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1

Surgery for brain edema.  

PubMed

Brain edema is a common pathophysiological process seen in many neurosurgical conditions. It can be localized in relation to focal lesions or generalized in diffuse types of brain injury. In addition to local adverse effects occurring at a cellular level, brain edema is associated with raised intracranial pressure (ICP), and both phenomena contribute to poor outcome in patients. One of the goals in treating patients with acute neurosurgical conditions in intensive care is to control brain edema and maintain ICP below target levels. The mainstay of treatment is medical therapy to reduce edema, but in certain patients--for example, those with diffuse severe traumatic brain injury (TBI) and malignant middle cerebral artery infarction--such treatment is not effective. In these patients, opening the skull (decompressive craniectomy) to reduce ICP is a potential option. In this review the authors discuss the role of decompressive craniectomy as a surgical option in patients with brain edema in the context of a variety of pathological entities. They also address the current evidence for the technique (predominantly observational series) and the ongoing randomized studies of decompressive craniectomy in TBI and ischemic stroke. PMID:17613232

Hutchinson, Peter; Timofeev, Ivan; Kirkpatrick, Peter

2007-01-01

2

Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia.  

PubMed

Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of L-arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood-brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limiting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2010-05-01

3

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. PMID:22563196

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

4

Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia.  

PubMed

Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39±4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23±3%, and Evans Blue extravasation was reduced by 31±2% (mean±SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke. PMID:25449874

Yao, Xiaoming; Derugin, Nikita; Manley, Geoffrey T; Verkman, A S

2015-01-01

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. PMID:24409307

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

2014-01-01

7

Radiosurgery for brain metastases and cerebral edema.  

PubMed

The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9years. During the 2months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6mg/day, the mean metastasis volume decreased from 3.79±4.12cc to 2.8±4.48cc (p=0.001), and the mean edema volume decreased from 16.91±30.15cc to 12.85±24.47cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0-2cc) and increased in four patients (by >10%, 2-14cc). In a subanalysis of eight metastases with baseline edema volume greater than 40cc, edema volume decreased from 77.27±37.21cc to 24.84±35.6cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

2015-03-01

8

Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood–brain barrier Na/H exchanger  

PubMed Central

Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood–brain barrier (BBB). Our previous studies provided evidence that the BBB Na–K–Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210?minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na–K–Cl cotransporter activity. PMID:23149557

O'Donnell, Martha E; Chen, Yi-Je; Lam, Tina I; Taylor, Kelleen C; Walton, Jeffrey H; Anderson, Steven E

2013-01-01

9

Osmotherapy in brain edema: a questionable therapy.  

PubMed

Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect on outcome, or leads to worse outcome. Here we describe the action and potentially beneficial and adverse effects of the 2 most commonly used osmotic solutions, mannitol and hypertonic saline, and present some critical aspects of their use. There is a well-documented transient intracranial pressure (ICP)-reducing effect of osmotherapy, but an adverse rebound increase in ICP after its withdrawal has been discussed extensively in the literature and is an expected pathophysiological phenomenon. From side effects related to renal and pulmonary failure, electrolyte disturbances, and a rebound increase in ICP, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate in the present journal on the general routine use of osmotherapy in brain edema. PMID:22955195

Grände, Per-Olof; Romner, Bertil

2012-10-01

10

International brain edema symposia 1967-2011.  

PubMed

This is a brief review of previous international brain edema symposia. The symposia that took place from 1965 to 1999 were summarized by Igor Klatzo and A. Marmarou in the proceedings Brain Edema XI [1]. In this article the author summarized the symposia, including latest five. Images from previous symposia such as the cover pages of the proceedings and snapshots of organizers were included. The outline and key words of the symposia were summarized in tables. The name of the prize winner and the title of the memorial lectures in recent symposia were also summarized in a table. PMID:23564096

Kuroiwa, Toshihiko

2013-01-01

11

Brain edema in diseases of different etiology.  

