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1

Edema and brain trauma  

Microsoft Academic Search

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury (TBI) as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries.Classically, two major types of traumatic brain edema exist: “vasogenic” due to blood–brain barrier (BBB) disruption resulting in extracellular water accumulation and “cytotoxic\\/cellular”

A. W. Unterberg; J. Stover; B. Kress; K. L. Kiening

2004-01-01

2

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats  

PubMed Central

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.

Odena, Gemma; Miquel, Mireia; Serafin, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartoli, Ramon

2012-01-01

3

Aquaporin4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke  

Microsoft Academic Search

Cerebral edema contributes significantly to morbidity and death associated with many common neurological disorders. However, current treatment options are limited to hyperosmolar agents and surgical decompression, therapies introduced more than 70 years ago. Here we show that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema

Miki Fujimura; Tonghui Ma; Nobuo Noshita; Ferda Filiz; Andrew W. Bollen; Pak Chan; A. S. Verkman; Geoffrey T. Manley

2000-01-01

4

Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria  

PubMed Central

Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP) increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5? diphosphate (2-MeSADP), an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y1R). At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP3)-dependent Ca2+ release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries.

Zheng, Wei; Watts, Lora Talley; Holstein, Deborah M.; Prajapati, Suresh I.; Keller, Charles; Grass, Eileen H.; Walter, Christi A.; Lechleiter, James D.

2010-01-01

5

Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.  

PubMed

Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. Peripheral leukocytes can infiltrate the injured brain, thereby aggravating BBB leakage and neuroinflammation. Thus, anti-inflammatory pharmacotherapies may ameliorate EBI and provide neuroprotection after SAH. Cannabinoid type 2 receptor (CB2R) agonism has been shown to reduce neuroinflammation; however, the precise protective mechanisms remain to be elucidated. This study aimed to evaluate whether the selective CB2R agonist, JWH133 can ameliorate EBI by reducing brain-infiltrated leukocytes after SAH. Adult male Sprague-Dawley rats were randomly assigned to the following groups: sham-operated, SAH with vehicle, SAH with JWH133 (1.0mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0mg/kg). SAH was induced by endovascular perforation, and JWH133 was administered 1h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24h after surgery. JWH133 improved neurological scores and reduced brain water content; however, SR144528 reversed these treatment effects. JWH133 reduced Evans blue dye extravasation after SAH. Furthermore, JWH133 treatment significantly increased TGF-?1 expression and prevented an SAH-induced increase in E-selectin and myeloperoxidase. Lastly, SAH resulted in a decreased expression of the tight junction protein zonula occludens-1 (ZO-1); however, JWH133 treatment increased the ZO-1 expression. We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-?1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH. PMID:24819918

Fujii, Mutsumi; Sherchan, Prativa; Krafft, Paul R; Rolland, William B; Soejima, Yoshiteru; Zhang, John H

2014-07-15

6

Inhibition of HIF prolyl-4-hydroxylases by FG-4497 Reduces Brain Tissue Injury and Edema Formation during Ischemic Stroke  

PubMed Central

Ischemic stroke results in disruption of the blood-brain barrier (BBB), edema formation and neuronal cell loss. Some neuroprotective factors such as vascular endothelial growth factor (VEGF) favor edema formation, while others such as erythropoietin (Epo) can mitigate it. Both factors are controlled by hypoxia inducible transcription factors (HIF) and the activity of prolyl hydroxylase domain proteins (PHD). We hypothesize that activation of the adaptive hypoxic response by inhibition of PHD results in neuroprotection and prevention of vascular leakage. Mice, subjected to cerebral ischemia, were pre- or post-treated with the novel PHD inhibitor FG-4497. Inhibition of PHD activity resulted in HIF-1? stabilization, increased expression of VEGF and Epo, improved outcome from ischemic stroke and reduced edema formation by maintaining BBB integrity. Additional in vitro studies using brain endothelial cells and primary astrocytes confirmed that FG-4497 induces the HIF signaling pathway, leading to increased VEGF and Epo expression. In an in vitro ischemia model, using combined oxygen and glucose deprivation, FG-4497 promoted the survival of neurons. Furthermore, FG-4497 prevented the ischemia-induced rearrangement and gap formation of the tight junction proteins zonula occludens 1 and occludin, both in cultured endothelial cells and in infarcted brain tissue in vivo. These results indicate that FG-4497 has the potential to prevent cerebral ischemic damage by neuroprotection and prevention of vascular leakage.

Reischl, Stefan; Li, Lexiao; Walkinshaw, Gail; Flippin, Lee A.; Marti, Hugo H.; Kunze, Reiner

2014-01-01

7

Treatment with the NK1 Antagonist Emend Reduces Blood Brain Barrier Dysfunction and Edema Formation in an Experimental Model of Brain Tumors  

PubMed Central

The neuropeptide substance P (SP) has been implicated in the disruption of the blood-brain barrier (BBB) and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg), dexamethasone (8 mg/kg) or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05). Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants further investigation as a potential anti-edematous treatment.

Harford-Wright, Elizabeth; Lewis, Kate M.; Ghabriel, Mounir N.; Vink, Robert

2014-01-01

8

[Pharmacological correction of traumatic brain edema].  

PubMed

Experiments on rats were made to study the action of the derivatives of benzodiazepine (diazepam, 0.5 mg/kg and phenazepam, 0.1 mg/kg), and GABA (phenibut, 50 mg/kg, pantogam, 160 mg/kg, nicotinoyl-GABA, 500 mg/kg, piracetam, 1000 mg/kg) on the development of a traumatic brain edema. Diazepam, phenazepam and phenibut were demonstrated to produce a marked antiedematous action. The drugs made water content in the brain return to normal and reduced marked biochemical alterations in the brain. It is suggested that the protective action of the drug under study on the development of brain edema is linked with the action on the mediator structures and brain tissue metabolism. PMID:6142833

Novikov, V E; Iasnetsov, V S

1984-01-01

9

Estradiol reduces activity of the blood–brain barrier Na–K–Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion  

Microsoft Academic Search

Estrogen has been shown to protect against stroke-induced brain damage, yet the mechanism is unknown. During the early hours of stroke, cerebral edema forms as increased transport of Na and Cl from blood into brain occurs across an intact blood–brain barrier (BBB). We showed previously that a luminal BBB Na–K–Cl cotransporter is stimulated by hypoxia and arginine vasopressin (AVP), factors

Martha E O'Donnell; Tina I Lam; Lien Q Tran; Shahin Foroutan; Steven E Anderson; ME O'Donnell

2006-01-01

10

Effect of ifenprodil, a polyamine site NMDA receptor antagonist, on brain edema formation following asphyxial cardiac arrest in rats  

Microsoft Academic Search

Objective: Brain edema occurs in experimental and clinical cardiac arrest (CA) and is predictive of a poor neurological outcome. N-Methyl-d-aspartate (NMDA) receptors contribute to brain edema elicited by focal cerebral ischemia\\/reperfusion (I\\/R). Ifenprodil, a NMDA receptor antagonist, attenuates brain edema and injury size in rats after focal cerebral I\\/R. We assessed the hypothesis that ifenprodil reduces CA-elicited brain edema. Methods:

Feng Xiao; Sibile Pardue; Thomas Arnold; Donna Carden; J. Steven Alexander; Jared Monroe; Christopher D Sharp; Richard Turnage; Steven Conrad

2004-01-01

11

Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.  

PubMed Central

The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia. Images

Patt, A; Harken, A H; Burton, L K; Rodell, T C; Piermattei, D; Schorr, W J; Parker, N B; Berger, E M; Horesh, I R; Terada, L S

1988-01-01

12

Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.  

PubMed

Abstract Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48?h of reperfusion. The effects of rapamycin (250??g/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin. PMID:24773551

Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

2014-06-01

13

RNase therapy assessed by magnetic resonance imaging reduces cerebral edema and infarction size in acute stroke.  

PubMed

Ischemic stroke causes cell necrosis with the exposure of extracellular ribonucleic acid (RNA) and other intracellular material. As shown recently, extracellular RNA impaired the blood-brain-barrier and contributed to vasogenic edema-formation. Application of ribonuclease 1 (RNase 1) diminished edema-formation and also reduced lesion volume in experimental stroke. Here we investigate whether reduction of lesion volume is due to the reduction of edema or of other neuroprotective means. Neuroprotective and edema protective effects of RNase 1 pretreatment were assessed using a temporary middle cerebral artery occlusion (MCAO) model in rats. Lesion volume was assessed on magnetic resonance imaging (MRI). T2-relaxation-time and midline-shift as well as brain water content (wet-dry-method) were measured to quantify edema formation. The impact of edema formation on infarct volume was evaluated in craniectomized animals. Exogenous RNase 1 was well tolerated and reduced edema-formation and infarct size (26.7% +/- 10.7% vs. 41.0% +/- 10.3%; p<0.01) at an optimal dose of 42 microg/kg as compared to placebo. Craniectomized animals displayed a comparable edema reduction but no reduction in infarct size. The present study introduces a hitherto unrecognized mechanism of ischemic brain damage and a novel neuroprotective approach towards acute stroke treatment. PMID:19355922

Walberer, Maureen; Tschernatsch, Marlene; Fischer, Silvia; Ritschel, Nouha; Volk, Kai; Friedrich, Carolin; Bachmann, Georg; Mueller, Clemens; Kaps, Manfred; Nedelmann, Max; Blaes, Franz; Preissner, Klaus T; Gerriets, Tibo

2009-02-01

14

Treatment of Brain Edema in Acute Liver Failure  

Microsoft Academic Search

Opinion statement  Cerebral edema is very common in patients with acute liver failure and encephalopathy. In severe cases, it produces brain\\u000a tissue shift and potentially fatal herniation. Brain swelling in acute liver failure is produced by a combination of cytotoxic\\u000a (cellular) and vasogenic edema. Accumulation of ammonia and glutamine leads to disturbances in the regulation of cerebral\\u000a osmolytes, increased free radical

Alejandro A. Rabinstein

2010-01-01

15

Pentoxifylline attenuates TNF-? protein levels and brain edema following temporary focal cerebral ischemia in rats.  

PubMed

Cerebral edema is the most common cause of neurological deterioration and mortality during acute ischemic stroke. Despite the clinical importance of cerebral ischemia, the underlying mechanisms remain poorly understood. Recent studies suggest a role for TNF-? in the brain edema formation. To further investigate whether TNF-? would play a role in brain edema formation, we examined the effects of pentoxifylline (PTX, an inhibitor of TNF-? synthesis) on the brain edema and TNF-? levels in a model of transient focal cerebral ischemia. The right middle cerebral artery (MCA) of rats was occluded for 60 min using the intraluminal filament method. The animals received PTX (60 mg/kg) immediately, 1, 3, or 6h post-ischemic induction. Twenty-four hours after induction of ischemic injury, permeability of the blood-brain barrier (BBB) and brain edema were determined by in situ brain perfusion of Evans Blue (EB) and wet-to-dry weight ratio, respectively. TNF-? protein levels in ischemic cortex were also measured at 1, 4, and 24h after the beginning of an ischemic stroke by using an enzyme-linked immunosorbent assay method. The administration of PTX up to 6h after occlusion of the MCA significantly reduced the brain edema. Moreover, PTX significantly reduced the concentration of TNF-? in ischemic brain cortex up to 4h post-transient focal stroke (P<0.002). Finally, treatment by PTX led to a significant decrease in EB extravasations (P<0.001). Our data demonstrate that PTX administration up to 6h after ischemia can reduce brain edema in a model of transient focal cerebral ischemia. The beneficial effects of PTX may be mediated, at least in part, through a decline in TNF-? production and BBB breakdown. PMID:21219888

Vakili, Abedin; Mojarrad, Somye; Akhavan, Maziar Mohammad; Rashidy-Pour, Ali

2011-03-01

16

Evaluation of brain edema using magnetic resonance proton relaxation times  

SciTech Connect

Experimental and clinical studies on the evaluation of water content in cases of brain edema were performed in vivo, using MR proton relaxation times (longitudinal relaxation time, T1; transverse relaxation time, T2). Brain edema was produced in the white matter of cats by the direct infusion method. The correlations between proton relaxation times obtained from MR images and the water content of white matter were studied both in autoserum-infused cats and in saline-infused cats. The correlations between T1 as well as T2 and the water content in human vasogenic brain edema were also examined and compared with the data obtained from the serum group. T1 and T2 showed good correlations with the water content of white matter not only in the experimental animals but also in the clinical cases. The quality of the edema fluid did not influence relaxation time and T1 seemed to represent almost solely the water content of the tissue. T2, however, was affected by the nature of existence of water and was more sensitive than T1 in detecting extravasated edema fluid. It seems feasible therefore to evaluate the water content of brain edema on the basis of T1 values.

Fu, Y.; Tanaka, K.; Nishimura, S. (Baba Memorial Hospital, Osaka (Japan))

1990-01-01

17

Effects of Chloride Flux Modulators in an in Vitro-model of Brain Edema Formation  

PubMed Central

Brain edema is a serious consequence of hemispheric stroke and traumatic brain injury and contributes significantly to patient mortality. In the present study, we measured water contents in hippocampal slices as an in vitro-model of edema formation. Excitotoxic conditions induced by N-methyl-d-aspartate (NMDA, 300 ?M), as well as ischemia induced by oxygen-glucose deprivation (OGD) caused cellular edema formation as indicated by an increase of slice water contents. In the presence of furosemide, an inhibitor of the Na,K,Cl-cotransporter, NMDA-induced edema were reduced by 64% while OGD-induced edema were unaffected. The same observation, i.e. reduction of excitotoxic edema formation but no effect on ischemia-induced edema, was made with chloride transport inhibitors such as DIDS and niflumic acid. Under ischemic conditions, modulation of GABAA receptors by bicuculline, a GABA antagonist, or by diazepam, a GABAergic agonist, did not significantly affect edema formation. Further experiments demonstrated that low chloride conditions prevented NMDA-induced, but not OGD-induced water influx. Omission of calcium ions had no effect. Our results show that NMDA-induced edema formation is highly dependent on chloride influx as it was prevented by low-chloride conditions and by various compounds that interfere with chloride influx. In contrast, OGD-induced edema observed in brain slices were not affected by modulators of chloride fluxes. The results are discussed with reference to ionic changes occurring during tissue ischemia. Section: Neurophysiology, Neuropharmacology and other forms of Intercellular Communication.

Kumar, Vikas; Naik, Runa S.; Hillert, Markus; Klein, Jochen

2006-01-01

18

Brain edema and protein expression of c-Fos and c-Jun in the brain after diffused brain injury  

PubMed Central

Objective: To investigate brain edema and protein expression of c-Fos and c-Jun in brain after diffuse brain injury, and to investigate the pathological change after brain injury, which may provide evidence for the clinical treatment of diffused brain injury. Methods: Marmarou method was used to establish the diffuse brain injury in rats. Results: After diffused brain injury, brain water content increased at 1 h, reached the peak at 1 d and remained at a high level at 7 d when compared with control group. One day after injury, diffuse subarachnoid hemorrhage was observed in the brain. HE staining showed vascular swelling and bleeding at the cortex and corpus callosum at 1 d. ?-APP expression was found at the brainstem, hippocampus, thalamus, corpus callosum and periventricular regions. Pathological examination of ultrathin sections showed evidence edema and fracture of axons at 3 d after brain injury. The brain injury caused severe cerebral ischemia. The c-Fos and c-Jun expression increased at 1 h. The c-Fos expression peaked at 3 h (P < 0.05), then reduced, reached a maximal level again at 3 d (P < 0.05), and reduced significantly at 7 d but remained at a higher level when compared with control group (P < 0.05). The number of c-Jun positive cells peaked at 6 h (P < 0.05), then reduced, reached a maximal level again at 3 d and reduced markedly but still remained at a higher level when compared with control group (P < 0.05). Conclusion: After diffuse brain injury, brain water content and c-Fos/c-Jun expression change over time.

Zheng, Wei; Niu, Lijian; Zhang, Chunpu; Zhu, Chao; Xie, Fangmin; Cao, Chunguang; Li, Gang

2014-01-01

19

The pathophysiology of brain edema in acute liver failure  

Microsoft Academic Search

Brain edema leading to intracranial hypertension is a cause of death in acute liver failure (ALF). The pathogenesis of this unique complication has been investigated in man, in experimental models and in isolated cell systems. From this experience, an integrated view has emerged, pointing at several mechanisms that contribute to cerebral swelling; an osmotic derangement in astrocytes, changes in cellular

Andres T. Blei

2005-01-01

20

The Effect of Dexmedetomidine on Brain Edema and Neurological Outcomes in Surgical Brain Injury in Rats  

PubMed Central

Background Surgical brain injury (SBI) is damage to functional brain tissue resulting from neurosurgical manipulations such as sharp dissection, electrocautery, retraction, and direct applied pressure. Brain edema is the major contributor to morbidity with inflammation, necrosis, oxidative stress and apoptosis likely playing smaller roles. Effective therapies for SBI may improve neurological outcomes and postoperative morbidities associated with brain surgery. Previous studies show an adrenergic correlation to blood-brain barrier control. The alpha-2 receptor agonist dexmedetomidine (DEX) has been shown to improve neurological outcomes in stroke models. We hypothesized that DEX may reduce brain edema and improve neurological outcomes in a rat model of SBI. Methods Male Sprague-Dawley rats (n=63) weighing 280–350g were randomly assigned to one of four intraperitoneal (IP) treatment groups: sham IP, vehicle IP, DEX 10 mg/kg, and DEX 30 mg/kg. Treatments were given 30 minutes before SBI. These treatment groups were repeated to observe the physiologic impact of DEX on mean arterial blood pressure (MAP), heart rate (HR), and blood glucose on SBI naïve animals. Rats were also assigned to four postinjury IV treatment groups: sham IV, vehicle IV, DEX 10/5, and DEX 30/15 (DEX group doses were 10 and 30 mg/kg/hr, with 5 and 15 mg/kg initial loading doses respectively). Initial loading doses began 20 minutes after SBI, followed by 2 hours of infusion. SBI animals were subjected to neurological testing 24 hours after brain injury by a blinded observer, promptly killed, and brain water content measured via the dry/wet weight method. Results All treatment groups showed a significant difference in ipsilateral frontal brain water content and neurological scores when compared with sham animals. However, there was no difference between DEX-treated and vehicle animals. Physiologic monitoring showed treatment with low or high doses of DEX significantly decreased MAP and HR, and briefly increased blood glucose compared with naïve or vehicle-treated animals. Conclusions DEX administration did not reduce brain edema or improve neurological function after SBI in this study. The statistical difference in brain water content and neurological scores when comparing sham treatment to vehicle and DEX treatments shows consistent reproduction of this model. Significant changes in MAP, HR, and blood glucose after DEX as compared to vehicle and sham treatments suggest appropriate delivery of drug.

Benggon, Michael; Chen, Han; Applegate, Richard; Martin, Robert; Zhang, John H.

2012-01-01

21

Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema  

Microsoft Academic Search

\\u000a Background Currently, there are no pharmacological treatments available for traumatically induced brain edema and the subsequent rise\\u000a of ICP. Evidence indicates that Aqua-porin-4 (AQP4) plays a significant role in the pathophys-iology of brain edema. Previously\\u000a we have reported that SR49059 reduced brain edema secondary to ischemia. We, therefore, examined whether the selective V1a\\u000a receptor antagonist, SR49059, reduces brain edema by

Keisuke Taya; Salih Gulsen; Kenji Okuno; Ruth Prieto; Christina R. Marmarou; Anthony Marmarou

22

Role of bradykinin B2 receptors in the formation of vasogenic brain edema in rats.  

PubMed

Bradykinin is a mediator of brain edema acting through B2 receptors. However, it is not known if bradykinin mediates the formation of cytotoxic or vasogenic brain swelling. To investigate this question we subjected rats to a cryogenic brain lesion over the left parietal cortex, a model well known to produce predominantly vasogenic brain edema. We inhibited bradykinin B2 receptors with the recently characterized nonpeptide B2 receptor antagonist, LF 16-0687. The animals were assigned to three groups (n = 10, each) receiving 10, or 100 microg/kg/min LF 16-0687 or vehicle (0.9% NaCl). Treatment started 15 min before trauma and was continued for 24 h. Another three groups of animals (n = 10, each) received 10 microg/kg/min LF 16-0687 starting 30 or 60 min after trauma or vehicle (0.9% NaCl) for 24 h. Animals were then sacrificed and swelling and water content of the brain were determined. In the vehicle treated group the traumatized hemisphere swelled by 9.3 +/- 1.1% as compared to the untraumatized contralateral side. Pretreatment with 10 microg/kg/min LF 16-0687 decreased brain swelling significantly to 6.4 +/- 1.3% (p < 0.05). Pre-treatment with 100 microg/kg/min was found to be less effective and did not result in a significant reduction of brain swelling (7.4 + 1.3%). Treatment with LF 16-0687 for 24 h (10 microg/kg/min) started 30 or 60 min after trauma did not reduce brain water content or hemispheric swelling. These results demonstrate that brain injury-mediated bradykinin production induces vasogenic brain edema by B2 receptor stimulation. Our findings further clarify the role of bradykinin in the pathophysiology of brain edema formation and confirm the therapeutic potency of bradykinin B2 receptor inhibition. PMID:11686492

Plesnila, N; Schulz, J; Stoffel, M; Eriskat, J; Pruneau, D; Baethmann, A

2001-10-01

23

Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats.  

PubMed

Steroids reduce permeability of the blood-brain barrier and inhibit active sodium transport by brain capillaries in vitro. Since the rate of edema formation during the early stages of ischemia is related to the rate of sodium transport from blood to brain, this study was designed to determine whether steroids reduce ischemic edema formation by inhibiting blood-brain barrier sodium transport. Dexamethasone was compared with progesterone since the latter is a more potent inhibitor of sodium transport in isolated capillaries. Sprague-Dawley rats were treated with vehicle (n = 22) or 2 mg/kg of either dexamethasone (n = 22) or progesterone (n = 17) 1 hour before occlusion of the middle cerebral artery. After 4 hours of ischemia, brain water content and blood-brain barrier permeability to [3H] alpha-aminoisobutyric acid and sodium-22 were determined. In controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 82.4 +/- 0.2%. Brain edema was significantly reduced following pretreatment with either dexamethasone (80.6 +/- 0.1%, p less than 0.001) or progesterone (81.5 +/- 0.3%, p less than 0.05). There was also a significant reduction in blood-brain barrier permeability to alpha-aminoisobutyric acid in normal brain following either treatment (e.g., 2.21 +/- 0.19 and 1.37 +/- 0.10 microliters/g/min, p less than 0.001, for control and dexamethasone treatments, respectively), but no effect on the permeability to sodium (e.g., 1.19 +/- 0.05 and 1.12 +/- 0.11 microliters/g/min for control and dexamethasone treatments, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2389301

Betz, A L; Coester, H C

1990-08-01

24

Proton-nuclear magnetic resonance relaxation times in brain edema  

SciTech Connect

Proton relaxation times of protein solutions, bovine brain, and edematous feline brain tissue were studied as a function of water concentration, protein concentration, and temperature. In accordance with the fast proton exchange model for relaxation, a linear relation could be established between R1 and the inverse of the weight fraction of tissue water. This relation also applied to R2 of gray matter and of protein solutions. No straightforward relation with water content was found for R2 of white matter. Temperature-dependent studies indicated that in this case, the slow exchange model for relaxation had to be applied. The effect of macromolecules in physiological relevant concentrations on the total relaxation behavior of edematous tissue was weak. Total water content changes predominantly affected the relaxation rates. The linear relation may have high clinical potential for assessment of the status of cerebral edema on the basis of T1 and T2 readings from MR images.

Kamman, R.L.; Go, K.G.; Berendsen, H.J. (Univ. of Groningen (Netherland))

1990-01-01

25

Treatment strategy for metastatic brain tumors from renal cell carcinoma: selection of gamma knife surgery or craniotomy for control of growth and peritumoral edema.  

PubMed

We retrospectively studied the efficacy of gamma knife surgery (GKS) for metastatic brain tumors from renal cell carcinoma (RCC). To evaluate the efficacy of GKS for control of peritumoral edema, we retrospectively studied 280 consecutive metastatic brain tumors (100 from lung cancers, 100 from breast cancers, and 80 from RCC) associated with peritumoral edema. In addition, this study included 11 patients with metastatic brain tumors from RCC who underwent direct surgery. The tumor growth control rate of GKS was 84.3%. The extent of edema of RCC metastases was significantly larger than those from lung and breast cancer. Primary site (renal or not renal) and delivered marginal dose (25 Gy or more) were significantly correlated with control of peritumoral edema. All tumors treated by direct surgery were more than 2 cm in maximum diameter. Peritumoral edema at surgery was extensive but disappeared within 1-3 months, and neurological symptoms also improved in many cases. Total removal of brain metastases from RCC was easy with little bleeding in most cases. Our results suggest that GKS is effective for growth control of metastatic brain tumors from RCC. Higher marginal dose such as 25 Gy or more is desirable to obtain peritumoral edema control, so GKS is not suitable for control of symptomatic peritumoral edema associated with relatively large tumors. Tumor removal of RCC metastases is relatively easy and rapidly reduces peritumoral edema. Treatment strategy for metastatic brain tumors from RCC depends on tumor size, number of tumors, and presence of symptomatic peritumoral edema. PMID:20405309

Shuto, Takashi; Matsunaga, Shigeo; Suenaga, Jun; Inomori, Shigeo; Fujino, Hideyo

2010-06-01

26

Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?  

PubMed Central

Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 minute post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1?, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1?-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of NF?B. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically-achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.

Laird, Melissa D.; SR, Sangeetha; Swift, Andrew E.B.; Meiler, Steffen E.; Vender, John R.; Dhandapani, Krishnan M.

2010-01-01

27

Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia  

PubMed Central

Background Although agmatine therapy in a mouse model of transient focal cerebral ischemia is highly protective against neurological injury, the mechanisms underlying the protective effects of agmatine are not fully elucidated. This study aimed to investigate the effects of agmatine on brain apoptosis, astrogliosis and edema in the rats with transient cerebral ischemia. Methods Following surgical induction of middle cerebral artery occlusion (MCAO) for 90 min, agmatine (100 mg/kg, i.p.) was injected 5 min after beginning of reperfusion and again once daily for the next 3 post-operative days. Four days after reperfusion, both motor and proprioception functions were assessed and then all rats were sacrificed for determination of brain infarct volume (2, 3, 5-triphenyltetrazolium chloride staining), apoptosis (TUNEL staining), edema (both cerebral water content and amounts of aquaporin-4 positive cells), gliosis (glial fibrillary acidic protein [GFAP]-positive cells), and neurotoxicity (inducible nitric oxide synthase [iNOS] expression). Results The results showed that agmatine treatment was found to accelerate recovery of motor (from 55 degrees to 62 degrees) and proprioception (from 54% maximal possible effect to 10% maximal possible effect) deficits and to prevent brain infarction (from 370 mm3 to 50 mm3), gliosis (from 80 GFAP-positive cells to 30 GFAP-positive cells), edema (cerebral water contents decreased from 82.5% to 79.4%; AQP4 positive cells decreased from 140 to 84 per section), apoptosis (neuronal apoptotic cells decreased from 100 to 20 per section), and neurotoxicity (iNOS expression cells decreased from 64 to 7 per section) during MCAO ischemic injury in rats. Conclusions The data suggest that agmatine may improve outcomes of transient cerebral ischemia in rats by reducing brain apoptosis, astrogliosis and edema.

2010-01-01

28

Brain edema development after MRI-guided focused ultrasound treatment.  

PubMed

The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4+/-.3 mm2, and for the bright hyperintensity surrounding the lesion, it was 2.3+/-.6 mm2 (n = 7). In the coronal plane, the corresponding values were .4+/-.1 mm2 and 3.4+/-.9 mm2 (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury. PMID:9500273

Mórocz, I A; Hynynen, K; Gudbjartsson, H; Peled, S; Colucci, V; Jólesz, F A

1998-01-01

29

Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema  

PubMed Central

Intracerebral hemorrhage (ICH) can cause secondary brain damage through inflammation-related pathways. Thrombin and one of its receptors, protease activated receptor-1 (PAR-1); matrix metalloproteinase (MMP)-9; and aquaporin (AQP)-4 are stroke-related inflammatory mediators that have been implicated in ICH pathology. To further characterize the inflammatory response after ICH, we studied the temporal profile of the expression of these inflammatory mediators and assessed their potential correlation with brain edema formation after brain hemorrhage in rats. ICH was modeled by infusing autologous blood into the striatum. Then mRNA and protein expression was assessed over the course of 5 days. We found that the mRNA and/or protein expression of thrombin, PAR-1, AQP-4, and MMP-9 was upregulated between 2 h and 5 days after ICH. Each reached a maximal level at day 2, except for AQP-4 protein, which peaked at day 5. Brain water content after ICH presented a similar trend; it was increased at 2 h, peaked at day 2, and then decreased but remained elevated at day 5. Our data provide novel evidence that upregulation of these selected inflammatory mediators occurs very early and persists for several days after ICH, and that temporal patterns of expression of thrombin and AQP-4 are associated with brain edema formation. These findings have important implications for efforts to reduce secondary brain damage after ICH.

Wu, He; Zhang, Zhiyi; Li, Ying; Zhao, Ruibo; Li, Heng; Song, Yuejia; Qi, Jiping; Wang, Jian

2010-01-01

30

Poly(ADP-ribose) polymerase activation and brain edema formation by hemoglobin after intracerebral hemorrhage in rats  

Microsoft Academic Search

Brain edema induced by intracerebral hemorrhage (ICH) is a serious problem in the treatment of ICH. However, the mechanisms\\u000a of brain edema formation following ICH are not well-understood. We have found that hemoglobin plays an important role in edema\\u000a development after ICH. In this study, we sought to explore the mechanism of brain edema formation caused by hemoglobin.\\u000a \\u000a Hemoglobin was

X. Bao; G. Wu; S. Hu; F. Huang

31

Influence of thermal stress and various agents on the brain edema formation in rats following a cryogenic brain lesion.  

PubMed

The influence of cold stress, heat stress, or various agents on the development of brain edema were assessed in rats following a cryogenic brain lesion. Brain edema was induced by local cold injury to the cortex. Cerebral edema was assessed 0.5, 3.0 or 24 h after a cryogenic brain lesion by measuring the water content of two hemispheres. Pretreatment of animals with sodium pentobarbital (15 or 30 mg/kg, i.p.) or lidocaine (15 mg/kg, i.p.) did not influence the development of brain edema. In addition, pretreatment with an external heat stress (heat exposure of 32 degrees C for 6 h) exaggerated significantly the development of brain edema in the rat following a cryogenic brain lesion. On the other hand, pretreatment of animals with either external cold stress (cold exposure of 8 degrees C for 6 h), glycerol (10% 10 ml, i.p.), mannitol (15% 10 ml, i.p.), gamma-hydroxybutyric acid (300 mg/kg, i.p.), metiamide (5 mg/kg, i.p.), dexamethasone (4 mg/kg, i.p.), aminophylline (100 mg/kg, i.p.), or ketamine (30 mg/kg, i.p.) inhibited significantly the brain edema formation. PMID:2517859

Lin, L S; Chiu, W T; Shih, C J; Lin, M T

1989-01-01

32

Effects of glucocorticoid and chemotherapy on the peritumoral edema and astrocytic reaction in experimental brain tumor  

Microsoft Academic Search

To study the effects of glucocorticoids and chemotherapeutic agents on the pathophysiology of the tumor-induced brain edema, the site of Evans blue-albumin extravasation, the distribution of extravasated serum albumin, and the extent of local astrocytic reaction were examined in a rat model of implanted brain tumor. Experimental brain tumors were produced by implanting small pellets of Walker 256 carcinosarcoma into

Jamshid Jamshidi; Toshiki Yoshimine; Yukitaka Ushio; Torn Hayakawa

1992-01-01

33

Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4  

PubMed Central

Vascular endothelial growth factor (VEGF) has protective effects on many neurological diseases. However, whether VEGF acts on brain edema following intracerebral hemorrhage (ICH) is largely unknown. Our previous study has shown aquaporin-4 (AQP4) plays an important role in brain edema elimination following ICH. Meanwhile, there is close relationship between VEGF and AQP4. In this study, we aimed to test effects of VEGF on brain edema following ICH and examine whether they were AQP4 dependent. Recombinant human VEGF165 (rhVEGF165) was injected intracerebroventricularly 1 d after ICH induced by microinjecting autologous whole blood into striatum. We detected perihemotomal AQP4 protein expression, then examined the effects of rhVEGF165 on perihemotomal brain edema at 1 d, 3 d, and 7 d after injection in wild type (AQP4+/+) and AQP4 knock-out (AQP4?/?) mice. Furthermore, we assessed the possible signal transduction pathways activated by VEGF to regulate AQP4 expression via astrocyte cultures. We found perihemotomal AQP4 protein expression was highly increased by rhVEGF165. RhVEGF165 alleviated perihemotomal brain edema in AQP4+/+ mice at each time point, but had no effect on AQP4?/? mice. Perihemotomal EB extravasation was increased by rhVEGF165 in AQP4?/? mice, but not AQP4+/+ mice. RhVEGF165 reduced neurological deficits and increased Nissl’s staining cells surrounding hemotoma in both types of mice and these effects were related to AQP4. RhVEGF165 up-regulated phospharylation of C-Jun amino-terminal kinase (p-JNK) and extracellular signal-regulated kinase (p-ERK) and AQP4 protein in cultured astrocytes. The latter was inhibited by JNK and ERK inhibitors. In conclusion, VEGF reduces neurological deficits, brain edema, and neuronal death surrounding hemotoma but has no influence on BBB permeability. These effects are closely related to AQP4 up-regulation, possibly through activating JNK and ERK pathways. The current study may present new insights to treatment of brain edema following ICH.

Dong, Qiang

2013-01-01

34

Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema  

NASA Astrophysics Data System (ADS)

The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (?s') and BWC. By recording ?s' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

Xie, J.; Qian, Z.; Yang, T.; Li, W.; Hu, G.

2011-01-01

35

Acute dimethyl sulfoxide therapy in brain edema. Part 3: effect of a 3-hour infusion.  

PubMed

Albino rabbits with experimental brain edema produced by a combined cryogenic left hemisphere lesion and metabolic 6-aminonicotinamide lesion were administered a 3-hour intravenous infusion of dimethyl sulfoxide (DMSO). Simultaneous recording of intracranial pressure (ICP), systolic arterial pressure (SAP), and central venous pressure (CVP) and electroencephalography were performed while the animals were being ventilated mechanically to produce a constant Pa CO2 value (38-42 torr). At the end of the infusion, the brain water and electrolyte contents were measured. There was a persistent and progressive reduction of ICP during the infusion, the nadir occurring at 3 hours (p less than 0.005 from zero time), with no change in SAP or CVP. There was a reduction of brain water in both hemispheres when compared to untreated controls, but this was significant for the right hemisphere only (p less than 0.005). There was a significant reduction of the brain sodium content for both hemispheres, but no significant change occurred in brain potassium content. The DMSO infusion was effective not only in reducing ICP, but also in sustaining this reduction for 3 hours. PMID:7057982

Del Bigio, M; James, H E; Camp, P E; Werner, R; Marshall, L F; Tung, H

1982-01-01

36

Biomechanics of brain edema and effects on local cerebral blood flow.  

PubMed

Brain edema represents a disturbance of the volume equilibrium which, in the early stages of formation, must be compensated for by a reduction in other fluid and blood compartments. When this compensation is inadequate, tissue pressure and intracranial pressure increase, the magnitude of which depends on the compliance of the tissue. Tissue pressure gradients develop within the same hemisphere and between hemispheres, but these pressure gradients are transient and dissipate within a few hours after injury. The rate of dissipation is proportional to the product of hydraulic tissue resistance and compliance. These tissue pressure gradients are small in magnitude, less than 15 mm Hg; however, studies with an infusion model of edema in animals show that they are more than sufficient to propel fluid through the parenchyma by a process of bulk flow. The distention caused by the fluid increases the conductance and compliance of the tissue. This biomechanical response favors the dissipation of pressure gradients, and as a result hydrostatic gradients can be sustained only with a continued leakage of fluid from the site of injury. Without a continued extravasation of fluid, equilibration of the tissue pressure to the level of the ICP occurs rapidly. For this reason, the role of hydrostatic gradients in the resorption process may be limited. The development of an infusion model allows more rigid control and simulates the edematous process. Ultrastructural studies of the infusion model have shown that the tissue changes are similar to those reported for vasogenic edema, with the exception that in the infusion model the blood-brain barrier remains intact in the vicinity of the lesion and is not compromised by the mechanical distention of the ECS. The response of the cerebrovasculature to the infusion edema is in contrast to the usual reduction of flow seen after cryogenic injury. The CBF remains constant despite increased tissue water, as confirmed by gravimetric technique. The CO2 reactivity of the vessels in the area of edema is reduced, but the autoregulation to changes in perfusion pressure remains intact. When arterial pressure is raised beyond the limit of autoregulation, the pressure increase of CBF in the edematous area is less than the rise of CBF in normal tissue and suggests a "false autoregulation" caused by an increased tissue pressure. The differences in both the intracranial pressure and CBF response between these two models suggests that other factors must be operative. The cryogenic injury is indeed a traumatic injury to the brain and cannot be simply characterized by the increase in brain tissue water. In some animals a vasomotor paralysis disrupting the vascular compartmental volume and leading to a rapid rise in ICP with eventual reduction of CPP and CBF may explain these differences. Release of vasoactive substances into the ECS is an exciting hypothesis and is an area of investigation ideally suited to the infusion edema process where chemical composition of the fluid can be easily controlled. PMID:7457251

Marmarou, A; Takagi, H; Shulman, K

1980-01-01

37

Intravenous Immunoglobulin Reduces Infarct Volume but Not Edema Formation in Acute Stroke  

Microsoft Academic Search

Objectives: Intravenous immunoglobulin (IVIG) is used for treatment of immunodeficiencies and autoimmune disorders. Recently, IVIG has also been shown to reduce infarct size in acute stroke. Since edema treatment can provide secondary neuroprotective effects, we conducted the present study to evaluate whether edema reduction is the underlying cause of the neuroprotective properties of IVIG in experimental stroke. Methods: Male Wistar

Maureen Walberer; Max Nedelmann; Nouha Ritschel; Clemens Mueller; Marlene Tschernatsch; Erwin Stolz; Georg Bachmann; Franz Blaes; Tibo Gerriets

2010-01-01

38

A comparative study of treatment for brain edema: magnesium sulphate versus dexamethasone sodium phosphate.  

PubMed

Treatments for brain edema are important and one of the major options is corticosteroids. Cell membrane stabilization and prevention of formation of free radicals are the main mechanisms of action of steroids in edema treatment. As an alternative therapeutic agent, magnesium sulphate has been used for its neuroprotective effect in various injury models. In our animal model of brain injury, cold has been used in Sprague-Dawley rats. After brain injury, magnesium sulphate (600 mg/kg) or dexamethasone sodium phosphate (0.2 mg/kg) were administered to experimental groups. The degree of brain edema and lipid peroxidation was evaluated using the wet-dry weight method, the determination of malondialdehyde (MDA) levels and an ultrastructural grading system. Magnesium sulphate treatment was found to be the most effective choice due to the absence of side effects and comparable efficacy to corticosteroids. PMID:18061457

Turkoglu, Omer Faruk; Eroglu, Hakan; Okutan, Ozerk; Tun, M Kagan; Bodur, Ebru; Sargon, Mustafa F; Oner, Levent; Beskonakli, Etem

2008-01-01

39

Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN  

Microsoft Academic Search

This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels.

Nandita Pradhan; A. K. Sinha

2008-01-01

40

Noninvasive quantification of brain edema and the space-occupying effect in rat stroke models using magnetic resonance imaging  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve

Tibo Gerriets; Erwin Stolz; Maureen Walberer; Clemens Muller; Alexander Kluge; A. Bachmann; Marc Fisher; Manfred Kaps; Georg Bachmann

2004-01-01

41

Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication  

Microsoft Academic Search

AIM: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen.

Camila Scorticati; Juan P. Prestifilippo; Francisco X. Eizayaga; José L. Castro; Salvador Romay; María A. Fernández; Abraham Lemberg; Juan C. Perazzo

2004-01-01

42

The Effects of Shilajit on Brain Edema, Intracranial Pressure and Neurologic Outcomes following the Traumatic Brain Injury in Rat.  

PubMed

Objective(s): Brain edema is one of the most serious causes of death within the first few days after trauma brain injury (TBI). In this study we have investigated the role of Shilajit on brain edema, blood-brain barrier (BBB) permeability, intracranial pressure (ICP) and neurologic outcomes following brain trauma. Materials and Methods: Diffuse traumatic brain trauma was induced in rats by drop of a 250 g weight from a 2 m high (Marmarou's methods). Animals were randomly divided into 5 groups including sham, TBI, TBI-vehicle, TBI-Shi150 group and TBI-Shi250 group. Rats were undergone intraperitoneal injection of Shilajit and vehicle at 1, 24, 48 and 72 hr after trauma. Brain water content, BBB permeability, ICP and neurologic outcomes were finally measured. Results: Brain water and Evans blue dye contents showed significant decrease in Shilajit-treated groups compared to the TBI-vehicle and TBI groups. Intracranial pressure at 24, 48 and 72 hr after trauma had significant reduction in Shilajit-treated groups as compared to TBI-vehicle and TBI groups (P<0.001). The rate of neurologic outcomes improvement at 4, 24, 48 and 72 hr after trauma showed significant increase in Shilajit-treated groups in comparison to theTBI- vehicle and TBI groups (P <0.001). Conclusion: The present results indicated that Shilajit may cause in improvement of neurologic outcomes through decreasing brain edema, disrupting of BBB, and ICP after the TBI. PMID:23997917

Khaksari, Mohammad; Mahmmodi, Reza; Shahrokhi, Nader; Shabani, Mohammad; Joukar, Siavash; Aqapour, Mobin

2013-07-01

43

The Effects of Shilajit on Brain Edema, Intracranial Pressure and Neurologic Outcomes following the Traumatic Brain Injury in Rat  

PubMed Central

Objective(s): Brain edema is one of the most serious causes of death within the first few days after trauma brain injury (TBI). In this study we have investigated the role of Shilajit on brain edema, blood-brain barrier (BBB) permeability, intracranial pressure (ICP) and neurologic outcomes following brain trauma. Materials and Methods: Diffuse traumatic brain trauma was induced in rats by drop of a 250 g weight from a 2 m high (Marmarou’s methods). Animals were randomly divided into 5 groups including sham, TBI, TBI-vehicle, TBI-Shi150 group and TBI-Shi250 group. Rats were undergone intraperitoneal injection of Shilajit and vehicle at 1, 24, 48 and 72 hr after trauma. Brain water content, BBB permeability, ICP and neurologic outcomes were finally measured. Results: Brain water and Evans blue dye contents showed significant decrease in Shilajit-treated groups compared to the TBI-vehicle and TBI groups. Intracranial pressure at 24, 48 and 72 hr after trauma had significant reduction in Shilajit-treated groups as compared to TBI-vehicle and TBI groups (P<0.001). The rate of neurologic outcomes improvement at 4, 24, 48 and 72 hr after trauma showed significant increase in Shilajit-treated groups in comparison to theTBI- vehicle and TBI groups (P <0.001). Conclusion: The present results indicated that Shilajit may cause in improvement of neurologic outcomes through decreasing brain edema, disrupting of BBB, and ICP after the TBI.

