal cortex before surgical procedure in 24 patients in comparison with control group are studied. Brain damage-induced intelligence impairment and a decrease of fluency, flexibility of figural divergent thinking, and originality of verbal one without specificity of tumor localization were found. Intelligence decrease was more presented while performing of figural tasks and least of all in verbal ones. The left prefrontal brain damage induced a decrease of all components of intelligence and a trend to a decrease of verbal creativity and figural fluency. The right parietal brain lesion was more associated with a decline of divergent thinking originality.

Cannabinoids and brain injury: therapeutic implications.

PubMed

Mechoulam, Raphael; Panikashvili, David; Shohami, Esther

2002-02-01

Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumour necrosis factor-alpha and reactive oxygen intermediates, which are factors in causing neuronal damage. The formation of the endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly enhanced after brain injury, and there is evidence that these compounds reduce the secondary damage incurred. Some plant and synthetic cannabinoids, which do not bind to the cannabinoid receptors, have also been shown to be neuroprotective, possibly through their direct effect on the excitatory glutamate system and/or as antioxidants.

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: The Effects of Exercise Interventions

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Erdeniz. B.; Kofman, I. S.; DeDios, Y. E.; Szecsy, D. L.; Riascos-Castaneda, R. F.; Wood, S. J.; Bloomberg, J. J.

2014-01-01

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. Our ongoing bed rest participants are also engaging in exercise studies directed by Dr. Lori Ploutz Snyder. In this presentation, I will briefly highlight the existing literature linking exercise and fitness to brain and behavioral functions. I will also overview the metrics from my study that could be investigated in relation to the exercise and control subgroups.

Behavioral consequences of selective damage to frontal pole and posterior cingulate cortices

PubMed Central

Mansouri, Farshad A.; Buckley, Mark J.; Mahboubi, Majid; Tanaka, Keiji

2015-01-01

Frontal pole cortex (FPC) and posterior cingulate cortex (PCC) have close neuroanatomical connections, and imaging studies have shown coactivation or codeactivation of these brain regions during performance of certain tasks. However, they are among the least well-understood regions of the primate brain. One reason for this is that the consequences of selective bilateral lesions to either structure have not previously been studied in any primate species. We studied the effects of circumscribed bilateral lesions to FPC or PCC on monkeys’ ability to perform an analog of Wisconsin Card Sorting Test (WCST) and related tasks. In contrast to lesions in other prefrontal regions, neither posttraining FPC nor PCC lesions impaired animals’ abilities to follow the rule switches that frequently occurred within the WCST task. However, FPC lesions were not without effect, because they augmented the ability of animals to adjust cognitive control after experiencing high levels of conflict (whereas PCC lesions did not have any effect). In addition, FPC-lesioned monkeys were more successful than controls or PCC-lesioned animals at remembering the relevant rule across experimentally imposed distractions involving either an intervening secondary task or a surprising delivery of free reward. Although prefrontal cortex posterior to FPC is specialized for mediating efficient goal-directed behavior to maximally exploit reward opportunities from ongoing tasks, our data led us to suggest that FPC is, instead, specialized for disengaging executive control from the current task and redistributing it to novel sources of reward to explore new opportunities/goals. PMID:26150522

Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo.

PubMed

Wong, Raymond; Abussaud, Ahmed; Leung, Joseph Wh; Xu, Bao-Feng; Li, Fei-Ya; Huang, Sammen; Chen, Nai-Hong; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

2018-05-01

Activation of swelling-induced Cl - current (I Cl,swell ) during neonatal hypoxia-ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes chronic neurological morbidity in neonates as well as acute mortality. In this study, we investigated the role of I Cl,swell in hypoxic-ischemic brain injury using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl) oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30% hypotonic solution activated I Cl,swell , which was completely blocked by the application of DCPIB (10 μmol/L). The role of I Cl,swell in neonatal hypoxic-ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic-ischemic brain injury model. Before receiving the ischemic insult, the mouse pups were injected with DCPIB (10 mg/kg, ip). We found that pretreatment with DCPIB significantly reduced the brain damage assessed using TTC staining, Nissl staining and whole brain imaging, and improved the sensorimotor and vestibular recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and cliff avoidance reflex). These results show that DCPIB has neuroprotective effects on neonatal hypoxic-ischemic brain injury, and that the I Cl,swell may serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy.

Inflammation and white matter degeneration persist for years after a single traumatic brain injury.

PubMed

Johnson, Victoria E; Stewart, Janice E; Begbie, Finn D; Trojanowski, John Q; Smith, Douglas H; Stewart, William

2013-01-01

A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.

Occult White Matter Damage Contributes to Intellectual Disability in Tuberous Sclerosis Complex

ERIC Educational Resources Information Center

Yu, Chunshui; Lin, Fuchun; Zhao, Li; Ye, Jing; Qin, Wen

2009-01-01

Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of…

Bilateral limbic system destruction in man

PubMed Central

Feinstein, Justin S.; Rudrauf, David; Khalsa, Sahib S.; Cassell, Martin D.; Bruss, Joel; Grabowski, Thomas J.; Tranel, Daniel

2010-01-01

We report here a case study of a rare neurological patient with bilateral brain damage encompassing a substantial portion of the so-called “limbic system.” The patient, Roger, has been studied in our laboratory for over 14 years and the current article presents his complete neuroanatomical and neuropsychological profiles. The brain damage occurred in 1980 following an episode of herpes simplex encephalitis. The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral. Despite the magnitude of his brain damage, Roger has a normal IQ, average to above average attention, working memory, and executive functioning skills, and very good speech and language abilities. In fact, his only obvious presenting deficits are a dense global amnesia and a severe anosmia and ageusia. Roger's case presents a rare opportunity to advance our understanding of the critical functions underlying the human limbic system, and the neuropsychological and neuroanatomical data presented here provide a critical foundation for such investigations. PMID:19763994

Examining Neural Correlates of Psychopathology Using a Lesion-Based Approach.