PubMed

Cerebral edema is a potentially life-threatening complication shared by diseases of different etiology, such as diabetic ketoacidosis, acute liver failure, high altitude exposure, dialysis disequilibrium syndrome, and salicylate intoxication. Pulmonary edema is also habitually present in these disorders, indicating that the microcirculatory disturbance causing edema is not confined to the brain. Both cerebral and pulmonary subclinical edema may be detected before it becomes clinically evident. Available evidence suggests that tissue hypoxia or intracellular acidosis is a commonality occurring in all of these disorders. Tissue ischemia induces physiological compensatory mechanisms to ensure cell oxygenation and carbon dioxide removal from tissues, including hyperventilation, elevation of red blood cell 2,3-bisphosphoglycerate content, and capillary vasodilatation. Clinical, laboratory, and necropsy findings in these diseases confirm the occurrence of low plasma carbon dioxide partial pressure, increased erythrocyte 2,3-bisphosphoglycerate concentration, and capillary vasodilatation with increased vascular permeability in all of them. Baseline tissue hypoxia or intracellular acidosis induced by the disease may further deteriorate when tissue oxygen requirement is no longer matched to oxygen delivery resulting in massive capillary vasodilatation with increased vascular permeability and plasma fluid leakage into the interstitial compartment leading to edema affecting the brain, lung, and other organs. Causative factors involved in the progression from physiological adaptation to devastating clinical edema are not well known and may include uncontrolled disease, malfunctioning adaptive responses, or unknown factors. The role of carbon monoxide and local nitric oxide production influencing tissue oxygenation is unclear. PMID:22579570

Adeva, María M; Souto, Gema; Donapetry, Cristóbal; Portals, Manuel; Rodriguez, Alberto; Lamas, David

2012-07-01

12

Involvement of bradykinin in brain edema development after ischemic stroke.  

PubMed

Stroke is the third leading cause of death in the Western world. Ischemic stroke is characterized by a rapid loss of brain function due to disturbance in the blood supply to a part of the brain. Due to fixed intracranial space, any increase in intracranial fluid volume, or progressive brain edema formation, contributes to further deterioration of the already impaired brain function. Bradykinin increases blood-brain barrier permeability and raises intracranial capillary blood pressure by arterial dilatation and venous constriction leading to brain edema formation. The aim of this paper is to summarize the recent research in the field of bradykinin function (structure, synthesis, signaling pathways, mechanism of action) followed by characterization of different types of brain edema development related to ischemic brain injury, together with the involvement of bradykinin in edema formation. Since there is currently no causal treatment addressing brain edema after ischemic stroke, specific bradykinin receptor antagonists are proposed as a possible new therapeutic approach. PMID:24756199

Dobrivojevi?, Marina; Špiranec, Katarina; Sin?i?, Aleksandra

2015-02-01

13

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

14

Effect of Small Molecule Vasopressin V1a and V2 Receptor Antagonists on Brain Edema Formation and Secondary Brain Damage following Traumatic Brain Injury in Mice.  

PubMed

The attenuation of brain edema is a major therapeutic target after traumatic brain injury (TBI). Vasopressin (AVP) is well known to play a major role in the regulation of brain water content and vasoendothelial functions and to be involved in brain edema formation. Therefore, the aim of the current study was to analyze the antiedematous efficacy of a clinically relevant, nonpeptidic AVP V1a and V2 receptor antagonists. C57Bl6 mice were subjected to controlled cortical impact (CCI) and V1a or V2 receptors were inhibited by using the highly selective antagonists SR-49059 or SR-121463A either by systemic (intraperitoneal, IP) or intracerebroventricular (ICV) application. After 24?h, brain edema, intracranial pressure (ICP), and contusion volume were assessed. Systemically applied AVP receptor antagonists could not reduce secondary lesion growth. In contrast, ICV administration of AVP V1a receptor antagonist decreased brain edema formation by 68%, diminished post-traumatic increase of ICP by 46%, and reduced secondary contusion expansion by 43% 24?h after CCI. The ICV inhibition of V2 receptors resulted in significant reduction of post-traumatic brain edema by 41% 24?h after CCI, but failed to show further influence on ICP and lesion growth. Hence, centrally applied vasopressin V1a receptor antagonists may be used to reduce brain edema formation after TBI. PMID:25111427

Krieg, Sandro M; Sonanini, Sebastian; Plesnila, Nikolaus; Trabold, Raimund

2015-02-15

15

Edema  

MedlinePLUS

Edema means swelling caused by fluid in your body's tissues. It usually occurs in the feet, ankles ... it can involve your entire body. Causes of edema include Eating too much salt Sunburn Heart failure ...

16

Predictors of malignant brain edema in middle cerebral artery infarction observed on CT angiography.  