Khaksari, Mohammad; Mahmmodi, Reza; Shahrokhi, Nader; Shabani, Mohammad; Joukar, Siavash; Aqapour, Mobin

2013-01-01

44

Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke  

PubMed Central

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2012-01-01

45

Effect of Polyphenols on Oxidative Stress and Mitochondrial Dysfunction in Neuronal Death and Brain Edema in Cerebral Ischemia  

PubMed Central

Polyphenols are natural substances with variable phenolic structures and are elevated in vegetables, fruits, grains, bark, roots, tea, and wine. There are over 8000 polyphenolic structures identified in plants, but edible plants contain only several hundred polyphenolic structures. In addition to their well-known antioxidant effects, select polyphenols also have insulin-potentiating, anti-inflammatory, anti-carcinogenic, anti-viral, anti-ulcer, and anti-apoptotic properties. One important consequence of ischemia is neuronal death and oxidative stress plays a key role in neuronal viability. In addition, neuronal death may be initiated by the activation of mitochondria-associated cell death pathways. Another consequence of ischemia that is possibly mediated by oxidative stress and mitochondrial dysfunction is glial swelling, a component of cytotoxic brain edema. The purpose of this article is to review the current literature on the contribution of oxidative stress and mitochondrial dysfunction to neuronal death, cell swelling, and brain edema in ischemia. A review of currently known mechanisms underlying neuronal death and edema/cell swelling will be undertaken and the potential of dietary polyphenols to reduce such neural damage will be critically reviewed.

Panickar, Kiran S.; Anderson, Richard A.

2011-01-01

46

Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1? (IL-1?) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1? expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation. PMID:22815977

Kimbler, Donald E; Shields, Jessica; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

2012-01-01

47

Activation of P2X7 Promotes Cerebral Edema and Neurological Injury after Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7?/? mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1? (IL-1?) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1? expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

Kimbler, Donald E.; Shields, Jessica; Yanasak, Nathan; Vender, John R.; Dhandapani, Krishnan M.

2012-01-01

48

Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain  

PubMed Central

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

Liu, Huimin; Yan, Gen; Liu, Baoguo; Kong, Lingmei; Ding, Yan; Tan, Hui; Zhang, Guishan

2014-01-01

49

Synaptic degenerative changes in human traumatic brain edema. An electron microscopic study of cerebral cortical biopsies.  

PubMed

The cerebral cortex of 9 patients with complicated brain trauma has been examined with the transmission electron microscope to study the distinctive degenerative synaptic changes induced by brain injury and associated vasogenic, moderate or severe, brain edema. The brain injury and the hematogenous edema fluid accumulated in the dilated extracellular space of cerebral cortex neuropil induced swelling and shrinkage of pre- and postsynaptic structures, increased amount of presynaptic axoplasmic granular substance and clumping, enlargement and depletion of synaptic vesicles. In severe brain edema, swollen and shrunken presynaptic endings with discontinuous limiting plasma appeared separated from the postsynaptic structures and detached from glial ensheathment (synaptic disassembly). Post-synaptic shaft dendrites and their spines showed swelling and vacuolization. Fragmen-tation and atrophic changes of spine apparatus were found in the dendritic spines. The clear and dark types of degeneration were observed in most cases examined, in both preand/or postsynaptic structures. Filamentous hypertrophy of presynaptic endings was observed only in two cases. Osmiophylic bodies, necrotic membranes, lipid inclusions and glycogen granules were seen in the synaptic terminals. Disappearance of synaptic densities was evident in some cases. Phagocytosis of isolated presynaptic endings or of the entire synaptic contacts by astrocytes, microglial cells and by non-nervous invading cells, such as monocytes and macrophages, was found. PMID:8568555

Castejòn, O J; Valero, C; Dìaz, M

1995-03-01

50

Cerebral edema following iodine-131 therapy for thyroid carcinoma metastatic to the brain  

SciTech Connect

Brain metastases are rare in well-differentiated thyroid carcinoma but when present they can lead to the patient's death. Iodine-131 therapy for intracerebral thyroid carcinoma metastases causes radiation-induced acute cerebral edema that can lead to CNS complications and even death. We present a case in which a patient with intracerebral /sup 131/I uptake developed seizures, slurred speech, and muscle weakness 12 hr following /sup 131/I therapy. The patient's CT scan, post-therapy, confirmed an intracranial metastasis with a significant amount of surrounding edema. Radiotherapists, when using external beam radiation to treat intracerebral metastases, commonly place these patients on steroids, glycerol, or mannitol prior to instituting therapy, to prevent complications from radiation-induced cerebral edema. This technique could be applied to /sup 131/I therapy of intracranial thyroid carcinoma metastases as well.

Datz, F.L.

1986-05-01

51

Stereotactic Aspiration-Thrombolysis of Intracerebral Hemorrhage and its Impact on Perihematoma Brain Edema  

PubMed Central

Background Recent reports suggest that when thrombolytic agents are administered within the clot, lysis rate accelerates at the expense of increased risk of worsening edema. To test this hypothesis, we report on the volumetric analysis of (1) the intraparenchymal hematoma and, (2) perihematomal edema in a cohort of ICH patients treated with intraclot rtPA. Methods A convenience sample of highly selected ICH patients underwent frameless stereotactic aspiration and thrombolysis (FAST) of the clot. Two milligrams of rtPA were administered every 12 h until ICH volume ?10 cc, or catheter fenestrations were no longer in continuity with the clot. ICH and perihematomal edema volumes were calculated from CT scans. Using random effects linear regression we estimated the rate of hematoma and edema volume resolution as well as their relationship during the first 8 days of lytic therapy. Results Fifteen patients were treated, mean age: 60.7 years, median time from ictus to FAST: 1 (range 0–3) day. Using a random effects model that considered volume resolution over the first 8 days following lytic therapy we found that the both percentage hematoma and percentage perihematoma edema resolution per day were quadratic with respect to time. Percentage residual hematoma volume on day K = 97.7% ? [24.36%*K] + [1.89%*K2]; P < 0.001 for both terms. Percentage residual edema on day K = 97.4% ? [13.94%*K] + [1.30%*K2]; P < 0.001 for K and P = 0.01 for K2. Examination of each patient’s volume data suggests that there exists a strong direct relationship between perihematoma edema volume and same day hematoma volume. Conclusions In this cohort of ICH patients treated using FAST, volumetric analysis of ICH and perihematomal edema seems to suggest that local use of rtPA does not exacerbate brain edema formation. Furthermore, there seems to be a strong association between reduction in ICH volume and reduction in edema volume, as would be expected following the concept of “hemotoxicity” postulated by some investigators.

Barrett, Ryan J.; Keyl, Penelope M.; Hanley, Daniel F.; Johnson, Robert R.

2010-01-01

52

The effects of Tanshinone IIA on blood–brain barrier and brain edema after transient middle cerebral artery occlusion in rats  

Microsoft Academic Search

Disruption of blood–brain barrier (BBB) and edema formation play a key role in the development of neurological dysfunction after cerebral ischemia. In this study, the effects of Tanshinone IIA (Tan IIA), one of the active ingredients of Salvia miltiorrhiza root, on the BBB and brain edema after transient middle cerebral artery occlusion in rats were examined. Our study demonstrated that

Chao Tang; Hongli Xue; Changlin Bai; Rong Fu; Anhua Wu

2010-01-01

53

Apelin-13 protects the brain against ischemic reperfusion injury and cerebral edema in a transient model of focal cerebral ischemia.  

PubMed

The adipocytokine apelin is a peptide that was isolated from a bovine stomach for the first time. This peptide and its receptor are abundantly expressed in the nervous and cardiovascular systems. According to previous studies, apelin-13 protects cardiomyocytes from ischemic injury as well as apoptosis. In addition, this peptide has a neuroprotective effect on hippocampal and cultured mouse cortical neurons against NMDA receptor-mediated excitotoxicity. The present study was conducted to determine whether apelin-13 provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and apelin-13 at doses of 25, 50, and 100 ?g were injected intracerebroventriculary (ICV) at the beginning of ischemia. Infarct volume ,brain edema, motor dysfunction, and apoptosis were assessed 24 h after MCAO. Treatment with apelin-13 at doses of 50 and 100 ?g ICV markedly reduced total infarct volumes by 45 and 55 %, respectively (P??0.05). In addition, apelin-13 at doses of 50 and 100 ?g reduced brain edema (P??0.05). PMID:22638858

Khaksari, Mehdi; Aboutaleb, Nahid; Nasirinezhad, Farinaz; Vakili, Abedin; Madjd, Zahra

2012-09-01

54

The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of rho a.  

PubMed

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction. PMID:24442989

Hu, Jinyang; Wen, Qingping; Wu, Yue; Li, Baozhu; Gao, Peng

2014-06-01

55

Multi-fractal texture features for brain tumor and edema segmentation  

NASA Astrophysics Data System (ADS)

In this work, we propose a fully automatic brain tumor and edema segmentation technique in brain magnetic resonance (MR) images. Different brain tissues are characterized using the novel texture features such as piece-wise triangular prism surface area (PTPSA), multi-fractional Brownian motion (mBm) and Gabor-like textons, along with regular intensity and intensity difference features. Classical Random Forest (RF) classifier is used to formulate the segmentation task as classification of these features in multi-modal MRIs. The segmentation performance is compared with other state-of-art works using a publicly available dataset known as Brain Tumor Segmentation (BRATS) 2012 [1]. Quantitative evaluation is done using the online evaluation tool from Kitware/MIDAS website [2]. The results show that our segmentation performance is more consistent and, on the average, outperforms other state-of-the art works in both training and challenge cases in the BRATS competition.

Reza, S.; Iftekharuddin, K. M.

2014-03-01

56

An Unusual Transudative Pleural Effusion Succeeded by Pulmonary and Brain Edema and Death  

PubMed Central

Here we report a 22-year old woman with massive and bilateral transudative effusion succeeded by pulmonary edema and brain edema and death. Investigations for systemic disorders were negative. Exacerbation of dyspnea after intravenous fluid infusion was a main problem. As effusion was refractory to medical treatment, the patient was referred for surgical pleurodesis and bilateral surgical pleurodesis were done separately. Postsurgically, dyspnea exacerbation occurred after each common cold infection. Vertigo and high intracranial pressure were also a problem postsurgically. CSF pressure was 225?mm/H2O. Therapeutic lumbar puncture was done in two sequential weeks, and the patient was on acetazolamide 250?mg/trivise a day. Despite the medical treatment, progressive dyspnea, headache, and high intracranial pressure followed by death nine months after pleurodesis. As there is a gradient of pressure between pleura and CSF, after pleurodesis brain edema must be a consequence of inversing this gradient. In conclusion, when there are any abnormalities about fluid volume or pressure in any of these cavities, we have to study other cavities.

Mortazavimoghaddam, Sayyed Gholam Reza; Riasi, H. R.

2012-01-01

57

Brain microbleeds: distribution and influence on hematoma and perihematomal edema in patients with primary intracerebral hemorrhage.  

PubMed

Brain microbleed is a marker of small vessel microhemorrhagic or microaneurysmal lesions, which may induce intracerebral hemorrhage (ICH). This study to prospectively evaluated the association between microbleeds, hematoma and perihematomal edema volume, and various clinical data, as well as patient outcome. Thirty-one patients with ICH and 31 healthy age-matched subjects were enrolled in our study. They were divided into two groups according to the presence or absence of microbleeds detected by MRI. Serial clinical and laboratory data were recorded. Modified Rankin Scale and Barthel Index were estimated three months after hemorrhage. The major location of microbleeds among patients with ICH was the basal ganglia. The volume of perihematomal edema was correlated with the initial hematoma volume on the first, fifth and seventh days after hemorrhage in patients with microbleeds. For patients without microbleeds, this correlation was also significant on the seventh day. Cerebral microbleeds in patients with ICH, especially in the basal ganglia region, represent micro-angiopathy, and are associated with leakage of blood and formation of perihemorrhage edema. Brain microbleeds found in patients with ICH warrant further investigation for evaluation of stroke risk. PMID:23859241

Lin, Wei-Ming; Yang, Tse-Yen; Weng, Hsu-Huei; Chen, Chih-Feng; Lee, Ming-Hsueh; Yang, Jen-Tsung; Ng Jao, Shaner Yeun; Tsai, Yuan-Hsiung

2013-04-01

58

Volumetric electromagnetic phase-shift spectroscopy of brain edema and hematoma.  

PubMed

Motivated by the need of poor and rural Mexico, where the population has limited access to advanced medical technology and services, we have developed a new paradigm for medical diagnostic based on the technology of "Volumetric Electromagnetic Phase Shift Spectroscopy" (VEPS), as an inexpensive partial substitute to medical imaging. VEPS, can detect changes in tissue properties inside the body through non-contact, multi-frequency electromagnetic measurements from the exterior of the body, and thereby provide rapid and inexpensive diagnostics in a way that is amenable for use in economically disadvantaged parts of the world. We describe the technology and report results from a limited pilot study with 46 healthy volunteers and eight patients with CT radiology confirmed brain edema and brain hematoma. Data analysis with a non-parametric statistical Mann-Whitney U test, shows that in the frequency range of from 26 MHz to 39 MHz, VEPS can distinguish non-invasively and without contact, with a statistical significance of p<0.05, between healthy subjects and those with a medical conditions in the brain. In the frequency range of between 153 MHz to 166 MHz it can distinguish with a statistical significance of p<0.05 between subjects with brain edema and those with a hematoma in the brain. A classifier build from measurements in these two frequency ranges can provide instantaneous diagnostic of the medical condition of the brain of a patient, from a single set of measurements. While this is a small-scale pilot study, it illustrates the potential of VEPS to change the paradigm of medical diagnostic of brain injury through a VEPS classifier-based technology. Obviously substantially larger-scale studies are needed to verify and expand on the findings in this small pilot study. PMID:23691001

Gonzalez, Cesar A; Valencia, Jose A; Mora, Alfredo; Gonzalez, Fernando; Velasco, Beatriz; Porras, Martin A; Salgado, Javier; Polo, Salvador M; Hevia-Montiel, Nidiyare; Cordero, Sergio; Rubinsky, Boris

2013-01-01

59

Enalapril Prevents Imminent and Reduces Manifest Cerebral Edema in Stroke-Prone Hypertensive Rats  

Microsoft Academic Search

Background and Purpose—Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria

Erwin L. A. Blezer; Klaas Nicolay; P. R. Dop Bar; Roel Goldschmeding; Gerard H. Jansen; Hein A. Koomans; Jaap A. Joles

60

LPS-induced endotoxic shock does not cause early brain edema formation – An MRI study in rats  

Microsoft Academic Search

.\\u000a Objective and design:  Early microcirculatory failure is assumed as a key factor in the development of a septic encephalopathy. However, brain edema\\u000a is also a common finding in sepsis syndromes possibly interfering with the vasoregulative mechanisms of the brain. We assessed\\u000a the occurrence of brain edema in a rat model of endotoxic shock.\\u000a \\u000a \\u000a \\u000a Material and subjects:  Eleven mechanically ventilated male CD-rats.

B. Rosengarten; M. Walberer; J. Allendoerfer; C. Mueller; N. Schwarz; G. Bachmann; T. Gerriets

2008-01-01

61

Amelioration of Cold Injury-Induced Cortical Brain Edema Formation by Selective Endothelin ETB Receptor Antagonists in Mice  

PubMed Central

Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

2014-01-01

62

Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases.  

PubMed

To analyze the prognostic value of the extent of peritumoral brain edema in patients operated for single brain metastases (BM), we retrospectively evaluated pre-operative magnetic resonance images in a discovery cohort of 129 patients and a validation cohort of 118 patients, who underwent neurosurgical resection of a single BM in two different hospitals. We recorded clinical parameters and immunohistochemically assessed the Ki67 index, the microvascularization patterns and the expression of hypoxia-induced factor 1 alpha (HIF1a) in the BM tissue specimens retrieved at neurosurgery. Statistical analysis including uni- and multivariate survival analyses were performed. Baseline characteristics were well balanced between the discovery and validation cohorts. In univariate analysis, we found a significant association of favorable overall survival time with young patient age, high Karnofsky performance score, low graded prognostic assessment (GPA) class, absence of extracranial metastases, adjuvant treatment with whole brain radiotherapy and, surprisingly, large brain edema. In multivariate analysis, only GPA and extent of brain edema remained independent prognostic parameters. The prognostic impact of the extent of brain edema was consistent in the two patient cohorts. Furthermore, we found a significant correlation of small brain edema with brain-invasive tumor growth pattern as assessed intraoperatively by the neurosurgeon, low neo-angiogenic activity and low expression of HIF1a. Extent of brain edema independently correlates with prognosis in patients operated for single BM. In conclusion, patients with small peritumoral edema have shorter survival times and their tumors are characterized by a more brain-invasive growth, lower HIF1a expression and less angiogenic activity. PMID:23076770

Spanberger, Thomas; Berghoff, Anna S; Dinhof, Carina; Ilhan-Mutlu, Aysegül; Magerle, Manuel; Hutterer, Markus; Pichler, Josef; Wöhrer, Adelheid; Hackl, Monika; Widhalm, Georg; Hainfellner, Johannes A; Dieckmann, Karin; Marosi, Christine; Birner, Peter; Prayer, Daniela; Preusser, Matthias

2013-04-01

63

The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.  

PubMed Central

Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention. Images Figure 1 Figure 2 Figure 3

Criscuolo, G. R.

1993-01-01

64

Celecoxib Induces Functional Recovery After Intracerebral Hemorrhage With Reduction of Brain Edema and Perihematomal Cell Death  

Microsoft Academic Search

The selective cyclooxygenase-2 (COX-2) inhibitor has been reported to have antiinflammatory, neuroprotective, and antioxidant effects in ischemia models. In this study, the authors examined whether a selective COX-2 inhibitor (cele-coxib) reduces cerebral inflammation and edema after intracerebral hemorrhage (ICH), and whether functional recovery is sustained with longer treatment. ICH was induced using collagenase in adult rats. Celecoxib (10 or 20

Kon Chu; Sang-Wuk Jeong; Keun-Hwa Jung; So-Young Han; Soon-Tae Lee; Manho Kim; Jae-Kyu Roh

2004-01-01

65

Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN  

NASA Astrophysics Data System (ADS)

This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels. The k-means algorithm is used to cluster the image based on the feature vectors of blocks forming different classes representing different regions in the whole image. With the knowledge of the feature vectors of different segmented regions, supervised technique is used to train Artificial Neural Network using fuzzy back propagation algorithm (FBPA). Segmentation for detecting healthy tissues and tumors has been reported by several researchers by using conventional MRI sequences like T1, T2 and PD weighted sequences. This work successfully presents segmentation of healthy and pathological tissues (both Tumors and Edema) using FLAIR images. At the end pseudo coloring of segmented and classified regions are done for better human visualization.

Pradhan, Nandita; Sinha, A. K.

2008-04-01

66

Minocycline reduces intracerebral hemorrhage-induced brain injury  

PubMed Central

Objectives Microglial activation and thrombin formation contribute to brain injury after intracerebral hemorrhage. Tumor necrosis factor-alpha and interleukin-1beta are two major pro-inflammatory cytokines. The present study investigated if thrombin stimulates tumor necrosis factor-alpha and interleukin-1beta secretion in vitro and if microglial inhibition reduces intracerebral hemorrhage -induced brain injury in vivo. Methods There were two parts in this study. In the first part, cultured rat microglial cells were treated with vehicle, thrombin (10 U/ml), or thrombin plus minocycline (1 or 10 ?M), an inhibitor of microglia activation. Levels of tumor necrosis factor-alpha and interleukin-1beta in culture medium were measured by Enzyme-Linked ImmunoSorbent Assay at 24 hours after thrombin treatment. In the second part, rats had an intracerebral injection of 100-?l autologous whole blood. Rats received minocycline or vehicle treatment. Brain edema was measured at day 3 and brain atrophy was determined at day 28 after intracerebral hemorrhage. Results Thrombin receptors were expressed in cultured microglia cells, and tumor necrosis factor-alpha and interleukin-1beta levels in the culture medium were increased after thrombin treatment. Minocycline reduced thrombin-induced upregulation of tumor necrosis factor-alpha and interleukin-1beta. In vivo, minocycline reduced perihematomal brain edema, neurological deficits and brain atrophy. Discussion Thrombin stimulates microglia to release the pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, and microglial inhibition with minocycline reduces brain injury after intracerebral hemorrhage suggesting a critical role of microglia activation in intracerebral hemorrhage -related brain injury.

Wu, Jimin; Yang, Shuxu; Xi, Guohua; Fu, Guosheng; Keep, Richard F; Hua, Ya

2009-01-01

67

Treadmill Pre-Training Ameliorates Brain Edema in Ischemic Stroke via Down-Regulation of Aquaporin-4: An MRI Study in Rats  

PubMed Central

Objective Treadmill pre-training can ameliorate blood brain barrier (BBB) dysfunction in ischemia-reperfusion injury, however, its role in ischemic brain edema remains unclear. This study assessed the neuroprotective effects induced by treadmill pre-training, particularly on brain edema in transient middle cerebral artery occluded model. Methods Transient middle cerebral artery occlusion to induce stroke was performed on rats after 2 weeks of treadmill pre-training. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after ischemia-reperfusion injury. In addition, measurements of wet and dry brain weight, Evans Blue assay and Garcia scores were performed to investigate the cerebral water content, BBB permeability and neurologic deficit, respectively. Moreover, during ischemia-reperfusion injury, the expression of Aquaporin 4 (AQP4) was detected using immunofluorescence and Western bloting analyses. Results Treadmill pre-training improved the relative apparent diffusion coefficient (rADC) loss in the ipsilateral cortex and striatum at 1 hour and 2.5 hours after cerebral ischemia. In the treadmill pre-training group, T2W1 values of the ipsilateral cortex and striatum increased less at 7.5 hours, 1 day, and 2 days after stroke while the brain water content decreased at 2 days after ischemia. Regarding the BBB permeability, the semi-quantitative amount of contrast agent leakage of treadmill pre-training group significantly decreased. Less Evans Blue exudation was also observed in treadmill pre-training group at 2 days after stroke. In addition, treadmill pre-training mitigated the Garcia score deficits at 2 days after stroke. Immunofluorescence staining and Western blotting results showed a significant decrease in the expression of AQP4 after treadmill ischemia following pre-training. Conclusions Treadmill pre-training may reduce cerebral edema and BBB dysfunction during cerebral ischemia/reperfusion injury via the down-regulation of AQP4.

Wu, Yi; Jia, Jie; Hu, Yongshan; Yang, Xiaojiao; Li, Jianqi; Fan, Mingxia; Zhang, Li; Guo, Jinchun; Leung, Mason C. P.

2014-01-01

68

Inhibition of carbonic anhydrase reduces brain injury after intracerebral hemorrhage  

PubMed Central

Carbonic anhydrase-1 (CA-1) is a metalloenzyme present at high concentrations in erythrocytes. Our previous studies showed that erythrocyte lysis contributes to brain edema formation after intracerebral hemorrhage (ICH) and a recent study indicates that CA-1 can cause blood-brain barrier disruption. The present study investigated the role of CA-1 in ICH-induced brain injury. There were three groups in the study. In the first, adult male Sprague-Dawley rats received 100 ?l autologous blood injection into the right caudate. Sham rats had a needle insertion. Rat brains were used for brain CA-1 level determination. In the second group, rats received an intracaudate injection of either 50 ?l CA-1 (1 ?g/?l) or saline. Brain water content, microglia activation and neuronal death (Fluoro-Jade C staining) were examined 24 hours later. In the third group, acetazolamide (AZA, 5 ?l, 1 mM), an inhibitor of carbonic anhydrases, or vehicle was co-injected with 100 ?l blood. Brain water content, neuronal death and behavioral deficits were measured. We found that CA-I levels were elevated in the ipsilateral basal ganglia at 24 hours after ICH. Intracaudate injection of CA-1 induced brain edema (79.0 ± 0.6 vs. 78.0±0.2% in saline group, p<0.01), microglia activation and neuronal death (p<0.01) at 24 hours. AZA, an inhibitor of CA, reduced ICH-induced brain water content (79.3 ± 0.7 vs. 81.0 ± 1.0% in the vehicle-treated group, p<0.05), neuronal death and improved functional outcome (p<0.05). These results suggest that CA-1 from erythrocyte lysis contributes to brain injury after ICH.

Guo, Fuyou; Hua, Ya; Wang, Jinhu; Keep, Richard F.; Xi, Guohua

2011-01-01

69

The neuroprotective effect of olive leaf extract is related to improved blood-brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia.  

PubMed

Recent studies suggest that olive extracts suppress inflammation and reduce stress oxidative injury. We sought to extend these observations in an in vivo study of rat cerebral ischemia-reperfusion injury. Four groups, each of 18 Wister rats, were studied. One (control) group received distilled water, while three treatment groups received oral olive leaf extract (50, 75 and 100mg/kg/day respectively). After 30 days, blood lipid profiles were determined, before a 60 min period of middle cerebral artery occlusion (MCAO). After 24h reperfusion, neurological deficit scores, infarct volume, brain edema, and blood-brain barrier permeability were each assessed in subgroups of six animals drawn from each main group. Olive leaf extract reduced the LDL/HDL ratio in doses 50, 75, and 100mg/kg/day in comparison to the control group (P<0.001), and offered cerebroprotection from ischemia-reperfusion. For controls vs. doses of 50mg/kg/day vs. 75 mg/kg/day vs. 100mg/kg/day, attenuated corrected infarct volumes were 209.79 ± 33.05 mm(3) vs. 164.36 ± 13.44 mm(3) vs. 123.06 ± 28.83 mm(3) vs. 94.71 ± 33.03 mm(3); brain water content of the infarcted hemisphere 82.33 ± 0.33% vs. 81.33 ± 0.66% vs. 80.75 ± 0.6% vs. 80.16 ± 0.47%, and blood-brain barrier permeability of the infarcted hemisphere 11.22 ± 2.19 ?g/g vs. 9.56 ± 1.74 ?g/g vs. 6.99 ± 1.48 ?g/g vs. 5.94 ± 1.73 ?g/g tissue (P<0.05 and P<0.01 for measures in doses 75 and 100mg/kg/day vs. controls respectively). Oral administration of olive leaf extract reduces infarct volume, brain edema, blood-brain barrier permeability, and improves neurologic deficit scores after transient middle cerebral artery occlusion in rats. PMID:21183324

Mohagheghi, Fatemeh; Bigdeli, Mohammad Reza; Rasoulian, Bahram; Hashemi, Payman; Pour, Marzyeh Rashidi

2011-01-15

70

Decompressive craniectomy with multi-dural stabs - A combined (SKIMS) technique to evacuate acute subdural hematoma with underlying severe traumatic brain edema  

PubMed Central

Context: The decompressive craniotomy alone or with dural flap opening to evacuate acute subdural hematoma with underlying brain edema in severe traumatic brain injury has proved either insufficient in the first place or has fatal complications secondly. Aims: To reduce the fatality of conventional procedures and to evacuate acute subdural hematoma with severe brain edema by a combination of decompressive craniotomy and multi-dural stabs (SKIMS-Technique) without brain pouting and lacerations in low Glasgow coma scale (GCS) score patients. Settings and Design: The prospective study was conducted in the Department of Neurosurgery, from June, 2006 to June 2011, under a uniform protocol. Materials and Methods: A total of 225 patients of severe brain trauma were admitted to the accident and emergency unit of Neurosurgery and after initial resuscitation a CT brain was performed. All patients had a GCS score of 8 and below. All patients were ventilated postoperatively and ICP was monitored. Statistical Analysis Used: The data was analyzed and evaluated by the statistical methods like student's T-test. The analysis of Variance was used where-ever applicable. Results: The survival of multi-dural stab group was 77.31% (92/119) with good recovery in 42.02% (50/119) and a mortality of 22.69% (27/119) as compared with 46.23% (49/106) survival in open dural flap (control) group with 15.09% (16/106) good recovery and mortality of 53.77% (57/106). Conclusions: This new approach, known as SKIMS-Technique or Combined Technique i.e., “decompressive craniectomy with multi-dural stabs”, proved much effective in increasing survival of low GCS and severe traumatic brain edema patients with acute subdural hematoma.

Bhat, Abdul Rashid; Kirmani, Altaf Rehman; Wani, Mohammed Afzal

2013-01-01

71

Midline-shift corresponds to the amount of brain edema early after hemispheric stroke--an MRI study in rats.  

PubMed

Vasogenic brain edema formation is a serious complication in hemispheric stroke. Its space-occupying effect can lead to midline-shift (MLS), cerebral herniation, and death. Clinical studies indicate that quantification of MLS can predict cerebral herniation and subsequent death at early time-points, even before clinical deterioration becomes apparent. The present experimental study was designed to determine the relation between MLS, absolute edema volume, lesion size, and clinical findings in a rat stroke model. Middle cerebral artery-occlusion was performed in 24 rats using the suture technique. Clinical evaluation and magnetic resonance imaging (MRI) (Bruker PharmaScan 7.0T) was performed 24 hours later. Lesion volume, the volume-increase within the affected hemisphere (%HEV), and MLS were quantified on T2-weighted images. The absolute increase of hemispheric water content (DeltaH2O) was determined in a subgroup using the wet-dry method (n=12). MLS correlated significantly with the total amount of brain edema (magnetic resonance imaging study: r=0.82; P<0.01; wet-dry analysis r=0.80; P<0.01). MLS correlated only moderately with T2-lesion volume (r=0.55; P<0.01). No significant correlation could be detected between MLS and clinical scores (r=0.26; P>0.05). MLS thus quantitatively reflects the amount of vasogenic brain edema within the affected hemisphere at early time-points. MLS quantification can be regarded as an easily assessable and valid global quantitative parameter for brain edema and thus might facilitate the surgical and nonsurgical management of edema in acute stroke patients. PMID:17413996

Walberer, Maureen; Blaes, Franz; Stolz, Erwin; Müller, Clemens; Schoenburg, Markus; Tschernatsch, Marlene; Bachmann, Georg; Gerriets, Tibo

2007-04-01

72

Antibodies to Dynorphin A (1–17) Attenuate Closed Head Injury Induced Blood–Brain Barrier Disruption, Brain Edema Formation and Brain Pathology in the Rat  

Microsoft Academic Search

\\u000a The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was\\u000a examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal\\u000a bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20

H. S. Sharma; R. Patnaik; S. Patnaik; A. Sharma; S. Mohanty; P. Vannemreddy

73

Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism  

Microsoft Academic Search

Adult rats intubated with a single dose of ethanol (alcohol;Ç5 g\\/kg) for 5 to 10 successive days incur neurodegeneration in the entorhinal cor- tex, dentate gyrus, and olfactory bulbs accompanied by cerebrocortical edema and electrolyte (Na\\/ ,K \\/ ) accumulation. The brain damage is not lessened by cotreatment with the NMDA receptor antagonist MK- 801; also, as reported elsewhere, MK-801

MICHAEL A. COLLINS; JIAN-YUN ZOU; EDWARD J. NEAFSEY

74

Cysteinyl-leukotrienes receptor activation in brain inflammatory reactions and cerebral edema formation: a role for transcellular biosynthesis of cysteinyl-leukotrienes.  

PubMed

We studied the effect of intravascular activation of human neutrophils on the synthesis of cysteinyl leukotrienes (cysLT) and the formation of cerebral edema in guinea-pig brains. Challenge with the chemotactic formylated tripeptide fMLP (0.1 microM) of neutrophil-perfused brain in vitro resulted in blood-brain barrier disruption associated with a significant increase of cysLT. Both events were completely prevented by neutrophil pretreatment with a specific 5-lipoxygenase (5-LO) inhibitor. Perfusion with the 5-LO metabolite leukotriene B4 (10 nM), together with neutrophils treated with the 5-LO inhibitor, did not restore the alteration in permeability observed upon perfusion with untreated and activated neutrophils. The dual cysLT1-cysLT2 receptor antagonist BAYu9773 was more potent and more effective than a selective cysLT1 antagonist in preventing the brain permeability alteration induced by neutrophil activation. RT-PCR showed significant expression of cysLT2 receptor mRNA in human umbilical vein endothelial cells. Intravital microscopy in mice showed that inhibition of leukotriene synthesis significantly reduced firm adhesion of neutrophils to cerebral vessels without affecting rolling. These data support the hypothesis that neutrophil and endothelial cells cooperate toward the local synthesis of cysLT within the brain vasculature and, acting via the cysLT2 receptor on endothelial cells, may represent a contributing pathogenic mechanism in the development of cerebral inflammation and edema. PMID:15001558

Di Gennaro, Antonio; Carnini, Chiara; Buccellati, Carola; Ballerio, Rossana; Zarini, Simona; Fumagalli, Francesca; Viappiani, Serena; Librizzi, Laura; Hernandez, Alicia; Murphy, Robert C; Constantin, Gabriela; De Curtis, Marco; Folco, Giancarlo; Sala, Angelo

2004-05-01

75

Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression  

PubMed Central

The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.

Ampawong, Sumate; Chaisri, Urai; Viriyavejakul, Parnpen; Nontprasert, Apichart; Grau, Georges E; Pongponratn, Emsri

2014-01-01

76

Blood-brain barrier disruption and exacerbation of ischemic brain edema after restoration of blood flow in experimental focal cerebral ischemia  

Microsoft Academic Search

The mechanism of exacerbation of ischemic brain edema after blood flow restoration was studied in 20 cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow was measured by the hydrogen clearance method, and the left middle cerebral artery (MCA) was occluded for 6 h in group A, and for 3 h with subsequent 3 h recirculation in group B.

T. Kuroiwa; M. Shibutani; R. Okeda

1988-01-01

77

PGJ(2) provides prolonged CNS stroke protection by reducing white matter edema.  

PubMed

Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NF?B-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-?(12,14)-prostaglandin J2 (PGJ(2)), an analog of the metabolically active PGD(2) metabolite. We evaluated PGJ(2)'s effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION); an in vivo white matter ischemia model. PGJ(2) administration systemically administered either acutely or 5 hours post-insult results in significant neuroprotection, with stereologic evaluation showing improved neuronal survival 30 days post-infarct. Quantitative capillary vascular analysis reveals that PGJ(2) improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ(2) acts by reducing NF?B signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ(2) showed no in vivo toxicity structurally as measured by optic nerve (ON) myelin thickness, functionally by ON-compound action potentials, on a cellular basis by oligodendrocyte precursor survival or changes in ON-myelin gene expression. PGJ(2) may be a clinically useful neuroprotective agent for ON and other CNS infarcts involving white matter, with mechanisms of action enabling effective treatment beyond the currently considered maximal time for intervention. PMID:23284631

Nicholson, James D; Puche, Adam C; Guo, Yan; Weinreich, Daniel; Slater, Bernard J; Bernstein, Steven L

2012-01-01

78

Exacerbated Brain Damage, Edema and Inflammation in Type-2 Diabetic Mice Subjected to Focal Ischemia  

PubMed Central

One of the limiting factors in stroke therapeutic development is the use of animal models that do not well represent the underlying medical conditions of patients. In humans, diabetes increases the risk of stroke incidence as well as post-stroke mortality. To understand the mechanisms that render diabetics to increased brain damage, we evaluated the effect of transient middle cerebral artery occlusion (MCAO) in adult db/db mice. The db/db mouse is a model of type-2 diabetes with 4 times higher blood sugar than its normoglycemic genetic control (db/+ mouse). Following transient MCAO, the db/db mice showed significantly higher mortality, bigger infarcts, increased cerebral edema, worsened neurological status compared to db/+ mice. The db/db mice also showed significantly higher post-ischemic inflammatory markers (ICAM1+ capillaries, extravasated macrophages/neutrophils and exacerbated proinflammatory gene expression) compared to db/+ mice. In addition, the post-ischemic neuroprotective heat-shock chaperone gene expression was curtailed in the db/db compared to db/+ mice.

Tureyen, Kudret; Bowen, Kellie; Liang, Jin; Dempsey, Robert J; Vemuganti, Raghu

2010-01-01

79

Fluoroquinolones reduce carrageenan-induced edema in rats and the involvement of the glucocorticoid receptor system.  

PubMed

We studied the effect of fluoroquinolones (FQs) on carrageenan-induced edema in the rat footpad. Ciprofloxacin, gatifloxacin, sparfloxacin, norfloxacin, and enoxacin (s.c., 100 mg/kg), which have piperazinyl and/or cyclopropyl groups, inhibited carrageenan-induced edema, whereas levofloxacin, tosufloxacin, and pazufloxacin did not. The reduction of edema by ciprofloxacin, sparfloxacin, and enoxacin was abolished by pretreatment with mifepristone, an antagonist of the glucocorticoid receptor. These results suggest that FQs with piperazinyl and/or cyclopropyl groups can modify biological responses through enhancing the glucocorticoid-glucocorticoid receptor system. PMID:19396522

Ogino, Hiromi; Yamada, Kaori; Yuhara, Mizuki; Tsuchida, Saori; Maezawa, Kayoko; Kizu, Junko; Hori, Seiji

2009-04-01

80

31P-magnetic resonance spectroscopic study on the effect of glycerol on cold-induced brain edema.  

PubMed

The aim of the present study was to determine the effects of a hyperosmotic agent, 10% glycerol, on both brain energy metabolism and intracellular pH (pHi) in experimental vasogenic brain edema. Vasogenic brain edema was induced by cold injury applied to bilateral parietal portions in 13 mongrel dogs (7 glycerol, 6 control) while, 3 dogs were used as control. Before and at 24 hours after the injury, sequential phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was performed for 2 hours in order to determine phosphocreatine (PCr), beta-adenosine triphosphate (beta-ATP), inorganic phosphate (Pi) levels and pHi. At 24 hours following cold injury, both PCr/Pi and ATP/Pi ratios significantly decreased from 7.75 to 3.97 and from 2.26 to 1.25, respectively. Furthermore, a moderate decrease in pHi of 7.16 to 7.01 was significantly demonstrated during the same experimental period. Administration of glycerol for 30 minutes significantly increased PCr/Pi from 3.97 to 5.06 and ATP/Pi from 1.25 to 1.72, respectively. Also, glycerol administration caused a significant increase in pHi from 7.01 to 7.11. This study indicates that cryogenic injury, in which formation and expansion of vasogenic brain edema a known to occur, results in disturbed brain energy metabolism and in intracellular acidosis; moreover, the administration of glycerol can ameliorate either or both of these derangements. PMID:7976629

Kamezawa, T; Asakura, T; Yatsushiro, K; Niiro, M; Kasamo, S; Fujimoto, T

1994-01-01

81

Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.  

PubMed

Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100 % O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI. PMID:24682753

Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

2014-05-01

82

The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema  

Microsoft Academic Search

Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent\\u000a causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of\\u000a fatal outcome. The underlying pathogenesis has been extensively studied and although the development of cerebral edema and\\u000a ICH is of a complex and

Peter Nissen Bjerring; Martin Eefsen; Bent Adel Hansen; Fin Stolze Larsen

2009-01-01

83

[Effect of nootropil and contvykal on the structural changes in the central nervous system in hypoxic brain edema].  

PubMed

The brain cortex of rabbits exposed to 15-minute ishemia in the presence of monitored hypotonia was studied in 27 experiments in order to verify the efficacy of nootropil and contrykal as agents intended for the treatment of posthypoxic edema of the brain. The therapeutic efficacy was assessed on the basis of the evidence obtained with the aid of light and electron microscopy. It was found that nootropil exerts a favourable action on the ultrastructure of intracellular organella of the neuron: mitochondria, lysosomes, ribosomal apparatus, nuclear envelope, etc. Under the effect of nootropil and contrykal the posthypoxic microcirculatory changes showed signs of compensation and proved reversible. Manifestations of posthypoxic edema of the brain were less pronounced. It is suggested that the efficacy of the treatment regimen offered is related to the normalizing effect of nootropil on metabolic and repair processes in neurons and cellular elements pertaining to the microcirculatory system as well as with a direct action of contrykal on the local factors of capillary permeability. PMID:316339

Polunin, B A; Tumanov, V P; Avrutski?, M Ia

1979-12-01

84

Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema.  

PubMed

Meningiomas are common primary brain tumors. However, they are often complicated by significant peritumoral brain edema, which leads to surgery difficulties and prolonged hospitalization. The aim of this study was to evaluate the presence of mast cells and expression of hypoxia inducible factor-1 (HIF-1) in correlation with the grade of meningioma and presence of peritumoral brain edema. Immunohistochemistry was performed with specific antibodies against tryptase (mast cells) and HIF-1 in low grade meningiomas (estimated as G1) and high grade meningiomas (estimated as G2 or G3). Peritumoral brain edema observed in MRI was graded using Steinhoff classification. Tryptase expression was observed in 40.4 % low grade meningiomas and in 90 % high grade cases; HIF-1 in 55.7 % low grade and in 84 % high grade meningiomas. There was a statistically significant correlation between HIF-1 and tryptase expression in both groups (p = 0.003). Presence of peritumoral brain edema statistically correlated with tryptase (p = 0.001) and HIF-1 expression (p = 0.004). Mast cells as well as hypoxia are involved in meningioma progression, and may be associated with the formation of peritumoral brain edema leading to surgery complication and recovery. Therefore, they may be useful markers in predicting the clinical course of meningioma cases. PMID:23877362

Reszec, Joanna; Hermanowicz, Adam; Rutkowski, Robert; Bernaczyk, Piotr; Mariak, Zenon; Chyczewski, Lech

2013-10-01

85

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.  

PubMed

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. PMID:24792709

Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

86

Thiobarbituric acid-reactive material content and enzymatic protection against peroxidative damage during the course of cryogenic rabbit brain edema.  

PubMed

The relationship between free radicals reactions and the cell detoxifying system was investigated during the development of brain edema following a cryogenic lesion in the rabbit cerebral cortex. The amount of TBA-reactive material present six hours after freezing was less than in the controls, then increased at 48 and 96 hours. The activity of superoxide dismutase (SOD) decreased 6 hours post-injury; at the same time, we observed a stimulation of catalase activity. The glutathione peroxidase activity (GSH-Px) rose 96 hours post-lesion. The decrease of TBA-reactive products could result from an elimination rate that exceeds generation. PMID:2215859

Avéret, N; Coussemacq, M; Cohadon, F

1990-08-01

87

[The effects of a benzopyrone derivative in experimental brain edema due to cold in the rabbit].  