PubMed

Calamia, Matthew; Markon, Kristian E; Sutterer, Matthew J; Tranel, Daniel

2018-06-22

Studies of individuals with focal brain damage have long been used to expand understanding of the neural basis of psychopathology. However, most previous studies were conducted using small sample sizes and relatively coarse methods for measuring psychopathology or mapping brain-behavior relationships. Here, we examined the factor structure and neural correlates of psychopathology in 232 individuals with focal brain damage, using their responses to the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Factor analysis and voxel-based lesion symptom mapping were used to examine the structure and neural correlates of psychopathology in this sample. Consistent with existing MMPI-2-RF literature, separate internalizing, externalizing, and psychotic symptom dimensions were found. In addition, a somatic dimension likely reflecting neurological symptoms was identified. Damage to the medial temporal lobe, including the hippocampus, was associated with scales related to both internalizing problems and psychoticism. Damage to the medial temporal lobe and orbitofrontal cortex was associated with both a general distrust of others and beliefs that one is being personally targeted by others. These findings provide evidence for the critical role of dysfunction in specific frontal and temporal regions in the development of psychopathology. Copyright © 2018. Published by Elsevier Ltd.

Can neuropsychological testing produce unequivocal evidence of brain damage? II. Testing for right vs. left differences.

PubMed

Reitan, Ralph M; Wolfson, Deborah

2008-01-01

Sensation and perception, as well as motor functions, have played an important role in the history of psychology. Although tests of these abilities are sometimes included in neuropsychological assessments, comparisons of intraindividual performances on the two sides of the body (as a basis for drawing conclusions and comparisons about the functional status of the two cerebral hemispheres) are in many instances neglected or considered only casually. This study, utilizing several motor and sensory-perceptual tests, compared intraindividual differences on the two sides of the body in a group of controls and a group of persons with brain damage. The results indicated that the sensory-perceptual tests were particularly effective in differentiating the groups. More than 60% of the group with brain damage had greater differences on the two sides of the body than did any of the controls. These findings suggest that a substantial proportion of persons with cerebral disease or damage may be subject to unequivocal identification using sensory-perceptual tests that take only about 20 minutes to administer. These tests may serve a valuable role as an adjunct to comprehensive neuropsychological evaluation and should be further evaluated in this respect.

Brain-peripheral cell crosstalk in white matter damage and repair.

PubMed

Hayakawa, Kazuhide; Lo, Eng H

2016-05-01

White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of rat optic nerve damage due to microbeam radiation therapy in the treatment of glioblastomas.

PubMed

Mohamed, A; Worobec, S; Schultke, E

2008-01-01

Glioblastomas are the most common and aggressive subtype of human primary brain tumors. Due to their uncontrolled cellular proliferation, intense invasion, and lack of apoptosis, they are extremely difficult to treat. Currently, different approaches such as surgery, chemotherapy and radiation therapy have been employed as possible treatments however thus far; these treatments are not curative. Currently, microbeam radiation therapy (MRT) is being trialed in animal models of malignant brain tumors (rats) to aid in treatment. Some of the protocols tested have been shown to significantly increase survival rates. However, due to the high x-ray doses uses in MRT, the surrounding tissue of the targeted Glioblastomas may be irreversibly damaged. In previous studies, lens damage and clouding of the cornea have been observed in microbeam exposed eyes. However, to date no studies have assessed optic nerve damage. Therefore, this study examines the potential rat optic nerve damage following exposure to microbeam radiation therapy in the treatment of Glioblastomas. Although there appears to be no significant damage to the optic nerve, slight inflammation was observed within the extra ocular muscle.

Critical care considerations in the management of the trauma patient following initial resuscitation

PubMed Central

2012-01-01

Background Care of the polytrauma patient does not end in the operating room or resuscitation bay. The patient presenting to the intensive care unit following initial resuscitation and damage control surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive repair. The intensive care physician must understand the respiratory, cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the patient and address potential complications. In this review, we address ongoing resuscitation in the intensive care unit along with potential complications in the trauma patient after initial resuscitation. Complications such as abdominal compartment syndrome, transfusion related patterns of acute lung injury and metabolic consequences subsequent to post-trauma resuscitation are presented. Methods A non-systematic literature search was conducted using PubMed and the Cochrane Database of Systematic Reviews up to May 2012. Results and conclusion Polytrauma patients with severe shock from hemorrhage and massive tissue injury present major challenges for management and resuscitation in the intensive care setting. Many of the current recommendations for “damage control resuscitation” including the use of fixed ratios in the treatment of trauma induced coagulopathy remain controversial. A lack of large, randomized, controlled trials leaves most recommendations at the level of consensus, expert opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will further influence how we manage these complex and challenging patients. PMID:22989116

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

PubMed

Kobus, Thiele; Vykhodtseva, Natalia; Pilatou, Magdalini; Zhang, Yongzhi; McDannold, Nathan

2016-02-01

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Brain heating induced by near-infrared lasers during multiphoton microscopy

PubMed Central

Ranganathan, Gayathri

2016-01-01

Two-photon imaging and optogenetic stimulation rely on high illumination powers, particularly for state-of-the-art applications that target deeper structures, achieve faster measurements, or probe larger brain areas. However, little information is available on heating and resulting damage induced by high-power illumination in the brain. In the current study we used thermocouple probes and quantum dot nanothermometers to measure temperature changes induced by two-photon microscopy in the neocortex of awake and anaesthetized mice. We characterized heating as a function of wavelength, exposure time, and distance from the center of illumination. Although total power is highest near the surface of the brain, heating was most severe hundreds of micrometers below the focal plane, due to heat dissipation through the cranial window. Continuous illumination of a 1-mm2 area produced a peak temperature increase of ∼1.8°C/100 mW. Continuous illumination with powers above 250 mW induced lasting damage, detected with immunohistochemistry against Iba1, glial fibrillary acidic protein, heat shock proteins, and activated caspase-3. Higher powers were usable in experiments with limited duty ratios, suggesting an approach to mitigate damage in high-power microscopy experiments. PMID:27281749

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

PubMed

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.