PubMed

Patients with middle cerebral artery (MCA) infarction accompanied by MCA occlusion with or without internal carotid artery (ICA) occlusion have a poor prognosis, as a result of brain cell damage caused by both the infarction and by space-occupying and life-threatening edema formation. Multiple treatments can reduce the likelihood of edema formation, but tend to show limited efficacy. Decompressive hemicraniectomy with duroplasty has been promising for improving functional outcomes and reducing mortality, particularly improved functional outcomes can be achieved with early decompressive surgery. Therefore, identifying patients at risk for developing fatal edema is important and should be performed as early as possible. Sixty-four patients diagnosed with major MCA infarction with MCA occlusion within 8hours of symptom onset were retrospectively reviewed. Early clinical, laboratory, and computed tomography angiography (CTA) parameters were analyzed for malignant brain edema (MBE). Twenty of the 64 patients (31%) had MBE, and the clinical outcome was poor (3month modified Rankin Scale >2) in 95% of them. The National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score, Clot Burden Score, and Collateral Score (CS) showed statically significant differences in both groups. Multivariable analyses adjusted for age and sex identified the independent predictors of MBE: NIHSS score >18 (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 1.2-16.0, p=0.023) and CS on CTA <2 (OR: 7.28, 95% CI: 1.7-30.3,p=0.006). Our results provide useful information for selecting patients in need of aggressive treatment such as decompressive surgery. PMID:25510537

Kim, Hoon; Jin, Seon Tak; Kim, Young Woo; Kim, Seong Rim; Park, Ik Seong; Jo, Kwang Wook

2015-03-01

17

A pre-injury high ethanol intake in rats promotes brain edema following traumatic brain injury.  

PubMed

Drinking is a risk factor for traumatic brain injury (TBI), and ethanol can aggravate the outcome by promoting brain edema. The mechanism involved is not fully understood. It has been confirmed that aquaporin-4 (AQP4) and vascular endothelial growth factor (VEGF) play pivotal roles in cytotoxic/vasogenic brain edema individually, and both of these proteins are downstream regulatory factors of hypoxia-inducible factor-1? (HIF-1?). In this study, we used a fluid percussion injury (FPI) model in rats to determine the effects of acute ethanol intake on the expression levels of HIF-1?, AQP4, and VEGF prior to FPI. The animals were sacrificed 1, 2, 3, and 4 days post-injury. We found that the expression levels of HIF-1? and AQP4 were significantly upregulated in the ethanol-pretreated groups, whereas the VEGF expression level was not. In addition, there was a positive correlation between HIF-1? and AQP4. The results of this study indicate that cytotoxic brain edema may play an important role in the early stage of FPI in ethanol-pre-treated animals and that HIF-1? and AQP4 might be involved. PMID:24814385

Wu, Weichuan; Tian, Runfa; Hao, Shuyu; Xu, Feifan; Mao, Xiang; Liu, Baiyun

2014-12-01

18

Inhibition of Rho kinase by Hydroxyfasudil Attenuates Brain Edema after Subarachnoid Hemorrhage in Rats  

PubMed Central

The blood-brain barrier (BBB) disruption and brain edema are important pathophysiologies of early brain injury after subarachnoid hemorrhage (SAH). This study is to evaluate whether Rho kinase (Rock) enhances BBB permeability via disruption of tight junction proteins during early brain injury. Adult male rats were assigned to five groups; sham-operated, SAH treated with saline, a Rock inhibitor hydroxyfasudil (HF) (10mg/kg) treatment at 0.5 hours after SAH, HF treatment at 0.5 and 6 hours (10mg/kg, each) after SAH, and another Rock inhibitor Y27632 (10mg/kg) treatment at 0.5 hrs after SAH. The perforation model of SAH was performed and neurological score and brain water content were evaluated 24 and 72 hours after surgery. Evans blue extravasation, Rock activity assay, and Western blotting analyses were evaluated 24 hours after surgery. Treatment of HF significantly improved neurological scores 24 hours after SAH. Single treatment with HF and Y27632, and two treatments with HF reduced brain water content in the ipsilateral hemisphere. HF reduced Evans blue extravasation in the ipsilateral hemisphere after SAH. Rock activity increased 24 hours after SAH, and HF reversed the activity. SAH significantly decreased the levels of tight junction proteins, occludin and zonula occludens-1 (ZO-1), and HF preserved the levels of occluding and ZO-1 in ipsilateral hemisphere. In conclusion, HF attenuated BBB permeability after SAH, possibly by protection of tight junction proteins. PMID:22226843

Fujii, Mutsumi; Duris, Kamil; Altay, Orhan; Soejima, Yoshiteru; Sherchan, Prativa; Zhang, John H.

2012-01-01

19

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

20

Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice  

PubMed Central

Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer's (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27?mm?Hg for 35?minutes. Mice (n=10/group) were then resuscitated with a 20?mL/kg bolus of 4% PNPH or LR followed by 10?mL/kg boluses targeting MAP>70?mm?Hg for 90?minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7?mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83?mm?Hg, P<0.001). The PNPH-treated mice required only 20?mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12?mm?Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68?mm?Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development. PMID:23801241

Brockman, Erik C; Bay?r, Hülya; Blasiole, Brian; Shein, Steven L; Fink, Ericka L; Dixon, CEdward; Clark, Robert SB; Vagni, Vincent A; Ma, Li; Hsia, Carleton JC; Tisherman, Samuel A; Kochanek, Patrick M

2013-01-01

21

Sequential change of brain edema by semiquantitative measurement on MRI in patients with hypertensive intracerebral hemorrhage.  