PubMed

On this study, parenchymal changes during a cerebral edema caused by thermic injury (cool) on the rabbit, are analyzed. The work was based on the ultrastructural findings obtained by transmission electronic microscopy and on the effects produced by a benzopironic derived (F-117 Hydrosmina). The injury was produced with solid CO2, previous a craniectomy, on the dura mater of the left hemisphere. Forty rabbits were included into the study, the animals were distributed into five groups (n = 8): a control group and 4 treatment groups. One of the groups received treatment without previous cerebral injury. The group of rabbits with doses of 50 mg/Kg of weight showed focal and diffuse areas of edema alternating with less damaged areas, the edema was evident on the white substance. This group also showed a dissociation of the myelinic fibers and an intracytoplasmatic tumefaction into the glial cells. These findings contrast with the histopathological findings obtained from the rabbits (V), the extracellular edema was poor, the myelinic fiber disorganization was minimal with no vacuolar degeneration and no structural mitochondrial changes had been showed. The discontinuance of the hematoencephalic barrier caused by the cool could be a possible mechanism that causes the opening of the endothelial unions from the capillary vessels, changing their membranes and resulting in a free penetration of the molecule into the cerebral parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8338248

Góngora Castillo, C; Gómez de Segura, I A; López Bravo, A; de Miguel del Campo, E

1993-01-01

88

Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice  

Microsoft Academic Search

BackgroundStroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by

Peter Kraft; Peter Michael Benz; Madeleine Austinat; Marc Elmar Brede; Kai Schuh; Ulrich Walter; Guido Stoll; Christoph Kleinschnitz

2010-01-01

89

The effect of intravenous fluid replacement on the response to mannitol in experimental cerebral edema: an analysis of intracranial pressure, serum osmolality, serum electrolytes, and brain water content.  

PubMed

Albino rabbits that had undergone a cryogenic insult over the left parieto-occipital cortex were analyzed for serum osmolality, serum electrolytes, brain water content, and intracranial pressure (ICP) following either a baseline infusion of intravenous (i.v.) fluid (45 mL total) for 3 hours or above-maintenance isotonic saline (73.5 +/- 12 mL or 90.5 +/- 1.5 mL) and mannitol therapy. The subgroups were compared amongst themselves and to sham-operated controls. Serum osmolality was elevated in the higher-dose mannitol subgroup compared with maintenance i.v. fluids subgroup (1 g/kg/h vs 1 g/kg/3 h; p < 0.05), accompanied by an insignificant reduction of serum sodium. A significant reduction in brain water in the injured left hemisphere was seen following high-dose mannitol in the subgroup that received less i.v. (maintenance) fluids than the group that received above-maintenance i.v. fluids (p < 0.025). No reduction in brain water was seen in the subgroup that received above-maintenance i.v. fluids (non-treated groups). Reduction of ICP was not found in the lower mannitol dose group. We conclude that the ability of mannitol to reduce cerebral edema is related to the total amount of i.v. fluid replacement. This implies that the amount of i.v. crystalloid fluid that is administered to patients with cerebral edema and raised ICP requiring mannitol for control needs to be carefully monitored. PMID:16671439

James, H E

2006-01-01

90

Acute administration of 3,4-methylenedioxymethamphetamine induces profound hyperthermia, blood-brain barrier disruption, brain edema formation, and cell injury.  

PubMed

The psychostimulant 3,4-,ethylenedioxymethamphetamine (MDMA, "ecstasy") is known to induce hyperthermia and alterations in neurochemical metabolism in the CNS. However, the detailed cellular or molecular mechanisms behind MDMA-induced neurotoxicity are still not well known. Since MDMA induces profound hyperthermia that could lead to intense cellular stress and cause disruption of the blood-brain barrier (BBB), this investigation examined the effects of acute MDMA on BBB dysfunction, brain edema, and cell injury in rats and mice. When MDMA (40 mg/kg, i.p.) was administered to rats or mice, these animals exhibited profound behavioral disturbances (hyperactivity and hyperlocomotion) and hyperthermia (>40 to 41 degrees C) at 4 h. At this time, the leakage of Evans blue dye was evident, particularly in the cerebellum, hippocampus, cortex, thalamus, and hypothalamus. This effect was most pronounced in mice compared to rats. Marked increase in brain water along with Na(+), K(+), and Cl(-) content was also seen in the aforementioned brain regions. Presence of distorted neuronal and glial cells in brain regions associated with leakage of Evans blue is quite common in MDMA-treated animals. Increased albumin immunoreactivity, indicating breakdown of the BBB, and upregulation of glial fibrillary acidic protein (GFAP), suggesting activation of astrocytes, were seen in most brain regions showing edematous changes. Upregulation of heat-shock protein (HSP72) immunoreactivity in the nuclei and cell cytoplasm of the neurons located in the edematous brain regions are quite common. Taken together, these observations are the first to show that MDMA has the capacity to disrupt BBB permeability to proteins and to induce the formation of edema, probably by inducing hyperthermia and cellular stress, as evident with HSP overexpression leading to cell injury. PMID:18991870

Sharma, Hari Shanker; Ali, Syed F

2008-10-01

91

Patient's Self-recognition of Reduced Visual Acuity Due to Recurrence of Macular Edema and Prompt Visitation to the Hospital in Retinal Vein Occlusion  

PubMed Central

Purpose To evaluate patients' self-recognition of reduced visual acuity due to recurring macular edema in retinal vein occlusion. Methods A retrospective review of medical records of patients who were diagnosed with recurring macular edema secondary to retinal vein occlusion was performed. The proportion of patients who recognized reduced visual acuity due to the recurrence of macular edema and who visited the hospital before the scheduled follow-up date was determined. Parameters including age, sex, diagnosis, visual acuity before recurrence of macular edema, and extent of visual acuity reduction due to recurrence of macular edema were compared in patients who recognized a reduction in visual acuity and those who did not. The proportion of patients who visited the hospital promptly was also determined. Results Forty eyes of 40 patients were included in the analysis. Sixteen and 24 patients were diagnosed with central retinal vein occlusion and branch retinal vein occlusion, respectively. Twenty-one patients (52.5%) recognized reduced visual acuity due to recurring macular edema. These patients were younger (59.2 ± 7.6 vs. 64.8 ± 9.4 years, p = 0.046), had better visual acuity before recurrence of macular edema (0.52 ± 0.48 vs. 1.02 ± 0.46, p = 0.002), and exhibited a greater reduction in visual acuity after recurrence of macular edema (0.34 ± 0.24 vs. 0.14 ± 0.13, p = 0.003). Only four patients visited the hospital before the scheduled follow-up date, and all of these patients lived relatively close to the hospital. Conclusions For prompt treatment of recurring macular edema, more intensive education about the self-estimation of visual acuity is necessary, particularly for elderly patients who have relatively poor visual acuity. In addition, a simple and easy way to identify the recurrence of macular edema at the local clinic should be established for patients who live relatively far from the hospital.

Jeong, Seong Hun; Kim, Jong Woo; Lee, Tae Gon; Kim, Chul Gu; Yoo, Su Jin; Choi, Mun Jung

2014-01-01

92

Hyperbaric oxygen reduces edema and necrosis of skeletal muscle in compartment syndromes associated with hemorrhagic hypotension  

SciTech Connect

This study examined the effect of exposures to hyperbaric oxygen on the development of the edema and necrosis of muscle that are associated with compartment syndromes that are complicated by hemorrhagic hypotension. A compartment syndrome (twenty millimeters of mercury for six hours) was induced by infusion of autologous plasma in the anterolateral compartment of the left hind limb of seven anesthetized dogs while the mean arterial blood pressure was maintained at sixty-five millimeters of mercury after 30 per cent loss of blood volume. These dogs were treated with hyperbaric oxygen (two atmospheres of pure oxygen) and were compared with six dogs that had an identical compartment syndrome and hypotensive condition but were not exposed to hyperbaric oxygen. Forty-eight hours later, edema was quantified by measuring the weights of the muscles (the pressurized muscle compared with the contralateral muscle), and necrosis of muscle was evaluated by measuring the uptake of technetium-99m stannous pyrophosphate. The ratio for edema was significantly (p = 0.01) greater in dogs that had not been exposed to hyperbaric oxygen (1.15 +/- 0.01) than in the dogs that had been treated with hyperbaric oxygen (1.01 +/- 0.03), and the ratio for necrosis of muscle was also significantly (p = 0.04) greater in dogs that had not had hyperbaric oxygen (1.96 +/- 0.41) than in those that had been treated with hyperbaric oxygen (1.05 +/- 0.11). Comparisons were also made with the muscles of four normal control dogs and separately with the muscles of six normotensive dogs that had an identical compartment syndrome and normal blood pressure and were not treated with hyperbaric oxygen.

Skyhar, M.J.; Hargens, A.R.; Strauss, M.B.; Gershuni, D.H.; Hart, G.B.; Akeson, W.H.

1986-10-01

93

The acute-phase protein PTX3 is an essential mediator of glial scar formation and resolution of brain edema after ischemic injury.  

PubMed

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood-brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders. PMID:24346689

Rodriguez-Grande, Beatriz; Swana, Matimba; Nguyen, Loan; Englezou, Pavlos; Maysami, Samaneh; Allan, Stuart M; Rothwell, Nancy J; Garlanda, Cecilia; Denes, Adam; Pinteaux, Emmanuel

2014-03-01

94

Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study  

PubMed Central

Introduction Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients with pulmonary edema. Methods This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. Results There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439) pg/mL and 119 (62-165) mg/L in ALI/ARDS, and 691 (416-1,194) pg/mL (p < 0.001) and 8 (2-42) mg/L (p < 0.001) in CPE. BNP or CRP alone offered good discriminatory performance (C-statistics 0.831 and 0.887), but the combination offered greater one [C-statistics 0.931 (p < 0.001 versus BNP) (p = 0.030 versus CRP)]. In multiple logistic-regression, BNP and CRP were independent predictors for the diagnosis after adjusting for other variables. Conclusions Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

2011-01-01

95

Forebrain Ischemia-Reperfusion Simulating Cardiac Arrest in Mice Induces Edema and DNA Fragmentation in the Brain  

PubMed Central

Brain injury affects one-third of persons who survive after heart attack, even with restoration of spontaneous circulation by cardiopulmonary resuscitation. We studied brain injury resulting from transient bilateral carotid artery occlusion (BCAO) and reperfusion by simulating heart attack and restoration of circulation, respectively, in live C57Black6 mice. This model is known to induce neuronal death in the hippocampus, striatum, and cortex. We report the appearance of edema after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in diffusion-weighted magnetic resonance imaging (MRI) was detectable in the striatum, thalamus, and cortex but not in the hippocampus. To determine whether damage to the hippocampus can be detected in live animals, we infused a T2 susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide nanoparticles [SPIONs]) that was linked to single-stranded deoxyribonucleic acid (DNA) complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos); we acquired in vivo T2*-weighted MRI 3 days later. SPION retention was measured as T2* (milliseconds) signal reduction or R2* value (s?1) elevation. We found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited significantly less SPION retention in the hippocampus and cortex than sham-operated animals. These findings suggest that brain injury induced by cardiac arrest can be detected in live animals.

Liu, Christina H.; Huang, Shuning; Kim, Young R.; Rosen, Bruce R.; Liu, Philip K.

2009-01-01

96

Transforming Growth Factor\\/32 Inhibits Cerebrovascular Changes and Brain Edema Formation in the Tumor Necrosis Factor c~- Independent Early Phase of Experimental Pneumococcal Meningitis  

Microsoft Academic Search

Summary Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor B (TGF-~) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-~ on regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain edema formation during the

Hans-Walter Pfister; Karl Frei; Barbara Ottnad; Uwe Koedel; Alexander Tomasz; Adriano Fontanar

97

Ischemic Postconditioning Decreases Cerebral Edema and Brain Blood Barrier Disruption Caused by Relief of Carotid Stenosis in a Rat Model of Cerebral Hypoperfusion  

PubMed Central

Background and Purpose Complications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. In this study, we investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis. Methods Wistar rat model of hypoperfusion due to severe carotid stenosis was established by binding a stainless microtube to both carotid arteries. Ischemic postconditioning procedure consisted of three cycles of 30 seconds ischemia and 30 seconds reperfusion. Brain edema was evaluated by measuring cerebral water content, and blood brain barrier permeability was assayed by examining cerebral concentration of Evans' Blue (EB) and fluorescein sodium (NaF). ELISA was used to analyze the expression of MMP-9, claudin-5 and occludin. The activity and location of MMP-9 was analyzed by gelatin zymography and in situ zymography, respectively. The distribution of tight junction proteins claudin-5 and occludin was observed by immunohistochemistry. Results The increased brain water content and cerebral concentration of EB and NaF were suppressed by administration of ischemic postconditioning prior to relief of carotid stenosis. Zymographic studies showed that MMP-9 was mainly located in the cortex and its activity was significantly improved by relief of carotid stenosis and, but the elevated MMP-9 activity was inhibited markedly by ischemic postconditioning. Immunohistochemistry revealed that ischemic postconditioning improved the discontinuous distribution of claudin-5 and occludin. ELISA detected that the expression of up-regulated MMP-9 and down-regulated claudin-5 and occludin caused by carotid relief were all attenuated by ischemic postconditioning. Conclusions Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis.

Yang, Fuwei; Zhang, Xiaojie; Sun, Ying; Wang, Boyu; Zhou, Chuibing; Luo, Yinan; Ge, Pengfei

2013-01-01

98

Pulmonary edema  

MedlinePLUS

Pulmonary edema is an abnormal buildup of fluid in the air sacs of the lungs, which leads to ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump blood ...

99

Pathophysiological and pathochemical aspects of cerebral edema  

Microsoft Academic Search

Conclusions and summary Cerebral edema is an increase in brain water content causing expansion of cerebral tissue volume. There are two different entities of cerebral edema occurring alone or together. Formation of vasogenic brain edema requires breakdown of the blood-brain barrier, while cytotoxic edema forms by alterations of the permeability of cell membranes, and\\/or disturbances of active, energy-dependent transport. In

A. Baethmann

1978-01-01

100

[Brain edema treatment procedure using continuous controlled infusion of mannitol in neurosurgical patients].  

PubMed

The paper evaluates the efficiency and safety of the developed osmotherapy protocol using controlled continuous infusion of 15% mannitol solution. Two hundred and nine patients with intracranial hypertension (ICH) syndrome of various etiologies had 15% mannitol infusion, the rate of which was determined by clinical criteria. The infusion rate was 50 ml/hr with midline brain structure dislocation of 8 mm or more and major depression of consciousness (a Glasgow coma scale (GCS) score of less than 8) and 25 ml/hr with brain dislocation of 7-mm or less and a GCS score of 8 or higher. The monitoring program was as follows: Block 1 comprised the clinical and instrumental data characterizing the adequacy of brain perfusion (GCS, the magnitude of focal neurological symptoms, ICH, mean blood pressure, computed tomographic dislocation); Block 2 involved the clinical and laboratory data identifying the extracerebral complications of osmotherapy (packed cell volume, plasma osmolarity, urine density, and renal ultrasonography); Block 3 consisted of cerebral oximetry (CO) and Neurotrend. The authors' early proposed integral indicators of OC, such as interhemispheric asymmetry coefficient and hemodynamic conformity index, were used to estimate the adequacy of brain perfusion. In cerebral vasospasm, a Neurotrend microsensor was implanted at 3-cm depth for the direct quantitative determination of pO2, pCO2, pH, and brain temperature. ICH was characterized by natural changes in the CO indicators. In vasospasm, the mean linear blood flow velocity was 245 +/- 14 cm/sec in the basilar arteries, which was attended by low pO2 and metabolic acidosis, as shown by readings. Optimization of artificial ventilation, stabilization of hemodynamics, and the use of postural exposures and osmo diuretics promoted ICH normalization and central perfusion pressure optimization, which was accompanied by the disappearance of tissue hypoxia and acidosis, as suggested by Neurotrend reading. The duration of mannitol infusion averaged 6.6 days. No urinary tract complications were observed. The proposed procedure of osmotherapy is effective and safe if the scope of monitoring is adequate. PMID:20919541

Taranova, I I; Kokhno, V N

2010-01-01

101

Acute dimethyl sulfoxide therapy in experimental brain edema: Part I. Effects on intracranial pressure, blood pressure, central venous pressure, and brain water and electrolyte content.  

PubMed

Albino rabbits with experimental brain edema produced by a cryogenic lesion or by a cryogenic lesion combined with a metabolic blocker, 6-aminonicotinamide, were given 1 g of a 10% solution of dimethyl sulfoxide (DMSO) per kg by intravenous bolus. Simultaneous recording of intracranial pressure (ICP), systemic arterial pressure (SAP), and central venous pressure and electroencephalography were performed while the animals were mechanically ventilated at a constant PaCO2 (PaCO2, 38 to 42 torr). One hour after the administration of DMSO, the rabbits were killed by air embolus, and the brain was removed promptly for the determination of wet and dry weights and electrolyte content. The ICP at 15, 30, and 60 minutes after DMSO was lower in both groups; ICP was significantly lower at 30 minutes (p less than 0.5) in the cold lesion group and at 15 minutes in the combined group (p less than 0.05). These was no significant change in SAP after DMSO in either group. There was s significant reduction of brain water content after DMSO in the combined lesion group (p less than 0.005 for the left hemisphere and p less than 0.025 for the right); there was no significant reduction of water content in the group with a cold lesion only. PMID:7279169

Camp, P E; James, H E; Werner, R

1981-07-01

102

Bifrontal decompressive craniectomy is a life-saving procedure for patients with nontraumatic refractory brain edema.  

PubMed

Despite advances in understanding, monitoring, and treatment, the outcome of patients with refractory brain oedema (RBE) remains poor. The concept of wide bone removal for treatment of RBE has been recognized since the nineteenth century. Bifrontal decompressive craniectomy (BDC) is performed as last resort treatment for patients with posttraumatic RBE. In this series the author treated 5 adult patients with non traumatic RBE using BDC. This is a retrospective review of all patients who developed RBE and herniation syndrome, all of them deteriorated to GCS 4-5/15 and had their pupils were dilated and fixed and had surgery after trial of medical management (mannitol and hyperventilation). The primary pathology was aneurysmal SAH in 2 patients, CNS infection in 2 patients, and one large calcified olfactory groove meningioma. The follow-up ranged from 6 months to 7 years, mean 3.9; there were no complications related to bone flap, no mortality or vegetative patients, one patient (20%) had good outcome, 2 patients (40%) had moderate disability (independent), and 2 patients (40%) had severe disability (dependent). BDC is an effective method of surgical decompression in patients with RBE; the procedure should be performed quickly after clinical deterioration to prevent irreversible secondary brain damage. Although difficult to accomplish, a randomized clinical trial is necessary to define criteria for surgical interference in patients with nontraumatic RBE. PMID:19234910

Elwatidy, Sherif

2009-02-01

103

Serial MRI After Transient Focal Cerebral Ischemia in Rats Dynamics of Tissue Injury, Blood-Brain Barrier Damage, and Edema Formation  

Microsoft Academic Search

Background and Purpose—With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats. Methods—Nineteen Sprague-Dawley rats

T. Neumann-Haefelin; A. Kastrup; A. de Crespigny; M. A. Yenari; T. Ringer; G. H. Sun; M. E. Moseley

104

A comparison of the effects of halothane, isoflurane, and pentobarbital anesthesia on intracranial pressure and cerebral edema formation following brain injury in rabbits.  

PubMed

To evaluate the impact of anesthetics on the evolution of a cerebral injury, 33 rabbits were subjected to a cryogenic brain lesion, followed by 10 h of anesthesia with 1 MAC halothane or isoflurane (n = 11 each) or with an equipotent dose of pentobarbital (n = 11). The lungs were ventilated to a PaCO2 = 30-35 mmHg with O2/air and normothermia was maintained. Intracranial pressure (ICP), mean arterial pressure (MAP), central venous pressure (CVP), arterial blood gases, and pH, osmolality, and other blood chemistries were recorded. Fifteen minutes after surgery, a left parietal injury was produced with liquid N2. A MAP greater than 70-75 mmHg was maintained throughout the study, using angiotensin II as needed, and CSF was removed if severe intracranial hypertension (ICP greater than 30 mmHg) threatened to reduce cerebral perfusion pressure (CPP = MAP-ICP) below 40 mmHg. 10 h after injury, the animals were killed, and edema formation assessed by: A) the wet weight of the two hemispheres; B) water content (%H2O; wet-dry weight) of the posterior aspect of the hemispheres; and C) specific gravity (SpGr) of tissue samples taken adjacent to and distant from the lesion. Animals given pentobarbital had higher MAP's until 3 h after the lesion had been induced. There were no subsequent intergroup differences in MAP, and no differences at any time in CVP, PaO2, PaCO2, pH, total fluids, or urine output. ICP increased in all animals, but with no significant intergroup differences (ICP in halothane animals was numerically lower). There were no clear differences in the incidence of ventricular drainage (1 halothane, 5 isoflurane, 3 pentobarbital; P = 0.16). In spite of CSF drainage and angiotensin, CPP PMID:2802214

Kaieda, R; Todd, M M; Weeks, J B; Warner, D S

1989-10-01

105

Comparison of compression stocking with elastic bandage in reducing postoperative edema in coronary artery bypass graft patient.  

PubMed

The removal of the saphenous veins in coronary artery bypass graft (CABG) surgery may cause leg edema. Compression therapy is often used to prevent postoperative edema. The objective of this study was to compare the efficacy of medical compression stocking (TED) and elastic bandage-type on donor limbs after CABG. The peripheries of lower limbs were measured at four regions (A: end of tarsal bones, H: heel , B: immediately above the ankle, C: largest circumference of the calf) at admission in 295 patients how CABG candidates and differences in these measurement points at discharge compared to measurements at admission time were calculated. The difference was considered as a measure of the effectiveness of two types of compression to prevent postoperative edema in donor limbs after CABG. The alterations of 396 donor limbs of 295 patients were examined after CABG at admission and discharge time. In 101 patients veins for graft were taken from both lower limbs. After analysis, if subjects had worn TED stockings, the peripheries of donor limbs at discharge were less than at admission time in the A and H regions compared to elastic bandage group (P(A) = 0/009), (P(H) = 0/012). The conclusion reached was that using the kind of knee length compression stocking (TED stocking , Kendall Co.) is more effective edema at foot and heel regions in donor limbs after CABG than elastic bandages. PMID:19914571

Khoshgoftar, Zohreh; Zohreh, Khoshgoftar; Ayat Esfahani, Farah; Farah, Ayat Esfahani; Marzban, Mehrab; Mehrab, Marzban; Salehi Omran, Abbas; Abbas, Salehi Omran; Haji Ghasemi, Alireza; Alireza, Hajighasemi; Movaghar, Soraya; Soraya, Movaghar; Saadat, Soheil; Soheil, Saadat

2009-12-01

106

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication.  

PubMed

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution. PMID:2392933

Hattori, H; Kimura, M; Takahashi, M; Hashimoto, S

1990-05-01

107

Molecular pathology of brain edema after severe burns in forensic autopsy cases with special regard to the importance of reference gene selection.  

PubMed

Brain edema is believed to be linked to high mortality incidence after severe burns. The present study investigated the molecular pathology of brain damage and responses involving brain edema in forensic autopsy cases of fire fatality (n?=?55) compared with sudden cardiac death (n?=?11), mechanical asphyxia (n?=?13), and non-brain injury cases (n?=?22). Postmortem mRNA and immunohistochemical expressions of aquaporins (AQPs), claudin5 (CLDN5), and matrix metalloproteinases (MMPs) were examined. Prolonged deaths due to severe burns showed an increase in brain water content, but relative mRNA quantification, using different normalization methods, showed inconsistent results: in prolonged deaths due to severe burns, higher expression levels were detected for all markers when three previously validated reference genes, PES1, POLR2A, and IPO8, were used for normalization, higher for AQP1 and MMP9 when GAPDH alone was used for normalization and higher for MMP9, but lower for MMP2 when B2M alone was used for normalization. Additionally, when B2M alone was used for normalization, higher expression of AQP4 was detected in acute fire deaths. Furthermore, the expression stability values of these five reference genes calculated by geNorm demonstrated that B2M was the least stable one, followed by GAPDH. In immunostaining, only AQP1 and MMP9 showed differences among the causes of death: they were evident in most prolonged deaths due to severe burns. These findings suggest that systematic analysis of gene expressions using real-time PCR might be a useful procedure in forensic death investigation, and validation of reference genes is crucial. PMID:23702882

Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

2013-09-01

108

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage.  

PubMed

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (?=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (? ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (?=0.24; P=0.12) or delayed (T3) PHE volume (?=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed. PMID:24710926

Lian, Li-Fei; Xu, Feng; Tang, Zhou-Ping; Xue, Zheng; Liang, Qi-Ming; Hu, Qi; Zhu, Wen-Hao; Kang, Hui-Cong; Liu, Xiao-Yan; Wang, Fu-Rong; Zhu, Sui-Qiang

2014-04-01

109

Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury.  

PubMed

We investigated the effect of taurine on inflammatory cytokine expression, on astrocyte activity and cerebral edema and functional outcomes, following traumatic brain injury (TBI) in rats. 72 rats were randomly divided into sham, TBI and Taurine groups. Rats subjected to moderate lateral fluid percussion injury were injected intravenously with taurine (200mg/kg) or saline immediately after injury or daily for 7days. Functional outcome was evaluated using Modified Neurological Severity Score (mNSS). Glial fibrillary acidic protein (GFAP) of the brain was measured using immunofluorescence. Concentration of 23 cytokines and chemokines in the injured cortex at 1 and 7days after TBI was assessed by Luminex xMAP technology. The results showed that taurine significantly improved functional recovery except 1day, reduced accumulation of GFAP and water content in the penumbral region at 7days after TBI. Compared with the TBI group, taurine significantly suppressed growth-related oncogene (GRO/KC) and interleukin (IL)-1? levels while elevating the levels of regulated on activation, normal T cell expressed and secreted (RANTES) at 1day. And taurine markedly decreased the level of 17 cytokine: eotaxin, Granulocyte colony-stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-?), IL-1?, IL-1?, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17, leptin, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-?), vascular endothelial growth factor (VEGF), and only increased the level of MIP-1? in a week. The results suggest that taurine effectively mitigates the severity of brain damage in TBI by attenuating the increase of astrocyte activity and edema as well as pro-inflammatory cytokines. PMID:24530657

Su, Y; Fan, W; Ma, Z; Wen, X; Wang, W; Wu, Q; Huang, H

2014-04-25

110

Regional cerebral edema and chloride space in galactosamine-induced liver failure in rats  

Microsoft Academic Search

The pathogenesis of cerebral edema, which is a major complication of fulminant hepatic failure, is poorly understood. In previous studies, increased regional brain water content was observed in rats at an early stage of acute liver failure caused by galactosamine. At a later stage when the animals had developed deep coma, brain water content was reduced, possibly as a result

CD Gove; RJ Ede; R Williams

1997-01-01

111

Hydrogen sulfide offers neuroprotection on traumatic brain injury in parallel with reduced apoptosis and autophagy in mice.  

PubMed

Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. The present study was undertaken to study the effects of exogenous H2S on traumatic brain injury (TBI) and the underlying mechanisms. The effects of exogenous H2S on TBI were examined by using measurement of brain edema, behavior assessment, propidium iodide (PI) staining, and Western blotting, respectively. Compared to TBI groups, H2S pretreatment had reduced brain edema, improved motor performance and ameliorated performance in Morris water maze test after TBI. Immunoblotting results showed that H2S pretreatment reversed TBI-induced cleavage of caspase-3 and decline of Bcl-2, suppressed LC3-II, Beclin-1 and Vps34 activation and maintained p62 level in injured cortex and hippocampus post TBI. The results suggest a protective effect and therapeutic potential of H2S in the treatment of brain injury and the protective effect against TBI may be associated with regulating apoptosis and autophagy. PMID:24466346

Zhang, Mingyang; Shan, Haiyan; Chang, Pan; Wang, Tao; Dong, Wenwen; Chen, Xiping; Tao, Luyang

2014-01-01

112

Hydrogen Sulfide Offers Neuroprotection on Traumatic Brain Injury in Parallel with Reduced Apoptosis and Autophagy in Mice  

PubMed Central

Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. The present study was undertaken to study the effects of exogenous H2S on traumatic brain injury (TBI) and the underlying mechanisms. The effects of exogenous H2S on TBI were examined by using measurement of brain edema, behavior assessment, propidium iodide (PI) staining, and Western blotting, respectively. Compared to TBI groups, H2S pretreatment had reduced brain edema, improved motor performance and ameliorated performance in Morris water maze test after TBI. Immunoblotting results showed that H2S pretreatment reversed TBI-induced cleavage of caspase-3 and decline of Bcl-2, suppressed LC3-II, Beclin-1 and Vps34 activation and maintained p62 level in injured cortex and hippocampus post TBI. The results suggest a protective effect and therapeutic potential of H2S in the treatment of brain injury and the protective effect against TBI may be associated with regulating apoptosis and autophagy.

Wang, Tao; Dong, Wenwen; Chen, Xiping; Tao, Luyang

2014-01-01

113

Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability  

PubMed Central

Chronic administration of mood stabilizers to rats downregulates the brain arachidonic acid (AA) cascade. This downregulation may explain their efficacy against bipolar disorder (BD), in which brain AA cascade markers are elevated. The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act against BD. When given to rats, both reduce brain cyclooxygenase activity and prostaglandin E2 concentration; OLZ also reduces rat plasma unesterified and esterified AA concentrations, and AA incorporation and turnover in brain phospholipid. To test whether CLZ produces similar changes, we used our in vivo fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days; or 1 day after CLZ washout. [1-14C]AA was infused intravenously for 5 min, arterial plasma was collected and microwaved brain was analyzed. CLZ increased incorporation coefficients ki? and rates Jin,i of plasma unesterified AA into brain phospholipids i, while decreasing plasma unesterified but not esterified AA. These effects disappeared after washout. Thus, CLZ and OLZ similarly downregulated kinetics and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma unesterified AA availability. Atypical antipsychotics and mood stabilizers may be therapeutic in BD by downregulating, indirectly or directly respectively, the elevated brain AA cascade of that disease.

Modi, Hiren R.; Taha, Ameer Y.; Kim, Hyung-Wook; Chang, Lisa; Rapoport, Stanley I.; Cheon, Yewon

2012-01-01

114

Astaxanthin reduces ischemic brain injury in adult rats  

PubMed Central

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats.

Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.

2009-01-01

115

Acute effects of changing plasma osmolality and colloid oncotic pressure on the formation of brain edema after cryogenic injury.  

PubMed

The cerebral effects of alterations in plasma osmolality (Osm) and colloid oncotic pressure (COP) were examined in normocarbic, normothermic, pentobarbital-anesthetized rabbits that had been subjected to cryogenic brain injury. Monitored variables in all animals included mean arterial, right atrial, and intracranial pressures (MAP, CVP, and ICP), electroencephalographic (EEG) recordings, and cerebral blood flow (CBF). When surgical preparation was complete, a left parietal lesion was produced with liquid nitrogen. Group 1 (control, n = 8) animals subsequently received only maintenance fluids [lactated Ringer's solution (LR)]. One hour after injury, 3 other groups of animals underwent 45 minutes of plasmapheresis, carried out by arterial phlebotomy (packed red cells returned), with separated plasma being replaced by one of three fluids given in amounts sufficient to maintain MAP and CVP at baseline values. The three fluids were 1) 6% hetastarch in hypo-osmotic LR [Group 2 (Hypo-Osm), n = 6; COP = 21 mm Hg, Osm = 130 mOsm/kg]; 2) iso-osmotic LR [Group 3 (Hypo-COP), n = 8; COP = 0; Osm = 305]; and 3) 6% hetastarch in iso-osmotic LR [Group 4 (Iso-Osm/COP), n = 8; COP = 21, Osm = 310]. The animals were killed by exsanguination 25 minutes after completion of plasmapheresis. The brain was removed, the hemispheres separated, weighed, and sliced, and the specific gravities (SpGr) of the regional tissue determined. There were no differences in MAP, CVP, regional CBF, or EEG activity among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2716975

Kaieda, R; Todd, M M; Cook, L N; Warner, D S

1989-05-01

116

TMEM106B expression is reduced in Alzheimer's disease brains  

PubMed Central

Introduction TMEM106B is a transmembrane glycoprotein of unknown function located within endosome/lysosome compartments expressed ubiquitously in various cell types. Previously, the genome-wide association study (GWAS) identified a significant association of TMEM106B single nucleotide polymorphisms (SNPs) with development of frontotemporal lobar degeneration with ubiquitinated TAR DNA-binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in the patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent studies indicate that TMEM106B plays a pathological role in various neurodegenerative diseases, including Alzheimer’s disease (AD). However, at present, the precise levels of TMEM106B expression in AD brains remain unknown. Methods By quantitative reverse transcription (RT)-PCR (qPCR), western blot and immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson’s disease, multiple system atrophy and non-neurological cases. Results In AD brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN mRNA levels were elevated, compared with the levels in non-AD brains. In all brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal neurons, and some populations of oligodendrocytes, reactive astrocytes and microglia with the location in the cytoplasm. In AD brains, surviving neurons expressed intense TMEM106B immunoreactivity, while senile plaques, neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B, intensely expressed PGRN. Conclusions We found an inverse relationship between TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains, suggesting a key role of TMEM106B in the pathological processes of AD.

2014-01-01

117

Fluid Balance, Complications, and Brain Tissue Oxygen Tension Monitoring Following Severe Traumatic Brain Injury  

Microsoft Academic Search

Background  Refractory intracranial hypertension (RIH) frequently complicates severe traumatic brain injury (TBI) and is associated with\\u000a worse outcomes. Aggressive fluid resuscitation contributes to the development of peripheral and pulmonary edema, but an effect\\u000a on cerebral edema is not well established. Some clinicians, including advocates of the “Lund Concept”, practice fluid restriction\\u000a as a means of limiting cerebral edema and reducing intracranial

Jeffrey J. Fletcher; Karen Bergman; Paul A. Blostein; Andreas H. Kramer

2010-01-01

118

Cilnidipine induced ankle edema  

PubMed Central

Cilnidipine is a 4th generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema.

Annil, Vishal R.; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-01-01

119

Treatment of Cerebral Edema  

Microsoft Academic Search

Background: Cerebral edema is a potentially devastating compli- cation of various acute neurologic disorders. Its successful treatment may save lives and preserve neurologic function. Review Summary: Different pathophysiological mechanisms are responsible for the formation of cytotoxic and vasogenic edema. Yet, these 2 types of edema often coexist and their treatment tends to overlap, with the exception of corticosteroids, which should

Alejandro A. Rabinstein

2006-01-01

120

Cilnidipine induced ankle edema.  

PubMed

Cilnidipine is a 4(th) generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema. PMID:24987189

Annil, Vishal R; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-05-01

121

Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing.  

PubMed

Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA methylation patterns in mammalian genomes such as human, mouse and rat. The methylome of the zebrafish, an important animal model, has not yet been characterized at base-pair resolution using RRBS. Therefore, we evaluated the technique of RRBS in this model organism by generating four single-nucleotide resolution DNA methylomes of adult zebrafish brain. We performed several simulations to show the distribution of fragments and enrichment of CpGs in different in silico reduced representation genomes of zebrafish. Four RRBS brain libraries generated 98 million sequenced reads and had higher frequencies of multiple mapping than equivalent human RRBS libraries. The zebrafish methylome indicates there is higher global DNA methylation in the zebrafish genome compared with its equivalent human methylome. This observation was confirmed by RRBS of zebrafish liver. High coverage CpG dinucleotides are enriched in CpG island shores more than in the CpG island core. We found that 45% of the mapped CpGs reside in gene bodies, and 7% in gene promoters. This analysis provides a roadmap for generating reproducible base-pair level methylomes for zebrafish using RRBS and our results provide the first evidence that RRBS is a suitable technique for global methylation analysis in zebrafish. PMID:23975027

Chatterjee, Aniruddha; Ozaki, Yuichi; Stockwell, Peter A; Horsfield, Julia A; Morison, Ian M; Nakagawa, Shinichi

2013-09-01

122

Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing  

PubMed Central

Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA methylation patterns in mammalian genomes such as human, mouse and rat. The methylome of the zebrafish, an important animal model, has not yet been characterized at base-pair resolution using RRBS. Therefore, we evaluated the technique of RRBS in this model organism by generating four single-nucleotide resolution DNA methylomes of adult zebrafish brain. We performed several simulations to show the distribution of fragments and enrichment of CpGs in different in silico reduced representation genomes of zebrafish. Four RRBS brain libraries generated 98 million sequenced reads and had higher frequencies of multiple mapping than equivalent human RRBS libraries. The zebrafish methylome indicates there is higher global DNA methylation in the zebrafish genome compared with its equivalent human methylome. This observation was confirmed by RRBS of zebrafish liver. High coverage CpG dinucleotides are enriched in CpG island shores more than in the CpG island core. We found that 45% of the mapped CpGs reside in gene bodies, and 7% in gene promoters. This analysis provides a roadmap for generating reproducible base-pair level methylomes for zebrafish using RRBS and our results provide the first evidence that RRBS is a suitable technique for global methylation analysis in zebrafish.

Chatterjee, Aniruddha; Ozaki, Yuichi; Stockwell, Peter A; Horsfield, Julia A; Morison, Ian M; Nakagawa, Shinichi

2013-01-01

123

Reduced predictable information in brain signals in autism spectrum disorder  

PubMed Central

Autism spectrum disorder (ASD) is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS)—a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the past state of a process and its next measurement. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG) signals in 10 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, 12 task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD.

Gomez, Carlos; Lizier, Joseph T.; Schaum, Michael; Wollstadt, Patricia; Grutzner, Christine; Uhlhaas, Peter; Freitag, Christine M.; Schlitt, Sabine; Bolte, Sven; Hornero, Roberto; Wibral, Michael

2014-01-01

124

Traumatic Brain Injury Reduces Soluble Extracellular Amyloid-? in Mice: A Methodologically Novel Combined Microdialysis- Controlled Cortical Impact Study  

PubMed Central

Acute amyloid-? peptide (A?) deposition has been observed in young traumatic brain injury (TBI) patients, leading to the hypothesis that elevated extracellular A? levels could underlie the increased risk of dementia following TBI. However, a recent microdialysis-based study in human brain injury patients found that extracellular A? dynamics correlate with changes in neurological status. Because neurological status is generally diminished following injury, this correlation suggested the alternative hypothesis that soluble extracellular A? levels may instead be reduced after TBI relative to baseline. We have developed a methodologically novel mouse model that combines experimental controlled cortical impact TBI with intracerebral microdialysis. In this model, we found that A? levels in microdialysates were immediately decreased by 25–50% in the ipsilateral hippocampus following TBI. This result was found in PDAPP, Tg2576, and Tg2576-ApoE2 transgenic mice producing human A? plus wild-type animals. Changes were not due to altered probe function, edema, changes in APP levels, or A? deposition. Similar decreases in A? were observed in phosphate buffered saline-soluble tissue extracts. Hippocampal electroencephalographic activity was also decreased up to 40% following TBI, and correlated with reduced microdialysate A? levels. These results support the alternative hypothesis that post-injury extracellular soluble A? levels are acutely decreased relative to baseline. Reduced neuronal activity may contribute, though the underlying mechanisms have not been definitively determined. Further work will be needed to assess the dynamics of insoluble and oligomeric A? after TBI.

Schwetye, Katherine E.; Cirrito, John R.; Esparza, Thomas J.; Mac Donald, Christine L.; Holtzman, David M.; Brody, David L.

2010-01-01

125

Diabetic ketoacidosis and cerebral edema.  

PubMed

Cerebral edema is the leading cause of death in children presenting in diabetic ketoacidosis and occurs in 0.2 to 1% of cases. The osmolar gradient caused by the high blood glucose results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space and contraction of cell volume. Correction with insulin and intravenous fluids can result in a rapid reduction in effective osmolarity, reversal of the fluid shift and the development of cerebral edema. The goals for treatment should be a combination of intravenous fluid and insulin that results in a gradual reduction of the effective osmolarity over a 36- to 48-hour period, thereby avoiding rapid expansion of the ICF compartment and brain swelling. PMID:12011666

Bohn, Desmond; Daneman, Denis

2002-06-01

126

Macular edema. Miscellaneous.  

PubMed

This chapter provides the reader with practical information to be applied to the various remaining causes of macular edema. Some clinical cases of macular edema linked to ocular diseases like postradiotherapy for ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edema occurring after retinal detachment or after diverse systemic or local treatment use is often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. In other cases, as in tractional myopic vitreoschisis, the delay to observe a significant improvement of the vision after surgery should be long. Finally, macular edema associated with hemangiomas or macroaneurysms should be treated, if symptomatic, using the same current treatment as in diabetic macular edema or exudative macular degeneration. PMID:20703051

Creuzot-Garcher, Catherine; Wolf, Sebastian

2010-01-01

127

Macular edema: miscellaneous.  

PubMed

This article provides the reader with practical information to be applied to the various remaining causes of macular edema. Some macular edemas linked to ocular diseases like radiotherapy after ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edemas occurring after retinal detachment or after some systemic or local treatment use are often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. However, the delay to observe a significant improvement of vision after surgery should be long, as usually observed in tractional myopic vitreoschisis. Finally, some circumstances of macular edemas such as hemangiomas or macroaneurysms should be treated, if symptomatic, with the treatments currently used in diabetic macular edema or exudative macular degeneration. PMID:23264332

Creuzot-Garcher, Catherine; Jonas, Jost; Wolf, Sebastian

2011-01-01

128

High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour  

PubMed Central

To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

2012-01-01

129

Changes in brain morphology in albinism reflect reduced visual acuity.  

PubMed

Albinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream. PMID:23039995

Bridge, Holly; von dem Hagen, Elisabeth A H; Davies, George; Chambers, Claire; Gouws, Andre; Hoffmann, Michael; Morland, Antony B

2014-07-01

130

Pathophysiology of Macular Edema  

Microsoft Academic Search

Macular edema is defined as an accumulation of fluid in the outer plexiform layer and the inner nuclear layer as well as a swelling of Müller cells of the retina. It consists of a localized expansion of the retinal extracellular space (sometimes associated with the intracellular space) in the macular area. Macular edema is a common cause of a sudden

Stefan Scholl; Janna Kirchhof; Albert J. Augustin

2010-01-01

131

High Altitude Cerebral Edema  

Microsoft Academic Search

Hackett, Peter H., and Robert C. Roach. High altitude cerebral edema. High Alt. Med. Biol. 5:136-146, 2004.—This review focuses on the epidemiology, clinical description, pathophysiol- ogy, treatment, and prevention of high altitude cerebral edema (HACE). HACE is an uncom- mon and sometimes fatal complication of traveling too high, too fast to high altitudes. HACE is distinguished by disturbances of consciousness

Peter H. Hackett; Robert C. Roach

2004-01-01

132

Cerebral edema complicating eclampsia  

Microsoft Academic Search

Objective: This study was undertaken to describe and correlate clinical findings with computed tomographic and magnetic resonance imaging scan results in 10 women with eclampsia and widespread cerebral edema. Study Design: This was a clinical descriptive study of 10 women with eclampsia and symptomatic cerebral edema who were encountered at Parkland Hospital from 1986 through 1998. During this 13-year period

F. Gary Cunningham; Diane Twickler

2000-01-01

133

Microhemorrhages in nonfatal high-altitude cerebral edema  

Microsoft Academic Search

Vasogenic edema in the corpus callosum is a characteristic finding in high-altitude cerebral edema (HACE). Furthermore, microhemorrhages have been found at autopsies in brains of HACE victims. The objective of this study was to determine if microhemorrhages also occur in nonlethal HACE. Consequently, magnetic resonance imaging (MRI) was performed in patients who had suffered from HACE and in patients who

Kai Kallenberg; Christoph Dehnert; Arnd Dörfler; Peter D Schellinger; Damian M Bailey; Michael Knauth; Peter D Bärtsch

2008-01-01

134

Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis  

Microsoft Academic Search

Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. We studied the roles of acidosis, plasma osmolality, and organic osmolytes in the pathogenesis of cerebral edema in an animal model of diabetes mellitus. Normonatremic rats with streptozotocin-induced nonketotic (NKD) and ketotic (DKA) diabetes were sacrificed before or after treatment with hypotonic saline and insulin. Brains were analyzed for water, electrolyte,

Stephen M Silver; Edward C Clark; Barbara M Schroeder; Richard H Sterns

1997-01-01

135

Inhibiting mitochondrial ?-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain.  