PubMed

Proia, Patrizia; Schiera, Gabriella; Salemi, Giuseppe; Ragonese, Paolo; Savettieri, Giovanni; Di Liegro, Italia

2009-12-01

An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB model, as indicated by the decrease of the transendothelial electrical resistance (TEER). Moreover, as shown by both immunofluorescence and Western blot analyses, BBB breaking is accompanied by a decrease of the synthesis as well as the peripheral localization of occludin, a structural protein of the tight junctions that are responsible for BBB properties.

Meningococcal ACWY Vaccines - MenACWY and MPSV4: What You Need to Know

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts. Meningococcal ACWY vaccines can help prevent meningococcal disease caused by serogroups ...

Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

PubMed Central

Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

2016-01-01

Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

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

Read, David J.; Li Yong; Chao, Moses V.

2010-05-15

Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but maymore » incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.« less

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

PubMed

Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2016-10-01

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

Does any aspect of mind survive brain damage that typically leads to a persistent vegetative state? Ethical considerations

PubMed Central

Panksepp, Jaak; Fuchs, Thomas; Garcia, Victor Abella; Lesiak, Adam

2007-01-01

Recent neuroscientific evidence brings into question the conclusion that all aspects of consciousness are gone in patients who have descended into a persistent vegetative state (PVS). Here we summarize the evidence from human brain imaging as well as neurological damage in animals and humans suggesting that some form of consciousness can survive brain damage that commonly causes PVS. We also raise the issue that neuroscientific evidence indicates that raw emotional feelings (primary-process affects) can exist without any cognitive awareness of those feelings. Likewise, the basic brain mechanisms for thirst and hunger exist in brain regions typically not damaged by PVS. If affective feelings can exist without cognitive awareness of those feelings, then it is possible that the instinctual emotional actions and pain "reflexes" often exhibited by PVS patients may indicate some level of mentality remaining in PVS patients. Indeed, it is possible such raw affective feelings are intensified when PVS patients are removed from life-supports. They may still experience a variety of primary-process affective states that could constitute forms of suffering. If so, withdrawal of life-support may violate the principle of nonmaleficence and be tantamount to inflicting inadvertent "cruel and unusual punishment" on patients whose potential distress, during the process of dying, needs to be considered in ethical decision-making about how such individuals should be treated, especially when their lives are ended by termination of life-supports. Medical wisdom may dictate the use of more rapid pharmacological forms of euthanasia that minimize distress than the de facto euthanasia of life-support termination that may lead to excruciating feelings of pure thirst and other negative affective feelings in the absence of any reflective awareness. PMID:18086316

Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats

PubMed Central

Bandegi, Ahmad Reza; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Ghadrdoost, Behshid

2014-01-01

Purpose: Chronic stress has been reported to induce oxidative damage of the brain. A few studies have shown that Crocus Sativus L., commonly known as saffron and its active constituent crocin may have a protective effect against oxidative stress. The present work was designed to study the protective effects of saffron extract and crocin on chronic – stress induced oxidative stress damage of the brain, liver and kidneys. Methods: Rats were injected with a daily dose of saffron extract (30 mg/kg, IP) or crocin (30 mg/kg, IP) during a period of 21 days following chronic restraint stress (6 h/day). In order to determine the changes of the oxidative stress parameters following chronic stress, the levels of the lipid peroxidation product, malondialdehyde (MDA), the total antioxidant reactivity (TAR), as well as antioxidant enzyme activities glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured in the brain, liver and kidneys tissues after the end of chronic stress. Results: In the stressed animals that receiving of saline, levels of MDA, and the activities of GPx, GR, and SOD were significantly higher (P<0.0001) and the TAR capacity were significantly lower than those of the non-stressed animals (P<0.0001). Both saffron extract and crocin were able to reverse these changes in the stressed animals as compared with the control groups (P<0.05). Conclusion: These observations indicate that saffron and its active constituent crocin can prevent chronic stress–induced oxidative stress damage of the brain, liver and kidneys and suggest that these substances may be useful against oxidative stress. PMID:25671180

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection.

PubMed

Koh, Eun-Kyoung; Yun, Woo-Bin; Kim, Ji-Eun; Song, Sung-Hwa; Sung, Ji-Eun; Lee, Hyun-Ah; Seo, Eun-Ji; Jee, Seung-Wan; Bae, Chang-Joon; Hwang, Dae-Youn

2016-06-01

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75(NTR) expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection

PubMed Central

Koh, Eun-Kyoung; Yun, Woo-Bin; Kim, Ji-Eun; Song, Sung-Hwa; Sung, Ji-Eun; Lee, Hyun-Ah; Seo, Eun-Ji; Jee, Seung-Wan

2016-01-01

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75NTR expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis. PMID:27382379

Direct stimulation of angiotensin II type 2 receptor initiated after stroke ameliorates ischemic brain damage.

PubMed

Min, Li-Juan; Mogi, Masaki; Tsukuda, Kana; Jing, Fei; Ohshima, Kousei; Nakaoka, Hirotomo; Kan-No, Harumi; Wang, Xiao-Li; Chisaka, Toshiyuki; Bai, Hui-Yu; Iwanami, Jun; Horiuchi, Masatsugu

2014-08-01

Stroke is a leading cause of death and disability; however, meta-analysis of randomized controlled trials of blood pressure-lowering drugs in acute stroke has shown no definite evidence of a beneficial effect on functional outcome. Accumulating evidence suggests that angiotensin II type 1 receptor blockade with angiotensin II type 2 (AT2) receptor stimulation could contribute to protection against ischemic brain damage. We examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) initiated even after stroke can prevent ischemic brain damage. Stroke was induced by middle cerebral artery (MCA) occlusion, and the area of cerebral infarction was measured by magnetic resonant imaging. C21 (10 µg/kg/day) treatment was initiated immediately after MCA occlusion by intraperitoneal injection followed by treatment with C21 once daily. We observed that ischemic area was enlarged in a time dependent fashion and decreased on day 5 after MCA occlusion. Treatment with C21 initiated after MCA occlusion significantly reduced the ischemic area, with improvement of neurological deficit in a time-dependent manner without affecting blood pressure. The decrease of cerebral blood flow after MCA occlusion was also ameliorated by C21 treatment. Moreover, treatment with C21 significantly attenuated superoxide anion production and expression of proinflammatory cytokines, monocyte chemoattractant protein 1, and tumor necrosis factor α. Interestingly, C21 administration significantly decreased blood-brain barrier permeability and cerebral edema on the ischemic side. These results provide new evidence that direct AT2 receptor stimulation with C21 is a novel therapeutic approach to prevent ischemic brain damage after acute stroke. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Body knowledge in brain-damaged children: a double-dissociation in self and other's body processing.