PubMed

Schönfeld and Reiser recently hypothesized that fatty acid ?-oxidation is a source of oxidative stress in the brain. To test this hypothesis, we inhibited brain mitochondrial ?-oxidation with methyl palmoxirate (MEP) and measured oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites were reduced with few effects on enzymatically derived metabolites. Our finding confirms the hypothesis that reduced fatty acid ?-oxidation decreases oxidative stress in the brain and ?-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress. PMID:24326387

Chen, Chuck T; Trépanier, Marc-Olivier; Hopperton, Kathryn E; Domenichiello, Anthony F; Masoodi, Mojgan; Bazinet, Richard P

2014-03-01

136

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.  

PubMed

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge. PMID:23904096

Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

2013-11-01

137

Acute Blast Injury Reduces Brain Abeta in Two Rodent Species  

PubMed Central

Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The ?-amyloid (A?) peptide associated with the development of Alzheimer’s disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain A? following experimental blast injury using enzyme-linked immunosorbent assays for A? 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain A? levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the ?-secretase, ?-site APP cleaving enzyme 1, and the ?-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering A? production may not be effective for treating acute blast injury to the brain.

De Gasperi, Rita; Gama Sosa, Miguel A.; Kim, Soong Ho; Steele, John W.; Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A.; DeKosky, Steven T.; McCarron, Richard M.; Nambiar, Madhusoodana P.; Gandy, Sam; Ahlers, Stephen T.; Elder, Gregory A.

2012-01-01

138

Role of vasopressin and its antagonism in stroke related edema.  

PubMed

Although many approaches have been tried in the attempt to reduce the devastating impact of stroke, tissue plasminogen activator for thromboembolic stroke is the only proved, effective acute stroke treatment to date. Vasopressin, an acute-phase reactant, is released after brain injury and is partially responsible for the subsequent inflammatory response via activation of divergent pathways. Recently there has been increasing interest in vasopressin because it is implicated in inflammation, cerebral edema, increased intracerebral pressure, and cerebral ion and neurotransmitter dysfunctions after cerebral ischemia. Additionally, copeptin, a byproduct of vasopressin production, may serve as a promising independent marker of tissue damage and prognosis after stroke, thereby corroborating the role of vasopressin in acute brain injury. Thus, vasopressin antagonists have a potential role in early stroke intervention, an effect thought to be mediated via interactions with aquaporin receptors, specifically aquaporin-4. Despite some ambiguity, vasopressin V1a receptor antagonism has been consistently associated with attenuated secondary brain injury and edema in experimental stroke models. The role of the vasopressin V2 receptor remains unclear, but perhaps it is involved in a positive feedback loop for vasopressin expression. Despite the encouraging initial findings we report here, future research is required to characterize further the utility of vasopressin antagonists in treatment of stroke. © 2014 Wiley Periodicals, Inc. PMID:24823792

Ameli, Pouya A; Ameli, Neema J; Gubernick, David M; Ansari, Saeed; Mohan, Shekher; Satriotomo, Irawan; Buckley, Alexis K; Maxwell, Christopher W; Nayak, Vignesh H; Shushrutha Hedna, Vishnumurthy

2014-09-01

139

High Altitude Pulmonary Edema.  

National Technical Information Service (NTIS)

A centrineurogenic etiology for the pulmonary changes of 'High Altitude Pulmonary Edema' (HAPE) has been established. Respiratory hypoxia leads to the pathological pulmonary complex in unprotected beagles. These pulmonary changes are induced by isolated c...

G. Moss

1973-01-01

140

Edema: diagnosis and management.  

PubMed

Edema is an accumulation of fluid in the interstitial space that occurs as the capillary filtration exceeds the limits of lymphatic drainage, producing noticeable clinical signs and symptoms. The rapid development of generalized pitting edema associated with systemic disease requires timely diagnosis and management. The chronic accumulation of edema in one or both lower extremities often indicates venous insufficiency, especially in the presence of dependent edema and hemosiderin deposition. Skin care is crucial in preventing skin breakdown and venous ulcers. Eczematous (stasis) dermatitis can be managed with emollients and topical steroid creams. Patients who have had deep venous thrombosis should wear compression stockings to prevent postthrombotic syndrome. If clinical suspicion for deep venous thrombosis remains high after negative results are noted on duplex ultrasonography, further investigation may include magnetic resonance venography to rule out pelvic or thigh proximal venous thrombosis or compression. Obstructive sleep apnea may cause bilateral leg edema even in the absence of pulmonary hypertension. Brawny, nonpitting skin with edema characterizes lymphedema, which can present in one or both lower extremities. Possible secondary causes of lymphedema include tumor, trauma, previous pelvic surgery, inguinal lymphadenectomy, and previous radiation therapy. Use of pneumatic compression devices or compression stockings may be helpful in these cases. PMID:23939641

Trayes, Kathryn P; Studdiford, James S; Pickle, Sarah; Tully, Amber S

2013-07-15

141

[Cardiogenic and non cardiogenic pulmonary edema: pathomechanisms and causes].  

PubMed

The development of pulmonary edema is divided in cardiogenic and non-cardiogenic. Cardiogenic edema pathogenically is caused by elevated hydrostatic pressure in the pulmonary capillaries due to left sided congestive heart failure. Non-cardiogenic pulmonary edema is categorized depending on the underlying pathogenesis in low-alveolar pressure, elevated permeability or neurogenic edema. Some important examples of causes are upper airway obstruction like in laryngeal paralysis or strangulation for low alveolar pressure, leptospirosis and ARDS for elevated permeability, and epilepsy, brain trauma and electrocution for neurogenic edema. The differentiation between cardiogenic versus non-cardiogenic genesis is not always straightforward, but most relevant, because treatment markedly differs between the two. Of further importance is the identification of the specific underlying cause in non-cardiogenic edema, not only for therapeutic but particularly for prognostic reasons. Depending on the cause the prognosis ranges from very poor to good chance of complete recovery. PMID:20582896

Glaus, T; Schellenberg, S; Lang, J

2010-07-01

142

Severe cerebral edema in a patient with anasarca and hypernatremia.  

PubMed

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure. PMID:1541060

Wacks, I; Oster, J R; Roth, D; Norenberg, M; Gardner, L B; Perez, G O; Burke, G; Milgrom, M

1992-01-01

143

Chronic oral or intraarticular administration of docosahexaenoic acid reduces nociception and knee edema and improves functional outcomes in a mouse model of Complete Freund's Adjuvant-induced knee arthritis  

PubMed Central

Introduction Clinical and preclinical studies have shown that supplementation with ?-3 polyunsaturated fatty acids (?-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ?-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ?-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis. Methods Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 ?g/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection. Results The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA. Conclusions To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and anti-inflammatory effects as individual ?-3 PUFAs following sustained systemic and intraarticular administration in a mouse model of CFA-induced knee arthritis. The results suggest that DHA treatment may offer a new therapeutic approach to alleviate inflammation as well as a beneficial effect on pain-related functional disabilities in RA patients.

2014-01-01

144

The use of Hypertonic Saline in the Treatment of Post-Traumatic Cerebral Edema: A Review  

Microsoft Academic Search

Effective methods for treating cerebral edema have recently become a matter of both extensive research and significant debate within the neurosurgery and trauma surgery communities. The pathophysiologic progression and outcome of different forms of cerebral edema associated with traumatic brain injury have yet to be fully elucidated. There are heterogeneous factors influencing the onset and progress of post-traumatic cerebral edema,

Jeffrey E. Catrambone; Wenzhuan He; Charles J. Prestigiacomo; Tracy K. McIntosh; Peter W. Carmel; Allen Maniker

2008-01-01

145

Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis  

Microsoft Academic Search

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, animal studies suggest an association between reduced hippocampal neurogenesis and depressive-like behavior. These associations were predominantly established based on responses to antidepressant drugs and alterations in BDNF levels and neurogenesis in depressive patients or animal models for depressive behavior. Nevertheless, there is no

D Taliaz; N Stall; D E Dar; A Zangen

2010-01-01

146

Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring  

Microsoft Academic Search

Object. An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is rec- ommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the

Michael F. Stiefel; Alejandro Spiotta; Vincent H. Gracias; Alicia M. Garuffe; Oscar Guillamondegui; Eileen Maloney-Wilensky; Stephanie Bloom; M. Sean Grady; Peter D. LeRoux

2005-01-01

147

Glutamate transporter type 3 knockout reduces brain tolerance to focal brain ischemia in mice  

PubMed Central

Excitatory amino-acid transporters (EAATs) transport glutamate into cells under physiologic conditions. Excitatory amino-acid transporter type 3 (EAAT3) is the major neuronal EAAT and also uptakes cysteine, the rate-limiting substrate for synthesis of glutathione. Thus, we hypothesize that EAAT3 contributes to providing brain ischemic tolerance. Male 8-week-old EAAT3 knockout mice on CD-1 mouse gene background and wild-type CD-1 mice were subjected to right middle cerebral artery occlusion for 90?minutes. Their brain infarct volumes, neurologic functions, and brain levels of glutathione, nitrotyrosine, and 4-hydroxy-2-nonenal (HNE) were evaluated. The EAAT3 knockout mice had bigger brain infarct volumes and worse neurologic deficit scores and motor coordination functions than did wild-type mice, no matter whether these neurologic outcome parameters were evaluated at 24?hours or at 4 weeks after brain ischemia. The EAAT3 knockout mice contained higher levels of HNE in the ischemic penumbral cortex and in the nonischemic cerebral cortex than did wild-type mice. Glutathione levels in the ischemic and nonischemic cortices of EAAT3 knockout mice tended to be lower than those of wild-type mice. Our results suggest that EAAT3 is important in limiting ischemic brain injury after focal brain ischemia. This effect may involve attenuating brain oxidative stress.

Li, Liaoliao; Zuo, Zhiyi

2011-01-01

148

Reduced Fluorescein Angiography and Fundus Photography Use in the Management of Neovascular Macular Degeneration and Macular Edema During the Past Decade  

PubMed Central

Purpose. We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME). Methods. Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared. Results. From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME. Conclusions. Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.

Schneider, Eric W.; Mruthyunjaya, Prithvi; Talwar, Nidhi; Harris Nwanyanwu, Kristen; Nan, Bin; Stein, Joshua D.

2014-01-01

149

The phosphodiesterase-4 inhibitor rolipram protects from ischemic stroke in mice by reducing blood-brain-barrier damage, inflammation and thrombosis.  

PubMed

Blood-brain-barrier (BBB) disruption, inflammation and thrombosis are important steps in the pathophysiology of acute ischemic stroke but are still inaccessible to therapeutic interventions. Rolipram specifically inhibits the enzyme phosphodiesterase (PDE) 4 thereby preventing the inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to relief inflammation and BBB damage in a variety of neurological disorders. We investigated the therapeutic potential of rolipram in a model of brain ischemia/reperfusion injury in mice. Treatment with 10mg/kg rolipram, but not 2 mg/kg rolipram, 2 h after 60 min of transient middle cerebral artery occlusion (tMCAO) reduced infarct volumes by 50% and significantly improved clinical scores on day 1 compared with vehicle-treated controls. Rolipram maintained BBB function upon stroke as indicated by preserved expression of the tight junction proteins occludin and claudin-5. Accordingly, the formation of vascular brain edema was strongly attenuated in mice receiving rolipram. Moreover, rolipram reduced the invasion of neutrophils as well as the expression of the proinflammatory cytokines IL-1? and TNF? but increased the levels of TGF?-1. Finally, rolipram exerted antithrombotic effects upon stroke and fewer neurons in the rolipram group underwent apoptosis. Rolipram is a multifaceted antiinflammatory and antithrombotic compound that protects from ischemic neurodegeneration in clinically meaningful settings. PMID:23570902

Kraft, Peter; Schwarz, Tobias; Göb, Eva; Heydenreich, Nadine; Brede, Marc; Meuth, Sven G; Kleinschnitz, Christoph

2013-09-01

150

Latest advances in edema  

NASA Technical Reports Server (NTRS)

Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

Villavicencio, J. L.; Hargens, A. R.; Pikoulicz, E.

1996-01-01

151

Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat  

Microsoft Academic Search

The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular

J. Y. Jiang; B. G. Lyeth; M. Z. Kapasi; L. W. Jenkins; J. T. Povlishock

1992-01-01

152

Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain  

NASA Astrophysics Data System (ADS)

In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

Rendon, Cesar A.; Lilge, Lothar

2004-10-01

153

Tracheal mucosal edema in hydrostatic pulmonary edema.  

PubMed

Airway edema has been described in heart failure, and, in animal experiments, airway narrowing was observed with elevated left atrial pressure (Pla). On the basis of double-indicator-dilution principles using helium and dimethylether, we were able to measure a water compartment of the tracheal mucosa (VH2O) in dogs. Hypervolemia with an attendant increase in Pla caused by infusion of 2 liters of dextran increased VH2O from 368 +/- 71 (SE) to 794 +/- 177 microliters (P < 0.01). Pulmonary arterial wedge and central venous pressures (Pcv) rose concomitantly. Increases in pulmonary arterial wedge and Pcv by a left atrial balloon catheter produced similar increases in VH2O, whereas increases in Pcv alone by a right atrial balloon did not increase VH2O. Increasing VH2O by dextran infusion was associated with an increase in pulmonary resistance from 1.16 +/- 0.19 to 2.15 +/- 0.24 cmH2O.l-1.s (P < 0.01). These observations show that fluid accumulation in the lung during pulmonary congestion also involves extraparenchymal airways and is related to Pla rather than right atrial pressure. This indicates that sufficient collateral drainage exists during right-sided but not left-sided pressure elevations. PMID:7961256

Baier, H; Onorato, D; Barker, J; Wanner, A

1994-07-01

154

Luteolin Reduces Alzheimer's Disease Pathologies Induced by Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer’s disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (A?) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in A? depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.

Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J.; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V.; Sanberg, Paul R.; Tan, Jun

2014-01-01

155

Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury.  

PubMed

Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (A?) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in A? depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI. PMID:24413756

Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V; Sanberg, Paul R; Tan, Jun

2014-01-01

156

EDeMa  

Microsoft Academic Search

Das Projekt E-DeMa ist eines der sechs hier vorgestellten Projekte (Bild 1). In diesem Projekt beschäftigen wir uns sehr intensiv\\u000a mit der Fragestellung des Marktplatzes und des IKT Gateways. Vorab jedoch möchte ich Ihnen gerne noch einmal die entsprechenden\\u000a Konsortialpartner vorstellen, die in diesem Projekt mitwirken. RWE als Konsortialführerin auf der einen Seite, auf der linken\\u000a Seite dieses Bildes sehen

Michael Laskowski

157

Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke  

Microsoft Academic Search

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in

Xiaodong Luan; Jie Li; James P. McAllister; Fernando G. Diaz; Justin C. Clark; Richard D. Fessler; Yuchuan Ding

2004-01-01

158

Pathophysiology and treatment of edema following femoropopliteal bypass surgery.  

PubMed

Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovascular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this edema is not well understood. The Cochrane Library and Medline were used to retrieve literature on edema following peripheral bypass surgery. Factors other than local wound healing alone are suggested in the literature to play a role, given the severity and duration of this edema. Hyperemia, microvascular permeability, reperfusion-associated inflammation and lymphatic disruptions are likely to facilitate the development of edema. Preventive methods could be lymphatic-sparing surgery, intraoperative antioxidative therapy and postoperative elevation. Successful treatment strategies to reduce postoperative edema are based on lymph massage and external compression. In conclusion, the pathophysiology of edema following peripheral surgery is not fully understood, although reperfusion-associated inflammation and lymphatic disruptions are likely to play a crucial role. When future less-invasive techniques prove to be successful, postoperative edema might be minimized. Until then, a careful lymphatic-sparing dissection should be executed when performing a peripheral bypass reconstruction. Postoperatively, the use of compression stockings and leg elevation are currently the golden standards. PMID:22983547

te Slaa, A; Dolmans, D E J G J; Ho, G H; Moll, F L; van der Laan, L

2012-12-01

159

Propofol reduces inflammatory reaction and ischemic brain damage in cerebral ischemia in rats.  

PubMed

Our previous studies demonstrated that inflammatory reaction and neuronal apoptosis are the most important pathological mechanisms in ischemia-induced brain damage. Propofol has been shown to attenuate ischemic brain damage via inhibiting neuronal apoptosis. The present study was performed to evaluate the effect of propofol on brain damage and inflammatory reaction in rats of focal cerebral ischemia. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion, then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 h of ischemia. Neurological deficit scores, cerebral infarct size and morphological characteristic were measured 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was assessed 24 h after cerebral ischemia. Nuclear factor-kappa B (NF-?B) p65 expression in ischemic rat brain was detected by western blot. Cyclooxygenase-2 (COX-2) expression in ischemic rat brain was determined by immunohistochemistry. ELISA was performed to detect the serum concentration of tumor necrosis factor-? (TNF-?). Neurological deficit scores, cerebral infarct size and MPO activity were significantly reduced by propofol administration. Furthermore, expression of NF-?B, COX-2 and TNF-? were attenuated by propofol administration. Our results demonstrated that propofol (10 and 50 mg/kg) reduces inflammatory reaction and brain damage in focal cerebral ischemia in rats. Propofol exerts neuroprotection against ischemic brain damage, which might be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory genes. PMID:24610527

Shi, Song-Sheng; Yang, Wei-Zhong; Chen, Ye; Chen, Jian-Ping; Tu, Xian-Kun

2014-05-01

160

Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rats  

Microsoft Academic Search

Oxygen radicals play a crucial role in brain injury. Grape seed extract is a potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid arteries permanently ligated followed by 2.5h of hypoxia (8% oxygen). Grape seed extract, 50mg\\/kg, or vehicle was administered by i.p. 5min prior to hypoxia and 4h

Yangzheng Feng; Yi-Ming Liu; Jonathan D. Fratkins; Michael H. LeBlanc

2005-01-01

161

Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis.  

PubMed

Stem cell transplantation was introduced as a mean of cell replacement therapy, but the mechanism by which it confers clinical improvement in experimental models of neurological diseases is not clear. Here, we transplanted neural precursor cells (NPCs) into the ventricles of mice at day 6 after induction of chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Transplanted cells migrated into white matter tracts and attenuated the clinical course of disease. NPC transplantation down-regulated the inflammatory brain process at the acute phase of disease, as indicated by a reduction in the number of perivascular infiltrates and of brain CD3+ T cells, an increase in the number and proportion of regulatory T cells and a reduction in the expression of ICAM-1 and LFA-1 in the brain. Demyelination and acute axonal injury in this model are considered to result mainly from the acute inflammatory process and correlate well with the chronic neurological residua. In consequence to inhibition of brain inflammation, precursor cell transplantation attenuated the primary demyelinating process and reduced the acute axonal injury. As a result, the size of demyelinated areas and extent of chronic axonal pathology were reduced in the transplanted brains. We suggest that the beneficial effect of transplanted NPCs in chronic EAE is mediated, in part, by decreasing brain inflammation and reducing tissue injury. PMID:16472805

Einstein, Ofira; Grigoriadis, Nikolaos; Mizrachi-Kol, Rachel; Reinhartz, Etti; Polyzoidou, Eleni; Lavon, Iris; Milonas, Ioannis; Karussis, Dimitrios; Abramsky, Oded; Ben-Hur, Tamir

2006-04-01

162

Diabetic Macular Edema  

NASA Astrophysics Data System (ADS)

The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

163

Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.  

PubMed

Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD. PMID:24463179

Zhang, Huizhen; Guo, Shang; Zhang, Linlin; Jia, Liting; Zhang, Zhan; Duan, Hongbao; Zhang, Jingbin; Liu, Jingyan; Zhang, Weidong

2014-03-15

164

Aging Reduces the Stimulating Effect of Blue Light on Cognitive Brain Functions  

PubMed Central

Study Objectives: Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Design: Cross-sectional study. Setting: Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Participants: Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Intervention: Blue light administration. Measurements: We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results: Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. Conclusion: The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging. Citation: Daneault V; Hébert M; Albouy G; Doyon J; Dumont M; Carrier J; Vandewalle G. Aging reduces the stimulating effect of blue light on cognitive brain functions. SLEEP 2014;37(1):85-96.

Daneault, Veronique; Hebert, Marc; Albouy, Genevieve; Doyon, Julien; Dumont, Marie; Carrier, Julie; Vandewalle, Gilles

2014-01-01

165

[Differential diagnosis of leg edema].  

PubMed

Both generalized and localized edema needs to be submitted to a differential diagnostic investigation. In the case of edema affecting the lower extremities, in particular the Stemmer sign which is the inability to tent the skin at the dorsum of the toes is a useful distinguishing aid. If there is acute unilateral swelling of a leg, other processes with diffuse space-consuming processes need to be distinguished from deep venous thrombosis and secondary lymphedema. Chronic bilateral leg edema is usually due to a venous flowoff obstruction (stasis edema). Less commonly, lipedema or a primary lymphedema may be responsible for the swelling. PMID:15222499

Fries, R

2004-04-15

166

Irradiation of rat brain reduces P-glycoprotein expression and function  

PubMed Central

The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats were irradiated with single doses of 2–25?Gy followed by 10?mg?kg?1 of the P-gp substrate cyclosporine A (CsA) intravenously (i.v.), with once 15?Gy followed by CsA (10, 15 or 20?mg?kg?1), or with fractionated irradiation (4 × 5?Gy) followed by CsA (10?mg?kg?1) 5 days later. Additionally, four groups of three rats received 25?Gy once and were killed 10, 15, 20 or 25 days later. The brains were removed and P-gp detected immunohistochemically. P-gp function was assessed by [11C]carvedilol uptake using quantitative autoradiography. Irradiation increased [11C]carvedilol uptake dose-dependently, to a maximum of 20% above non irradiated hemisphere. CsA increased [11C]carvedilol uptake dose-dependently in both hemispheres, but more (P<0.001) in the irradiated hemisphere. Fractionated irradiation resulted in a lost P-gp expression 10 days after start irradiation, which coincided with increased [11C]carvedilol uptake. P-gp expression decreased between day 15 and 20 after single dose irradiation, and increased again thereafter. Rat brain irradiation results in a temporary decreased P-gp function.

Bart, J; Nagengast, W B; Coppes, R P; Wegman, T D; van der Graaf, W T A; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N H

2007-01-01

167

Reduced functional brain connectivity prior to and after disease onset in Huntington's disease???  

PubMed Central

Background Huntington's disease (HD) is characterised by both regional and generalised neuronal cell loss in the brain. Investigating functional brain connectivity patterns in rest in HD has the potential to broaden the understanding of brain functionality in relation to disease progression. This study aims to establish whether brain connectivity during rest is different in premanifest and manifest HD as compared to controls. Methods At the Leiden University Medical Centre study site of the TRACK-HD study, 20 early HD patients (disease stages 1 and 2), 28 premanifest gene carriers and 28 healthy controls underwent 3 T MRI scanning. Standard and high-resolution T1-weighted images and a resting state fMRI scan were acquired. Using FSL, group differences in resting state connectivity were examined for eight networks of interest using a dual regression method. With a voxelwise correction for localised atrophy, group differences in functional connectivity were examined. Results Brain connectivity of the left middle frontal and pre-central gyrus, and right post central gyrus with the medial visual network was reduced in premanifest and manifest HD as compared to controls (0.05 > p > 0.0001). In manifest HD connectivity of numerous widespread brain regions with the default mode network and the executive control network were reduced (0.05 > p > 0.0001). Discussion Brain regions that show reduced intrinsic functional connectivity are present in premanifest gene carriers and to a much larger extent in manifest HD patients. These differences are present even when the potential influence of atrophy is taken into account. Resting state fMRI could potentially be used for early disease detection in the premanifest phase of HD and for monitoring of disease modifying compounds.

Dumas, Eve M.; van den Bogaard, Simon J.A.; Hart, Ellen P.; Soeter, Roelof P.; van Buchem, Mark A.; van der Grond, Jeroen; Rombouts, Serge A.R.B.; Roos, Raymund A.C.

2013-01-01

168

Impaired geranylgeranyltransferase-I regulation reduces membrane-associated Rho protein levels in aged mouse brain.  

PubMed

Synaptic impairment rather than neuronal loss may be the leading cause of cognitive dysfunction in brain aging. Certain small Rho-GTPases are involved in synaptic plasticity, and their dysfunction is associated with brain aging and neurodegeneration. Rho-GTPases undergo prenylation by attachment of geranylgeranylpyrophosphate (GGPP) catalyzed by GGTase-I. We examined age-related changes in the abundance of Rho and Rab proteins in membrane and cytosolic fractions as well as of GGTase-I in brain tissue of 3- and 23-month-old C57BL/6 mice. We report a shift in the cellular localization of Rho-GTPases toward reduced levels of membrane-associated and enhanced cytosolic levels of those proteins in aged mouse brain as compared with younger mice. The age-related reduction in membrane-associated Rho proteins was associated with a reduction in GGTase-I? levels that regulates binding of GGPP to Rho-GTPases. Proteins prenylated by GGTase-II were not reduced in aged brain indicating a specific targeting of GGTase-I in the aged brain. Inhibition of GGTase-I in vitro modeled the effects of aging we observed in vivo. We demonstrate for the first time a decrease in membrane-associated Rho proteins in aged brain in association with down-regulation of GGTase-I?. This down-regulation could be one of the mechanisms causing age-related weakening of synaptic plasticity. Rho-GTPases are geranylgeranylated by transferase GGTase-I. Their prenylation is essential for their localization in membranes, the site of their activation and function. Despite elevated GGPP levels in brains of aged (23 months) mice compared to younger (3 months) mice as well as in GGTI-2133-treated SH-SY5Y cells, the amount of total (homogenate) Rho-GTPases (Rac1, RhoA, and Cdc42) was unchanged. Treatment with the GGTaseI-inhibitor GGTI-2133 decreased prenylation of Rho-GTPases in membrane preparations of aged mice and SH-SY5Y, correlating with the reduction of relative GGTase activity, GGTaseIß protein, and mRNA levels. As Rac1, RhoA, and Cdc42 are associated with synaptogenesis, we examined the synaptic marker proteins GAP43 and synaptophysin. GAP43 and synaptophysin declined in an age-related manner in the mouse brain and were also reduced in our in vitro model. Faulty regulation of Rho proteins in aged brain is associated with a specific deficit in GGTase-I?, which could contribute to age-related deficits in neuronal outgrowth. PMID:24428713

Afshordel, Sarah; Wood, Wellington Gibson; Igbavboa, Urule; Muller, Walter E; Eckert, Gunter P

2014-05-01

169

Cerebral embolism: local CFBF and edema measured by CT scanning and Xe inhalation. [Baboons  

SciTech Connect

Serial CT scans were made in baboons after cerebral embolization during stable Xe inhalation for measuring local values for CBF and lambda (brain-blood partition or solubility coefficients), followed by iodine infusion for detecting blood-brain barrier (BBB) damage. Persistent zones of zero flow surrounded by reduced flow were measured predominantly in subcortical regions, which showed gross and microscopic evidence of infarction at necropsy. Overlying cortex was relatively spared. Reduced lambda values attributed to edema appeared within 3 to 5 minutes and progressed up to 60 minutes. Damage to BBB with visible transvascular seepage of iodine began to appear 1 to 1 1/2 hours after embolism. In chronic animals, lambda values were persistently reduced in areas showing histologic infarction. Contralateral hemispheric CBF increased for the first 15 minutes after embolism, followed by progressive reduction after 30 minutes (diaschisis).

Meyer, J.S.; Yamamoto, M.; Hayman, L.A.; Sakai, F.; Nakajima, S.; Armstrong, D.

1980-01-01

170

Cerebral embolism: local CBF and edema measured by CT scanning and Xe inhalation  

SciTech Connect

Serial CT scans were made in baboons after cerebral embolization during stable Xe inhalation for measuring local values for CBF and lambda (brain-blood partition or solubility coefficients), followed by iodine infusion for detecting blood-brain barrier (BBB) damage. Supplementary 133Xe CBF measurements were made at corresponding intervals. Persistent zones of zero flow surrounded by reduced flow were measured predominantly in subcortical regions, which showed gross and microscopic evidence of infarction at necropsy. Overylng cortex was relatively spared. Reduced lambda values attributed to edema appeared with in 3 to 5 minutes and progressed up to 60 minutes. Damage to BBB with visible transvascular seepage of iodine began to appear 1-11/2 hours after embolism. In chronic animals, lambda values were persistently reduced in areas showing histologic infarction. Contralateral hemispheric CBF increased for the first 15 minutes after embolism, followed by progressive reduction after 30 minutes (diaschisis).

Meyer, J.S.; Yamamoto, M.; Hayman, L.A.; Sakai, F.; Nakajima, S.; Armstrong, D.

1980-01-01

171

Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.  

PubMed

Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. PMID:23956805

Ostrowski, Robert P; Schulte, Reinhard W; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S; Zhang, John H

2012-12-01

172

Acute Splenic Irradiation Reduces Brain Injury in the Rat Focal Ischemic Stroke Model  

PubMed Central

Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen’s inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain.

Ostrowski, Robert P.; Schulte, Reinhard W.; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S.; Zhang, John H.

2013-01-01

173

Reduced Inflammatory Phenotype in Microglia Derived from Neonatal Rat Spinal Cord versus Brain  

PubMed Central

Microglia are the primary immune cells of the central nervous system (CNS). Membrane bound sensors on their processes monitor the extracellular environment and respond to perturbations of the CNS such as injury or infection. Once activated, microglia play a crucial role in determining neuronal survival. Recent studies suggest that microglial functional response properties vary across different regions of the CNS. However, the activation profiles of microglia derived from the spinal cord have not been evaluated against brain microglia in vitro. Here, we studied the morphological properties and secretion of inflammatory and trophic effectors by microglia derived from the brain or spinal cord of neonatal rats under basal culture conditions and after activation with lipopolysaccharide (LPS). Our results demonstrate that spinal microglia assume a less inflammatory phenotype after LPS activation, with reduced release of the inflammatory effectors tumor necrosis factor alpha, interleukin-1 beta, and nitric oxide, a less amoeboid morphology, and reduced phagocytosis relative to brain-derived microglia. Phenotypic differences between brain and spinal microglia are an important consideration when evaluating anti-inflammatory or immunomodulatory therapies for brain versus spinal injury.

Baskar Jesudasan, Sam Joshva; Todd, Kathryn G.; Winship, Ian R.

2014-01-01

174

Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis  

PubMed Central

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, animal studies suggest an association between reduced hippocampal neurogenesis and depressive-like behavior. These associations were predominantly established based on responses to antidepressant drugs and alterations in BDNF levels and neurogenesis in depressive patients or animal models for depressive behavior. Nevertheless, there is no direct evidence that the actual reduction of the BDNF protein in specific brain sites can induce depressive-like behaviors or affect neurogenesis in vivo. Using BDNF knockdown by RNA interference and lentiviral vectors injected into specific subregions of the hippocampus we show that a reduction in BDNF expression in the dentate gyrus, but not the CA3, reduces neurogenesis and affects behaviors associated with depression. Moreover, we show that BDNF has a critical function in neuronal differentiation, but not proliferation in vivo. Finally, we found that a specific BDNF knockdown in the ventral subiculum induces anhedonic-like behavior. These findings provide substantial support for the neurotrophic hypothesis of depression and specify anatomical and neurochemical targets for potential antidepressant interventions. Moreover, the specific effect of BDNF reduction on neuronal differentiation has broader implications for the study of neurodevelopment and neurodegenerative diseases.

Taliaz, D; Stall, N; Dar, D E; Zangen, A

2009-01-01

175

Edema and elasticity of a fronto-temporal decompressive craniectomy  

PubMed Central

Background: Decompressive craniectomy is undertaken for relief of brain herniation caused by acute brain swelling. Brain stiffness can be estimated by palpating the decompressive cranial defect and can provide some relatively subjective information to the neurosurgeon to help guide care. The goal of the present study was to objectively evaluate transcutaneous stiffness of the cranial defect using a tactile resonance sensor and to describe the values in patients with a decompressive window in order to characterize the clinical association between brain edema and stiffness. Methods: Data were prospectively collected from 13 of 37 patients who underwent a decompressive craniectomy in our hospital during a 5-year period. Transcutaneous stiffness was measured as change in frequency and as elastic modulus. Results: Stiffness variables of the decompressive site were measured without any adverse effect and subsequent calculations revealed change in frequency = 101.71 ± 36.42 Hz, and shear elastic modulus = 1.99 ± 1.11 kPa. Conclusions: The elasticity of stiffness of a decompressive site correlated with brain edema, cisternal cerebrospinal fluid pressure, and brain shift, all of which are related to acute brain edema.

Takada, Daikei; Nagai, Hidemasa; Moritake, Kouzo; Akiyama, Yasuhiko

2012-01-01

176

Cystoid Macular Edema in Bietti's Crystalline Retinopathy  

PubMed Central

A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole.

2014-01-01

177

Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency  

PubMed Central

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA.

Zhou, Fei; Guo, Jingchun; Cheng, Jieshi; Wu, Gencheng

2011-01-01

178

Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain  

PubMed Central

Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy (HIE). Methods This investigation employed primary cortical neuron cultures derived from neonatal rats subjected to oxygen and glucose deprivation (OGD) and a well-established neonatal rat hypoxia-ischemia model. Results HI caused brain tissue loss and impaired sensorimotor function and spatial memory while SP significantly reduced brain damage and improved neurological performance. These neuroprotective effects of SP are likely the result of improved cerebral metabolism as demonstrated by maintaining ATP levels and preventing an increase in intracellular reactive oxygen species (ROS) levels. SP treatment also decreased levels of Bax, a death signal for immature neurons, blocked caspases-3 activation, and activated a key survival signaling kinase, Akt, both in vitro and in vivo. Conclusion SP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.

Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua

2013-01-01

179

Chronic lithium feeding reduces upregulated brain arachidonic acid metabolism in HIV-1 transgenic rat  

PubMed Central

Background HIV-1 transgenic (Tg) rats, a model for human HIV-1 associated neurocognitive disorder (HAND), show upregulated markers of brain arachidonic acid (AA) metabolism with neuroinflammation after 7 months of age. Since lithium decreases AA metabolism in a rat lipopolysaccharide model of neuroinflammation, and may be useful in HAND, we hypothesized that lithium would dampen upregulated brain AA metabolism in HIV-1 Tg rats. Methods Regional brain AA incorporation coefficients k* and rates Jin, markers of AA signaling and metabolism, were measured in 81 brain regions using quantitative autoradiography, after intravenous [1-14C] AA infusion in unanesthetized 10-month-old HIV-1 Tg and age-matched wildtype rats that had been fed a control or LiCl diet for 6 weeks. Results k* and Jin for AA were significantly higher in HIV-1 Tg than wildtype rats fed the control diet. Lithium feeding reduced plasma unesterified AA concentration in both groups and Jin in wildtype rats, and blocked increments in k* (19 of 54 regions) and Jin (77 of 81 regions) in HIV-1 Tg rats. Conclusion These in vivo neuroimaging data indicate that lithium treatment dampened upregulated brain AA metabolism in HIV-1 Tg rats. Lithium may improve cognitive dysfunction and be neuroprotective in HIV-1 patients with HAND through a comparable effect.

Ramadan, Epolia; Basselin, Mireille; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

2012-01-01

180

The impact of erythropoietin on short-term changes in phosphorylation of brain protein kinases in a rat model of traumatic brain injury.  

PubMed

We found that recombinant human erythropoietin (rhEPO) reduced significantly the development of brain edema in a rat model of diffuse traumatic brain injury (TBI) (impact-acceleration model). In this study, we investigated the molecular and intracellular changes potentially involved in these immediate effects. Brain tissue nitric oxide (NO) synthesis, phosphorylation level of two protein kinases (extracellular-regulated kinase (ERK)-1/-2 and Akt), and brain water content were measured 1 (H1) and 2 h (H2) after insult. Posttraumatic administration of rhEPO (5,000 IU/kg body weight, intravenously, 30 mins after injury) reduced TBI-induced upregulation of ERK phosphorylation, although it increased Akt phosphorylation at H1. These early molecular changes were associated with a reduction in brain NO synthesis at H1 and with an attenuation of brain edema at H2. Intraventricular administration of the ERK-1/-2 inhibitor, U0126, or the Akt inhibitor, LY294002, before injury showed that ERK was required for brain edema formation, and that rhEPO-induced reduction of edema could involve the ERK pathway. These results were obtained in the absence of any evidence of blood-brain barrier damage on contrast-enhanced magnetic resonance images. The findings of our study indicate that the anti edematous effect of rhEPO could be mediated through an early inhibition of ERK phosphorylation after diffuse TBI. PMID:19809465

Valable, Samuel; Francony, Gilles; Bouzat, Pierre; Fevre, Marie-Cécile; Mahious, Nouara; Bouet, Valentine; Farion, Régine; Barbier, Emmanuel; Lahrech, Hana; Remy, Chantal; Petit, Edwige; Segebarth, Christoph; Bernaudin, Myriam; Payen, Jean-François

2010-02-01

181

The impact of erythropoietin on short-term changes in phosphorylation of brain protein kinases in a rat model of traumatic brain injury  

PubMed Central

We found that recombinant human erythropoietin (rhEPO) reduced significantly the development of brain edema in a rat model of diffuse traumatic brain injury (TBI) (impact-acceleration model). In this study, we investigated the molecular and intracellular changes potentially involved in these immediate effects. Brain tissue nitric oxide (NO) synthesis, phosphorylation level of two protein kinases (extracellular-regulated kinase (ERK)-1/-2 and Akt), and brain water content were measured 1 (H1) and 2?h (H2) after insult. Posttraumatic administration of rhEPO (5,000?IU/kg body weight, intravenously, 30?mins after injury) reduced TBI-induced upregulation of ERK phosphorylation, although it increased Akt phosphorylation at H1. These early molecular changes were associated with a reduction in brain NO synthesis at H1 and with an attenuation of brain edema at H2. Intraventricular administration of the ERK-1/-2 inhibitor, U0126, or the Akt inhibitor, LY294002, before injury showed that ERK was required for brain edema formation, and that rhEPO-induced reduction of edema could involve the ERK pathway. These results were obtained in the absence of any evidence of blood–brain barrier damage on contrast-enhanced magnetic resonance images. The findings of our study indicate that the anti edematous effect of rhEPO could be mediated through an early inhibition of ERK phosphorylation after diffuse TBI.

Valable, Samuel; Francony, Gilles; Bouzat, Pierre; Fevre, Marie-Cecile; Mahious, Nouara; Bouet, Valentine; Farion, Regine; Barbier, Emmanuel; Lahrech, Hana; Remy, Chantal; Petit, Edwige; Segebarth, Christoph; Bernaudin, Myriam; Payen, Jean-Francois

2010-01-01

182

Perspectives on Neonatal Hypoxia\\/Ischemia-Induced Edema Formation  

Microsoft Academic Search

Neonatal hypoxia\\/ischemia (HI) is the most common cause of developmental neurological, cognitive and behavioral deficits in\\u000a children, with hyperoxia (HHI) treatment being a clinical therapy for newborn resuscitation. Although cerebral edema is a\\u000a common outcome after HI, the mechanisms leading to excessive fluid accumulation in the brain are poorly understood. Given\\u000a the rigid nature of the bone-encased brain matter, knowledge

Diana Carolina Ferrari; Olivera Nesic; Jose Regino Perez-Polo

2010-01-01

183

Glioma-related edema: new insight into molecular mechanisms and their clinical implications  

PubMed Central

Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.

Lin, Zhi-Xiong

2013-01-01

184

Combined Immunochemotherapy With Reduced Whole-Brain Radiotherapy for Newly Diagnosed Primary CNS Lymphoma  

Microsoft Academic Search

Purpose Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR. Patients and Methods Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70)

Gaurav D. Shah; Joachim Yahalom; Denise D. Correa; Rose K. Lai; Jeffrey J. Raizer; David Schiff; Renato LaRocca; Barbara Grant; Lisa M. DeAngelis; Lauren E. Abrey

2010-01-01

185

Treatment of Experimental Cerebral Edema.  

National Technical Information Service (NTIS)

The edema associated with hemorrhagic cerebral lesions produced by focal freezing in subhuman primates (rhesus monkeys) was studied by quantitative chemical methods. This research involved measuring not only the hemispheric water, potassium, sodium, chlor...

G. M. Hass R. A. Clasen

1971-01-01

186

Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice.  

PubMed

Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice. PMID:12182887

Spittaels, K; Van den Haute, C; Van Dorpe, J; Terwel, D; Vandezande, K; Lasrado, R; Bruynseels, K; Irizarry, M; Verhoye, M; Van Lint, J; Vandenheede, J R; Ashton, D; Mercken, M; Loos, R; Hyman, B; Van der Linden, A; Geerts, H; Van Leuven, F

2002-01-01

187

Pulmonary Edema in Myasthenic Crisis  

PubMed Central

We report a previously asymptomatic 50-year-old lady who came with myasthenic crisis as initial presentation of myasthenia gravis. She developed pulmonary edema following intravenous immunoglobulin administration and had ischemic changes in ECG and left ventricular dysfunction on echocardiography. She improved with diuretics, dobutamine, and fluid restriction alone. This is the first report in English-language medical literature describing the association between myasthenic crisis and likely takotsubo cardiomyopathy-related pulmonary edema following intravenous immunoglobulin administration.

Anand, Uttara Swati; Arulneyam, Jayanthi

2013-01-01

188

Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial.  

PubMed

It is believed that glycogen synthase kinase-3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase-3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double-blind, placebo-controlled trial in patients with mild-to-moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52-week MRI. Automated, observer-independent, atlas-based, and mask-based volumetry was done on high-resolution, T1-weighted, three-dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: -1.3% ± 1.4% vs. -3.1% ± 2.3%, respectively), cerebrum (-1.3% ± 1.5% vs. -3.2% ± 2.1%, respectively), parietal lobe (-1.6% ± 1.9% vs. -4.1% ± 3.0%, respectively), and occipital lobe (-0.3% ± 1.8% vs. -2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. PMID:24488721

Höglinger, Günter U; Huppertz, Hans-Jürgen; Wagenpfeil, Stefan; Andrés, María V; Belloch, Vincente; León, Teresa; Del Ser, Teodoro

2014-04-01

189

[Symptomatic management of brain metastasis].  

PubMed

Indications and choice of antiepileptic drugs (AED), treatments for cerebral edema and prophylactic and curative treatments of thromboembolic complications of brain metastasis are discussed. PMID:23360760

Le Rhun, Emilie; Taillandier, Luc; Beauchene, Patrick; Bailon, Olivier; Dubois, François

2013-01-01

190

Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury.  

PubMed

After trauma brain injury, a large number of cells die, releasing neurotoxic chemicals into the extracellular medium, decreasing cellular glutathione levels and increasing reactive oxygen species that affect cell survival and provoke an enlargement of the initial lesion. Alpha-lipoic acid is a potent antioxidant commonly used as a treatment of many degenerative diseases such as multiple sclerosis or diabetic neuropathy. Herein, the antioxidant effects of lipoic acid treatment after brain cryo-injury in rat have been studied, as well as cell survival, proliferation in the injured area, gliogenesis and angiogenesis. Thus, it is shown that newborn cells, mostly corresponded with blood vessels and glial cells, colonized the damaged area 15 days after the lesion. However, lipoic acid was able to stimulate the synthesis of glutathione, decrease cell death, promote angiogenesis and decrease the glial scar formation. All those facts allow the formation of new neural tissue. In view of the results herein, lipoic acid might be a plausible pharmacological treatment after brain injury, acting as a neuroprotective agent of the neural tissue, promoting angiogenesis and reducing the glial scar formation. These findings open new possibilities for restorative strategies after brain injury, stroke or related disorders. PMID:22917609

Rocamonde, B; Paradells, S; Barcia, J M; Barcia, C; García Verdugo, J M; Miranda, M; Romero Gómez, F J; Soria, J M

2012-11-01

191

Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury  

PubMed Central

Delayed secondary biochemical and cellular changes after traumatic brain injury continue for months to years, and are associated with chronic neuroinflammation and progressive neurodegeneration. Physical activity can reduce inflammation and facilitate recovery after brain injury. Here, we investigated the time-dependent effects, and underlying mechanisms of post-traumatic exercise initiation on outcome after moderate traumatic brain injury using a well-characterized mouse controlled cortical impact model. Late exercise initiation beginning at 5 weeks after trauma, but not early initiation of exercise at 1 week, significantly reduced working and retention memory impairment at 3 months, and decreased lesion volume compared to non-exercise injury controls. Cognitive recovery was associated with attenuation of classical inflammatory pathways, activation of alternative inflammatory responses and enhancement of neurogenesis. In contrast, early initiation of exercise failed to alter behavioral recovery or lesion size, while increasing the neurotoxic pro-inflammatory responses. These data underscore the critical importance of timing of exercise initiation after trauma and its relation to neuroinflammation, and challenge the widely held view that effective neuroprotection requires early intervention.

Piao, Chun-Shu; Stoica, Bogdan A.; Wu, Junfang; Sabirzhanov, Boris; Zhao, Zaorui; Cabatbat, Rainier; Loane, David J.; Faden, Alan I.

2013-01-01

192

Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model.  

PubMed

We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species. PMID:11941374

Dodart, Jean-Cosme; Bales, Kelly R; Gannon, Kimberley S; Greene, Stephen J; DeMattos, Ronald B; Mathis, Chantal; DeLong, Cynthia A; Wu, Su; Wu, Xin; Holtzman, David M; Paul, Steven M

2002-05-01

193

Impaired brain development and reduced cognitive function in phospholipase D-deficient mice.  

PubMed

The phospholipases D (PLD1 and 2) are signaling enzymes that catalyze the hydrolysis of phosphatidylcholine to phosphatidic acid, a lipid second messenger involved in cell proliferation, and choline, a precursor of acetylcholine (ACh). In the present study, we investigated development and cognitive function in mice that were deficient for PLD1, or PLD2, or both. We found that PLD-deficient mice had reduced brain growth at 14-27 days post partum when compared to wild-type mice. In adult PLD-deficient mice, cognitive function was impaired in social and object recognition tasks. Using brain microdialysis, we found that wild-type mice responded with a 4-fold increase of hippocampal ACh release upon behavioral stimulation in the open field, while PLD-deficient mice released significantly less ACh. These results may be relevant for cognitive dysfunctions observed in fetal alcohol syndrome and in Alzheimer' disease. PMID:24813107

Burkhardt, Ute; Stegner, David; Hattingen, Elke; Beyer, Sandra; Nieswandt, Bernhard; Klein, Jochen

2014-06-20

194

Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.  

PubMed

We have previously shown that Idazoxan (IDA), an imidazoline 2 receptor ligand, is neuroprotective against spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE) in mouse, an animal modal of multiple sclerosis (MS). However, the protective mechanism remains unclear. Here, we provided evidence to show that IDA confers neuroprotection through reduction in blood-brain barrier (BBB) damage. EAE was induced by immunizing C57 BL/6 mice with myelin oligodendrocyte glycoprotein35-55 amino acid peptide (MOG35-55). IDA was administrated for 14 days after MOG immunization at 2mg/kg (i.p., bid). Significant reduction in BBB damage occurred in the IDA-treated group of mice compared with the saline-treated group, as evidenced by the reduction in Evan?s blue content in the brain tissue and the reduced BBB tight junction damage viewed under a transmission electron microscope. Moreover, EAE-induced reductions in tight junction proteins (JAM-1, Occludin, Claudin-5 and ZO-1) were also significantly ameliorated in IDA-treated mice, all of which supported the notion that IDA reduced BBB damage. Interestingly, the expression levels of extracellular matrix metalloproteinase-9 (MMP-9) and the ratio of MMP-9 against tissue inhibitor of metalloproteinase-1 (TIMP-1), which is known to be associated with MS-induced BBB damage, were significantly reduced in IDA-treated group, lending further support to the hypothesis that IDA confers brain protection through reducing BBB damage. This study raised a possibility that IDA is a promising pro-drug for development against MS. PMID:24797785

Wang, Xin-Shi; Fang, Hui-Lin; Chen, Yu; Liang, Shan-Shan; Zhu, Zhen-Guo; Zeng, Qing-Yi; Li, Jia; Xu, Hui-Qin; Shao, Bei; He, Jin-Cai; Hou, Sheng-Tao; Zheng, Rong-Yuan

2014-08-01

195

Neurotrophic factors attenuate alterations in spinal cord evoked potentials and edema formation following trauma to the rat spinal cord.  

PubMed

Influence of brain derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF-1) on spinal cord injury induced disturbances in spinal cord conduction, edema formation and cellular stress response was examined in a rat model. Pretreatment with BDNF or IGF-1 significantly attenuated the loss of SCEP negative amplitude seen immediately after spinal cord injury. In these neurotrophins treated rats, upregulation of heat shock protein (HSP 72 kD) immunoreactivity, a measure of cellular stress response and spinal cord edema formation were considerably reduced 5 h after injury. These results suggest that neurotrophic factors improve spinal cord conduction after trauma and this beneficial effect of growth factors may be related with their ability to attenuate trauma induced cellular stress response, not reported earlier. PMID:11450028

Winkler, T; Sharma, H S; Stålberg, E; Badgaiyan, R D

2000-01-01

196

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid  

PubMed Central

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (?7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of ?7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of ?7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferre, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

197

Cytoprotective Role of Haptoglobin in Brain After Experimental Intracerebral Hemorrhage  

Microsoft Academic Search

\\u000a After intracerebral hemorrhage (ICH), hemoglobin (Hb) that is released from erythrocytes within the brain hematoma is highly\\u000a cytotoxic and leads to severe brain edema and direct neuronal damage. Therefore, neutralization of Hb could represent an important\\u000a target for reducing the secondary injury after ICH. Haptoglobin (Hp), an endogenous Hb-binding protein in blood plasma, is\\u000a found in this study to be

Xiurong Zhao; Shen Song; Guanghua Sun; Jie Zhang; Roger Strong; Lihua Zhang; James C. Grotta; Jaroslaw Aronowski

198

Topiramate reduces non-convulsive seizures after focal brain ischemia in the rat.  

PubMed

Acute "silent" seizures after brain injury are associated with a worsening of patient outcome and are often refractory to anti-epileptic drug (AED) therapy. In the present study we evaluated topiramate (TPM, 1-30 mg/kg, i.v.) in a rodent model of spontaneous non-convulsive seizure (NCS) activity induced by focal cerebral ischemia. For seizure detection, electroencephalographic (EEG) activity was continuously recorded for 24h in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAo). Infarct volume, neurological deficit, and NCS were evaluated by an experimenter blinded to the treatment group. All vehicle treated rats (7/7) exhibited NCS following MCAo. TPM treatment, delivered at 20 min post-occlusion and prior to onset of NCS activity, dose-dependently reduced the incidence of NCS (ED(50)=21.1mg/kg). The highest dose of TPM tested (30 mg/kg) exhibited maximal reductions of 76% in the number of NCS/rat (vehicle=22.1+/-5.3, TPM=4.4+/-3.2, P<0.05), 80% in the total time of NCS (vehicle=1259+/-337 s, TPM=253+/-220 s, P<0.05), 20% in core brain infarction (vehicle=45+/-1%, TPM=36+/-4%, percent of ipsilateral volume corrected for swelling, P<0.05), and 38% in neurological deficit score (vehicle=7.4+/-1.2, TPM=4.6+/-1.5, P<0.05). Despite efficacy as a pre-seizure treatment, TPM was not effective when delivered immediately following onset of the first NCS event (36+/-5 min post-MCAo). In conclusion, TPM exhibited significant efficacy for the prophylactic treatment of brain-injury induced NCS and represents a novel class of AED for treatment of this type of silent brain seizure. PMID:18063309

Williams, Anthony J; Tortella, Frank C; Gryder, Divina; Hartings, Jed A

2008-01-01

199

Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction  

PubMed Central

We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure), brain (or hypothalamic) inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress), multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

Hsu, Shu-Fen; Lin, Mao-Tsun

2013-01-01

200

Edema: a silent but important factor.  

PubMed

Edema is a normal response to injury. Even the smallest injury is associated with some inflammation, and initial edema is part of the normal inflammatory process. However, edema becomes a concern when it persists beyond the inflammatory phase. Once we have progressed into the rebuilding, or fibroplastic phase of healing, edema will delay healing and contribute to complications such as pain and stiffness. Early prevention and management to prevent this progression are therefore critical. This article discusses edema in relation to stages of healing and presents the research behind techniques available to the clinician to manage localized extracellular upper extremity edema in the patient with an intact lymphatic system. PMID:22212492

Villeco, June P

2012-01-01

201

Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage.  

PubMed

Free radicals are involved in neurodegenerative disorders, such as ischemia and aging. We have previously demonstrated that treatment with diets enriched with blueberry, spinach, or spirulina have been shown to reduce neurodegenerative changes in aged animals. The purpose of this study was to determine if these diets have neuroprotective effects in focal ischemic brain. Adult male Sprague-Dawley rats were fed with equal amounts of diets (blueberry, spinach, and spirulina) or with control diet. After 4 weeks of feeding, all animals were anesthetized with chloral hydrate. The right middle cerebral artery was ligated with a 10-O suture for 60 min. The ligature was later removed to allow reperfusional injury. Animals were sacrificed and brains were removed for caspase-3 enzymatic assays and triphenyltetrazolium chloride staining at 8 and 48 h after the onset of reperfusion. A subgroup of animals was used for locomotor behavior and biochemical assays. We found that animals which received blueberry, spinach, or spirulina enriched diets had a significant reduction in the volume of infarction in the cerebral cortex and an increase in post-stroke locomotor activity. There was no difference in blood biochemistry, blood CO2, and electrolyte levels among all groups, suggesting that the protection was not indirectly mediated through the changes in physiological functions. Animals treated with blueberry, spinach, or spirulina had significantly lower caspase-3 activity in the ischemic hemisphere. In conclusion, our data suggest that chronic treatment with blueberry, spinach, or spirulina reduces ischemia/reperfusion-induced apoptosis and cerebral infarction. PMID:15817266

Wang, Yun; Chang, Chen-Fu; Chou, Jenny; Chen, Hui-Ling; Deng, Xiaolin; Harvey, Brandon K; Cadet, Jean Lud; Bickford, Paula C

2005-05-01

202

Platelet involvement in rat paw edema induced by 2-methoxy-PAF  

Microsoft Academic Search

PAF-acether (PAF) or 2-methoxy-PAF (2-MX) caused a dose-dependent paw edema showing a 1: 25 ratio between their inflammatory activities. 2-MX caused a thrombocytopenia, whereas PAF did not alter the number of these cells. Both phospholipids induced reductions in total leukocyte count. Rat antiplatelet serum produced platelet depletion by PAF-induced paw edema was unaffected. The edema of 2-MX was significantly reduced

P. M. R. Silva; R. S. B. Cordeiro; M. A. Martins; M. G. M. O. Henriques; B. B. Vargaftig

1986-01-01

203

Recurrent Negative Pressure Pulmonary Edema  

PubMed Central

An African-American man, aged 34 years, underwent an elective uncomplicated right wrist laceration repair while under general anesthesia. Following extubation, the patient developed hypoxemia, tachypnea, shortness of breath, pulmonary rales, frothy sputum, decreased oxygen saturation, and evidence of upper airway obstruction. Chest radiograph showed pulmonary edema. The patient was diagnosed with post-extubation pulmonary edema (aka. negative pressure pulmonary edema [NPPE]) and was treated with intravenous furosemide and oxygen therapy; he improved remarkably within a few hours. Once stabilized, the patient described a similar episode 10 years earlier following surgery for multiple gunshot wounds. Negative pressure pulmonary edema following tracheal extubation is an uncommon (0.1%) and life-threatening complication of patients undergoing endotracheal intubation and general anesthesia for surgical procedures. The common pattern in these cases is the occurrence of an episode of airway obstruction upon emergence from general anesthesia, usually caused by laryngospasm. Patients who are predisposed to airway obstruction may have an increased risk of airway complications upon extubation after general anesthesia. Prevention and early relief of upper airway obstruction should decrease incidence. Recurrent NPPE has not been previously described in the literature. Herein, we describe the first case of recurrent NPPE in the same patient following extubation.

Pathak, Vikas; Rendon, Iliana S. Hurtado; Ciubotaru, Ronald L.

2011-01-01

204

Pulmonary edema: pathophysiology and diagnosis.  

PubMed

Healthy human lungs are normally the sites of fluid and solute filtration across the pulmonary capillary endothelium. Unlike other organs, the filtrate in the lungs is confined anatomically within adjacent interstitial spaces, through which it moves by a built-in pressure gradient from its site of formation to its site of removal through pulmonary lymphatic channels. The quantity of fluid filtered and its protein content depend on the transvascular hydrostatic and protein osmotic (colloid) pressure differences, and the leakiness of the endothelial barrier to water and protein. Lymphatic drainage can increase several-fold, which means that pulmonary edema-defined as an increase in extravascular water content of the lungs-cannot occur until the rate of fluid filtration exceeds the rate of lymphatic removal. Two main types of pulmonary edema are recognized: first, cardiogenic (or hydrostatic) pulmonary edema from, as the name implies, an elevated pulmonary capillary pressure from left-sided heart failure; second, noncardiogenic (increased permeability) pulmonary edema from injury to the endothelial and (usually) epithelial barriers. Owing to their fundamental differences, each occurs in distinct clinical conditions, requires separate therapy, and has a different prognosis. PMID:21219673

Murray, J F

2011-02-01

205

Effect of lavender oil (Lavandula angustifolia) on cerebral edema and its possible mechanisms in an experimental model of stroke.  

PubMed

Lavender belongs to the family Labiatae and has a variety of cosmetic uses as well as therapeutic purposes in herbal medicine. The present study was conducted to evaluate the protective effect of lavender oil against brain edema and its possible mechanisms in an experimental model of stroke. Under Laser-Doppler Flowmetry, focal cerebral ischemia was induced by the transient occlusion of the middle cerebral artery for 1h in rats. Lavender oil (100, 200, and 400 mg/kg ip (and/or vehicle was injected at the onset of ischemia. Infarct size, cerebral edema, functional outcome, and oxidative stress biomarkers were evaluated using standard methods. Western blotting was used to determine the protein expression of VEGF, Bax, and Bcl-2. Treatment with lavender oil at doses of 200 and 400 mg/kg significantly diminished infarct size, brain edema, and improved functional outcome after cerebral ischemia (P<0.001). Lavender oil (200 mg/kg) also reduced the content of malondialdehyde and increased the activities of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity (P<0.001). Although lavender oil enhanced VEGF expression (P=0.026), it could not decrease the Bax-to-Bcl-2 ratio (pro- to anti-apoptotic proteins) in the rat brain (P>0.05). The results indicated that lavender oil has neuroprotective activity against cerebral ischemia and alleviated neurological function in rats, and the mechanism may be related to augmentation in endogenous antioxidant defense, inhibiting oxidative stress, and increasing VEGF expression in the rat brain. However, lavender oil could not suppress the apoptosis pathway. PMID:24384140

Vakili, Abedin; Sharifat, Shaghayegh; Akhavan, Maziar Mohammad; Bandegi, Ahmad Reza

2014-02-22

206

[Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice.  

PubMed

Humanin (HN) has been identified as an endogenous peptide that inhibited AD-relevant neuronal cell death. HNG, a variant of HN in which the 14th amino acid serine was replaced with glycine, can reduce infarct volume and improve neurological deficits after ischemia/reperfusion injury. In this study, we aimed to examine the neuroprotective effect of HNG on traumatic brain injury (TBI) in mice and explored whether the protective effect was associated with regulating apoptosis and autophagy. Compared to vehicle-treated groups, mice administered HNG intracerebroventricularly (i.c.v.) prior to TBI had decreased cells with plasmalemma permeability in the injured cortex and hippocampus (48 h, P<0.01), reduced brain lesion volume (days 14 and 28, P<0.05), improved motor performance (days 1-4, P<0.05) and ameliorated performance in the Morris water maze test (days 11-13, P<0.05) post TBI. Reduced lesion volume (day 14, P<0.05) was also observed even when HNG was administered intraperitoneally (i.p.) at 1h and 2h post TBI, and minor amelioration in motor and Morris water maze test deficits was also observed. Immunoblotting results showed that HNG pretreatment (i.c.v.) reversed TBI-induced cleavage of cysteinyl aspartate-specific protease-3 and poly ADPribose-polymerase and decline of Bcl-2, suppressed LC3II, Beclin-1 and vacuolar sorting protein 34 activation and maintained p62 levels in the injured cortex and hippocampus post TBI (compared with vehicle). In conclusion, HNG treatment improved morphological and functional outcomes after TBI in mice and the protective effect of HNG against TBI may be associated with down-regulating apoptosis and autophagy. PMID:23178909

Wang, T; Zhang, L; Zhang, M; Bao, H; Liu, W; Wang, Y; Wang, L; Dai, D; Chang, P; Dong, W; Chen, X; Tao, L

2013-02-12

207

Molecular Mechanisms of Ischemic Cerebral Edema: Role of Electroneutral Ion Transport  

NSDL National Science Digital Library

The brain achieves homeostasis of its intracellular and extracellular fluids by precisely regulating the transport of solute and water across its major cellular barriers: endothelia of the blood-brain barrier (BBB), choroid plexus epithelia, and neuroglial cell membranes. Cerebral edema, the pathological accumulation of fluid in the brainÃÂs intracellular and extracellular spaces, is a major cause of morbidity and mortality following stroke and other forms of ischemic brain injury. Until recently, mechanisms of cerebral edema formation have been obscure; consequently, its treatment has been empiric and suboptimal. Here, we provide a paradigm for understanding ischemic cerebral edema, showing that its molecular pathogenesis is a complex yet step-wise process that results largely from impaired astrocytic cell volume regulation and permeability alterations in the cerebral microvasculature, both of which arise from pathological changes in the activities of specific ion channels and transporters. Recent data has implicated the bumetanide-sensitive NKCC1, an electroneutral cotransporter expressed in astrocytes and the BBB, in cerebral edema formation in several different rodent models of stroke. Pharmacological inhibition or genetic deficiency of NKCC1 decreases ischemia-induced cell swelling, BBB breakdown, cerebral edema, and neurotoxicity. Combination pharmacological strategies that include NKCC1 as a target might thus prove beneficial for the treatment of ischemic, and potentially other types of, cerebral edema.

Kristopher Kahle (Massachusetts General Hospital and Harvard Medical School Neurosurgery)

2009-08-01

208

Therapeutic hypothermia for traumatic brain injury.  

PubMed

Experimental evidence demonstrates that therapeutic temperature modulation with the use of mild induced hypothermia (MIH, defined as the maintenance of body temperature at 32-35 °C) exerts significant neuroprotection and attenuates secondary cerebral insults after traumatic brain injury (TBI). In adult TBI patients, MIH has been used during the acute "early" phase as prophylactic neuroprotectant and in the sub-acute "late" phase to control brain edema. When used to control brain edema, MIH is effective in reducing elevated intracranial pressure (ICP), and is a valid therapy of refractory intracranial hypertension in TBI patients. Based on the available evidence, we recommend: applying standardized algorithms for the management of induced cooling; paying attention to limit potential side effects (shivering, infections, electrolyte disorders, arrhythmias, reduced cardiac output); and using controlled, slow (0.1-0.2 °C/h) rewarming, to avoid rebound ICP. The optimal temperature target should be titrated to maintain ICP <20 mmHg and to avoid temperatures <35 °C. The duration of cooling should be individualized until the resolution of brain edema, and may be longer than 48 h. Patients with refractory elevated ICP following focal TBI (e.g. hemorrhagic contusions) may respond better to MIH than those with diffuse injury. Randomized controlled trials are underway to evaluate the impact of MIH on neurological outcome in adult TBI patients with elevated ICP. The use of MIH as prophylactic neuroprotectant in the early phase of adult TBI is not supported by clinical evidence and is not recommended. PMID:22836524

Urbano, L A; Oddo, Mauro

2012-10-01

209

[Effect of suloctidil on the reduced evoked potentials in brain slices in low glucose perfusate].  

PubMed

Effects of suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] on reduced evoked potentials in low glucose perfusate were studied using guinea-pig prepyriform cortex in vitro. The amplitude of evoked potential to paired electrical stimulation of the olfactory tract in cerebral slices was consistently and reversibly suppressed by the perfusion with low glucose (3 mM)-Krebs-Ringer's solution. The amplitude reduction after 10 min exposure to the perfusate was fairly reproducible in the same preparation. The amplitude reduction was always accompanied with significant facilitation of "postactivation potentiation", estimated from the size of the first and second response to paired stimulation. Perfusion of brain slices with low glucose Krebs-Ringer's solution containing 10(-7)-10(-6) g/ml suloctidil for 10 min, however, effectively prevented the reduction of amplitude of evoked potentials to below 30-50% of the control value. The facilitation of postactivation potentiation under the low glucose condition was also suppressed by the drug. Dihydroergotoxin, 3 X 10(-6) g/ml, also showed a comparable effect as 10(-6) g/ml suloctidil. These data suggest that suloctidil possesses a brain energy economizing effect such as activation of oxygen, glucose uptake or production of high energy substance. PMID:6323287

Nishi, H; Hori, N; Katsuda, N

1983-11-01

210

The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat.  

PubMed

While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17?-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) were achieved 4h after onset of ischemia, and maintained until the end of the procedure (24h). Neurofunctional score and volume of the damaged brain regions were the main end points. At 24h after ischemia-reperfusion, neurofunctional examination of the animals did not show significant differences among the three experimental groups. By contrast, both E2- and BZA-treated groups showed significantly lower total infarct volumes, BZA acting mainly in the cortical region and E2 acting mainly at the subcortical level. Our results demonstrate that: (1) E2 at physiological plasma levels in female rats is neuroprotective in male rats when given at the acute stage of the ischemic challenge and (2) BZA at clinically relevant plasma levels mimics the neuroprotective action of E2 and could be, therefore, a candidate in stroke treatment. PMID:24861515

Castelló-Ruiz, María; Torregrosa, Germán; Burguete, María C; Miranda, Francisco J; Centeno, José M; López-Morales, Mikahela A; Gasull, Teresa; Alborch, Enrique

2014-07-11

211

Expression of Na-K-Cl cotransporter and edema formation are age dependent after ischemic stroke  

PubMed Central

Age is the most important independent risk factor for stroke; however aging animals are rarely used in stroke studies. Previous work demonstrated that young male mice had more edema formation after an induced stroke than aging animals. An important contributor to cerebral edema formation is the Na-K-Cl cotransporter (NKCC). We examined the expression of NKCC in young (10-12 week) and aging (15-16 months) C57BL6 male mice after middle cerebral artery occlusion (MCAO) and investigated the effect of pharmacological inhibition of NKCC with Bumetanide on cerebral edema formation. Both immunofluorescent staining and Western blotting analysis showed that NKCC expression was significantly higher in the ischemic penumbra of young compared to aging mice after stroke. Edema formation was significantly more robust in young mice and was reduced with Bumetanide. Bumetanide had no effect on cerebral edema in aging mice after MCAO. This suggests that NKCC expression and edema formation are age dependent after ischemic stroke.

Liu, Fudong; Akella, Padmastuti; Benashski, Sharon E.; Xu, Yan; McCullough, Louise D.

2010-01-01

212

9-Cis-Retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein  

PubMed Central

Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein -7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin –mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RTPCR, in rat cerebral cortex at 24 hours after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at one day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by BMP antagonist noggin given at one day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia -induced injury and these effects involve BMPs.

Shen, Hui; Luo, Yu; Kuo, Chi-Chung; Deng, Xiaolin; Chang, Chen-Fu; Harvey, Brandon K.; Hoffer, Barry J; Wang, Yun

2008-01-01

213

Reduced brain responses to novel sounds in depression: P3 findings in a novelty oddball task  

PubMed Central

There have been conflicting findings as to whether the P3 brain potential to targets in oddball tasks is reduced in depressed patients. The P3 to novel distracter stimuli in a three-stimulus oddball task has a more frontocentral topography than P3 to targets and is associated with different cognitive operations and neural generators. The novelty P3 potential was predicted to be reduced in depressed patients. EEG was recorded from 30 scalp electrodes (nose reference) in 20 unmedicated depressed patients and 20 matched healthy controls during a novelty oddball task with three stimuli: infrequent target tones (12%), frequent standard tones (76%) and nontarget novel stimuli, e.g., animal or environment sounds (12%). Novel stimuli evoked a P3 potential with shorter peak latency and more frontocentral topography than the parietal-maximum P3b to target stimuli. The novelty P3 was markedly reduced in depressed patients compared to controls. Although there was a trend for patients to also have smaller parietal P3b to targets, this group difference was not statistically significant. Nor was there a group difference in the earlier N1 or N2 potentials. The novelty P3 reduction in depressed patients is indicative of a deficit in orienting of attention and evaluation of novel environmental sounds.

Bruder, Gerard E.; Kroppmann, Christopher J.; Kayser, Jurgen; Stewart, Jonathan W.; McGrath, Patrick J.; Tenke, Craig E.

2012-01-01

214

Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress.  

PubMed

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17?-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner. PMID:20579403

Huang, Yan-Hong; Zhang, Qing-Hong

2010-11-01

215

Preventing Flow-Metabolism Uncoupling Acutely Reduces Axonal Injury after Traumatic Brain Injury  

PubMed Central

Abstract We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3?h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24?h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3?h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of ?-APP-stained axons at 24?h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3–24?h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of ?-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons.

Mironova, Yevgeniya A.; Chen, Szu-Fu; Richards, Hugh K.; Pickard, John D.

2012-01-01

216

Classification of the cerebral edemas with reference to hydrocephalus and pseudotumor cerebri  

Microsoft Academic Search

Cerebral edema is a common clinical disorder that results from an abnormal increase in water content within the extracellular (EC) compartment of the brain. It is distinguished from two other types of brain bulk enlargement: (1) vascular swelling, caused by arterial dilatation or venous obstruction; and (2) cellular swelling, caused by cytotoxic injuries or metabolic storage. Under normal conditions, the

Thomas H. Milhorat

1992-01-01

217

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation  

Microsoft Academic Search

Background\\/Aims: Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and 1H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis.Methods: Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent 1H-MR of the

Juan Córdoba; Juli Alonso; Alex Rovira; Carlos Jacas; Francesc Sanpedro; Llu??s Castells; V??ctor Vargas; Carles Margarit; Jaime Kulisewsky; Rafael Esteban; Jaume Guardia

2001-01-01

218

Lifesaving decompressive craniectomy for diffuse cerebral edema during an episode of new-onset diabetic ketoacidosis  

Microsoft Academic Search

Purpose  Diabetic ketoacidosis (DKA), a well-known complication of diabetes mellitus, is associated with severe diffuse cerebral edema\\u000a leading to brain herniation and death. Survival from an episode of symptomatic cerebral edema has been associated with debilitating\\u000a neurological sequelae, including motor deficits, visual impairment, memory loss, seizures, and persistent vegetative states.\\u000a A review of the literature reveals scant information regarding the potential

Ha Son Nguyen; James D. Callahan; Aaron A. Cohen-Gadol

2011-01-01

219

Blockade of Nociceptin Signaling Reduces Biochemical, Structural and Cognitive Deficits after Traumatic Brain Injury.  

National Technical Information Service (NTIS)

Protecting military personnel from blast-induced traumatic brain injury (TBI) has been a tremendous challenge. TBI results in hypoxia and ischemia reperfusion injury to the brain. Nociceptin (Noc), an endogenous peptide, is upregulated within one hour of ...

C. Donica H. O. Awwad K. M. Standifer L. Gonzalez V. I. Ramirez

2010-01-01

220

Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats  

PubMed Central

Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases.

Taguchi, Akihiko; Zhu, Pengxiang; Cao, Fang; Kikuchi-Taura, Akie; Kasahara, Yukiko; Stern, David M; Soma, Toshihiro; Matsuyama, Tomohiro; Hata, Ryuji

2011-01-01

221

Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain  

PubMed Central

Background Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT) and in dogs with a mutation in hypocretin receptor 2 (HCRTR2). However, little is known about molecular alterations downstream of the hypocretin signals. Results By using microarray technology we have screened the expression of 29760 genes in the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for the canarc-1 [HCRTR-2-2] mutation), and their unaffected heterozygous siblings. We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1) and Proenkephalin (PENK), that together with Suppressor of cytokine signaling 2 (SOCS2), showed reduced expression in narcoleptic brains. The difference was particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2 showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results obtained from microarray experiments were confirmed by real-time RT-PCR. Interestingly, it was previously shown that a single dose of amphetamine-like stimulants able to increase wakefulness in the dogs, also produce an increase in the expression of both TAC1 and PENK in mice. Conclusion These results suggest that TAC1, PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans.

Lindberg, Julia; Saetre, Peter; Nishino, Seiji; Mignot, Emmanuel; Jazin, Elena

2007-01-01

222

Combined antiretroviral therapy reduces brain viral load and pathological features of HIV encephalitis in a mouse model.  

PubMed

The role of brain HIV load in the pathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. To try and determine if the amount of HIV drives the severity of pathology, a severe combined immunodeficient (SCID) mouse model of HIV encephalitis (HIVE) was utilized to determine the effectiveness of a systemically administered combined antiretroviral (cART) regimen. SCID mice were inoculated intracerebrally with HIV-infected or uninfected (control) human macrophages and treated subcutaneously with cART or saline for 10 days. Immunohistochemistry was then used to examine gliosis and neuronal damage. Drug levels were measured in brain and plasma using high-performance liquid chromatography. Peak plasma and brain levels of atazanavir, tenofovir, and emtricitabine were determined to be 1 h post-injection of cART therapy. cART significantly reduced neuropathological features of HIVE, including astrogliosis and the presence of mononuclear phagocytes, and ameliorated reduced MAP2 (neuronal integrity) staining. However, cART did not eradicate HIV from the brain. Using this animal model of HIVE, these data indicate effective penetration of cART reduces brain viral loads and HIV pathology, possibly by eliminating the production of HIV proteins, virus infected cells, or both. Importantly, these data suggest that viral load directly affects the extent of pathology seen in the brain, particularly neuronal damage, which implies that more effective suppression of HIV in the CNS could reduce currently highly prevalent forms of HAND. However, these data also strongly suggest that cART will not eliminate HIV from the brain and that adjunctive therapies must be developed. PMID:24415129

Koneru, Rajeth; Olive, M Foster; Tyor, William R

2014-02-01

223

Corticosterone reduces brain mitochondrial function and expression of mitofusin, BDNF in depression-like rodents regardless of exercise preconditioning.  

PubMed

Both chronic mild stress and an injection of corticosterone induce depression-like states in rodents. To further link mitochondrial dysfunction to the pathophysiology of major depression, here we describe two rat models of a depressive-like state induced by chronic unpredictable mild stress (CUMS) or corticosterone treatment (CORT). It is also a model that allows the simultaneous study of effects of exercise preconditioning on behavioral, electrophysiological, biochemical and molecular markers in the same animal. Exercise preconditioning ahead of CUMS and CORT treatment prevents many behavioral abnormalities resulted from CUMS. The changes in mitochondrial activity in brain and reduced expressions of superoxide dismutase (SOD1, SOD2), mitofusin (Mfn1, Mfn2) as well as brain-derived neurotrophic factor (BDNF) suggest that both CORT and CUMS may impair mitochondrial function and/or expressions of mitofusion and antioxidant enzymes that, in turn, may increase oxidative stress and reduce energy production in brain with depression-like behaviors. These findings suggest an underlying mechanism by which CORT, as well as CUMS, induces brain mitochondrial dysfunction that is associated with depressive-like states. Remarkably, physical exercise is identified as a helpful and preventive measure to promote mitochondrial function and expressions of mitofusin, BDNF and antioxidant enzymes in brain, so as to protect brain energy metabolism against CUMS, rather than the compound of corticosterone. PMID:22244747

Liu, Weina; Zhou, Chenglin

2012-07-01

224

Involvement of nitric oxide pathways in neurogenic pulmonary edema induced by vagotomy  

PubMed Central

OBJECTIVE: The objective of this study was to evaluate the involvement of peripheral nitric oxide (NO) in vagotomy-induced pulmonary edema by verifying whether the nitric oxide synthases (NOS), constitutive (cNOS) and inducible (iNOS), participate in this mechanism. INTRODUCTION: It has been proposed that vagotomy induces neurogenic pulmonary edema or intensifies the edema of other etiologies. METHODS: Control and vagotomized rats were pretreated with 0.3 mg/kg, 3.0 mg/kg or 39.0 mg/kg of L-NAME, or with 5.0 mg/kg, 10.0 mg/kg or 20.0 mg/kg of aminoguanidine. All animals were observed for 120 minutes. After the animals' death, the trachea was catheterized in order to observe tracheal fluid and to classify the severity of pulmonary edema. The lungs were removed and weighed to evaluate pulmonary weight gain and edema index. RESULTS: Vagotomy promoted pulmonary edema as edema was significantly higher than in the control. This effect was modified by treatment with L-NAME. The highest dose, 39.0 mg/kg, reduced the edema and prolonged the survival of the animals, while at the lowest dose, 0.3 mg/kg, the edema and reduced survival rates were maintained. Aminoguanidine, regardless of the dose inhibited the development of the edema. Its effect was similar to that observed when the highest dose of L-NAME was administered. It may be that the non-selective blockade of cNOS by the highest dose of L-NAME also inhibited the iNOS pathway. CONCLUSION: Our data suggest that iNOS could be directly involved in pulmonary edema induced by vagotomy and cNOS appears to participate as a protector mechanism.

Blanco, Eleonora; Martins-Pinge, Marli; Oliveira-Sales, Elizabeth; Busnardo, Cristiane

2011-01-01

225

Ranibizumab in diabetic macular edema.  

PubMed

By 2050 the prevalence of diabetes will more than triple globally, dramatically increasing the societal and financial burden of this disease worldwide. As a consequence of this growth, it is anticipated that there will be a concurrent rise in the numbers of patients with diabetic macular edema (DME), already among the most common causes of severe vision loss worldwide. Recent available therapies for DME target the secreted cytokine, vascular endothelial growth factor (VEGF). This review focuses on the treatment of DME using the first humanized monoclonal antibody targeting VEGF that has been Food and Drug Administration-approved for the use in the eye, ranibizumab (Lucentis(®)). PMID:24379922

Krispel, Claudia; Rodrigues, Murilo; Xin, Xiaoban; Sodhi, Akrit

2013-12-15

226

Doxycycline Reduces Mortality and Injury to the Brain and Cochlea in Experimental Pneumococcal Meningitis  

Microsoft Academic Search

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflam- mation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory

Damian N. Meli; Roney S. Coimbra; Dominik G. Erhart; Gerard Loquet; Caroline L. Bellac; Martin G. Tauber; Ulf Neumann; Stephen L. Leib

2006-01-01

227

Diabetic papillopathy with macular edema treated with intravitreal ranibizumab  

PubMed Central

We report a case of diabetic papillopathy that demonstrated a resolution of optic disk swelling and rapid visual recovery when intravitreal ranibizumab was administered. A 51-year-old male presented with acute painless visual loss in his right eye. His vision was 20/320 in the right eye and 20/50 in the left eye. Fundus examination of the right eye showed nonproliferative diabetic retinopathy with macular edema and a swollen optic disk. Fluorescein angiography showed dye leakage from the right optic disk. Optical coherent tomography revealed a significant increase in retinal nerve fiber-layer thickness. Magnetic resonance imaging of the brain was normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks following injection, there was marked regression of the disk swelling and improvement of macular edema, with vision improving to 20/100. Three months following injection, there was complete resolution of the optic disk swelling. No further treatment was required.

Kim, Moosang; Lee, Jang-Hun; Lee, Seung-Jun

2013-01-01

228

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism  

PubMed Central

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[18F]fluoro-2-deoxy-d-glucose–positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH?). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH? and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH? subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

Mosconi, Lisa; Brys, Miroslaw; Switalski, Remigiusz; Mistur, Rachel; Glodzik, Lidia; Pirraglia, Elizabeth; Tsui, Wai; De Santi, Susan; de Leon, Mony J.

2007-01-01

229

Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease  

PubMed Central

Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear. We hypothesize that one function of ASPA is to provide acetate for the increased lipid synthesis that occurs during postnatal CNS myelination. The gene encoding ASPA has been inactivated in the mouse model of CD, and here we show significant decreases in the synthesis of six classes of myelinassociated lipids, as well as reduced acetate levels, in the brains of these mice at the time of peak postnatal CNS myelination. Analysis of the lipid content of white matter from a human CD patient showed decreased cerebroside and sulfatide relative to normal white matter. These results demonstrate that myelin lipid synthesis is significantly compromised in CD and provide direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-derived acetate, is involved in the pathogenesis of CD.

Madhavarao, Chikkathur N.; Arun, Peethambaran; Moffett, John R.; Szucs, Sylvia; Surendran, Sankar; Matalon, Reuben; Garbern, James; Hristova, Diana; Johnson, Anne; Jiang, Wei; Namboodiri, M. A. Aryan

2005-01-01

230

Radiosurgery Facilitates Resection of Brain Arteriovenous Malformations and Reduces Surgical Morbidity  

PubMed Central

OBJECTIVE Stereotactic radiosurgery makes brain arteriovenous malformations (AVM) more manageable during their microsurgical resection. To better characterize these effects, we compared results of microsurgical resection of radiated (RS+) and non-radiated (RS?) AVMs to demonstrate that prior radiosurgery facilitates surgery and decreases operative morbidity. METHODS From of series of 344 patients who had AVM resections at the University of California, San Francisco (1997–2007), 21 RS+ patients were matched with 21 RS? patients based on pre-treatment clinical and AVM characteristics. Matching was blinded to outcomes, which were assessed with the modified Rankin Scale (mRS). RESULTS Mean AVM volume was reduced by 78% (P<0.01) and Spetzler-Martin grades were reduced in 52% of RS+ patients (P < 0.001). Preoperative embolization was used less in RS+ than in RS? patients (P< 0.001). Mean operative time (P< 0.01), blood loss (P < 0.05), and length of hospital stay (P< 0.05) were lower in the RS+ group. Surgical morbidity was 14% higher in RS? patients, and they had significant worsening in mRS scores after surgery while RS+ patients did not (P<0.01). RS+ patients deteriorated between AVM diagnosis and surgery due to hemorrhages during the latency period (P< 0.05). CONCLUSION Prior radiosurgery facilitates AVM microsurgery and decreases operative morbidity. Radiosurgery is recommended for unruptured AVMs that are not favorable for microsurgical resection. Microsurgical resection is recommended for radiated AVMs that are not completely obliterated after the 3-year latency period, but altered favorably for surgery, even in asymptomatic patients. Prompt resection of persistent AVMs should be considered to avoid the risk of post-latency hemorrhage and to optimize patient outcomes.

Sanchez-Mejia, Rene O.; McDermott, Michael W.; Tan, Jeffery; Kim, Helen; Young, William L.; Lawton, Michael T.

2010-01-01

231

Molecular Mechanisms of Reduced Nerve Toxicity by Titanium Dioxide Nanoparticles in the Phoxim-Exposed Brain of Bombyx mori  

PubMed Central

Bombyx mori (B. mori), silkworm, is one of the most important economic insects in the world, while phoxim, an organophosphorus (OP) pesticide, impact its economic benefits seriously. Phoxim exposure can damage the brain, fatbody, midgut and haemolymph of B. mori. However the metabolism of proteins and carbohydrates in phoxim-exposed B. mori can be improved by Titanium dioxide nanoparticles (TiO2 NPs). In this study, we explored whether TiO2 NPs treatment can reduce the phoxim-induced brain damage of the 5th larval instar of B. mori. We observed that TiO2 NPs pretreatments significantly reduced the mortality of phoxim-exposed larva and relieved severe brain damage and oxidative stress under phoxim exposure in the brain. The treatments also relieved the phoxim-induced increases in the contents of acetylcholine (Ach), glutamate (Glu) and nitric oxide (NO) and the phoxim-induced decreases in the contents of norepinephrine (NE), Dopamine (DA), and 5-hydroxytryptamine (5-HT), and reduced the inhibition of acetylcholinesterase (AChE), Na+/K+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase activities and the activation of total nitric oxide synthase (TNOS) in the brain. Furthermore, digital gene expression profile (DGE) analysis and real time quantitative PCR (qRT-PCR) assay revealed that TiO2 NPs pretreatment inhibited the up-regulated expression of ace1, cytochrome c, caspase-9, caspase-3, Bm109 and down-regulated expression of BmIap caused by phoxim; these genes are involved in nerve conduction, oxidative stress and apoptosis. TiO2 NPs pretreatment also inhibited the down-regulated expression of H+ transporting ATP synthase and vacuolar ATP synthase under phoxim exposure, which are involved in ion transport and energy metabolism. These results indicate that TiO2 NPs pretreatment reduced the phoxim-induced nerve toxicity in the brain of B. mori.