PubMed

Frassinetti, Francesca; Fiori, Simona; D'Angelo, Valentina; Magnani, Barbara; Guzzetta, Andrea; Brizzolara, Daniela; Cioni, Giovanni

2012-01-01

Bodies are important element for self-recognition. In this respect, in adults it has been recently shown a self vs other advantage when small parts of the subjects' body are visible. This advantage is lost following a right brain lesion underlying a role of the right hemisphere in self body-parts processing. In order to investigate the bodily-self processing in children and the development of its neuronal bases, 57 typically developing healthy subjects and 17 subjects with unilateral brain damage (5 right and 12 left sided), aged 4-17 years, were submitted to a matching-to-sample task. In this task, three stimuli vertically aligned were simultaneously presented at the centre of the computer screen. Subjects were required which of two stimuli (the upper or the lower one) matched the central target stimulus, half stimuli representing self and half stimuli representing other people's body-parts and face-parts. The results showed that corporeal self recognition is present since at least 4 years of age and that self and others' body parts processing are different and sustained by separate cerebral substrates. Indeed, a double dissociation was found: right brain damaged patients were impaired in self but not in other people's body parts, showing a self-disadvantage, whereas left brain damaged patients were impaired in others' but not in self body parts processing. Finally, since the double dissociation self/other was found for body-parts but not for face parts, the corporal self seems to be dissociated for body and face-parts. This opens the possibility of independent and lateralized functional modules for the processing of self and other body parts during development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

PubMed

Tyler, Lorraine K; Wright, Paul; Randall, Billi; Marslen-Wilson, William D; Stamatakis, Emmanuel A

2010-11-01

The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

The distribution of apolipoprotein E alleles in Scottish perinatal deaths

PubMed Central

Becher, J‐C; Keeling, J W; McIntosh, N; Wyatt, B; Bell, J

2006-01-01

Background The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investigated. Methods ApoE genotyping was undertaken in a Scottish cohort of perinatal deaths (n = 261), some of whom had prenatal brain damage. The distribution of ApoE alleles in perinatal deaths was compared with that in healthy liveborn infants and in adults in Scotland. Results ApoE e2 was over‐represented in 251 perinatal deaths (13% v 8% in healthy newborns, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.13 to 2.36 and 13% v 8% in adults, OR = 1.67, 95% CI 1.16 to 2.41), both in liveborn and stillborn perinatal deaths. In contrast, the prevalence of ApoE e4 was raised in healthy liveborn infants (19%) compared with stillbirths (13%, OR = 1.59, 95% CI 1.11 to 2.26) and with adults (15%, OR = 1.35, 95% CI 1.04 to 1.76). However, no correlation was found between ApoE genotype and the presence or absence of perinatal brain damage. Conclusions This study shows a shift in ApoE allelic distribution in early life compared with adults. The raised prevalence of ApoE e2 associated with perinatal death suggests that this allele is detrimental to pregnancy outcome, whereas ApoE e4 may be less so. However, ApoE genotype did not appear to influence the vulnerability for perinatal hypoxic/ischaemic brain damage, in agreement with findings in adult brains and in animal models. PMID:16183800

Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

PubMed

Chen, Jing; Chen, Yan-Hui; Lv, Hong-Yan; Chen, Li-Ting

2016-07-01

The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P<0.01) and the SOD activities were lower while the MDA levels were higher (P<0.01) in the HIBD group. No significant differences in ultrastructure, the latency of F-VEPs or SOD/MDA levels were identified between the HBO-treated HIBD group and the normal control group (P>0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

PubMed Central

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Language and the Brain. Cambridge Approaches to Linguistics.

ERIC Educational Resources Information Center

Obler, Loraine K.; Gjerlow, Kris

This book examines how the brain enables people to speak creatively and build up an understanding of language. The discussion looks at the linguistic and neuro-anatomical underpinnings of language and considers how language skills can systematically break down in individuals with different types of brain damage. By studying children with language…

Blueberries and strawberries activate neuronal housekeeping in critical brain regions of stress-induced young rats

USDA-ARS?s Scientific Manuscript database

Dysfunctional autophagy, where accumulation of damaged or complex cellular components in neurons in response to sublethal cell stress has been implicated in an array of brain disorders. This phenomenon plays a pivotal role in aging, because of the increased vulnerability of the aging brain to incre...

Stroke - risk factors

MedlinePlus

... is cut off for longer than a few seconds, the brain cannot get nutrients and oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of getting a disease or condition. This article ...

31 CFR 346.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2014 CFR

2014-07-01

... transportation, or doing small chores. (iv) Cancer which is inoperable and progressive. (v) Damage to the brain or brain abnormality which has resulted in severe loss of judgment, intellect, orientation, or memory...

Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention

PubMed Central

Ewell, Laura A.; Liang, Liang; Armstrong, Caren; Soltész, Ivan; Leutgeb, Stefan

2015-01-01

Neural dynamics preceding seizures are of interest because they may shed light on mechanisms of seizure generation and could be predictive. In healthy animals, hippocampal network activity is shaped by behavioral brain state and, in epilepsy, seizures selectively emerge during specific brain states. To determine the degree to which changes in network dynamics before seizure are pathological or reflect ongoing fluctuations in brain state, dorsal hippocampal neurons were recorded during spontaneous seizures in a rat model of temporal lobe epilepsy. Seizures emerged from all brain states, but with a greater likelihood after REM sleep, potentially due to an observed increase in baseline excitability during periods of REM compared with other brains states also characterized by sustained theta oscillations. When comparing the firing patterns of the same neurons across brain states associated with and without seizures, activity dynamics before seizures followed patterns typical of the ongoing brain state, or brain state transitions, and did not differ until the onset of the electrographic seizure. Next, we tested whether disparate activity patterns during distinct brain states would influence the effectiveness of optogenetic curtailment of hippocampal seizures in a mouse model of temporal lobe epilepsy. Optogenetic curtailment was significantly more effective for seizures preceded by non-theta states compared with seizures that emerged from theta states. Our results indicate that consideration of behavioral brain state preceding a seizure is important for the appropriate interpretation of network dynamics leading up to a seizure and for designing effective seizure intervention. SIGNIFICANCE STATEMENT Hippocampal single-unit activity is strongly shaped by behavioral brain state, yet this relationship has been largely ignored when studying activity dynamics before spontaneous seizures in medial temporal lobe epilepsy. In light of the increased attention on using single-unit activity for the prediction of seizure onset and closed-loop seizure intervention, we show a need for monitoring brain state to interpret correctly whether changes in neural activity before seizure onset is pathological or normal. Moreover, we also find that the brain state preceding a seizure determines the success of therapeutic interventions to curtail seizure duration. Together, these findings suggest that seizure prediction and intervention will be more successful if tailored for the specific brain states from which seizures emerge. PMID:26609157

Retinal Atherosclerosis, Ophthalmologically Reported and Documented with OSA in 1987, is now Totally Reversed, and Recorded, Photographically. The Supposition then was that Equivalent Cortical Damage could Respond to the same Healing Protocol.

NASA Astrophysics Data System (ADS)

Niemi, Paul N.; O., D.; Mc Leod, David M.; Mc Leod, Roger D.

2007-10-01

Documented retinal atherosclerosis, ``silver streaking'' of retinal capillaries, was reported and documented with OSA, in October 1987. That retinal damage, despite claims it usually progresses and is nonreversible, is now completely cleared. The original OSA presentation proposed that equivalent cortical damage was probably present throughout the brain at that time, as attested by failing short-term memory performance and transient ischemic attacks, TIAs, brief vision strokes. The supposition then was that ophthalmologic access to the retina, by some accounts the progenitor of all brain evolution, could provide a means of monitoring the actual circulatory state of inaccessible parts of the brain. To the extent that retinal health was naturopathically restored, and memory performance seems also to have significantly kept pace, is it a tenable premise that such protocols have rather general importance? Can applied optics help establish more appropriate diagnoses, and evaluate treatments for dementia and Alzheimer's disease?

Right hemisphere specialization for the identification of emotional words and sentences: evidence from stroke patients.

PubMed

Borod, J C; Andelman, F; Obler, L K; Tweedy, J R; Welkowitz, J

1992-09-01

This study examines the contribution of the lexical/verbal channel to emotional processing in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD) and 16 normal control (NC) right-handed adults. Emotional lexical perception tasks were developed; analogous nonemotional tasks were created to control for cognitive and linguistic factors. The three subject groups were matched for gender, age and education. The brain-damaged groups were similar with respect to cerebrovascular etiology, months post-onset, sensory-motor status and lesion location. Parallel emotional and nonemotional tasks included word identification, sentence identification and word discrimination. For both word tasks, RBDs were significantly more impaired than LBDs and NCs in the emotional condition. For all three tasks, RBDs showed a significantly greater performance discrepancy between emotional and nonemotional conditions than did LBDs or NCs. Results were not affected by the valence (i.e. positive/negative) of the stimuli. These findings suggest a dominant role for the right hemisphere in the perception of lexically-based emotional stimuli.

The Sequelae of Acute Purulent Meningitis in Childhood

PubMed Central

Hutchison, Patricia A.; Kovacs, Michael C.

1963-01-01

Of a series of 122 children suffering from acute purulent meningitis at the Children's Hospital, Winnipeg, in the years 1952-56, 12 (9.8%) succumbed, all deaths occurring in those 12 months of age or less. Fortyone of the survivors were re-studied 2.5 to 7.5 years after their acute illness to assess the nature and incidence of sequelae, the relationship of sequelae to the severity of the acute illness, and the correlation between the various methods of identifying sequelae. Five children exhibited psychiatric evidence of organic brain damage; seven, neurological abnormality; 11, electroencephalographic abnormality. Three had defective intelligence and nine psychological test evidence of organic brain damage. Children with sequelae tended to have several abnormal test results, the total number with neuropsychiatric and/or psychological sequelae being 11 (26%). There was a positive correlation between the severity of the acute illness and the presence of neuropsychiatric sequelae; also between neuropsychiatric sequelae, defective intelligence and psychological evidence of brain damage. No correlation existed between the electroencephalographic abnormality and neuropsychiatric defect. PMID:13955939

A simple behavioral test for locomotor function after brain injury in mice.

PubMed

Tabuse, Masanao; Yaguchi, Masae; Ohta, Shigeki; Kawase, Takeshi; Toda, Masahiro

2010-11-01

To establish a simple and reliable test for assessing locomotor function in mice with brain injury, we developed a new method, the rotarod slip test, in which the number of slips of the paralytic hind limb from a rotarod is counted. Brain injuries of different severity were created in adult C57BL/6 mice, by inflicting 1-point, 2-point and 4-point cryo-injuries. These mice were subjected to the rotarod slip test, the accelerating rotarod test and the elevated body swing test (EBST). Histological analyses were performed to assess the severity of the brain damage. Significant and consistent correlations between test scores and severity were observed for the rotarod slip test and the EBST. Only the rotarod slip test detected the mild hindlimb paresis in the acute and sub-acute phase after injury. Our results suggest that the rotarod slip test is the most sensitive and reliable method for assessing locomotor function after brain damage in mice. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro, and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia.

PubMed

Chazalviel, Laurent; Haelewyn, Benoit; Degoulet, Mickael; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

2016-01-01

Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro , and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo . In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

PubMed

Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

2015-02-01

The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of GABAA receptor expression in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

DART Support for Hurricane Matthew

NASA Image and Video Library

2016-10-13

Members of the Disaster Assessment and Recovery Team (DART) work on flooring repairs to the Beach House at NASA’s Kennedy Space Center in Florida. The effort is part of the spaceport’s ongoing recovery from Hurricane Matthew, which passed to the east of Kennedy on Oct. 6 and 7, 2016. The center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected.

Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

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

Cakmak G.; Miller L.; Zorlu, F.

2012-03-03

Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{submore » 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.« less

The effects of Mucuna pruriens extract on histopathological and biochemical features in the rat model of ischemia.

PubMed

Nayak, Vanishri S; Kumar, Nitesh; D'Souza, Antony S; Nayak, Sunil S; Cheruku, Sri P; Pai, K Sreedhara Ranganath

2017-12-13

Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease. Although this plant has different pharmacological actions, its neuroprotective activity has received minimal attention. Thus, this study was carried out with the aim of evaluating the neuroprotective action of M. pruriens in bilateral carotid artery occlusion-induced global cerebral ischemia in Wistar rats. The carotid arteries of both sides were occluded for 30 min and reperfused to induce global cerebral ischemia. The methanolic plant extract was administered to the study animals for 10 days. The brains of the Wistar rats were isolated by decapitation and observed for histopathological and biochemical changes. Cerebral ischemia resulted in significant neurological damage in the brains of the rats that were not treated by M. pruriens. The group subjected to treatment by the M. pruriens extract showed significant protection against brain damage compared with the negative control group, which indicates the therapeutic potential of this plant in ischemia.

[Impact of acquired brain injury towards the community integration: employment outcome, disability and dependence two years after injury].

PubMed

Luna-Lario, P; Ojeda, N; Tirapu-Ustarroz, J; Pena, J

2016-06-16

To analyze the impact of acquired brain injury towards the community integration (professional career, disability, and dependence) in a sample of people affected by vascular, traumatic and tumor etiology acquired brain damage, over a two year time period after the original injury, and also to examine what sociodemographic variables, premorbid and injury related clinical data can predict the level of the person's integration into the community. 106 adults sample suffering from acquired brain injury who were attended by the Neuropsychology and Neuropsychiatry Department at Hospital of Navarra (Spain) affected by memory deficit as their main sequel. Differences among groups have been analyzed by using t by Student, chi squared and U by Mann-Whitney tests. 19% and 29% of the participants who were actively working before the injury got back their previous status within one and two years time respectively. 45% of the total sample were recognized disabled and 17% dependant. No relationship between sociodemographic and clinical variables and functional parameters observed were found. Acquired brain damage presents a high intensity impact on affected person's life trajectory. Nevertheless, in Spain, its consequences at sociolaboral adjustment over the the two years following the damage through functional parameters analyzed with official governmental means over a vascular, traumatic and tumor etiology sample had never been studied before.

Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage.

PubMed

Yang, Lijun; Cui, Hong; Cao, Ting

2014-03-01

Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair. miRNA-9 is involved in the occurrence of many related neurological disorders. Bioinformatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups: control group; oxygen-glucose deprivation group (treatment with 8% O2 + 92% N2 and sugar-free medium for 60 minutes); transfection control group (after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid) and miRNA-9 transfection group (after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid). From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligodendrocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.

[Pharmacological study of nicergoline. (II). Protective effect on ischemic brain damages in animals].

PubMed

Shintomi, K; Itakura, T; Yoshimoto, K; Ogawa, Y; Fukushima, T; Matsuoka, Y

1986-04-01

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.

Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study.

PubMed

Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride

2012-04-15

Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

From the left to the right: How the brain compensates progressive loss of language function.

PubMed

Thiel, Alexander; Habedank, Birgit; Herholz, Karl; Kessler, Josef; Winhuisen, Lutz; Haupt, Walter F; Heiss, Wolf-Dieter

2006-07-01

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.

Dual-Polarimetric Radar-Based Tornado Debris Paths Associated with EF-4 and EF-5 Tornadoes over Northern Alabama During the Historic Outbreak of 27 April 2011

NASA Technical Reports Server (NTRS)

Carey, Lawrence D.; Schultz, Christopher J.; Schultz, Elise V.; Petersen, Walter A.; Gatlin, Patrick N.; Knupp, Kevin R.; Molthan, Andrew L.; Darden, Christopher B.

2011-01-01

An historic tornado and severe weather outbreak devastated much of the southeastern United States between 25 and 28 April 2011. On 27 April 2011, northern Alabama was particularly hard hit by a large number of tornadoes, including several that reached EF-4 and EF-5 on the Enhanced Fujita damage scale. In northern Alabama alone, there were approximately 100 fatalities and hundreds of more people who were injured or lost their homes during the havoc caused by these violent tornadic storms. Two long-track and violent (EF-4 and EF-5) tornadoes occurred within range of the University of Alabama in Huntsville (UAHuntsville) Advanced Radar for Meteorological and Operational Research (ARMOR, C-band dual-polarimetric). A unique capability of dual-polarimetric radar is the near-real time identification of lofted debris associated with ongoing tornadoes on the ground. The focus of this paper is to analyze the dual-polarimetric radar-inferred tornado debris signatures and identify the associated debris paths of the long-track EF-4 and EF-5 tornadoes near ARMOR. The relative locations of the debris and damage paths for each tornado will be ascertained by careful comparison of the ARMOR analysis with NASA MODIS (Moderate Resolution Imaging Spectroradiometer) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery of the tornado damage scenes and the National Weather Service tornado damage surveys. With the ongoing upgrade of the WSR-88D (Weather Surveillance Radar - 1988 Doppler) operational network to dual-polarimetry and a similar process having already taken place or ongoing for many private sector radars, dual-polarimetric radar signatures of tornado debris promise the potential to assist in the situational awareness of government and private sector forecasters and emergency managers during tornadic events. As such, a companion abstract (Schultz et al.) also submitted to this conference explores "The use of dual-polarimetric tornadic debris signatures in an operational setting."

Dual-Polarimetric Radar-Based Tornado Debris Paths Associated with EF-4 and EF-5 Tornadoes over Northern Alabama During the Historic Outbreak of 27 April 2011

NASA Technical Reports Server (NTRS)

Carey, Lawrence D.; Schultz, Chrstopher J.; Schultz, Elise V.; Petersen, Walter A.; Gatlin, Patrick N.; Knupp, Kevin R.; Molthan, Andrew L.; Jedlovec, Gary J.; Darden, Christopher B.