Ni, Min; Shen, Weide; Hong, Fashui; Li, Bing

2014-01-01

232

Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain  

PubMed Central

Niemann-Pick Type C (NPC) disease is a devastating developmental disorder with progressive and fatal neurodegeneration. Previous work has shown that a single injection of the neurosteroid allopregnanolone at postnatal day 7 significantly prolonged lifespan of Npc1-/- mice. However, the cellular/molecular basis for this beneficial effect remains undefined. Here, we further characterized the effect of allopregnanolone treatment on cholesterol accumulation, a pathological hallmark of NPC, as well as on autophagic/lysosomal dysfunction, myelination and inflammation in Npc1-/- mouse brains. At 1 month postnatal, accumulation of filipin-labeled unesterified cholesterol was clearly evident not only in neurons but also in microglia in untreated mutant mice, but was mostly absent in allopregnanolone-treated animals. Brain levels of the lysosomal enzymes cathepsins B and D were significantly higher in Npc1-/- than in wild-type mice. Levels of LC3-II, an autophagy marker, were also increased in mutant mouse brain as compared to wild-type mouse brain. Both changes were significantly reduced by allopregnanolone treatment. Injection of the neurosteroid also significantly reduced astrocyte proliferation and microglial activation. Furthermore, allopregnanolone treatment significantly enhanced myelination in mutant mice. Taken together, our results clearly show that allopregnanolone treatment not only reduces cholesterol accumulation and improves autophagic/lysosomal function but also enhances myelination and reduces inflammation. These results provide further support for the potential usefulness of allopregnanolone for treating NPC disease.

Liao, Guanghong; Cheung, Simon; Galeano, James; Ji, Angela X.; Qin, Qingyu; Bi, Xiaoning

2009-01-01

233

Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis  

PubMed Central

Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis.

Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

2013-01-01

234

A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo.  

PubMed

We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca(2+) accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 ?M) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca(2+) accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat acute ischemic stroke. PMID:24953828

Nuñez-Figueredo, Yanier; Ramírez-Sánchez, Jeney; Hansel, Gisele; Simões Pires, Elisa Nicoloso; Merino, Nelson; Valdes, Odalys; Delgado-Hernández, René; Parra, Alicia Lagarto; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Salbego, Christianne; Costa, Silvia L; Souza, Diogo O; Pardo-Andreu, Gilberto L

2014-10-01

235

Short communication Radiotherapy for a solitary brain metastasis during pregnancy: a method for reducing fetal dose  

Microsoft Academic Search

A patient presented during the second half of pregnancy with a solitary brain metastasis from lung cancer. This case shows that, using a new patient position, it is possible to shield the fetus efficiently. This new method consisted of whole brain irradiation with parallel pair treatment by lateral fields with the patient in a supine position with maximal neck extension.

N MAGNE ´; S MARCIE ´; J-P PIGNOL; F CASAGRANDE

236

Reduced Expression of the Melanocortin-1 Receptor in Human Liver during Brain Death  

Microsoft Academic Search

Objective: There is evidence that brain death has detrimental effects on peripheral organs. Clinical and experimental studies on organ donors showed marked inflammation in tissue samples of livers and kidneys collected during brain death. The inflammatory reaction is characterized by release of cytokines and inflammatory cell infiltration. Because melanocortins and their receptors are significant modulators of inflammation, we hypothesized that

Stefano Gatti; Gualtiero Colombo; Flavia Turcatti; Caterina Lonati; Andrea Sordi; Ferruccio Bonino; James M. Lipton; Anna Catania

2006-01-01

237

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats  

Microsoft Academic Search

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient)

Milos Cekic; Sarah M. Cutler; Jacob W. VanLandingham; Donald G. Stein

2011-01-01

238

Reduced FDG-PET brain metabolism and executive function predict clinical progression in elderly healthy subjects.  

PubMed

Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects. PMID:24286024

Ewers, Michael; Brendel, Matthias; Rizk-Jackson, Angela; Rominger, Axel; Bartenstein, Peter; Schuff, Norbert; Weiner, Michael W

2013-01-01

239

Reduced FDG-PET brain metabolism and executive function predict clinical progression in elderly healthy subjects???  

PubMed Central

Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects.

Ewers, Michael; Brendel, Matthias; Rizk-Jackson, Angela; Rominger, Axel; Bartenstein, Peter; Schuff, Norbert; Weiner, Michael W.

2013-01-01

240

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.  

PubMed

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. PMID:23994447

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2013-10-16

241

Does induced hypertension reduce cerebral ischaemia within the traumatized human brain?  

PubMed

Recent changes in published guidelines for the management of patients with severe head injury are based on data showing that aggressive maintenance of cerebral perfusion pressure (CPP) can worsen outcome due to extracranial complications of therapy. However, it remains unclear whether CPP augmentation could reduce cerebral ischaemia, a finding which might prompt the search for CPP augmentation protocols that avoid these extracranial complications. We studied 10 healthy volunteers and 20 patients within 6 days of closed head injury. All subjects underwent imaging of cerebral blood flow (CBF), blood volume (CBV), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) using 15O PET. In addition, for patients, the EEG power ratio index (PRI), burst suppression ratio and somatosensory evoked potentials (SEP) were obtained and CPP was increased from 68 +/- 4 to 90 +/- 4 mmHg using an infusion of norepinephrine and measurements were repeated. Following elevation of CPP, CBF and CBV were increased and CMRO2 and OEF were reduced (P < 0.001 for all comparisons). Regions with a reduction in CMRO2 were associated with the greatest reduction in OEF (r2 = 0.3; P < 0.0001). Although CPP elevation produced a significant fall in the ischaemic brain volume (IBV) (from 15 +/- 16 to 5 +/- 4 ml; P < 0.01) and improved flow metabolism coupling, the IBV was small and clinically insignificant in the majority of these patients. However, the reduction in IBV was directly related to the baseline IBV (r2 = 0.97; P < 0.001) and patients with large baseline IBV showed substantial and clinically significant reductions. CPP augmentation increased the EEG PRI (5.0 +/- 1.5 versus 4.3 +/- 1.4, P < 0.01), implying an overall decrease in neural activity, but these changes did not correlate with the reduction in CMRO2 and there was no change in SEP cortical amplitude (N20-P27). These data provide support for recent changes in recommended CPP levels for head injury management across populations of patients with significant head injury. However, they do not provide guidance on whether the intervention may be more appropriate at earlier stages after injury, or in patients selected because of high baseline IBV. It also remains unclear whether CPP values below 65 mmHg can be safely used in this population. Clarification of the significance of a reduction in CMRO2 and neuronal electrical function will require further study. PMID:15456706

Coles, Jonathan P; Steiner, Luzius A; Johnston, Andrew J; Fryer, Tim D; Coleman, Martin R; Smieleweski, Peter; Chatfield, Doris A; Aigbirhio, Franklin; Williams, Guy B; Boniface, Simon; Rice, Kenneth; Clark, John C; Pickard, John D; Menon, David K

2004-11-01

242

Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.  

PubMed

The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

2014-09-01

243

Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases  

Microsoft Academic Search

Purpose Brain metastases are an increasingly common complication in breast cancer patients. The Metastasis Suppressor Genes (MSG) Nm23, KISS1, KAI1, BRMS1, and Mkk4 have been associated with the metastatic potential of breast cancer in vitro and in vivo.Methods The mRNA expression of Nm23, KISS1, KAI1, BRMS1, and Mkk4 in fresh frozen tissue samples of brain metastases from ductal invasive breast

Andreas M. Stark; Kerrin Tongers; Nicolai Maass; H. Maximilian Mehdorn; Janka Held-Feindt

2005-01-01

244

Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement  

Microsoft Academic Search

CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinal fluid (CSF) velocities and flow rates in the brain of\\u000a six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI\\u000a images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible\\u000a for pulsatile CSF flow between the

Andreas A. Linninger; Brian Sweetman; Richard Penn

2009-01-01

245

N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis  

Microsoft Academic Search

GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid b-galactosidase (b-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired

Julie L. Kasperzyk; Mohga M. El-Abbadi; Eric C. Hauser; Alessandra d'Azzo; Frances M. Platt; Thomas N. Seyfried

2004-01-01

246

Laparoscopic treatment of massive ovarian edema.  

PubMed

Massive ovarian edema is an unusual cause of ovarian enlargement in young girls and women. A woman with the disorder was managed laparoscopically by wedge resection of the ovary. We believe that endoscopic surgery is the appropriate approach for ovarian edema, as it establishes the diagnosis by minimally invasive means and at the same time ensures conservative treatment. PMID:10548716

Kallipolitis, G; Sklia, E; Milingos, S; Michalas, S

1999-11-01

247

Modulation of ABCA1 by an LXR Agonist Reduces Beta-Amyloid Levels and Improves Outcome after Traumatic Brain Injury  

PubMed Central

Abstract Traumatic brain injury (TBI) increases brain beta-amyloid (A?) in humans and animals. Although the role of A? in the injury cascade is unknown, multiple preclinical studies have demonstrated a correlation between reduced A? and improved outcome. Therefore, therapeutic strategies that enhance A? clearance may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1) transporters can enhance A? clearance through an apolipoprotein E (apoE)-mediated pathway. By measuring A? and ABCA1 after experimental TBI in C57BL/6J mice, we found that A? peaked early after injury (1–3 days), whereas ABCA1 had a delayed response (beginning at 3 days). As ABCA1 levels increased, A? levels returned to baseline levels—consistent with the known role of ABCA1 in A? clearance. To test if enhancing ABCA1 levels could block TBI-induced A?, we treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post-injury treatment increased ABCA1 levels at 24?h post-injury, and reduced the TBI-induced increase in A?. This reduction in A? was not due to decreased amyloid precursor protein processing, or a shift in the solubility of A?, indicating enhanced clearance. T0901317 also limited motor coordination deficits in injured mice and reduced brain lesion volume. These data indicate that activation of LXR can reduce A? accumulation after TBI, and is accompanied by improved functional recovery.

Loane, David J.; Washington, Patricia M.; Vardanian, Lilit; Pocivavsek, Ana; Hoe, Hyang-Sook; Duff, Karen E.; Cernak, Ibolja; Rebeck, G. William; Faden, Alan I.

2011-01-01

248

Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts  

PubMed Central

Background and Purpose Atrial fibrillation (AF) has been associated with cognitive decline independant of stroke, suggesting additional effects of AF on the brain. We aimed to assess the association between AF and brain function and structure in a general elderly population. Methods This is a cross-sectional analysis on 4251 non-demented participants (mean age 76 ± 5 years) in the population-based AGES-Reykjavik Study. Medical record data were collected on the presence, subtype and time from first diagnosis of AF; 330 participants had AF. Brain volume measurements, adjusted for intracranial volume, and presence of cerebral infarcts were determined with MRI. Memory, speed of processing and executive function composites were calculated from a cognitive test battery. In a multivariable linear regression model, adjustments were made for demographic, cardiovascular risk factors and cerebral infarcts. Results Participants with AF had lower total brain volume compared to those without AF (p<0.001). The association was stronger with persistent/permanent than paroxysmal AF and with increased time from the first diagnosis of the disease. Of the brain tissue volumes, AF was associated with lower volume of gray and white matter (p<0.001 and p=0.008 respectively) but not of white matter hyperintesities (p=0.49). Participants with AF scored lower on tests on memory. Conclusions AF is associated with smaller brain volume and the association is stronger with increasing burden of the arrhythmia. These findings suggest that AF has a cumulative negative effect on the brain independent of cerebral infarcts.

Stefansdottir, Hrafnhildur; Arnar, David O.; Aspelund, Thor; Sigurdsson, Sigurdur; Jonsdottir, Maria K.; Hjaltason, Haukur; Launer, Lenore J.; Gudnason, Vilmundur

2013-01-01

249

Analysis of lymphatic drainage in various forms of leg edema using two compartment lymphoscintigraphy.  

PubMed

The anatomical and functional status of the epifascial and subfascial lymphatic compartments was analyzed using two compartment lymphoscintigraphy in five groups of patients (total 55) with various forms of edema of the lower extremities. Digital whole body scintigraphy enabled semiquantitative estimation of radiotracer transport with comparison of lymphatic drainage between those individuals without (normal) and those with leg edema by calculating the uptake of the radiopharmaceutical transported to regional lymph nodes. A visual assessment of the lymphatic drainage pathways of the legs was also performed. In patients with cyclic idiopathic edema, an accelerated rate of lymphatic transport was detected (high lymph volume overload or dynamic insufficiency). In those with venous (phlebo) edemas, high volume lymphatic overload (dynamic insufficiency) of the epifascial compartment was scintigraphically detected by increased tracer uptake in regional nodes. In patients with deep femoral venous occlusion (post-thrombotic syndrome). subfascial lymphatic transport was uniformly markedly reduced (safety valve lymphatic insufficiency). On the other hand, in the epifascial compartment, lymph transport was accelerated. In those patients with recurrent or extensive skin ulceration, lymph transport was reduced. Patients with lipedema (obesity) scintigraphically showed no alteration in lymphatic transport. This study demonstrates that lymphatic drainage is notably affected (except in obesity termed lipedema) in various edemas of the leg. Lymphatic drainage varied depending on the specific compartment and the pathophysiologic mechanism accounting for the edema. Two compartment lymphoscintigraphy is a valuable diagnostic tool for accurate assessment of leg edema of known and unknown origin. PMID:9664268

Bräutigam, P; Földi, E; Schaiper, I; Krause, T; Vanscheidt, W; Moser, E

1998-06-01

250

Adaptive decreases in amino acids (taurine in particular), creatine, and electrolytes prevent cerebral edema in chronically hyponatremic mice: Rapid correction (experimental model of central pontine myelinolysis) causes dehydration and shrinkage of brain  

Microsoft Academic Search

The experimental model of central pontine myelinolysis—chronic (4-day) hyponatremia induced by daily injections of hypotonic dextrose solutions and vasopressin followed by rapid correction with saline—was used in young fasted and thirsted mice. In normal controls, chronic fasting and thirsting lowered plasma and brain glucose levels and cerebral glycolytic and tricarboxylic acid cycle metabolic fluxes. The fasting state had little effect

Jean Holowach Thurston; Richard E. Hauhart; James S. Nelson

1987-01-01

251

Hyaluronidase injection for the treatment of eyelid edema: a retrospective analysis of 20 patients  

PubMed Central

Background Hyaluronidase (Hylase Dessau®) is a hyaluronic acid-metabolizing enzyme, which has been shown to loosen the extracellular matrix, thereby improving the diffusion of local anesthetics. Lower eyelid edema is a common post-interventional complication of cosmetic procedures performed in the lid region, such as the injection of hyaluronic acid fillers for tear-trough augmentation. The purpose of this study was to validate the efficacy of hyaluronidase in the management of lower eyelid edema. Methods We performed a retrospective analysis with 20 patients with lower eyelid edema. Most patients (n?=?14) presented with edema following hyaluronic acid injection (tear-trough augmentation), whereas the minority (n?=?6) were treated due to idiopathic edema (malar edema or malar mounds). Patients were treated by local infiltration of approximately 0.2 ml to 0.5 ml of hyaluronidase (Hylase Dessau® 20 IU to 75 IU) per eyelid. Photographs were taken prior to and seven days after infiltration. Results Hyaluronidase was found to reduce effectively and rapidly or resolve eyelid edema after a single injection. No relevant adverse effects were observed. However, it must be noted that a hyaluronidase injection may also dissolve injected hyaluronic acid fillers and may therefore negatively affect tear-trough augmentations. While the effects of a treatment for edema due to tear-trough augmentation were permanent, malar edema and malar mounds reoccurred within two to three weeks. Conclusion The infiltration of hyaluronidase is rapid, safe and currently the only effective option for the management of eyelid edema. No relevant adverse effects were observed.

2014-01-01

252

Single administration of tripeptide ?-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice.  

PubMed

Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (?-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of ?-MSH, the C-terminal tripeptide ?-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of ?-MSH(11-13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg ?-MSH(11-13) or 0.9% NaCl) showed a considerable smaller trauma in ?-MSH(11-13) injected mice. The expression of the inflammatory markers TNF-? and IL-1? as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single ?-MSH(11-13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury. PMID:23940690

Schaible, Eva-Verena; Steinsträßer, Arne; Jahn-Eimermacher, Antje; Luh, Clara; Sebastiani, Anne; Kornes, Frida; Pieter, Dana; Schäfer, Michael K; Engelhard, Kristin; Thal, Serge C

2013-01-01

253

Matrix Metalloproteinase Inhibition Prevents Oxidative Stress-Associated Blood–Brain Barrier Disruption After Transient Focal Cerebral Ischemia  

Microsoft Academic Search

Oxidative stress generated during stroke is a critical event leading to blood–brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion–induced BBB disruption in mice deficient in copper\\/zinc-superoxide dismutase (SOD1) was reduced by 88% (P < 0.0001) and 73% (P <

Yvan Gasche; Jean-Christophe Copin; Taku Sugawara; Miki Fujimura; Pak H. Chan

2001-01-01

254

HIV clades B and C are associated with reduced brain volumetrics.  

PubMed

The human immunodeficiency virus (HIV) has multiple genetic clades with varying prevalence throughout the world. Both HIV clade C (HIV-C) and HIV clade B (HIV-B) can cause cognitive impairment, but it is unclear if these clades are characterized by similar patterns of brain dysfunction. We examined brain volumetrics and neuropsychological performance among highly active antiretroviral therapy (HAART)-naïve HIV-B and HIV-C participants. Thirty-four HAART-naïve HIV-infected (HIV+) participants [17 HIV-B (USA); 17 HIV-C (South Africa)] and 34 age- and education-matched HIV-uninfected (HIV?) participants were evaluated. All participants underwent similar laboratory, neuropsychological, and neuroimaging studies. Brain volume measures were assessed within the caudate, putamen, amygdala, thalamus, hippocampus, corpus callosum, and cortical (gray and white matter) structures. A linear model that included HIV status, region, and their interaction assessed the effects of the virus on brain volumetrics. HIV? and HIV+ individuals were similar in age. On laboratory examination, HIV-C participants had lower CD4 cell counts and higher plasma HIV viral loads than HIV-B individuals. In general, HIV+ participants performed significantly worse on neuropsychological measures of processing speed and memory and had significantly smaller relative volumetrics within the thalamus, hippocampus, corpus callosum, and cortical gray and white matter compared to the respective HIV? controls. Both HIV-B and HIV-C are associated with similar volumetric declines when compared to matched HIV? controls. HIV-B and HIV-C were associated with significant reductions in brain volumetrics and poorer neuropsychological performance; however, no specific effect of HIV clade subtype was evident. These findings suggest that HIV-B and HIV-C both detrimentally affect brain integrity. PMID:24078556

Ortega, Mario; Heaps, Jodi M; Joska, John; Vaida, Florin; Seedat, Soraya; Stein, Dan J; Paul, Robert; Ances, Beau M

2013-10-01

255

Curcumin reduces oxidative damage by increasing reduced glutathione and preventing membrane permeability transition in isolated brain mitochondria.  

PubMed

Mitochondria are critical regulators of energy metabolism and programmed cell death pathways. Mitochondria are also the major site for the production of reactive oxygen species which make this organelle more susceptible to oxidative damage and impairments of mitochondrial functions. Antioxidants have been of limited therapeutic success to ameliorate the toxic effects of oxidative stress in mitochondria. One reason may be the inability of mitochondria to selectively take up antioxidants. In the present study we synthesized mitochondrially targeted curcumin with an aim of delivering this polyphenolic compound to isolated mitochondria. Our observations show the strong anti-oxidative effects of curcumin and mitochondrially targeted curcumin against the lipid peroxidation, protein carbonylation and mitochondrial permeability transition induced by tert-butylhydroperoxide. Both curcumin and mitochondrially targeted curcumin significantly enhanced endogenous reduced glutathione level in the mitochondria thus preserving mitochondrial defense system against oxidative stress. We concluded that curcumin and mitochondrially targeted curcumin protected mitochondria against tert-butylhydroperoxide by lowering the oxidative damage, increasing the availability of endogenous reduced glutathione and preserving the mitochondrial integrity. Importantly, mitochondrially targeted curcumin was found most effective in ameliorating oxidative stress and preserving mitochondrial integrity than curcumin. PMID:24461330

Jat, D; Parihar, P; Kothari, S C; Parihar, M S

2013-01-01

256

Orally bioavailable and brain-penetrant pyridazine and pyridine-derived ?-secretase modulators reduced amyloidogenic A? peptides in vivo.  

PubMed

Accumulation of amyloid ? (A?) in brain is a pathological hallmark of Alzheimer's disease (AD). A? is generated after sequential cleavage of its parental molecule, amyloid precursor protein (APP), by ?- and ?-secretases. Inhibition of ?-secretase activity is an effective approach for the reduction of A? levels. Since ?-secretase targets many different substrates, selective inhibition of its cleavage of APP is believed to be critical in order to avoid undesirable side effects. ?-Secretase modulator (GSM) shifts the cleavage site on APP and production of amyloidogenic to non-amyloidogenic A? fragments. Since GSMs only modulate and do not block cleavage of ?-secretase substrates, they are believed less likely to produce untoward adverse reactions. Here, we report in vivo A?-lowering profiles of a pyridazine and a pyridine-derived GSM: GSM-C (Wan et al., 2011a) and GSM-D (Wan et al., 2011b). Both compounds reduced A?40 and A?42 productions, increased shorter A? fragments, and had little effect on Notch signaling (?100-fold selective). They had excellent oral bioavailability (97.8% for GSM-C, ?100% for GSM-D) and good brain permeability (free brain to free blood AUC ratio of 0.41 and 1.10 for GSM-C and GSM-D, respectively). Oral administration of these compounds in both acute and sub-chronic conditions reduced A? levels in plasma and brain in rats in a dose- and time-dependent manner. Therefore, GSM-C and GSM-D represent two GSMs that are orally bioavailable and brain-permeable. They could serve as excellent tools in the investigation of the role of A? peptides in AD pathogenesis. PMID:23485401

Huang, Yunhong; Li, Ting; Eatherton, Andrew; Mitchell, William L; Rong, Na; Ye, Liang; Yang, Xiu-Juan; Jin, Shiyi; Ding, Yu; Zhang, Jinqiang; Li, Yi; Wu, Yiwen; Jin, Yun; Sang, Yingxia; Cheng, Ziqiang; Browne, Edward R; Harrison, David C; Hussain, Ishrut; Wan, Zehong; Hall, Adrian; Lau, Lit-Fui; Matsuoka, Yasuji

2013-07-01

257

Mild Hypothermia Prevents Cerebral Edema and CSF Lactate Accumulation in Acute Liver Failure  

Microsoft Academic Search

Evidence from both clinical and experimental studies demonstrates that mild hypothermia prevents encephalopathy and brain edema in acute liver failure (ALF). As part of a series of studies to elucidate the mechanism(s) involved in this protective effect, groups of rats with ALF resulting from hepatic devascularization were maintained at either 37°C (normothermic) or 35°C (hypothermic), and neurological status was monitored

Nicolas Chatauret; Christopher Rose; Guy Therrien; Roger F. Butterworth

2001-01-01

258

Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral edema  

Microsoft Academic Search

The effect of an extract of Ginkgo biloba was studied on cerebral edema in rats intoxicated with triethyltin chloride (TET). Brains of TET-treated rats showed elevated water and sodium levels and a significant increase in the sodium\\/potassium ratio. Animals treated with TET plus the extract did not show water and electrolyte changes. The course of intoxication and treatment was studied

M. Otani; S. S. Chatterjee; B. Gabard; G. W. Kreutzberg

1986-01-01

259

Reduced N400 Semantic Priming Effects in Adult Survivors of Paediatric and Adolescent Traumatic Brain Injury  

ERIC Educational Resources Information Center

The immediate and long-term neural correlates of linguistic processing deficits reported following paediatric and adolescent traumatic brain injury (TBI) are poorly understood. Therefore, the current research investigated event-related potentials (ERPs) elicited during a semantic picture-word priming experiment in two groups of highly functioning…

Knuepffer, C.; Murdoch, B. E.; Lloyd, D.; Lewis, F. M.; Hinchliffe, F. J.

2012-01-01

260

An Online Family Intervention to Reduce Parental Distress Following Pediatric Brain Injury  

Microsoft Academic Search

This study examined whether an online problem-solving intervention could improve parental adjustment following pediatric traumatic brain injury (TBI). Families of children with moderate-to-severe TBI were recruited from the trauma registry of a large children's hospital and randomly assigned to receive online family problem solving therapy (FPS; n = 20) or Internet resources (IRC; n = 20) in addition to usual

Shari L. Wade; JoAnne Carey; Christopher R. Wolfe

2006-01-01

261

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats  

SciTech Connect

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals.

Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr. (Univ. of Washington, Seattle (USA))

1990-05-01

262

Estrogen treatment following severe burn injury reduces brain inflammation and apoptotic signaling  

Microsoft Academic Search

BACKGROUND: Patients with severe burn injury experience a rapid elevation in multiple circulating pro-inflammatory cytokines, with the levels correlating with both injury severity and outcome. Accumulations of these cytokines in animal models have been observed in remote organs, however data are lacking regarding early brain cytokine levels following burn injury, and the effects of estradiol on these levels. Using an

Joshua W. Gatson; David L. Maass; James W. Simpkins; Ahamed H. Idris; Joseph P. Minei; Jane G. Wigginton

2009-01-01

263

Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain  

Microsoft Academic Search

Exposure to stressful events and elevated level of stress hormones are associated with impaired spatial memory and neuronal damage in the hippocampus. These neurons are considered to be maintained by neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) and trk family of neurotrophin receptors. Male Wistar rats (6 weeks old) were exposed to immobilization

Takashi Ueyama; Yoshinori Kawai; Kiyomitsu Nemoto; Masashi Sekimoto; Shigenobu Toné; Emiko Senba

1997-01-01

264

Intrauterine exposure to halothane increases murine postnatal autotolerance to halothane and reduces brain weight.  

PubMed

The effect of halothane on prenatal development was assessed using the appearance of postnatal tolerance to the anesthetic and its effect on brain weight. Eighteen 3-month-old mice were repeatedly tested in a rotating cage for loss of righting reflex during exposure to increasing concentrations of halothane on 15 occasions to determine whether or not tolerance to halothane developed. Of these, nine mice were born to dams exposed for 30 min to 2% halothane on days 14 and 17 of gestation. The other nine mice (controls) were born to dams exposed to 100% oxygen for 30 min at the same stage of pregnancy. There was no significant difference in tolerance to halothane between the groups during the first nine days of repeated exposure to halothane. By the 13th and 15th days, however, mice exposed to halothane in utero became more tolerant to 1% halothane than did controls (P less than 0.025). In addition, the mean total brain weight of six 7-week-old mice exposed to 2% halothane in utero for 30 min on days 14 and 17 of gestation was found to be significantly less than the mean total brain weight of six control mice not exposed to halothane in utero (20.83 +/- 0.27 g and 23.07 +/- 0.51 g, respectively, P less than 0.0025). This difference occurred mainly in the brain stem rather than in the forebrain and cerebellum. PMID:6846877

Chalon, J; Hillman, D; Gross, S; Eisner, M; Tang, C K; Turndorf, H

1983-06-01

265

Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils  

Microsoft Academic Search

Metabolism of arachidonic acid by cyclooxygenase is one of the primary sources of reactive oxygen species in the ischemic brain. Neuronal overexpression of cyclooxygenase-2 has recently been shown to contribute to neurodegeneration following ischemic injury. In the present study, we examined the possibility that the neuroprotective effects of the cyclooxygenase-2 inhibitor nimesulide would depend upon reduction of oxidative stress following

Eduardo Candelario-Jalil; Dalia Alvarez; Nelson Merino; Olga Sonia León

2003-01-01

266

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats  

PubMed Central

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNF?, IL-1?, IL-6, NF?B p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D3 (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected.

Cekic, Milos; Cutler, Sarah M.; VanLandingham, Jacob W.; Stein, Donald G.

2013-01-01

267

Calorie restriction reduces psychological stress reactivity and its association with brain volume and microstructure in aged rhesus monkeys  

PubMed Central

Background Heightened stress reactivity is associated with hippocampal atrophy, age-related cognitive deficits, and increased risk for Alzheimer s disease. This temperament predisposition may aggravate age-associated brain pathology or be reflective of it. This association may be mediated through repeated activation of the stress hormone axis over time. Dietary interventions, such as calorie restriction (CR), affect stress biology and may moderate the pathogenic relationship between stress reactivity and brain in limbic and prefrontal regions. Methods Rhesus monkeys (Macaca mulatta) aged 19–31 years consumed either a standard diet (N=18) or were maintained on 30% CR relative to baseline intake (N=26) for 13–19 years. Behavior was rated in both normative and aversive contexts. Urinary cortisol was collected. Animals underwent magnetic resonance imaging and diffusion tensor imaging (DTI) to acquire volumetric and tissue microstructure data respectively. Voxel-wise statistics regressed a global stress reactivity factor, cortisol, and their interaction on brain indices across and between dietary groups. Results CR significantly reduced stress reactivity during aversive contexts without affecting activity, orientation, or attention behavior. Stress reactivity was associated with less volume and tissue density in areas important for emotional regulation and the endocrine axis including prefrontal cortices, hippocampus, amygdala, and hypothalamus. CR reduced these relationships. A Cortisol by Stress Reactivity voxel-wise interaction indicated that only monkeys with high stress reactivity and high basal cortisol demonstrated lower brain volume and tissue density in prefrontal cortices, hippocampus, and amygdala. Conclusions High stress reactivity predicted lower volume and microstructural tissue density in regions involved in emotional processing and modulation. A CR diet reduced stress reactivity and regional associations with neural modalities. High levels of cortisol appear to mediate some of these relationships.

Willette, Auriel A.; Coe, Christopher L.; Colman, Ricki J.; Bendlin, Barbara B; Kastman, Erik K; Field, Aaron S.; Alexander, Andrew L.; Allison, David B.; Weindruch, Richard H.; Johnson, Sterling C.

2011-01-01

268

Optic disc edema associated with spinocerebellar degeneration.  

PubMed

A 58-year-old man presented with optic disc edema as a rare association with spinocerebellar degeneration (SCD). The patient also had chronic idiopathic intestinal pseudo-obstruction with hypoalbuminemia. No elevation of intraspinal pressure and no intracranial lesion was observed. The hypoalbuminemia reacted promptly to treatment, whereas the optic disc edema regressed gradually. An association between SCD and optic atrophy has often been described, but to our knowledge this is the first report of SCD in association with optic disc edema. PMID:9672220

Nakazawa, T; Abe, T; Hasegawa, T; Tamai, M

1998-01-01

269

Acute pulmonary edema associated with naphazoline ingestion.  

PubMed

In published reports of naphazoline ingestion, clinical effects are hypertension, bradycardia, pallor, diaphoresis, and respiratory distress. We report three cases of acute pulmonary edema after the intentional ingestion of naphazoline-containing antiseptic first aid liquid. These cases presented with altered mental status, hypertension, bradycardia, and diaphoresis. Chest x-ray on admission revealed acute pulmonary edema. Two cases required mechanical ventilation. All of these clinical effects resolved within 24 hours and the patients were discharged with no sequelae. Since naphazoline stimulates the peripheral alpha-2 adrenergic receptor, we speculate that intense vasoconstriction may have elevated cardiac afterload and left atrial-ventricular blood volume and caused acute pulmonary edema. PMID:17852165

Fukushima, Hidetada; Norimoto, Kazunobu; Seki, Tadahiko; Nishiguchi, Takashi; Nakamura, Tatsuya; Konobu, Toshifumi; Nishio, Kenji; Okuchi, Kazuo

2008-03-01

270

Caffeic Acid phenethyl ester protects blood-brain barrier integrity and reduces contusion volume in rodent models of traumatic brain injury.  

PubMed

A number of studies have established a deleterious role for inflammatory molecules and reactive oxygen species (ROS) in the pathology of traumatic brain injury (TBI). Caffeic acid phenethyl ester (CAPE) has been shown to exert both antioxidant and anti-inflammatory effects. The primary objective of the present study was to examine if CAPE could be used to reduce some of the pathological consequences of TBI using rodent models. Male Sprague-Dawley rats and C57BL/6 mice were subjected to controlled cortical impact (CCI) injury. Blood-brain barrier (BBB) integrity was assessed by examining claudin-5 expression and the extravasation of Evans blue dye. The effect of post-injury CAPE administration on neurobehavioral function was assessed using vestibulomotor, motor, and two hippocampus-dependent learning and memory tasks. We report that post-TBI administration of CAPE reduces Evans blue extravasation both in rats and mice. This improvement was associated with preservation of the levels of the tight junction protein claudin-5. CAPE treatment did not improve performance in either vestibulomotor/motor function (tested using beam balance and foot-fault tests), or in learning and memory function (tested using the Morris water maze and associative fear memory tasks). However, animals treated with CAPE were found to have significantly less cortical tissue loss than vehicle-treated controls. These findings suggest that CAPE may provide benefit in the treatment of vascular compromise following central nervous system injury. PMID:22150135

Zhao, Jing; Pati, Shibani; Redell, John B; Zhang, Min; Moore, Anthony N; Dash, Pramod K

2012-04-10

271

Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes.  

PubMed

Testis-brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport and storage. To better define the biological roles of TB-RBP, we generated mice lacking TB-RBP. Matings between heterozygotes gave rise to viable, apparently normal homozygous mutant mice at a normal Mendelian ratio. The TB-RBP-related and -interacting protein Translin-associated factor X was reduced to 50% normal levels in heterozygotes and was absent in TB-RBP-null animals. The null mice were 10 to 30% smaller than their wild-type or heterozygote littermates at birth and remained so to about 6 to 9 months of age, showed normal B- and T-cell development, and accumulated visceral fat. TB-RBP-null male mice were fertile and sired offspring but had abnormal seminiferous tubules and reduced sperm counts. Null female mice were subfertile and had reduced litter sizes. Microarray analysis of total brain RNA from null and wild-type mice revealed an altered gene expression profile with the up-regulation of 14 genes and the down-regulation of 217 genes out of 12,473 probe sets. Numerous neurotransmitter receptors and ion channels, including gamma-aminobutyric acid A receptor alpha1 and glutamate receptor alpha3, were strongly down-regulated. Behavioral abnormalities were also seen. Compared to littermates, the TB-RBP-null mice appeared docile and exhibited reduced Rota-Rod performance. PMID:12944470

Chennathukuzhi, Vargheese; Stein, Joel M; Abel, Ted; Donlon, Stacy; Yang, Shicheng; Miller, Juli P; Allman, David M; Simmons, Rebecca A; Hecht, Norman B

2003-09-01

272

Mice Deficient for Testis-Brain RNA-Binding Protein Exhibit a Coordinate Loss of TRAX, Reduced Fertility, Altered Gene Expression in the Brain, and Behavioral Changes  

PubMed Central

Testis-brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport and storage. To better define the biological roles of TB-RBP, we generated mice lacking TB-RBP. Matings between heterozygotes gave rise to viable, apparently normal homozygous mutant mice at a normal Mendelian ratio. The TB-RBP-related and -interacting protein Translin-associated factor X was reduced to 50% normal levels in heterozygotes and was absent in TB-RBP-null animals. The null mice were 10 to 30% smaller than their wild-type or heterozygote littermates at birth and remained so to about 6 to 9 months of age, showed normal B- and T-cell development, and accumulated visceral fat. TB-RBP-null male mice were fertile and sired offspring but had abnormal seminiferous tubules and reduced sperm counts. Null female mice were subfertile and had reduced litter sizes. Microarray analysis of total brain RNA from null and wild-type mice revealed an altered gene expression profile with the up-regulation of 14 genes and the down-regulation of 217 genes out of 12,473 probe sets. Numerous neurotransmitter receptors and ion channels, including ?-aminobutyric acid A receptor ?1 and glutamate receptor ?3, were strongly down-regulated. Behavioral abnormalities were also seen. Compared to littermates, the TB-RBP-null mice appeared docile and exhibited reduced Rota-Rod performance.

Chennathukuzhi, Vargheese; Stein, Joel M.; Abel, Ted; Donlon, Stacy; Yang, Shicheng; Miller, Juli P.; Allman, David M.; Simmons, Rebecca A.; Hecht, Norman B.

2003-01-01

273

THERAPEUTIC NEUTRALIZATION OF THE NLRP1 INFLAMMASOME REDUCES THE INNATE IMMUNE RESPONSE AND IMPROVES HISTOPATHOLOGY AFTER TRAUMATIC BRAIN INJURY  

PubMed Central

Traumatic brain injury (TBI) elicits acute inflammation that in turn exacerbates primary brain damage. A crucial part of innate immunity in the immune privileged central nervous system involves production of proinflammatory cytokines mediated by inflammasome signaling. Here we show that the nucleotide-binding, leucine-rich repeat pyrin domain containing protein 1 (NLRP1) inflammasome consisting of NLRP1, caspases-1 and -11, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), the X-linked inhibitor of apoptosis protein (XIAP) and pannexin 1 is expressed in neurons of the cerebral cortex. Moderate parasagittal fluid percussion injury (FPI) induced processing of interleukin-1? (IL-1?), activation of caspase-1, cleavage of XIAP and promoted assembly of the NLRP1 inflammasome complex. Anti-ASC neutralizing antibodies administered immediately after FPI to injured rats reduced caspase-1 activation, XIAP cleavage and processing of IL-1? resulting in a significant decrease in contusion volume. These studies show that the NLRP1 inflammasome constitutes an important component of the innate CNS inflammatory response after TBI and may be a novel therapeutic target for reducing the damaging effects of post-traumatic brain inflammation.

de Rivero Vaccari, Juan Pablo; Lotocki, George; Alonso, Ofelia F.; Bramlett, Helen M.; Dietrich, W. Dalton; Keane, Robert W.

2010-01-01

274

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain.  

PubMed

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug. PMID:9503280

Rose, S; Hindmarsh, J G; Collins, P; Jenner, P

1997-01-01

275

Mesencephalic astrocyte-derived neurotrophic factor (MANF) reduces ischemic brain injury and promotes behavioral recovery in rats  

PubMed Central

Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as Arginine-rich, Mutated in Early Stage of Tumors (ARMET), is a secreted protein which reduces endoplasmic reticulum (ER) stress. Previous studies have shown that MANF mRNA expression and protein levels are increased in the cerebral cortex after brain ischemia, a condition which induces ER stress. The function of MANF during brain ischemia is still not known. The purpose of this study was to examine the protective effect of MANF after ischemic brain injury. Recombinant human MANF was administrated locally to the cerebral cortex before a 60-min middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium chloride (TTC) staining indicated that pretreatment with MANF significantly reduced the volume of infarction at two days after MCAo. MANF also attenuated TUNEL labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex.

Airavaara, Mikko; Shen, Hui; Kuo, Chi-Chung; Peranen, Johan; Saarma, Mart; Hoffer, Barry; Wang, Yun

2009-01-01

276

Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.  

PubMed

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS. PMID:24532118

Prianti, Antonio Carlos Guimarães; Silva, José Antonio; Dos Santos, Regiane Feliciano; Rosseti, Isabela Bueno; Costa, Maricilia Silva

2014-07-01

277

[Volumetric verification of edema protection with Serrapeptase after third molar osteotomy].  

PubMed

Preventive edema protection using Serrapeptase after standardized one-stage osteotomy procedures of 4 third molars was verified by means of an opto-electronic measuring instrument. This measuring technique proved to be a sensitive tool for demonstrating the efficacy of Serrapeptase in reducing postoperative edema. Although statistically significant, the reduction of soft tissue swelling was only approximately 15% when compared with a patient group without Serrapeptase medication. PMID:1816962

Merten, H A; Müller, K; Drubel, F; Halling, F

1991-01-01

278

Reduced N400 semantic priming effects in adult survivors of paediatric and adolescent traumatic brain injury.  

PubMed

The immediate and long-term neural correlates of linguistic processing deficits reported following paediatric and adolescent traumatic brain injury (TBI) are poorly understood. Therefore, the current research investigated event-related potentials (ERPs) elicited during a semantic picture-word priming experiment in two groups of highly functioning individuals matched for various demographic variables and behavioural language performance. Participants in the TBI group had a recorded history of paediatric or adolescent TBI involving injury mechanisms associated with diffuse white matter pathology, while participants in the control group never sustained any insult to the brain. A comparison of N400 Mean Amplitudes elicited during three experimental conditions with varying semantic relatedness between the prime and target stimuli (congruent, semantically related, unrelated) revealed a significantly smaller N400 response in the unrelated condition in the TBI group, indicating residual linguistic processing deviations when processing demands required the quick detection of a between-category (unrelated) violation of semantic expectancy. PMID:22819620

Knuepffer, C; Murdoch, B E; Lloyd, D; Lewis, F M; Hinchliffe, F J

2012-10-01

279

5-Oxoproline Reduces NonEnzymatic Antioxidant Defenses in vitro in Rat Brain  

Microsoft Academic Search

5-Oxoproline (pyroglutamic acid) accumulates in glutathione synthetase deficiency, an inborn metabolic defect of the ?-glutamyl\\u000a cycle. This disorder is clinically characterized by hemolytic anemia, metabolic acidosis and severe neurological disorders.\\u000a Considering that the mechanisms of brain damage in this disease are poorly known, in the present study we investigated whether\\u000a oxidative stress is elicited by 5-oxoproline. The in vitro effect

Carolina D. Pederzolli; Ângela M. Sgaravatti; César A. Braum; Cristina C. Prestes; Giovanni K. Zorzi; Mirian B. Sgarbi; Angela T. S. Wyse; Clóvis M. D. Wannmacher; Moacir Wajner; Carlos S. Dutra-Filho

2007-01-01

280

Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging  

PubMed Central

Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18–83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G × A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging.

Glahn, David C.; Kent, Jack W.; Sprooten, Emma; Diego, Vincent P.; Winkler, Anderson M.; Curran, Joanne E.; McKay, D. Reese; Knowles, Emma E.; Carless, Melanie A; Goring, Harald H. H.; Dyer, Thomas D.; Olvera, Rene L.; Fox, Peter T.; Almasy, Laura; Charlesworth, Jac; Kochunov, Peter; Duggirala, Ravi; Blangero, John

2013-01-01

281

ERK1/2 in the brain mediates the effects of central resistin on reducing thermogenesis in brown adipose tissue  

PubMed Central

We investigated the role of ERK1/2 in the brain on the effects of centrally administered resistin on thermogenesis. Resistin (7 ?g) into anaesthetized rats significantly decreased brown adipose tissue temperature by 1.0 ± 0.4 °C (P < 0.005). This response was significantly attenuated by over 60% when ERK1/2 was inhibited by U0126 (7 ?g) (P < 0.05). Resistin reduced uncoupling protein-1 mRNA expression (0.11 ± 0.01 vs 1.24 ± 0.85 resistin vs control respectively) and the expression of peroxisome proliferator-activated receptor gamma co-activator 1-?, but the effects were not statistically significant. The results suggest that ERK1/2 in the brain contributes to resistin’s effects on thermogenesis.

Kosari, Samin; Camera, Donny M; Hawley, John A; Stebbing, Martin; Badoer, Emilio

2013-01-01

282

The histone deacetylase inhibitor sodium butyrate in combination with brain-derived neurotrophic factor reduces the viability of DAOY human medulloblastoma cells  

Microsoft Academic Search

Purpose  Histone deacetylase inhibitors (HDACis) are a promising class of anticancer agents for the treatment of brain tumors. HDACis\\u000a can increase the expression of brain-derived neurotrophic factor (BDNF) in brain cells. We have previously shown that BDNF\\u000a reduces the viability of medulloblastoma cells. The aim of the present study was to examine the effect of the HDACi sodium\\u000a butyrate (NaB) combined

Carolina Nör; Caroline Brunetto de Farias; Ana Lucia Abujamra; Gilberto Schwartsmann; Algemir Lunardi Brunetto; Rafael Roesler

2011-01-01

283

Xylazine-induced pulmonary edema in rats.  

PubMed

Inhibitors of cytochrome P450, such as SK&F 525-A, prolong the duration of xylazine-ketamine anesthesia and cause pulmonary edema (PE) and death in rats. To determine the cause of PE, Sprague-Dawley rats were given a single dose of xylazine (21 mg/kg, im) alone or in combination with ketamine (45 mg/kg, im) and/or SK&F 525-A (50 mg/kg, ip) and percentage lung to body weight (%LW/BW) ratios (as an indicator of PE) were compared. The results indicated that xylazine caused PE which was independent of ketamine and was enhanced by SK&F 525-A. Subsequently, it was determined that 42 mg/kg xylazine, im, is an optimal edemagenic dose. Xylazine (42 mg/kg, im) increased the %LW/BW ratio as compared to control. Pleural effusion (PLE) of various amounts was observed in 75% of the animals. The pleural fluid to serum protein ratio for xylazine was similar to that obtained for alpha-naphthylthiourea (5 mg/kg, ip). Extensive serous PLE and alveolar edema with hemorrhage were found at necropsy in xylazine-treated rats. Pretreatment with yohimbine (4.2 mg/kg), prazosin (20 mg/kg), tolazoline (20 mg/kg), yohimbine (4.2 mg/kg) plus prazosin (20 mg/kg), atropine (20 mg/kg), dimethyl sulfoxide (DMSO) (7.8 g/kg), allopurinol (50 mg/kg), superoxide dismutase (20,000 U/kg), catalase (20,000 U/kg), BW755C (50 mg/kg), ibuprofen (50 mg/kg), cystathionine (100 mg/kg) plus taurine (100 mg/kg) did not affect the %LW/BW ratio. PLE was increased by yohimbine, yohimbine plus prazosin, and allopurinol, reduced by DMSO, and not changed in other groups. The results indicate that xylazine caused increased-permeability PE characterized by rapid onset, cellular damage and protein-rich pleural fluid. PE may not be mediated by adverse cardiovascular effects of xylazine and oxygen radicals are possibly involved in its etiology. PMID:1902333

Amouzadeh, H R; Sangiah, S; Qualls, C W; Cowell, R L; Mauromoustakos, A

1991-05-01

284

Treatment of systemic hypertension is important for improvement of macular edema associated with retinal vein occlusion  

PubMed Central

Background We report our findings in three cases of unilateral macular edema associated with retinal vein occlusion (RVO) that improved after successful treatment of systemic hypertension alone. Methods All three cases had systemic hypertension but no diabetes mellitus or other ocular diseases associated with macular edema. All patients were treated only with medication for systemic hypertension. Optical coherence tomography was performed to determine the foveal thickness before and after treatment. Results Case one was a 72-year-old woman with a central RVO who had macular edema in her left eye and a visual acuity (VA) of 20/50. Her blood pressure (BP) was 169/96 mmHg. One month after the initiation of a calcium blocker to treat her systemic hypertension, her BP was decreased, macular edema was reduced, and her VA improved to 20/20. Case two was a 62-year-old woman with branch RVO. Her VA was 20/40 and her BP was 165/97 mmHg. Six weeks after initiation of medication to treat her systemic hypertension, her RVO-related macular edema had decreased and her VA improved to 20/20. Case three was a 71-year-old man with branch RVO. His VA was 20/50 and his BP was 165/87 mmHg. One month after initiation of treatment for systemic hypertension, his RVO-related macular edema had disappeared and his VA improved to 20/20. All three cases had nonischemic RVO by fluorescein angiography, and they did not develop ischemic changes for at least 1 year. Conclusion The reduction of macular edema following a decrease in the systemic hypertension suggests that the edema was most likely caused by leakage of fluids from the blood vessels. We recommend that the blood pressure should be measured in all patients with macular edema before initiating intravitreal anti-VEGF therapy.

Kida, Teruyo; Morishita, Seita; Kakurai, Keigo; Suzuki, Hiroyuki; Oku, Hidehiro; Ikeda, Tsunehiko

2014-01-01

285

Selective activation of PKC epsilon in mitochondria is neuroprotective in vitro and reduces focal ischemic brain injury in mice  

PubMed Central

Activation of PKC? confers protection against neuronal ischemia/reperfusion. Since activation of PKC? leads to its translocation to multiple intracellular sites, a mitochondrial-selective PKC? activator was used to test the importance of mitochondrial activation to the neuroprotective effect of PKC?. PKC? can regulate key cytoprotective mitochondrial functions including electron transport chain activity, reactive oxygen species (ROS) generation, mitochondrial permeability transition, and detoxification of reactive aldehydes. We tested the ability of mitochondrial selective activation of PKC? to protect primary brain cell cultures or mice subjected to ischemic stroke. Pre-treatment with either general PKC? activator peptide, ??RACK, or mitochondrial-selective PKC? activator, ??HSP90, reduced cell death induced by simulated ischemia/reperfusion in neurons, astrocytes, and mixed neuronal cultures. The protective effects of both ??RACK and ??HSP90 were blocked by the PKC? antagonist, ?V1–2, indicating protection requires PKC? interaction with its anchoring protein, ?RACK. Further supporting a mitochondrial mechanism for PKC?, neuroprotection by ??HSP90 was associated with a marked delay in mitochondrial membrane depolarization and significantly attenuated ROS generation during ischemia. Importantly, ??HSP90 reduced infarct size and reduced neurological deficit in C57/BL6 mice subjected to middle cerebral artery occlusion and 24 hours of reperfusion. Thus selective activation of mitochondrial PKC? preserves mitochondrial function in vitro and improves outcome in vivo, suggesting potential therapeutic value clinically when brain ischemia is anticipated, including neurosurgery and cardiac surgery.

Sun, Xiaoyun; Budas, Grant R.; Xu, Lijun; Barreto, George E.; Mochly-Rosen, Daria; Giffard, Rona

2014-01-01

286

Induced Normothermia Attenuates Intracranial Hypertension and Reduces Fever Burden after Severe Traumatic Brain Injury  

Microsoft Academic Search

Introduction  Hyperthermia following a severe traumatic brain injury (TBI) is common, potentiates secondary injury, and worsens neurological\\u000a outcome. Conventional fever treatment is often ineffective. An induced normothermia protocol, utilizing intravascular cooling,\\u000a was used to assess the impact on fever incidence and intracranial pressure (ICP) in patients with severe TBI.\\u000a \\u000a \\u000a \\u000a Methods  A comparative cohort study of 21 adult patients with severe TBI (GCS ? 8)

Ava M. Puccio; Michael R. Fischer; Brian T. Jankowitz; Howard Yonas; Joseph M. Darby; David O. Okonkwo

2009-01-01

287

Reduced hippocampal brain-derived neurotrophic factor (BDNF) in neonatal rats after prenatal exposure to propylthiouracil (PTU).  

PubMed

Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy. PMID:22253429

Chakraborty, Goutam; Magagna-Poveda, Alejandra; Parratt, Carolyn; Umans, Jason G; MacLusky, Neil J; Scharfman, Helen E

2012-03-01

288

Reduced Hippocampal Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Rats after Prenatal Exposure to Propylthiouracil (PTU)  

PubMed Central

Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy.

Chakraborty, Goutam; Magagna-Poveda, Alejandra; Parratt, Carolyn; Umans, Jason G.; MacLusky, Neil J.

2012-01-01

289

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats  

PubMed Central

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.

2013-01-01

290

Calorie restriction reduces the influence of glucoregulatory dysfunction on regional brain volume in aged rhesus monkeys.  

PubMed

Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships. PMID:22415875

Willette, Auriel A; Bendlin, Barbara B; Colman, Ricki J; Kastman, Erik K; Field, Aaron S; Alexander, Andrew L; Sridharan, Aadhavi; Allison, David B; Anderson, Rozalyn; Voytko, Mary-Lou; Kemnitz, Joseph W; Weindruch, Richard H; Johnson, Sterling C

2012-05-01

291

Calorie Restriction Reduces the Influence of Glucoregulatory Dysfunction on Regional Brain Volume in Aged Rhesus Monkeys  

PubMed Central

Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19–31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.

Willette, Auriel A.; Bendlin, Barbara B.; Colman, Ricki J.; Kastman, Erik K.; Field, Aaron S.; Alexander, Andrew L.; Sridharan, Aadhavi; Allison, David B.; Anderson, Rozalyn; Voytko, Mary-Lou; Kemnitz, Joseph W.; Weindruch, Richard H.; Johnson, Sterling C.

2012-01-01

292

CDC grand rounds: reducing severe traumatic brain injury in the United States.  

PubMed

A traumatic brain injury (TBI) is caused by a bump, blow, jolt, or penetrating wound to the head that disrupts the normal functioning of the brain. In 2009, CDC estimated that at least 2.4 million emergency department visits, hospitalizations, or deaths were related to a TBI, either alone or in combination with other injuries. Approximately 75% of TBIs are mild, often called concussions. Children, adolescents, and older adults are most likely to sustain a TBI. Nearly one third (30.5%) of all injury deaths included a diagnosis of TBI. In addition, an estimated 5.3 million U.S. residents are living with TBI-related disabilities, including long-term cognitive and psychologic impairments. A severe TBI not only affects a person's life and family, but also has a large societal and economic toll. The economic costs of TBIs in 2010 were estimated at $76.5 billion, including $11.5 billion in direct medical costs and $64.8 billion in indirect costs (e.g., lost wages, lost productivity, and nonmedical expenditures). These data underestimate the national burden because they include neither TBIs managed in nonhospital settings nor >31,000 military personnel diagnosed with TBI and treated in the U.S. Department of Defense or Veterans Administration medical systems in 2010. PMID:23842444

2013-07-12

293

Reduced brain somatostatin in mood disorders: a common pathophysiological substrate and drug target?  

PubMed Central

Our knowledge of the pathophysiology of affect dysregulation has progressively increased, but the pharmacological treatments remain inadequate. Here, we summarize the current literature on deficits in somatostatin, an inhibitory modulatory neuropeptide, in major depression and other neurological disorders that also include mood disturbances. We focus on direct evidence in the human postmortem brain, and review rodent genetic and pharmacological studies probing the role of the somatostatin system in relation to mood. We also briefly go over pharmacological developments targeting the somatostatin system in peripheral organs and discuss the challenges of targeting the brain somatostatin system. Finally, the fact that somatostatin deficits are frequently observed across neurological disorders suggests a selective cellular vulnerability of somatostatin-expressing neurons. Potential cell intrinsic factors mediating those changes are discussed, including nitric oxide induced oxidative stress, mitochondrial dysfunction, high inflammatory response, high demand for neurotrophic environment, and overall aging processes. Together, based on the co-localization of somatostatin with gamma-aminobutyric acid (GABA), its presence in dendritic-targeting GABA neuron subtypes, and its temporal-specific function, we discuss the possibility that deficits in somatostatin play a central role in cortical local inhibitory circuit deficits leading to abnormal corticolimbic network activity and clinical mood symptoms across neurological disorders.

Lin, Li-Chun; Sibille, Etienne

2013-01-01

294

Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography  

PubMed Central

The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual “palpation” of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination.

Schregel, Katharina; Wuerfel nee Tysiak, Eva; Garteiser, Philippe; Gemeinhardt, Ines; Prozorovski, Timour; Aktas, Orhan; Merz, Hartmut; Petersen, Dirk; Wuerfel, Jens; Sinkus, Ralph

2012-01-01

295

Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography.  

PubMed

The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual "palpation" of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination. PMID:22492966

Schregel, Katharina; Wuerfel, Eva; Garteiser, Philippe; Gemeinhardt, Ines; Prozorovski, Timour; Aktas, Orhan; Merz, Hartmut; Petersen, Dirk; Wuerfel, Jens; Sinkus, Ralph

2012-04-24

296

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model  

Microsoft Academic Search

Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior

P Mukherjee; M M El-Abbadi; J L Kasperzyk; M K Ranes; T N Seyfried

2002-01-01

297

Cerebral edema in children with diabetic ketoacidosis: vasogenic rather than cellular?  

PubMed

Cerebral edema (CE) is accumulation of water in the intracellular or extracellular spaces of the brain. Vasogenic edema occurs when there is breakdown of the tight endothelial junctions of the blood-brain barrier (BBB), leading to extravasation of intravascular protein and fluid into the interstitial space of the brain. In cellular edema the BBB remains intact and there is swelling of astrocytes with corresponding reduction in extracellular space. In this review we bring together clinical evidence from neuropathology and cerebral magnetic resonance (MR) studies in pediatric patients presenting in diabetic ketoacidosis (DKA), and use applied physiology to understand whether CE complicating DKA is vasogenic, rather than cellular in origin. Because the first-line of defense against CE is the interface between the intravascular compartment and the extracellular space in the brain much of the focus in this review is the BBB. The principal pathologic finding in fatal cases is perivascular with BBB disruption and albumin extravasation, suggesting increased vascular permeability. DKA induces an inflammatory response and the mechanism of BBB transcellular permeability may be an immunologic cascade that disrupts tight junctions. The principal MR finding in subclinical cases of CE is vasogenic rather than cellular edema. We propose that the following physiology be considered when treating cases: bolus dose of intravenous mannitol may result in fall in serum sodium concentration, and therefore clinical worsening. Failure to respond to mannitol should prompt the use of 3% hypertonic saline (HS). Bolus dose of intravenous 3% HS is expected to effect vasogenic edema provided that the reflection coefficient is close to 1. Failure to respond to 3% HS should prompt the use of mannitol. PMID:24866062

Tasker, Robert C; Acerini, Carlo L

2014-06-01

298

Preoperative neurogenic pulmonary edema: A dilemma for decision making  

PubMed Central

Neurogenic pulmonary edema may be a less-recognized consequence of obstructive hydrocephalus. The authors report a patient with acute obstructive hydrocephalus due to cerebellar metastatic lesion, who presented with neurogenic pulmonary edema. The edema resolved on placement of the ventriculoperitonial shunt. This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure and the issues involved with anesthetic management of co-existing neurogenic pulmonary edema and intracranial hypertension.

Lakkireddigari, Siva Kumar Reddy; Durga, Padmaja; Nayak, Madhukar; Ramchandran, Gopinath

2012-01-01

299

Nanoparticulate flurbiprofen reduces amyloid-?42 generation in an in vitro blood-brain barrier model  

PubMed Central

Introduction The amyloid-?42 (A?42) peptide plays a crucial role in the pathogenesis of Alzheimer’s disease (AD), the most common neurodegenerative disorder affecting the elderly. Over the past years, several approaches and compounds developed for the treatment of AD have failed in clinical studies, likely in part due to their low penetration of the blood–brain barrier (BBB). Since nanotechnology-based strategies offer new possibilities for the delivery of drugs to the brain, this technique is studied intensively for the treatment of AD and other neurological disorders. Methods The A?42 lowering drug flurbiprofen was embedded in polylactide (PLA) nanoparticles by emulsification-diffusion technique and their potential as drug carriers in an in vitro BBB model was examined. First, the cytotoxic potential of the PLA-flurbiprofen nanoparticles on endothelial cells and the cellular binding and uptake by endothelial cells was studied. Furthermore, the biological activity of the nanoparticulate flurbiprofen on ?-secretase modulation as well as its in vitro release was examined. Furthermore, the protein corona of the nanoparticles was studied as well as their ability to transport flurbiprofen across an in vitro BBB model. Results PLA-flurbiprofen nanoparticles were endocytosed by endothelial cells and neither affected the vitality nor barrier function of the endothelial cell monolayer. The exposure of the PLA-flurbiprofen nanoparticles to human plasma occurred in a rapid protein corona formation, resulting in their decoration with bioactive proteins, including apolipoprotein E. Furthermore, luminally administered PLA-flurbiprofen nanoparticles in contrast to free flurbiprofen were able to modulate ?-secretase activity by selectively decreasing A?42 levels in the abluminal compartment of the BBB model. Conclusions In this study, we were able to show that flurbiprofen can be transported by PLA nanoparticles across an in vitro BBB model and most importantly, the transported flurbiprofen modulated ?-secretase activity by selectively decreasing A?42 levels. These results demonstrate that the modification of drugs via embedding in nanoparticles is a promising tool to facilitate drug delivery to the brain, which enables future development for the treatment of neurodegenerative disorders like AD.

2013-01-01

300

Enhanced proteolytic clearance of plasma A? by peripherally administered neprilysin does not result in reduced levels of brain A? in mice.  

PubMed

Accumulation of ?-amyloid (A?) in the brain is believed to contribute to the pathology of Alzheimer's Disease (AD). A? levels are controlled by the production of A? from amyloid precursor protein, degradation by proteases, and peripheral clearance. In this study we sought to determine whether enhancing clearance of plasma A? with a peripherally administered A?-degrading protease would reduce brain A? levels through a peripheral sink. Neprilysin (NEP) is a zinc-dependent metalloprotease that is one of the key A?-degrading enzymes in the brain. We developed a NEP fusion protein with in vitro degradation of A? and a 10 day plasma half-life in mouse. Intravenous administration of NEP to wild-type and APP23 transgenic mice resulted in dose-dependent clearance of plasma A?. However, this did not correspond to reduced levels of soluble brain A? with treatment up to 5 weeks in WT mice or formic acid-extractable brain A? with 3 month treatment in aged APP23. In contrast, intracranial injection of NEP resulted in an acute decrease in soluble brain A?. We found no change in amyloid precursor protein gene expression in mice treated with intravenous NEP, suggesting that the lack of effects in the brain following this route of administration was not caused by compensatory upregulation of A? production. Taken together, these results suggest a lack of a robust peripheral A? efflux sink through which brain amyloid burdens can be therapeutically reduced. PMID:23392674

Walker, John R; Pacoma, Reynand; Watson, James; Ou, Weijia; Alves, Juliano; Mason, Daniel E; Peters, Eric C; Urbina, Hugo D; Welzel, Gus; Althage, Alana; Liu, Bo; Tuntland, Tove; Jacobson, Laura H; Harris, Jennifer L; Schumacher, Andrew M

2013-02-01

301

Electroacupuncture reduces stress-induced expression of c-fos in the brain of the rat.  

PubMed

We have previously shown that electroacupuncture (EA) at Shaohai and Neiguan (HT3-PC6) points significantly attenuated stress-induced peripheral responses, including increases in blood pressure, heart rate and plasma catecholamines. In this study, we examined the central effect of EA on the expression of c-fos, one of the immediate-early genes in the brain of rats subjected to immobilization stress. Immobilization stress (180 minutes) preferentially produced a significant increase in Fos-like immunoreactivity (FLI) in stress-relevant regions including the paraventricular hypothalamic nucleus (PVN), arcuate nucleus (ARN), supraoptic nucleus (SON), suprachiasmatic nucleus (SCN), medial amygdaloid nucleus (AMe), bed nucleus of the stria terminalis (BST), hippocampus, lateral septum (LS), nucleus accumbens, and the locus coeruleus (LC). EA (3 Hz, 0.2 ms rectangular pulses, 20 mA) at HT3-PC6 on the heart and pericardium channels for 30 minutes during stress, significantly attenuated stress-induced FLI in the parvocellular PVN, SON, SCN, AMe, LS and the LC. However, EA stimulations at HT3-PC6 had no effect on FLI in the magnocelluar PVN, ARN, BST or the hippocampus. EA stimulation at HT3-PC6 had a greater inhibitory effect on stress-induced FLI than that at TE5-LI11, the triple energizer and large intestine meridian, or non-acupoints. These results demonstrated that EA attenuated stress-induced c-fos expression in brain areas. These results suggest that decreased c-fos expression in hypothalamic and LC neurons, among stress-related areas, may reflect the integrative action of acupuncture in stress response. PMID:15633814

Lee, Hye-Jung; Lee, Bombi; Choi, Sun-Hye; Hahm, Dae-Hyun; Kim, Mi-Rye; Roh, Pyung-Ui; Pyun, Kwang-Ho; Golden, Gregory; Yang, Chae-Ha; Shim, Insop

2004-01-01

302

Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.  

PubMed

Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n?=?8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n?=?4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID:22295102

Melega, William P; Lacan, Goran; Gorgulho, Alessandra A; Behnke, Eric J; De Salles, Antonio A F

2012-01-01

303

Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model  

PubMed Central

Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n?=?8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n?=?4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.

Melega, William P.; Lacan, Goran; Gorgulho, Alessandra A.; Behnke, Eric J.; De Salles, Antonio A. F.

2012-01-01

304

Schools-based interventions for reducing stigmatization of acquired brain injury: the role of interpersonal contact and visible impairment.  

PubMed

The purpose of this study was to determine the effectiveness of contact versus education interventions for adolescents in reducing stigmatizing attitudes toward people with acquired brain injury (ABI), and whether visibility of ABI affects the intervention outcome. 408 students (age range = 14-17 years) from 13 schools in the Mid-West of Ireland were randomly allocated to one of the three interventions: Education only, Contact (Visible Disability), or Contact ("Invisible" Disability). Stigmatizing attitudes were measured before and after intervention. Results suggest that a Contact intervention was more effective in reducing stigmatizing attitudes in terms of social restrictiveness, benevolence, and community mental health beliefs than education alone. Visibility of ABI impacted the effectiveness of the contact intervention on Community Mental Health beliefs only. Contact with a person with ABI is thus more effective in promoting positive attitudes than ABI education alone, while the presence of visible impairment was not found to increase this intervention effect. PMID:24473119

Irwin, Lynn G; Fortune, Dónal G

2014-03-01

305

Acetate supplementation reduces microglia activation and brain interleukin-1? levels in a rat model of Lyme neuroborreliosis  

PubMed Central

Background We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. Methods In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16). Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1?. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. Results We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1? by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. Conclusions These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.

2012-01-01

306

Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edema.  

PubMed

Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral deficits in children with hyperoxia treatment (HHI) being the current therapy for newborn resuscitation. HI induces cerebral edema that is associated with poor neurological outcomes. Our objective was to characterize cerebral edema after HI and determine the consequences of HHI (40% or 100% O(2)). Dry weight analyses showed cerebral edema 1 to 21 days after HI in the ipsilateral cortex; and 3 to 21 days after HI in the contralateral cortex. Furthermore, HI increased blood-brain barrier (BBB) permeability 1 to 7 days after HI, leading to bilateral cortical vasogenic edema. HHI failed to prevent HI-induced increase in BBB permeability and edema development. At the molecular level, HI increased ipsilateral, but not contralateral, AQP4 cortical levels at 3 and up to 21 days after HI. HHI treatment did not further affect HI-induced changes in AQP4. In addition, we observed developmental increases of AQP4 accompanied by significant reduction in water content and increase permeability of the BBB. Our results suggest that the ipsilateral HI-induced increase in AQP4 may be beneficial and that its absence in the contralateral cortex may account for edema formation after HI. Finally, we showed that HI induced impaired motor coordination 21 days after the insult and HHI did not ameliorate this behavioral outcome. We conclude that HHI treatment is effective as a resuscitating therapy, but does not ameliorate HI-induced cerebral edema and impaired motor coordination. PMID:20143414

Ferrari, Diana Carolina; Nesic, Olivera B; Perez-Polo, J Regino

2010-07-01

307

Efficiency of mitochondrially targeted gallic acid in reducing brain mitochondrial oxidative damage.  

PubMed

Oxidative stress is associated with mitochondrial impairments. Supplying mitochondria with potent antioxidants can reduce oxidative stress—induced mitochondrial impairment. Gallic acid can be used to reduce oxidative burden in mitochondria. In order to increase the bioavailability of gallic acid inside the mitochondria we synthesized mitochondrially targeted gallic acid and explored its preventive effects against sodium nitroprusside induced oxidative stress in isolated mitochondria. Our observations revealed an increase in oxidative stress,decrease in reduced glutathione in mitochondria and increase in the mitochondrial permeability pore transition due to sodium nitroprusside treatment. Pre—treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference. Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid. We conclude that mitochondrially targeted gallic acid can be used for preventing mitochondrial impairment caused by oxidative stress. PMID:24998301

Parihar, P; Jat, D; Ghafourifar, P; Parihar, M S

2014-01-01

308

Diabetic macular edema: New promising therapies.  

PubMed

The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

2013-12-15

309

Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction.  

PubMed

Glycyrrhizin (GL) is a major constituent of licorice root and has been suggested to inhibit the release of high mobility group box-1 (HMGB1), a protein considered representative of damage-associated molecular patterns. We found that GL bound HMGB1 but not RAGE with a moderate equilibrium dissociation constant value based on surface plasmon resonance analysis. This complex formation prevented HMGB1 from binding to RAGE in vitro. The effects of glycyrrhizin on traumatic brain injury (TBI) induced by fluid percussion were examined in rats or mice in the present study. GL was administered intravenously after TBI. Treatment of rats with GL dose-dependently suppressed the increase in BBB permeability and impairment of motor functions, in association with the inhibition of HMGB1 translocation in neurons in injured sites. The beneficial effects of GL on motor and cognitive functions persisted for 7 days after injury. The expression of TNF-?, IL-1? and IL-6 in injured sites was completely inhibited by GL treatment. In RAGE-/- mice, the effects of GL were not observed. These results suggested that GL may be a novel therapeutic agent for TBI through its interference with HMGB1 and RAGE interaction. PMID:24859607

Okuma, Yu; Liu, Keyue; Wake, Hidenori; Liu, Rui; Nishimura, Yoshito; Hui, Zhong; Teshigawara, Kiyoshi; Haruma, Jun; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Date, Isao; Takahashi, Hideo K; Mori, Shuji; Nishibori, Masahiro

2014-10-01

310

Reduced Mortality and Brain Damage After Locomotor Activity in Gerbil Forebrain Ischemia  

Microsoft Academic Search

With 20-minute ischemia all runners survived compared with 21% of nonrunners. Quantitative histology (15-minute isch- emia) revealed selective nerve cell injury in various cerebral regions in both groups. In runners, however, with the excep- tion of the CA1 sector, damage was attenuated in cortex, striatum, and hippocampus. Furthermore, the extent of tha- lamic infarction was reduced (P<.05). Conclusions Locomotor activity

W. Stummer; K. Weber; B. Tranmer; A. Baethmann; O. Kempski

311

Clinical review: post-extubation laryngeal edema and extubation failure in critically ill adult patients.  

PubMed

Laryngeal edema is a frequent complication of intubation. It often presents shortly after extubation as post-extubation stridor and results from damage to the mucosa of the larynx. Mucosal damage is caused by pressure and ischemia resulting in an inflammatory response. Laryngeal edema may compromise the airway necessitating reintubation. Several studies show that a positive cuff leak test combined with the presence of risk factors can identify patients with increased risk for laryngeal edema. Meta-analyses show that pre-emptive administration of a multiple-dose regimen of glucocorticosteroids can reduce the incidence of laryngeal edema and subsequent reintubation. If post-extubation edema occurs this may necessitate medical intervention. Parenteral administration of corticosteroids, epinephrine nebulization and inhalation of a helium/oxygen mixture are potentially effective, although this has not been confirmed by randomized controlled trials. The use of non-invasive positive pressure ventilation is not indicated since this will delay reintubation. Reintubation should be considered early after onset of laryngeal edema to adequately secure an airway. Reintubation leads to increased cost, morbidity and mortality. PMID:20017891

Wittekamp, Bastiaan H J; van Mook, Walther N K A; Tjan, Dave H T; Zwaveling, Jan Harm; Bergmans, Dennis C J J

2009-01-01

312

Autofluorescence Imaging for Diagnosis and Follow-up of Cystoid Macular Edema  

PubMed Central

Lipofuscin results from digestion of photoreceptor outer segments by the retinal pigment epithelium (RPE) and is the principal compound that causes RPE fluorescence during autofluorescence imaging. Absorption of the 488-nanometer blue light by macular pigments, especially by the carotenoids lutein and zeaxanthin, causes normal macular hypo-autofluorescence. Fundus autofluorescence imaging is being increasingly employed in ophthalmic practice to diagnose and monitor patients with a variety of retinal disorders. In macular edema for example, areas of hyper-autofluorescence are usually present which are postulated to be due to dispersion of macular pigments by pockets of intraretinal fluid. For this reason, the masking effect of macular pigments is reduced and the natural autofluorescence of lipofuscin can be observed without interference. In cystic types of macular edema, e.g. cystoid macular edema due to retinal vein occlusion, diabetic macular edema and post cataract surgery, hyper-autofluorescent regions corresponding to cystic spaces of fluid accumulation can be identified. In addition, the amount of hyper-autofluorescence seems to correspond to the severity of edema. Hence, autofluorescence imaging, as a noninvasive technique, can provide valuable information on cystoid macular edema in terms of diagnosis, follow-up and efficacy of treatment.

Ebrahimiadib, Nazanin; Riazi-Esfahani, Mohammad

2012-01-01

313

[Uvular edema : Rare complication in anesthesia].  

PubMed

A uvular edema can be associated with angioedema, urticaria and anaphylaxis. Furthermore, it can be caused by medications, such as angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs and angiotensin II receptor antagonists. Other reasons can be cannabis or cocaine use or a traumatic irritation of the uvula. This article presents the case of a patient who underwent kidney transplantation and developed extensive edema of the uvula that occurred postoperatively after general anaesthesia. The case report describes the diagnosis and therapy of this rare disease. PMID:25052718

Löser, B; Zöllner, C

2014-07-01

314

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers  

PubMed Central

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the ?/? ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-01-01

315

Establishment and evaluation of an experimental animal model of high altitude cerebral edema.  

PubMed

The aim of our study was to develop a model of high altitude cerebral edema (HACE) using an acute, hypobaric hypoxia environment combined with exhaustive exercise. Forty healthy male Sprague-Dawley rats were randomly divided into a plains control group (PC group) and a plateau altitude hypoxia group (AH group). After 2 days of treadmill adaptation under normoxic conditions, the AH group was housed in hypobaric conditions (simulating 4000 m above sea level) for 2 days while performing exhaustive exercise. The simulated altitude was then increased to 8000 m for 3 days of simple hypobaric hypoxia exposure. Compared with the PC group, the AH group showed significantly greater (P<0.01) water content and Evans blue staining in their brain tissue. Furthermore, the hippocampal formation was seriously damaged, and the number of pyramidal cells decreased. In addition, the brain structure was altered into a loose state with notable edema, which was demonstrated by the leakage of lanthanum nitrate particles from brain microvessels into the surrounding tissue through widened tight junctions. Some neurons and glial cell organelles were swollen and some nerve fibers were demyelinated as well. We have shown that acute hypobaric hypoxia exposure with exhaustive exercise increases the permeability of the blood-brain barrier and leads to cerebral edema, making this a valid animal model of HACE. PMID:23680461

Guo, Ping; Luo, Han; Fan, Yong; Luo, Yongjun; Zhou, Qiquan

2013-06-28

316

Etazolate, an ?-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) evokes an intense neuroinflammatory reaction that is essentially mediated by activated microglia and that has been reported to act as a secondary injury mechanism that further promotes neuronal death. It involves the excessive production of inflammatory cytokines and the diminution of neuroprotective and neurotrophic factors, such as the soluble form alpha of the amyloid precursor protein (sAPP?), generated by the activity of ?-secretases. Hence, the aim of this study was to examine the effects of etazolate, an ?-secretase activator, on acute and belated post-TBI consequences. The mouse model of TBI by mechanical percussion was used and injured mice received either the vehicle or etazolate at the dose of 1, 3 or 10 mg/kg at 2 h post-TBI. Neurological score, cerebral œdema, IL-1? and sAPP? levels, microglial activation and lesion size were evaluated from 6 to 24 h post-TBI. Spontaneous locomotor activity was evaluated from 48 h to 12 weeks post-TBI, memory function at 5 weeks and olfactory bulb lesions at 13 weeks post-TBI. A single administration of etazolate exerted a dose-dependent anti-inflammatory and anti-œdematous effect accompanied by lasting memory improvement, reduction of locomotor hyperactivity and olfactory bulb tissue protection, with a therapeutic window of at least 2 h. These effects were associated with the restoration of the levels of the sAPP? protein post-TBI. Taken together, these results highlight for the first time the therapeutic interest of an ?-secretase activator in TBI. PMID:23178198

Siopi, Eleni; Llufriu-Dabén, Gemma; Cho, Angelo H; Vidal-Lletjós, Sandra; Plotkine, Michel; Marchand-Leroux, Catherine; Jafarian-Tehrani, Mehrnaz

2013-04-01

317

Traumatic brain injury reduces striatal tyrosine hydroxylase activity and potassium-evoked dopamine release in rats  

PubMed Central

There is increasing evidence that traumatic brain injury (TBI) induces hypofunction of the striatal dopaminergic system, the mechanisms of which are unknown. In this study, we analyzed the activity of striatal tyrosine hydroxylase (TH) in rats at 1 day, 1 week, and 4 weeks after TBI using the controlled cortical impact model. There were no changes in the level of TH phosphorylated at serine 40 site (pser40TH) at 1 day or 4 weeks. At 1 week, injured animals showed decreased pser40TH to 73.9±7.3% (p?0.05) of sham injured rats. The in vivo TH activity assay showed no significant difference between injured and sham rats at 1 day. However, there was a decreased activity in injured rats to 62.1±8.2% (p?0.05) and 68.8±6.2% (p?0.05) of sham injured rats at 1 and 4 weeks, respectively. Also, the activity of protein kinase A, which activates TH, decreased at 1 week (injured: 87.8±2.8%, sham: 100.0± 4.2%, p?0.05). To study the release activity of dopamine after injury, potassium (80 mM)-evoked dopamine release was measured by microdialysis in awake, freely moving rats. Dialysates were collected and analyzed by high-performance liquid chromatography. There were no significant differences in dopamine release at 1 day and 4 weeks between sham and injured groups. At 1 week, there was a significant decrease (injured: 0.067±0.015 ?M, sham: 0.127 ± 0.027 ?M, p ? 0.05). These results suggest that TBI-induced dopamine neurotransmission deficits are, at least in part, attributable to deficits in TH activity.

Shin, Samuel S.; Bray, Eric R.; Zhang, Cathy Q.; Dixon, C. Edward

2010-01-01

318

TNF? siRNA reduces brain TNF and EEG delta wave activity in rats  

Microsoft Academic Search

Tumor necrosis factor alpha (TNF?) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNF? were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNF? siRNA treatment specifically reduced TNF? mRNA by 45% in vitro without affecting interleukin-6

Ping Taishi; Lynn Churchill; Mingxiang Wang; Daniel Kay; Christopher J. Davis; Xin Guan; Alok De; Tadanobu Yasuda; Fan Liao; James M. Krueger

2007-01-01

319

Cyclosporine Treatment Reduces Oxygen Free Radical Generation and Oxidative Stress in the Brain of Hypoxia-Reoxygenated Newborn Piglets  

PubMed Central

Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H2O2) production and markers of oxidative stress. Piglets (1–4 d, 1.4–2.5 kg) were block-randomized into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation)(n?=?8/group). At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls) or cyclosporine (2.5 or 10 mg/kg i.v. bolus) in a blinded-randomized fashion. An additional sham-operated group (n?=?4) underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H2O2 production (electrochemical sensor), cerebral tissue glutathione (ELISA) and cytosolic cytochrome-c (western blot) levels were examined. Hypoxic piglets had cardiogenic shock (cardiac output 40–48% of baseline), hypotension (mean arterial pressure 27–31 mmHg) and acidosis (pH 7.04) at the end of 2 h of hypoxia. Post-resuscitation cyclosporine treatment, particularly the higher dose (10 mg/kg), significantly attenuated the increase in cortical H2O2 concentration during reoxygenation, and was associated with lower cerebral oxidized glutathione levels. Furthermore, cyclosporine treatment significantly attenuated the increase in cortical cytochrome-c and lactate levels. Carotid blood arterial flow was similar among groups during reoxygenation. Conclusively, post-resuscitation administration of cyclosporine significantly attenuates H2O2 production and minimizes oxidative stress in newborn piglets following hypoxia-reoxygenation.

Liu, Jiang-Qin; Chaudhary, Hetal; Brocks, Dion R.; Bigam, David L.; Cheung, Po-Yin

2012-01-01

320

Treatment with a Monoclonal Antibody against Methamphetamine and Amphetamine Reduces Maternal and Fetal Rat Brain Concentrations in Late Pregnancy.  

PubMed

We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ?15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP. PMID:24839971

White, Sarah J; Hendrickson, Howard P; Atchley, William T; Laurenzana, Elizabeth M; Gentry, W Brooks; Williams, D Keith; Owens, S Michael

2014-08-01

321

Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity associated with reducing oxidative stress in the brain of hypertensive rats.  

PubMed

It has been demonstrated that the antihypertensive drugs with the antioxidant action on the brainstem inhibit the sympathetic activity and consequently decrease blood pressure and heart rate (HR) in hypertensive rats. Combination drugs of the angiotensin receptor blocker and calcium channel blocker, such as olmesartan (OLM)/azelnidipine (AZ) and candesartan (CAN)/amlodipine (AM), are widely used for treating hypertension in Japan. In this study, it was investigated whether there are differences in the antioxidant effect in the brain and the sympathoinhibitory effect between OLM/AZ and CAN/AM combination therapies in stroke-prone spontaneously hypertensive rats (SHRSP). OLM/AZ (10/8 mg kg(-1) day(-1)), CAN/AM (4/2.5 mg kg(-1) day(-1)), or vehicle was orally administered for 30 days to SHRSP. OLM/AZ and CAN/AM markedly decreased systolic blood pressure to the same extent. OLM/AZ decreased HR to a greater extent than CAN/AM. Urinary norepinephrine excretion as a marker of sympathetic activity was unchanged in the CAN/AM group, but reduced in the OLM/AZ group. Oxidative stress in the whole brain assessed using the in vivo electron spin resonance method was similarly decreased in both OLM/AZ and CAN/AM groups. Importantly, thiobarbituric acid reactive substance levels in the brainstem were significantly lower in the OLM/AZ group, but not in the CAN/AM group, than in the vehicle group. These results suggest that combination therapy of either OLM/AZ or CAN/AM does not induce reflex-mediated sympathetic activation despite the marked blood pressure reduction, which is associated with an antioxidant effect in the brain regions affecting the sympathetic activity. Furthermore, the antioxidant effect in the brainstem and the sympathoinhibitory effect of OLM/AZ combination may be greater than those of CAN/AM combination treatment. PMID:22471901

Shinohara, Keisuke; Hirooka, Yoshitaka; Ogawa, Kiyohiro; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2012-01-01

322

Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema  

PubMed Central

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

2013-01-01

323

Characterization of reduced and oxidized dopamine and 3, 4- dihydrophenylacetic acid, on brain mitochondrial electron transport chain activities  

PubMed Central

Loss of dopamine (DA) homeostasis may be a contributing factor to cell damage in Parkinson’s disease (PD). Past studies showing deleterious effects of DA on mitochondrial function, however, have been inconsistent raising questions about mitochondria as a downstream target for DA. Issues such as the dopamine species i.e., reduced or oxidized, time of exposure and the effect of major metabolites such as 3,4-dihydrophenylacetic acid (DOPAC) may contribute to the disparate findings. The present study used isolated, lysed rat brain mitochondria to characterize the effects of oxidized or reduced DA and DOPAC on complex activities of the electron transport chain (ETC). Time of exposure and quantitation of reduced or oxidized catachols for DA and DOPAC were monitored for all experiments. Reduced DA and DOPAC with or without a 30 min preincubation had no affect on NADH oxidase activity which monitors the activities of complexes I, III and IV. Complex II activity was inhibited by reduced DA (?500uM), but not by reduced DOPAC and was significantly attenuated by SOD suggesting reactive oxygen species involvement. In contrast, fully oxidized DA and DOPAC dose dependently inhibited NADH oxidase, complex I and complex III activities with IC50s in the 50–200 uM range. No preincubation was required for inhibition with the catechols when they were fully oxidized. Oxidized DA inhibited complex I only when exposure occurred during stimulated electron flow, suggesting covalent binding of quinones to proteins within active sites of the complex. In intact, well coupled mitochondria, extramitochondrial DA was shown to access the mitochondrial matrix in a dose, time and energy-dependent fashion. The findings suggest that many of the reported inconsistencies with regards to the effects of DA and DOPAC on ETC function can be attributed to the oxidized state of the catechol at the time of exposure. In addition, the findings provide possible downstream targets for DA that could contribute to the vulnerability of dopaminergic neurons in PD.

Gautam, Alpa H.; Zeevalk, Gail D.

2011-01-01

324

Activation of adenosine A3 receptors reduces ischemic brain injury in rodents.  

PubMed

Adenosine A3 receptor (A3R) agonists have been shown to reduce cardiac and lung injury, but the protective roles of A3R agonists in the CNS are not well characterized. The protective effect of selective A3R agonist chloro-N(6)-(3-iodo-benzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA) was first examined in primary cortical cultures. In cortical culture, Cl-IB-MECA pretreatment antagonized the hypoxia-mediated decrease in cell viability. In vivo, Cl-IB-MECA or vehicle was given intracerebroventricularly or intravenously to anesthetized rats. Animals were subjected to focal cerebral ischemia induced by transient middle cerebral artery (MCA) ligation. Intracerebroventricular or repeated intravenous administration (i.e., at 165 min and 15 min before MCA ligation) of Cl-IB-MECA did not alter blood pressure during ischemia but increased locomotor activity and decreased cerebral infarction 2 days after. In these animals, Cl-IB-MECA also reduced the density of TUNEL labeling in the lesioned cortex. The possibility of endogeneous neuroprotection was further examined in A3R knockout mice. After MCA ligation, an increase in cerebral infarction was found in the A3R knockouts compared with the A3R wild-type controls, suggesting that A3Rs are tonically activated during ischemia. Additionally, intracerebroventricular pretreatment with Cl-IB-MECA decreased the size of infarction in the wild-type controls, but not in the A3R knockout animals, suggesting that Cl-IB-MECA-induced protection was mediated through the A3 receptors. Collectively, these data suggest that Cl-IB-MECA reduced cerebral infarction through the activation of A3Rs and suppression of apoptosis. PMID:17016854

Chen, Guann-Juh; Harvey, Brandon K; Shen, Hui; Chou, Jenny; Victor, Adrienne; Wang, Yun

2006-12-01

325

Traumatic brain injury during development reduces minimal clonic seizure thresholds at maturity.  