2012-01-01

An historic tornado and severe weather outbreak devastated much of the southeastern United States between 25 and 28 April 2011. On 27 April 2011, northern Alabama was particularly hard hit by a large number of tornadoes, including several that reached EF-4 and EF-5 on the Enhanced Fujita damage scale. In northern Alabama alone, there were approximately 100 fatalities and hundreds of more people who were injured or lost their homes during the havoc caused by these violent tornadic storms. Two long-track and violent (EF-4 and EF-5) tornadoes occurred within range of the University of Alabama in Huntsville (UAHuntsville) Advanced Radar for Meteorological and Operational Research (ARMOR, C-band dual-polarimetric). A unique capability of dual-polarimetric radar is the near-real time identification of lofted debris associated with ongoing tornadoes on the ground. The focus of this paper is to analyze the dual-polarimetric radar-inferred tornado debris signatures and identify the associated debris paths of the long-track EF-4 and EF-5 tornadoes near ARMOR. The relative locations of the debris and damage paths for each tornado will be ascertained by careful comparison of the ARMOR analysis with NASA MODIS (Moderate Resolution Imaging Spectroradiometer) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery of the tornado damage scenes and the National Weather Service tornado damage surveys. With the ongoing upgrade of the WSR-88D (Weather Surveillance Radar 1988 Doppler) operational network to dual-polarimetry and a similar process having already taken place or ongoing for many private sector radars, dual-polarimetric radar signatures of tornado debris promise the potential to assist in the situational awareness of government and private sector forecasters and emergency managers during tornadic events. As such, a companion abstract (Schultz et al.) also submitted to this conference explores The use of dual-polarimetric tornadic debris signatures in an operational setting.

A neuropsychological test of belief and doubt: damage to ventromedial prefrontal cortex increases credulity for misleading advertising.

PubMed

Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Cole, Catherine A; Denburg, Natalie L; Tranel, Daniel

2012-01-01

We have proposed the False Tagging Theory (FTT) as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) would cause a "doubt deficit" that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC damage were (1) more credulous to misleading ads; and (2) showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was "corrected" by a disclaimer. The evidence is consistent with our proposal that damage to the vmPFC disrupts a "false tagging mechanism" which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging) are exposed to persuasive information.

A Neuropsychological Test of Belief and Doubt: Damage to Ventromedial Prefrontal Cortex Increases Credulity for Misleading Advertising

PubMed Central

Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Cole, Catherine A.; Denburg, Natalie L.; Tranel, Daniel

2012-01-01

We have proposed the False Tagging Theory (FTT) as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) would cause a “doubt deficit” that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC damage were (1) more credulous to misleading ads; and (2) showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was “corrected” by a disclaimer. The evidence is consistent with our proposal that damage to the vmPFC disrupts a “false tagging mechanism” which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging) are exposed to persuasive information. PMID:22787439

Superficial white matter damage in anti-NMDA receptor encephalitis.

PubMed

Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

2018-05-01

Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neurophysiologic intraoperative monitoring of the vestibulocochlear nerve.

PubMed

Simon, Mirela V

2011-12-01

Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery.CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes.

[Organic brain damage in garage workers after long-term exposure to diesel exhaust fumes].

PubMed

Jensen, L K; Klausen, H; Elsnab, C

1989-09-04

Diesel motors are employed to an increasing extent for occupational transport and fumes from diesel driven vehicles constitute an increasing problem as regards atmospheric pollution but, in particular, they constitute a considerable risk to health for the workers exposed to diesel exhaust fumes in their daily work. In the clinic for occupational medicine, The University Hospital, Copenhagen, 14 garage workers were examined. Eleven of these had been exposed to great quantities of diesel exhaust fumes for 2 to 29 years. All 11 presented acute symptoms due to diesel exhaust fumes in the form of headache, vertigo, fatigue, irritation of mucous membranes, nausea, abdominal discomfort or diarrhoea. Seven persons had been employed for more than five years as garage workers. Six complained of failure of memory, difficulty in concentration, irritability, increased sleep requirement, psychological changes or reduced libido. Neuropsychological examination was undertaken in these six persons and in five of them organic brain damage, mainly of slight extent, was demonstrated. Diesel exhaust fumes contain many toxic substances: carbon monoxide, nitrous gases, sulphur oxides, aldehydes and hydrocarbons. It is not possible to indicate a single compound which is responsible for possible brain damage and a combination effect may well be concerned. This is a casuistic material. Only few investigations have previously been available which illustrated a possible connection between the neurotoxic effects and, in particular, brain damage. It is now considered important to emphasize that this may constitute a problem on exposure to diesel exhaust fumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease.

PubMed

Aliev, Gjumrakch; Palacios, Hector H; Walrafen, Brianna; Lipsitt, Amanda E; Obrenovich, Mark E; Morales, Ludis

2009-10-01

Alzheimer's disease (AD) and cerebrovascular accidents are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. In this regard, hypoperfusion appears to induce oxidative stress (OS), which is largely due to reactive oxygen species (ROS), and over time initiates mitochondrial failure which is known as an initiating factor of AD. Recent evidence indicates that chronic injury stimulus induces hypoperfusion seen in vulnerable brain regions. This reduced regional cerebral blood flow (CBF) then leads to energy failure within the vascular endothelium and associated brain parenchyma, manifested by damaged mitochondrial ultrastructure (the formation of large number of immature, electron-dense "hypoxic" mitochondria) and by overproduction of mitochondrial DNA (mtDNA) deletions. Additionally, these mitochondrial abnormalities co-exist with increased redox metal activity, lipid peroxidation, and RNA oxidation. Interestingly, vulnerable neurons and glial cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels, and, moreover, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We summarize the large body of evidence which indicates that sporadic, late-onset AD results from a vascular etiology by briefly reviewing mitochondrial damage and vascular risk factors associated with the disease and then we discuss the cerebral microvascular changes reason for the energy failure that occurs in normal aging and, to a much greater extent, AD.