PubMed

Post-traumatic seizures affect 12-35% of children after traumatic brain injury (TBI) and are associated with worse cognitive and functional outcome, even after adjustment for severity of injury. Unfortunately, experimental models of pediatric post-traumatic epilepsy are lacking, and pathogenesis remains poorly understood. We have applied a standard model of TBI in immature rats to determine the effect of TBI on electroconvulsive seizure thresholds later in life. Male rats underwent controlled cortical impact to left parietal cortex on post-natal day (PND) 16-18. Hindbrain, forebrain, and limbic seizure thresholds were assessed, respectively, by tonic hindlimb extension (THE), minimal clonic, and partial psychomotor seizure responses during adolescence (PND 34-40) and at maturity (PND 60-63). Post-traumatic seizure thresholds were compared to those obtained in age- and litter-matched sham craniotomy and naïve controls. TBI during immaturity had no clear effect on THE seizure thresholds. In contrast, TBI lowered minimal clonic seizure thresholds at maturity (p<0.05 vs. sham or naïve rats), but not during adolescence. Consequently, minimal clonic seizure thresholds increased with age for sham and naïve rats but remained similar for TBI rats during adolescence and at maturity. TBI also tended to lower partial psychomotor seizure thresholds, which were determined only during adolescence (p<0.1 vs. naïve). Controlled cortical impact causes both focal cortical injury at the site of impact and ipsilateral hippocampal neuronal death. Since minimal clonic seizures are mediated by the forebrain, partial psychomotor seizures by the limbic system, and THE seizures by the brainstem, the observed pattern of changes in post-traumatic seizure thresholds is not surprising. The apparent age-dependent effects of TBI, however, are unexpected and likely due to a combination of attenuated maturational increases and progressive epileptogenesis. Additional study is needed to delineate the relative contributions of these processes. Given the sustained reduction in post-traumatic minimal clonic seizure thresholds, controlled cortical impact may hold promise as an experimental model of pediatric post-traumatic epilepsy. PMID:18490145

Statler, Kimberly D; Swank, Seth; Abildskov, Tracy; Bigler, Erin D; White, H Steve

2008-08-01

326

Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data.  

PubMed

Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([(11)C]SB207145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC. PMID:24361666

Greve, Douglas N; Svarer, Claus; Fisher, Patrick M; Feng, Ling; Hansen, Adam E; Baare, William; Rosen, Bruce; Fischl, Bruce; Knudsen, Gitte M

2014-05-15

327

Abstinent adult daily smokers show reduced anticipatory but elevated saccade-related brain responses during a rewarded antisaccade task.  

PubMed

Chronic smoking may result in reduced sensitivity to non-drug rewards (e.g., money), a phenomenon particularly salient during abstinence. During a quit attempt, this effect may contribute to biased decision-making (smoking>alternative reinforcers) and relapse. Although relevant for quitting, characterization of reduced reward function in abstinent smokers remains limited. Moreover, how attenuated reward function affects other brain systems supporting decision-making has not been established. Here, we use a rewarded antisaccade (rAS) task to characterize non-drug reward processing and its influence on inhibitory control, key elements underlying decision-making, in abstinent smokers vs. non-smokers. Abstinent (12-hours) adult daily smokers (N=23) and non-smokers (N=11) underwent fMRI while performing the rAS. Behavioral performances improved on reward vs. neutral trials. Smokers showed attenuated activation in ventral striatum during the reward cue and in superior precentral sulcus and posterior parietal cortex during response preparation, but greater responses during the saccade response in posterior cingulate and parietal cortices. Smokers? attenuated anticipatory responses suggest reduced motivation from monetary reward, while heightened activation during the saccade response suggests that additional circuitry may be engaged later to enhance inhibitory task performance. Overall, this preliminary study highlights group differences in decision-making components and the utility of the rAS to characterize these effects. PMID:24914005

Geier, Charles F; Sweitzer, Maggie M; Denlinger, Rachel; Sparacino, Gina; Donny, Eric C

2014-08-30

328

Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model.  

PubMed

Na?/H? exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (³¹P) and proton (¹H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model. PMID:23171224

Robertson, Nicola J; Kato, Takenori; Bainbridge, Alan; Chandrasekaran, Manigandan; Iwata, Osuke; Kapetanakis, Andrew; Faulkner, Stuart; Cheong, Jeanie; Iwata, Sachiko; Hristova, Mariya; Cady, Ernest; Raivich, Gennadij

2013-03-01

329

Postoperative pulmonary edema in young, athletic adults  

Microsoft Academic Search

Pulmonary edema secondary to postextubation laryn gospasm is a potentially life-threatening problem, de manding early diagnosis and prompt treatment. We believe that this problem has been grossly underesti mated in its incidence, as only seven adults have been reported in the English literature, whereas seven adults have been observed at our institution in only a 24 month period. All were

James R. Holmes; Robert N. Hensinger; Edward W. Wojtys

1991-01-01

330

Pathogenesis of edema formation in burn injuries  

Microsoft Academic Search

One of the obvious acute features of cutaneous thermal injury is the swelling of the involved tissue. This swelling is caused by a fluid shift from circulating plasma. Along with the evolution of intravenous fluid therapy in trauma and surgery, the implementation of such therapy to burn victims has improved survival. Edema generation aggravated by fluid therapy may, however, represent

Tjøstolv Lund; Henning Onarheim; Rolf K. Reed

1992-01-01

331

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat  

NASA Technical Reports Server (NTRS)

The effect of administering the serotonin precursor 5-l-hydroxytryptophan, in conjunction with a monamine oxidase inhibitor phenelzine and a l-amino acid decarboxylase inhibitor carbidopa, on neurochemical changes in the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid of the cat were investigated. Results showed that this drug regimen led to increases of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid by 330 and 830 percent, respectively. Concomitantly, the threshold of ventricular fibrillation was found to be elevated by 42 percent and the effective refractory period was prolonged by 7 percent; the efferent sympathetic neural activity was suppressed in the normal heart. The results indicate that the enhancement of central serotoninergic neurotransmission can reduce the susceptibility of the heart to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

Lehnert, Hendrik; Lombardi, Federico; Raeder, Ernst A.; Lorenzo, Antonio V.; Verrier, Richard L.; Lown, Bernard; Wurtman, Richard J.

1987-01-01

332

Ranolazine reduces neuronal excitability by interacting with inactivated states of brain sodium channels.  

PubMed

Ranolazine is an approved drug for chronic stable angina that acts by suppressing a noninactivating current conducted by the cardiac sodium channel [persistent sodium ion current (INa)]. Ranolazine has also been shown to inhibit the increased persistent INa carried by NaV1.1 channels encoding epilepsy- and migraine-associated mutations. Here, we investigate the antiepileptic properties of ranolazine exhibited through the reduction of hippocampal neuronal excitability. At therapeutically relevant concentrations, ranolazine reduced action potential firing frequency of hippocampal neurons in response to repetitive depolarizing current injections. Similarly, using a single current injection paradigm, ranolazine required a long depolarization (4 seconds) to produce significant inhibition of excitability, which was similar to that observed for the anticonvulsants phenytoin (slowly binds to the fast-inactivated state) and lacosamide (binds to the slow-inactivated state). Ranolazine enhanced the development of fast and slow inactivation assessed with conditioning prepulses of 100, 1000, or 10,000 milliseconds. Recovery of channels from inactivated states was also slowed in the presence of ranolazine. Interestingly, the use-dependent inhibition of hippocampal neurons was dependent on the duration of the voltage step, suggesting ranolazine does not selectively affect the open state and may also interact with inactivated states. NEURON (Yale University, New Haven, CT) computational simulations predict equal inhibition of action potential generation for binding to either fast-inactivated or slow-inactivated states. Binding of ranolazine to either preopen or open states did not affect the excitability of the simulation. Ranolazine was able to significantly reduce the epileptiform activity of the neuronal cultures, suggesting possible antiepileptic activity. PMID:24202911

Kahlig, Kristopher M; Hirakawa, Ryoko; Liu, Lynda; George, Alfred L; Belardinelli, Luiz; Rajamani, Sridharan

2014-01-01

333

Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in A?PP/PS1 transgenic mouse brain.  

PubMed

Metal dyshomeostasis in the brain helps promote amyloid-? (A?) deposition in Alzheimer's disease (AD). Therefore, targeting the interactions between metal and A? is a potential therapeutic approach for AD. The metal chelator, clioquinol (CQ), is thought to reduce A? deposits in the AD transgenic mouse brain, and attenuate the clinical symptoms of AD patients. However, whether oral administration of CQ reduces zinc accumulation in A? plaques and inhibits the amyloidogenic pathway have not been properly established in AD transgenic mice. By means of autometallographic analysis, we show for the first time that both the number and size of the zinc-containing plaques were significantly reduced in the brain of amyloid-? protein precursor (A?PP)/presenilin 1 (PS1) double transgenic mice treated with CQ (30 mg/kg/day) orally for 2 months. This was accompanied by a reduction in A? burden in the CQ-treated mouse brain. Furthermore, CQ treatment markedly reduced the expression levels of A?PP protein, the ?-site of A?PP cleaving enzyme 1 (BACE1), PS1, and the secreted ?-secretase-derived fragments of A?PP (sA?PP?). The present data indicate that CQ is able to reduce zinc accumulation in the neuritic plaques and inhibit amyloidogenic A?PP processing in the A?PP/PS1 mouse brain. PMID:22269164

Wang, Tao; Wang, Chun-Yan; Shan, Zhong-Yan; Teng, Wei-Ping; Wang, Zhan-You

2012-01-01

334

The Detection of Pulmonary Edema by Means of Electrical Impedance.  

National Technical Information Service (NTIS)

The detection, localization, and quantification of pulmonary edema by electrical impedance were investigated using band, circumferential, and longitudinal electrode arrays in a series of four studies utilizing 35 dogs. Pulmonary edema was induced with all...

J. C. Denniston L. E. Baker

1975-01-01

335

Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain sickness  

Microsoft Academic Search

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours

Kai Kallenberg; Damian M Bailey; Stefan Christ; Alexander Mohr; Robin Roukens; Elmar Menold; Thorsten Steiner; Peter Bärtsch; Michael Knauth

2007-01-01

336

Effects of Interstitial Edema on Brain Cell Transplantation  

Microsoft Academic Search

Fetal raphe cells were transplanted into the anterior part of the corpus cal-losum of serotonin denervated hydrocephalic rats using a cell suspension method. Hydrocephalus was induced by intracisternal injection of kaolin. The survival of the transplanted cells and fiber outgrowth were evaluated according to the level of serotonin and its metabolite, hydroxyindoleacetic acid, using high-performance liquid chromatography with electrochemical detection

S. Miyazaki; Y. Katayama; T. Tsubokawa; M. Iwasaki; O. Owawa; K. Ishikawa

1990-01-01

337

Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury.  

PubMed

Physical exercise preconditioning is known to ameliorate stroke-induced injury. In addition to several other mechanisms, the beneficial effect of preischemic exercise following stroke is due to an upregulated capacity to maintain energy supplies. Adult male Sprague-Dawley rats were used in exercise and control groups. After 1-3 weeks of exercise, several enzymes were analyzed as a gauge of the direct effect of physical exercise on cerebral metabolism. As a measure of metabolic capacity, an ADP/ATP ratio was obtained. Glucose transporters (GLUT1 and GLUT3) were monitored to assess glucose influx, and phosphofructokinase (PFK) was measured to determine the rate of glycolysis. Hypoxia-induced factor-1? (HIF-1?) and 5'AMP-activated protein kinase (AMPK) levels were also determined. These same analyses were performed on preconditioned and control rats following an ischemic/reperfusion (I/R) insult. Our results show that GLUT1, GLUT3, PFK, AMPK, and HIF-1? were all increased following 3 weeks of exercise training. In addition, the ADP/ATP ratio was chronically elevated during these 3 weeks. After I/R injury, HIF-1? and AMPK were significantly higher in exercised rats. The ADP/ATP ratio was reduced in preconditioned rats in the acute phase after stroke, suggesting a lower level of metabolic disorder. GLUT1 and GLUT3 were also increased in the acute phase in exercise rats, indicating that these rats were better able to increase rates of metabolism immediately after ischemic injury. In addition, PFK expression was increased in exercise rats showing an enhanced glycolysis resulting from exercise preconditioning. Altogether, exercise preconditioning increased the rates of glucose metabolism, allowing a more rapid and more substantial increase in ATP production following stroke. PMID:23553672

Dornbos, David; Zwagerman, Nathan; Guo, Miao; Ding, Jamie Y; Peng, Changya; Esmail, Fatema; Sikharam, Chaitanya; Geng, Xiaokun; Guthikonda, Murali; Ding, Yuchuan

2013-06-01

338

Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain.  

PubMed

The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1? and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation. PMID:24373829

Ahmad, Aliya; Ramasamy, Kalavathy; Jaafar, Siti Murnirah; Majeed, Abu Bakar Abdul; Mani, Vasudevan

2014-03-01

339

Use of video laryngoscopy and camera phones to communicate progression of laryngeal edema in assessing for extubation: a case series.  

PubMed

Video laryngoscopy has demonstrated utility in airway management. For the present case series, we report the use of video laryngoscopy to evaluate the airway of critically ill, mechanically ventilated patients, as a means to reduce the risk of immediate postextubation stridor by assessing the degree of laryngeal edema. We also describe the use of cellular phone cameras to document and communicate airway edema in using video laryngoscopy for the patients' medical records. We found video laryngoscopy to be an effective method of assessing airway edema, and cellular phone cameras were useful for recording and documenting video laryngoscopy images for patients' medical records. PMID:22337710

Newmark, Jordan L; Ahn, Young K; Adams, Mark C; Bittner, Edward A; Wilcox, Susan R

2013-01-01

340

Intravitreal Cortisone Injection for Refractory Diffuse Diabetic Macular Edema  

Microsoft Academic Search

Purpose: The purpose of this study was to evaluate the safety and efficacy of intravitreal triamcinolone acetonide injection in patients with diffuse diabetic macular edema. We also compared the effect of intravitreal triamcinolone with macular grid laser photocoagulation in macular edema. Patients and Methods: Thirty patients with diabetic diffuse macular edema unresponsive to grid laser photocoagulation for at least 4

Hamdi Er

2005-01-01

341

5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis.  

PubMed Central

1. An intracerebral perfusion method, brain microdialysis, was used to assess changes of 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of the chloral hydrate-anaesthetized rat in response to systemic administration of a variety of 5-HT1 receptor agonists. 2. A stable output of reliably detectable endogenous 5-HT was measured in dialysates collected from ventral hippocampus with the 5-HT reuptake inhibitor, citalopram, present in the perfusion medium. 3. Under these conditions the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused a dose-dependent (5-250 micrograms kg-1, s.c.) reduction of 5-HT in hippocampal dialysates. 4. Similarly, the putative 5-HT1A agonists gepirone (5 mg kg-1, s.c.), ipsapirone (5 mg kg-1, s.c.) and buspirone (5 mg kg-1, s.c.) markedly reduced levels of 5-HT in hippocampal perfusates whereas their common metabolite 1-(2-pyrimidinyl) piperazine (5 mg kg-1, s.c.), which does not bind to central 5-HT1A recognition sites, had no effect. 5. 5-Methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), a drug with reported high affinity for brain 5-HT1B binding sites, also produced a dose-dependent (0.25-5 mg kg-1, s.c.) decrease of hippocampal 5-HT output. 6. These data are direct biochemical evidence that systemically administered putative 5-HT1A and 5-HT1B agonists markedly inhibit 5-HT release in rat ventral hippocampus in vivo.

Sharp, T.; Bramwell, S. R.; Grahame-Smith, D. G.

1989-01-01

342

N-acetylcysteine improves hemodynamics and reduces oxidative stress in the brains of newborn piglets with hypoxia-reoxygenation injury.  

PubMed

Reactive oxygen species have been implicated in the pathogenesis of hypoxic-ischemic injury. It has been shown previously that treating an animal with N-acetyl-L-cysteine (NAC), a scavenger of free radicals, significantly minimizes hypoxic-ischemic-induced brain injury in various acute models. Using a subacute swine model of neonatal hypoxia-reoxygenation (H-R), we evaluated the long-term beneficial effect of NAC against oxidative stress-induced brain injury. Newborn piglets were randomly assigned to a sham-operated group (without H-R, n?=?6), and two H-R experimental groups (n?=?8 each), with 2?h normocapnic alveolar hypoxia and 1?h of 100% oxygen reoxygenation followed by 21% oxygen for 47?h. Five minutes after reoxygenation, the H-R piglets received either normal saline (H-R controls) or NAC (150?mg/kg bolus and 20?mg/kg/h IV for 24?h) in a blinded randomized fashion. Treating the piglets with NAC significantly increased both common carotid arterial flow (CCAF) and oxygen delivery during the early phase of rexoygenation, while both CCAF and carotid oxygen delivery of the H-R group remained lower than the sham-operated groups throughout the experimental period. Compared with H-R controls, significantly higher amounts of anesthetic and sedative medications were required to maintain the NAC-treated piglets in stable condition throughout the experimental period, indicating a stronger recovery. Post-resuscitation NAC treatment also significantly attenuated the increase in cortical caspase-3 and lipid hydroperoxide concentrations. Our findings suggest that post-resuscitation administration of NAC reduces cerebral oxidative stress with improved cerebral oxygen delivery, and probably attenuates apoptosis in newborn piglets with H-R insults. PMID:20649480

Liu, Jiang-Qin; Lee, Tze-Fun; Chen, Chao; Bagim, David L; Cheung, Po-Yin

2010-10-01

343

Inhibition of central angiotensin-converting enzyme with enalapril protects the brain from ischemia/reperfusion injury in normotensive rat  

PubMed Central

Background and the Purpose of the study Central Angiotensin Converting Enzyme (ACE) has an important role on cerebral microcirculation and metabolism. However, its role in terms of protecting the brain from ischemic/reperfusion (I/R) injury are debatable. This study evaluated the role of ACE, using enalapril as ACE inhibitor, in protection of the brain from I/R injury during transient focal cerebral ischemia (TFCI) in normotensive rat. Method Male Sprague Dawley rats (280–320g) randomly assigned to control ischemic and enalapril pre-treated ischemic groups. Enalapril was injected intraperitoneally 1 h before middle cerebral artery occlusion (MCAO) at the dose of 0.03 or 0.1 mg/kg. Cerebral ischemia was induced by 60 min MCAO followed by 24 hrs reperfusion. After evaluation of neurological deficit scores (NDS) the animal was sacrificed for assessment of cerebral infarction and edema. Results TFCI induced cerebral infarctions (283±18 mm3), brain edema (4.1±0.4%) and swelling (9.8±1.5%) with NDS of 3.11±0.36. Non-hypotensive dose of enalapril (0.03 mg/kg) improved NDS (1.37±0.26), reduced cerebral infarction (45%), brain edema (54%) and swelling of the lesioned hemispheres (34%) significantly. However, hypotensive dose of enalapril (0.1 mg/kg) could improve neurological activity (1.67±0.31) and failed to reduce cerebral infarction (276±39 mm3) and swelling (10.4±1.4%). Conclusion In the rat model of transient focal cerebral ischemia, inhibition of angiotensin converting enzyme with non-hypotensive doses of enalapril has the benefit of improving neurological activity, reducing cerebral infarction, brain swelling and edema of acute ischemic stroke. Therefore, it is reasonable to conclude that central renin-angiotensin system may participate in ischemic/reperfusion injury of the cerebral cortex.

Panahpour, H.; Dehghani, G.A.

2010-01-01

344

Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis  

PubMed Central

Background Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. Objectives To assess the effectiveness of interventions in the treatment of uveitic macular edema. Search strategy Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. Selection criteria Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. Data collection and analysis Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. Conclusion More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient.

Karim, Rushmia; Sykakis, Evripidis; Lightman, Susan; Fraser-Bell, Samantha

2013-01-01

345

Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus.  

PubMed

In the present study we analyzed aquaporin-4 (AQP4) immunoreactivity in the piriform cortex (PC) and the hippocampus of pilocarpine-induced rat epilepsy model to elucidate the roles of AQP4 in brain edema following status epilepticus (SE). In non-SE-induced animals, AQP4 immunoreactivity was diffusely detected in the PC and the hippocampus. AQP4 immunoreactivity was mainly observed in the endfeet of astrocytes. Following SE the AQP4-deleted area was clearly detected in the PC, not in the hippocampus. Decreases in dystrophin and ?-syntrophin immunoreactivities were followed by reduction in AQP4 immunoreactivity. These alterations were accompanied by the development of vasogenic edema and the astroglial loss in the PC. In addition, acetazolamide (an AQP4 inhibitor) treatment exacerbated vasogenic edema and astroglial loss both in the PC and in the hippocampus. These findings suggest that SE may induce impairments of astroglial AQP4 functions via disruption of the dystrophin/?-syntrophin complex that worsen vasogenic edema. Subsequently, vasogenic edema results in extensive astroglial loss that may aggravate vasogenic edema. PMID:20886625

Kim, Ji-Eun; Yeo, Seong-Il; Ryu, Hea Jin; Kim, Min-Ju; Kim, Duk-Soo; Jo, Seung-Mook; Kang, Tae-Cheon

2010-11-15

346

Myocardial Edema Imaging in Acute Coronary Syndromes  

PubMed Central

Acute coronary syndromes (ACS) continue to be the most common morbid condition of industrialized nations. The advent of and technical improvements in revascularization and medical therapy have led to a steady decline in mortality rates. However, many patients who suffer unstable angina or myocardial infarction require further testing and risk stratification to guide therapeutic selection and prognosis assignment. Myocardial edema imaging with cardiac magnetic resonance (CMR) affords the ability to define the amount of myocardium at risk, refine estimates of prognosis and provide guidance for therapies with excellent sensitivity compared to standard clinical markers. This review will discuss the rationale for edema imaging, how it is performed using CMR and its potential clinical applications.

Walls, Michael C.; Verhaert, David; Raman, Subha V.

2011-01-01

347

Mechanical Tissue Resuscitation Treatment Reduces Brain Tissue Volume and Intracerebral Hemorrhage and Increases Blood Perfusion in a Traumatic Brain Injury Model in Swine.  

National Technical Information Service (NTIS)

Each major war tends to have a 'signature injury' with traumatic brain injury (TBI) associated with the Iraq war (Operation Iraqi Freedom II and Operation Enduring Freedom) due to the high incidence of personnel injured by IED (improvised explosive device...

A. Bryant L. Argenta M. Morykwas Z. Zheng

2010-01-01

348

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology  

SciTech Connect

Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.

Testylier, Guy [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France)]. E-mail: guytestylier@crssa.net; Lahrech, Hana [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Montigon, Olivier [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Foquin, Annie [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Delacour, Claire [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Bernabe, Denis [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Segebarth, Christoph [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Dorandeu, Frederic [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Carpentier, Pierre [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France)

2007-04-15

349

Pigmentary epitheliopathy, disc edema, and lead intoxication.  

PubMed

A 52-year-old lead-exposed worker presented with disc edema, nerve fiber layer infarcts, and an acute bilateral pigment epitheliopathy that phenotypically resembled APMPPE. The patient had definite laboratory evidence of increased total body lead burden. The simultaneous involvement of retina, disc, and choriocapillaris suggests that what has been reported as the spectrum of APMPPE may represent a nonspecific vascular response to multiple injurious stimuli, including lead. PMID:3420315

Schubert, H D; Lucier, A C; Bosley, T M

1988-01-01

350

High altitude cerebral and pulmonary edema.  

PubMed

Altitude illness, which comprises of acute mountain sickness (AMS) and its life threatening complications, high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE) is now a well recognized disease process. AMS and HACE are generally thought to be a continuum. Some historical facts about the illness, its new intriguing pathophysiological processes, and clinical picture are discussed here. Although the review deals with both HACE and HAPE, HAPE is covered in greater detail due to the recent important findings related to its pathophysiology and prevention mechanisms. Relevant clinical correlation, the differential diagnosis of altitude sickness for a more sophisticated approach to the disease phenomenon, the possibility of dehydration being a risk factor for altitude sickness, the hypothetical role of angiogenesis in cerebral edema, and the emphasis on some vulnerable groups at high altitude are some of the other newer material discussed in this review. A clear-cut treatment and basic prevention guidelines are included in two panels, and finally the limited literature on the role of genetic factors on susceptibility to altitude sickness is briefly discussed. PMID:17292039

Basnyat, Buddha

2005-11-01

351

Impact of Clipping versus Coiling on Postoperative Hemodynamics and Pulmonary Edema after Subarachnoid Hemorrhage  

PubMed Central

Volume management is critical for assessment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This multicenter prospective cohort study compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema in patients with SAH. Hemodynamic parameters were measured for 14 days using a transpulmonary thermodilution system. The study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF), cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were significantly higher in the clipping group in the vasospasm period. Postoperative C-reactive protein (CRP) level was higher in the clipping group and was significantly correlated with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema, and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the vasospasm period, suggesting noncardiogenic edema. In conclusion, clipping affects postoperative CRP level and may thereby increase noncardiogenic pulmonary edema in the vasospasm period. His trial is registered with University Hospital Medical Information Network UMIN000003794.

Horie, Nobutaka; Iwaasa, Mitsutoshi; Ishizaka, Shunsuke; Inoue, Tooru; Nagata, Izumi

2014-01-01

352

Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis  

PubMed Central

Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

Wang, Shih-Min; Lei, Huan-Yao; Liu, Ching-Chuan

2012-01-01

353

Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis.  

PubMed

Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema. PMID:22956971

Wang, Shih-Min; Lei, Huan-Yao; Liu, Ching-Chuan

2012-01-01

354

Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca(2+)-loaded brain neurons.  

PubMed

The antioxidant action of myricetin and quercetin, the flavonoid constituents of the extract of Ginkgo biloba (EGb), on oxidative metabolism of brain neurons dissociated from the rats was examined using 2',7'-dichlorofluorescin (DCFH) which is retained within the neuron and then is oxidized by cellular hydrogen peroxide to be highly fluorescent. Incubation with myricetin or quercetin reduced the oxidation of DCFH in resting brain neurons, more profoundly than EGb. Myricetin decreased the oxidative metabolism at concentrations of 3 nM or more. It was 10 nM or more for the case of quercetin. Incubation with each flavonoid constituent also reduced the Ca(2+)-induced increase in the oxidative metabolism without affecting the cellular content of DCFH or the intracellular concentrations of Ca2+. Such an antioxidant action of myricetin or quercetin may be responsible for a part of the beneficial effects of EGb on brain neurons subject to ischemia. PMID:8173947

Oyama, Y; Fuchs, P A; Katayama, N; Noda, K

1994-01-28

355

Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats.  

PubMed

Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability of Rhodiola crenulata extract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1 ? ) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications of Rhodiola crenulata for antihigh altitude illness. PMID:23710233

Lee, Shih-Yu; Li, Min-Hui; Shi, Li-Shian; Chu, Hsin; Ho, Cheng-Wen; Chang, Tsu-Chung

2013-01-01

356

Structure-based redesign of an edema toxin inhibitor  

PubMed Central

Edema Factor toxin (EF) of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3?,5?-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-Oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 ?g/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin-(ET) catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria.

Chen, Deliang; Ma, Lili; Kanalas, John J.; Gao, Jian; Pawlik, Jennifer; Jimenez, Maria Estrella; Walter, Mary A.; Peterson, Johnny W.; Gilbertson, Scott R.; Schein, Catherine H.

2011-01-01

357

Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats  

PubMed Central

Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability of Rhodiola crenulata extract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1?) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications of Rhodiola crenulata for antihigh altitude illness.

Li, Min-Hui; Shi, Li-Shian; Ho, Cheng-Wen

2013-01-01

358

Reduced brain activation during imitation and observation of others in children with pervasive developmental disorder: a pilot study  

PubMed Central

Background Children with pervasive developmental disorder (PDD) are thought to have poor imitation abilities. Recently, this characteristic has been suggested to reflect impairments in mirror neuron systems (MNS). We used near-infrared spectroscopy (NIRS) to examine the brain activity of children with PDD during tasks involving imitation and observations of others. Findings The subjects were 6 male children with PDD (8–14 years old) and 6 age- and gender-matched normal subjects (9–13 years old). A video in which a woman was opening and closing a bottle cap was used as a stimulus. Hemoglobin concentration changes around the posterior part of the inferior frontal gyrus and the adjacent ventral premotor cortex were measured with a 24-channel NIRS machine during action observation and action imitation tasks. Regional oxygenated hemoglobin concentration changes were significantly smaller in the PDD group than in the control group. Moreover, these differences were clearer in the action observation task than in the action imitation task. Conclusions Dysfunction in the MNS in children with PDD was suggested by the reduced activation in key MNS regions during tasks involving observations and imitations of others. These preliminary results suggest that further studies are needed to verify MNS dysfunction in children with PDD.

2013-01-01

359

Towards reducing impact-induced brain injury: lessons from a computational study of army and football helmet pads.  

PubMed

We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterise the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the head injury criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry and material stiffness. We find that (1) the football pad materials do not outperform the currently used military pad material in militarily relevant impact scenarios; (2) optimal material properties for a pad depend on impact energy and (3) thicker pads perform better at all velocities. Although we considered only the isolated response of pad materials, not entire helmet systems, our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be reduced. PMID:23244512

Moss, William C; King, Michael J; Blackman, Eric G

2014-08-01

360

[Precursor brain-derived neurotrophic factor reduces survival and axonal sprouting of rat spiral ganglion neurons in vitro].  

PubMed

The aim of the present study was to investigate the effect of precursor brain-derived neurotrophic factor (proBDNF) on survival and neurite outgrowth of cultured rat spiral ganglion neurons (SGNs). Spiral ganglions (SG) were collected from postnatal day 5 Sprague Dawley (SD) rats, then enzymatically digested and suspended. Dissociated SGNs were plated on poly-D-lysine/laminin coated eight-well chamber plates and maintained at 37 °C for 4 h to promote the attachment of the neurons. Cultured SGNs were randomly divided into five groups: control group, BDNF group (BDNF 10 ng/mL), C10 group (proBDNF 10 ng/mL), C50 group (proBDNF 50 ng/mL), and C100 group (proBDNF 100 ng/mL). All groups were incubated in a serum-free medium. 48 h after incubation, SGNs were fixed and stained for ?III tubulin. Immunostaining of the cultured SGNs showed that, compared with the control group, the cellular survival of C50 group and C100 group were significantly reduced (P < 0.001). Furthermore, surviving numbers of the three proBDNF-treated groups were all lower than the BDNF group. In order to assess the effect of proBDNF on cell morphology, SGNs were divided into two categories: SGNs with or without neurites. The results demonstrated that proBDNF significantly increased the proportions of SGNs without neurites in C10, C50 and C100 groups compared with that in control group (P < 0.001). In addition, c-Jun N-terminal kinase (JNK) inhibitor, SP600125 (20 ?mol/L) significantly increased the surviving number of SGNs in C50 group. These results suggest that proBDNF reduces the survival rate of cultured SGNs and inhibits the sprouting of neurites. Furthermore, the inhibition of JNK signaling attenuates the effect of proBDNF on SGNs survival. PMID:24777405

Tong, Hua; Zhou, Lei; Liu, Jian-Ping; Gao, Li; Shen, Na; Huang, Xin-Sheng

2014-04-25

361

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D'Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

362

Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke  

Microsoft Academic Search

Uric acid is a natural antioxidant that protects the brain in a model of transient focal ischemia in rats. Here we sought to investigate whether uric acid was protective in a model of thromboembolic brain ischemia in rats, and whether the global benefit of recombinant tissue plasminogen activator (rt-PA) was improved by the combined treatment. Adult male Sprague–Dawley rats underwent

Eduardo Romanos; Anna M Planas; Sergio Amaro; Ángel Chamorro

2007-01-01

363

Fissured tongue: A sign of tongue edema?  

PubMed

Fissured tongue (FT) is a condition frequently seen in the general population. Clinically, FT is characterized by grooves that vary in depth and are noted along the dorsal and/or dorsolateral aspects of the tongue. Furthermore, FT presents many enlarged, smooth filiform papillae and subepithelial inflammatory infiltration. Despite of many studies, the etiology of FT remains obscure. FT is believed to be a congenital anomaly associated with several disorders and with geographic tongue (GT). We hypothesize that FT is not a congenital anomaly, and FT with swollen filiform papillae may represent edema in the subepithelial tissue of the tongue. According to the literature, the difference in prevalence among different age groups indicates that FT is not a congenital disorder. FT appears to occur more commonly in adults, and it is very rare or not at all in children younger than 10 years old. An association between FT and GT is well established in the literature, supporting the results of previous authors suggesting that FT might be a consequence of GT. The most remarkable finding in the region of swollen papillae of FT samples has been the subepithelial infiltrates of polymorphonuclear leucocytes and lymphocytes causing the subepithelial edema. The clinically visible grooves and large edematic papillae clustered on the region of the fissures might be caused by the inflammation and edema underneath the epithelium. In the future, FT and GT must be researched together as two different entities of the same disease so that GT is a prestage of FT. The diagnosis of FT must be taken to consideration whether the tongue surface have smooth and swollen papillae or normal-appearing filiform papillae. PMID:24698850

Järvinen, Jaana; Mikkonen, Jopi J W; Kullaa, Arja M

2014-06-01

364

Bradykinin in blood and cerebrospinal fluid after acute cerebral lesions: correlations with cerebral edema and intracranial pressure.  

PubMed

Bradykinin (BK) was shown to stimulate the production of physiologically active metabolites, blood-brain barrier disruption, and brain edema. The aim of this prospective study was to measure BK concentrations in blood and cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke and to correlate BK levels with the extent of cerebral edema and intracranial pressure (ICP). Blood and CSF samples of 29 patients suffering from acute cerebral lesions (TBI, 7; SAH,: 10; ICH, 8; ischemic stroke, 4) were collected for up to 8 days after insult. Seven patients with lumbar drainage were used as controls. Edema (5-point scale), ICP, and the GCS (Glasgow Coma Score) at the time of sample withdrawal were correlated with BK concentrations. Though all plasma-BK samples were not significantly elevated, CSF-BK levels of all patients were significantly elevated in overall (n=73) and early (?72?h) measurements (n=55; 4.3±6.9 and 5.6±8.9 fmol/mL), compared to 1.2±0.7 fmol/mL of controls (p=0.05 and 0.006). Within 72?h after ictus, patients suffering from TBI (p=0.01), ICH (p=0.001), and ischemic stroke (p=0.02) showed significant increases. CSF-BK concentrations correlated with extent of edema formation (r=0.53; p<0.001) and with ICP (r=0.49; p<0.001). Our results demonstrate that acute cerebral lesions are associated with increased CSF-BK levels. Especially after TBI, subarachnoid and intracerebral hemorrhage CSF-BK levels correlate with extent of edema evolution and ICP. BK-blocking agents may turn out to be effective remedies in brain injuries. PMID:23638655

Kunz, Mathias; Nussberger, Juerg; Holtmannspötter, Markus; Bitterling, Harro; Plesnila, Nikolaus; Zausinger, Stefan

2013-10-01

365

Subclinical pulmonary edema in endurance athletes.  

PubMed

Strenuous exercise may cause progressive and proportional haemodynamic overload damage to the alveolar membrane, even in athletes. Despite the high incidence of arterial desaturation reported in endurance athletes has been attributed, into other factors, also to the damage of the alveolar-capillary membrane this evidence is equivocal. Some studies demonstrated flood of the interstitial space and consequent increase in pulmonary water content, but most of them were able to show this through indirect signs of interstitial oedema. The present review illustrates the literature's data in favour or against pulmonary interstitial edema due to intense exercise in athletes. PMID:23193844

Bussotti, M; Di Marco, S; Marchese, G; Agostoni, P G

2012-06-01

366

Lymphoscintigraphy in the evaluation of limb edema.  

PubMed

Lymphedema is a chronic condition caused by ineffective lymphatic transport that results in edema and skin damage. Distinguishing lymphedema from other causes can be difficult. Lymphoscintigraphy is a simple and noninvasive functional test for the evaluation of the lymphatic system. (99m)Technetium-labeled sulfur colloid is injected intradermally at the interdigital web spaces of the upper/lower limbs. Once injected, the radiolabeled colloid particles travel through the superficial lymphatic channels. Thus, their lymphatic transport is monitored with dual-head gamma camera. The typical patterns of upper and lower limb lymphedema on lymphoscintigraphy are summarized in this section. PMID:24089069

Sundaram, P Shanmuga; Subramanyam, Padma

2013-11-01

367

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia  

PubMed Central

Opioid conjugate vaccines have shown promise in attenuating the behavioral effects of heroin or morphine in animals. The goal of this study was to extend this approach to oxycodone (OXY), a commonly abused prescription opioid. Haptens were generated by adding tetraglycine (Gly)4 or hemisuccinate (HS) linkers at the 6-position of OXY. Immunization of rats with OXY(Gly)4 conjugated to the carrier proteins bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) produced high-titer antibodies to OXY and its metabolite oxymorphone with substantially lower affinities for other structurally related opioid agonists and antagonists. There was no measurable binding of antibody by the (Gly)4 linker alone or off-target opioids methadone and buprenorphine. OXY(HS) conjugates were less immunogenic despite achieving protein haptenation ratios comparable to OXY(Gly)4-BSA. In rats given a single intravenous dose of OXY, immunization with OXY(Gly)4-KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain. Vaccine efficacy correlated with serum antibody titers, and it was greatest in rats given the lowest OXY dose (0.05 mg/kg) but was significant even after a larger OXY dose (0.5 mg/kg), equivalent to the high end of the therapeutic range in humans. These effects of OXY(Gly)4-KLH on drug disposition were comparable to those of nicotine or cocaine vaccines that are in clinical trials as addiction treatments. Immunization with OXY(Gly)4-KLH also reduced OXY analgesia in a thermal nociception test. These data support further study of vaccination with the OXY(Gly)4-KLH immunogen as a potential treatment option for OXY abuse or addiction.

Le Naour, M.; Harmon, T. M.; Tucker, A. M.; Portoghese, P. S.; Pentel, P. R.

2012-01-01

368

Reduced GABAergic Inhibition in the Basolateral Amygdala and the Development of Anxiety-Like Behaviors after Mild Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified. We assessed the functional alterations in inhibitory synaptic transmission in the BLA and one mechanism that modulates excitatory synaptic transmission, the ?7 containing nicotinic acetylcholine receptor (?7-nAChR), after mTBI, to shed light on the mechanisms that contribute to increased anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact (CCI) injury, animals displayed significantly greater anxiety-like behavior. This was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the mIPSC amplitude were associated with reduced surface expression of ?1, ?2, and ?2 GABAA receptor subunits. However, significant increases in the surface expression and current mediated by ?7-nAChR, were observed, signifying increases in the excitability of principal neurons within the BLA. These results suggest that mTBI causes not only a significant reduction in inhibition in the BLA, but also an increase in neuronal excitability, which may contribute to hyperexcitability and the development of anxiety disorders.

Almeida-Suhett, Camila P.; Prager, Eric M.; Pidoplichko, Volodymyr; Figueiredo, Taiza H.; Marini, Ann M.; Li, Zheng; Eiden, Lee E.; Braga, Maria F. M.

2014-01-01

369

Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats.  

PubMed

Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)(4) linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

Pravetoni, M; Raleigh, M D; Le Naour, M; Tucker, A M; Harmon, T M; Jones, J M; Birnbaum, A K; Portoghese, P S; Pentel, P R

2012-06-29

370

An oxycodone conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia.  

PubMed

Opioid conjugate vaccines have shown promise in attenuating the behavioral effects of heroin or morphine in animals. The goal of this study was to extend this approach to oxycodone (OXY), a commonly abused prescription opioid. Haptens were generated by adding tetraglycine (Gly)(4) or hemisuccinate (HS) linkers at the 6-position of OXY. Immunization of rats with OXY(Gly)(4) conjugated to the carrier proteins bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) produced high-titer antibodies to OXY and its metabolite oxymorphone with substantially lower affinities for other structurally related opioid agonists and antagonists. There was no measurable binding of antibody by the (Gly)(4) linker alone or off-target opioids methadone and buprenorphine. OXY(HS) conjugates were less immunogenic despite achieving protein haptenation ratios comparable to OXY(Gly)(4)-BSA. In rats given a single intravenous dose of OXY, immunization with OXY(Gly)(4)-KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain. Vaccine efficacy correlated with serum antibody titers, and it was greatest in rats given the lowest OXY dose (0.05 mg/kg) but was significant even after a larger OXY dose (0.5 mg/kg), equivalent to the high end of the therapeutic range in humans. These effects of OXY(Gly)(4)-KLH on drug disposition were comparable to those of nicotine or cocaine vaccines that are in clinical trials as addiction treatments. Immunization with OXY(Gly)(4)-KLH also reduced OXY analgesia in a thermal nociception test. These data support further study of vaccination with the OXY(Gly)(4)-KLH immunogen as a potential treatment option for OXY abuse or addiction. PMID:22262924

Pravetoni, M; Le Naour, M; Harmon, T M; Tucker, A M; Portoghese, P S; Pentel, P R

2012-04-01

371

Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats  

PubMed Central

Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components.

Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

2012-01-01

372

New insights of aquaporin 5 in the pathogenesis of high altitude pulmonary edema  

PubMed Central

Background High altitude pulmonary edema (HAPE) affects individuals and is characterized by alveolar flooding with protein-rich edema as a consequence of blood-gas barrier disruption. In this study, we hypothesized that aquaporin 5 (AQP5) which is one kind of water channels may play a role in preservation of alveolar epithelial barrier integrity in high altitude pulmonary edema (HAPE). Methods Therefore, we established a model in Wildtype mice and AQP5 ?/? mice were assingned to normoxic rest (NR), hypoxic rest (HR) and hypoxic exercise (HE) group. Mice were produced by training to walk at treadmill for exercising and chamber pressure was reduced to simulate climbing an altitude of 5000 m for 48 hours. Studies using BAL in HAPE mice to demonstrated that edema is caused leakage of albumin proteins and red cells across the alveolarcapillary barrier in the absence of any evidence of inflammation. Results In this study, the Lung wet/dry weight ratio and broncholalveolar lavage protein concentrations were slightly increased in HE AQP5 ?/? mice compared to wildtype mice. And histologic evidence of hemorrhagic pulmonary edema was distinctly shown in HE group. The lung Evan’s blue permeability of HE group was showed slightly increased compare to the wildtype groups, and HR group was showed a medium situation from normal to HAPE development compared with NR and HE group. Conclusions Deletion of AQP5 slightly increased lung edema and lung injury compared to wildtype mice during HAPE development, which suggested that the AQP5 plays an important role in HAPE formation induced by high altitude simulation.

2013-01-01