Challenges of NDE simulation tool validation, optimization, and utilization for composites

NASA Astrophysics Data System (ADS)

Leckey, Cara A. C.; Seebo, Jeffrey P.; Juarez, Peter

2016-02-01

Rapid, realistic nondestructive evaluation (NDE) simulation tools can aid in inspection optimization and prediction of inspectability for advanced aerospace materials and designs. NDE simulation tools may someday aid in the design and certification of aerospace components; potentially shortening the time from material development to implementation by industry and government. Furthermore, ultrasound modeling and simulation are expected to play a significant future role in validating the capabilities and limitations of guided wave based structural health monitoring (SHM) systems. The current state-of-the-art in ultrasonic NDE/SHM simulation is still far from the goal of rapidly simulating damage detection techniques for large scale, complex geometry composite components/vehicles containing realistic damage types. Ongoing work at NASA Langley Research Center is focused on advanced ultrasonic simulation tool development. This paper discusses challenges of simulation tool validation, optimization, and utilization for composites. Ongoing simulation tool development work is described along with examples of simulation validation and optimization challenges that are more broadly applicable to all NDE simulation tools. The paper will also discuss examples of simulation tool utilization at NASA to develop new damage characterization methods for composites, and associated challenges in experimentally validating those methods.

Serogroup B Meningococcal vaccine (MenB) - What you need to know

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts. Serogroup B meningococcal (MenB) vaccines can help prevent meningococcal disease caused by serogroup ...

Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

2014-11-01

Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

Frontal white matter damage impairs response inhibition in children following traumatic brain injury.

PubMed

Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

2014-05-01

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.

Neuroprotective effects of tanshinone I from Danshen extract in a mouse model of hypoxia-ischemia

PubMed Central

Lee, Jae-Chul; Park, Joon Ha; Park, Ok Kyu; Kim, In Hye; Yan, Bing Chun; Ahn, Ji Hyeon; Kwon, Seung-Hae; Choi, Jung Hoon

2013-01-01

Hypoxia-ischemia leads to serious neuronal damage in some brain regions and is a strong risk factor for stroke. The aim of this study was to investigate the neuroprotective effect of tanshinone I (TsI) derived from Danshen (Radix Salvia miltiorrhiza root extract) against neuronal damage using a mouse model of cerebral hypoxia-ischemia. Brain infarction and neuronal damage were examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin histochemistry, and Fluoro-Jade B histofluorescence. Pre-treatment with TsI (10 mg/kg) was associated with a significant reduction in infarct volume 1 day after hypoxia-ischemia was induced. In addition, TsI protected against hypoxia-ischemia-induced neuronal death in the ipsilateral region. Our present findings suggest that TsI has strong potential for neuroprotection against hypoxic-ischemic damage. These results may be used in research into new anti-stroke medications. PMID:24179693

Ammonium Accumulation and Cell Death in a Rat 3D Brain Cell Model of Glutaric Aciduria Type I

PubMed Central

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I. PMID:23326493

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

PubMed

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

Effects of the Oral Ingestion of Probiotics on Brain Damage in a Transient Model of Focal Cerebral Ischemia in Mice

PubMed Central

Akhoundzadeh, Kobra; Vakili, Abedin; Shadnoush, Mahdi; Sadeghzadeh, Jafar

2018-01-01

Background: Probiotics are microorganisms that may influence brain function via altering brain neurochemistry. New research evidence suggests that probiotic bacteria might protect tissue damage through diminishing the production of free radicals and/or inflammatory cytokines. Therefore, this study was designed to evaluate the effects of probiotic bacteria on the prevention or reduction of brain damage in an experimental model of stroke in mice. Methods: In this study, 30 male BLC57 mice were randomly divided into 6 equal groups. Focal cerebral ischemia was induced via middle cerebral artery occlusion for 45 minutes, followed by 24 hours of reperfusion, in the mice. Probiotics at a concentration of 107 CFU/mL were administered by oral gavage daily for 14 days before ischemia. Infarct size, neurological outcome, and biochemical markers were measured 24 hours after brain ischemia. Statistical analysis were performed using the one-way ANOVA and/or Kruskal–Wallis ANOVA on rank by Sigma Stat (2.0; Jandel Scientific) software. Results: Our results indicated that pretreatment with probiotics significantly reduced infarct size by 52% (P=0.001) but could not improve neurological function (P=0.26). Moreover, the administration of probiotics significantly decreased the malondialdehyde content (P=0.001) and the tumor necrosis factor-alpha level (P=0.004) in the ischemic brain tissue. Conclusion: The findings of the present study showed that probiotic supplements might be useful in the prevention or attenuation of brain ischemic injury in patients at risk of stroke. Probiotics may open new therapeutic alternatives for the prevention of stroke. More preclinical and clinical studies are, however, needed to clarify their efficacy in cerebral stroke. PMID:29398750

Dynamical Signatures of Structural Connectivity Damage to a Model of the Brain Posed at Criticality.

PubMed

Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

2016-12-01

Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These interareal functional interactions develop in the background of a complex network of axonal connections linking cortical and subcortical neurons, termed the human "structural connectome." Theoretical considerations and experimental evidence support the view that the human brain can be modeled as a system operating at a critical point between ordered (subcritical) and disordered (supercritical) phases. Here, we explore the hypothesis that pathologies resulting from brain injury of different etiologies are related to this model of a critical brain. For this purpose, we investigate how damage to the integrity of the structural connectome impacts on the signatures of critical dynamics. Adopting a hybrid modeling approach combining an empirical weighted network of human structural connections with a conceptual model of critical dynamics, we show that lesions located at highly transited connections progressively displace the model toward the subcritical regime. The topological properties of the nodes and links are of less importance when considered independently of their weight in the network. We observe that damage to midline hubs such as the middle and posterior cingulate cortex is most crucial for the disruption of criticality in the model. However, a similar effect can be achieved by targeting less transited nodes and links whose connection weights add up to an equivalent amount. This implies that brain pathology does not necessarily arise due to insult targeted at well-connected areas and that intersubject variability could obscure lesions located at nonhub regions. Finally, we discuss the predictions of our model in the context of clinical studies of traumatic brain injury and neurodegenerative disorders.