PubMed

The progression of brain edema in seven patients with hypertensive intracerebral hemorrhage (ICH) was evaluated. Five were of putaminal and two were of thalamic hemorrhage. The hematoma volume in the patients was 4 approximately 40 ml (18.9 +/- 8.0 ml). Sequential MRI (SE: 2000/40) was performed at one, two and four weeks after onset. The edema volume (EV) was calculated as 1/2.(long diameter).(short diameter).(thickness) of the high intensity area (HIA) on MRI. In comparison with the EV at one week after onset, the EV at two weeks was increased and the EV at four weeks returned to the same level of that at one week (132.3 +/- 26.1%, 100 +/- 10.6%, respectively). In contrast, the consciousness level and motor weakness of the patients had already improved at two weeks after onset. Our results demonstrate that progression of brain edema after small or medium size ICH may not bring about a deterioration of the clinical course. Moreover, progression of brain edema to the cerebral cortex and ventricle as indicated by MRI suggested an absorption pathway for the edema fluid, and implying that brain edema following ICH could play a part in the healing process after ICH. PMID:7976651

Suga, S; Sato, S; Yunoki, K; Mihara, B

1994-01-01

22

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

Microsoft Academic Search

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

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

2011-01-01

23

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer  

Microsoft Academic Search

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate

Elizabeth R. Gerstner; Dan G. Duda; Emmanuelle di Tomaso; Peter A. Ryg; Jay S. Loeffler; A. Gregory Sorensen; Percy Ivy; Rakesh K. Jain; Tracy T. Batchelor

2009-01-01

24

Relationship between specific gravity, water content, and serum protein extravasation in various types of vasogenic brain edema  

Microsoft Academic Search

Vasogenic brain edema was induced in cats by cold injury (six animals), brain tumors (five animals), and brain abscesses (six animals). Water and electrolyte content, specific gravity, blood volume, and the amount of extravasated serum proteins were determined in small tissue samples taken from gray and white matter at various distances from the lesion. Edema was strictly confined to the

H.-W. Bothe; W. Bodsch; K.-A. Hossmann

1984-01-01

25

Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice  

PubMed Central

After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1? expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation without major differences in morphological brain damage compared to young. PMID:22952778

Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

2012-01-01

26

MRI Reveals Edema in Larynx (But Not in Brain) During Anaphylactic Hypotension in Anesthetized Rats  

PubMed Central

Purpose Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Methods Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Results Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Conclusion Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain. PMID:24179686

Toyota, Ichiro; Tanida, Mamoru; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-01-01

27

Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: possible role in edema resolution?  

PubMed Central

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. The neuropathological sequelae that result from TBI are a complex cascade of events including edema formation, which occurs more frequently in the pediatric than the adult population. This developmental difference in the response to injury may be related to higher water content in the young brain and also to molecular mechanisms regulating water homeostasis. Aquaporins (AQPs) provide a unique opportunity to examine the mechanisms underlying water mobility, which remain poorly understood in the juvenile post-traumatic edema process. We examined the spatiotemporal expression pattern of principal brain AQPs (AQP1, 4, and 9) after juvenile TBI (jTBI) related to edema formation and resolution observed using magnetic resonance imaging (MRI). Using a controlled cortical impact in post-natal 17 day-old rats as a model of jTBI, neuroimaging analysis showed a global decrease in water mobility (apparent diffusion coefficient, ADC) and an increase in edema (T2-values) at 1 day post-injury, which normalized by 3 days. Immunohistochemical analysis of AQP4 in perivascular astrocyte endfeet was increased in the lesion at 3 and 7 days post-injury as edema resolved. In contrast, AQP1 levels distant from the injury site were increased at 7, 30, and 60 days within septal neurons but did not correlate with changes in edema formation. Group differences were not observed for AQP9. Overall, our observations confirm that astrocytic AQP4 plays a more central role than AQP1 or AQP9 during the edema process in the young brain. PMID:22728101

Fukuda, Andrew M; Pop, Viorela; Spagnoli, David; Ashwal, Stephen; Obenaus, André; Badaut, Jérôme

2012-01-01

28

Acupuncture and moxibustion reduces neuronal edema in Alzheimer's disease rats  

PubMed Central

To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer's disease, we established a rat model of Alzheimer's disease and measured axin and ?-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacupuncture, or both, at Baihui (GV20) and Shenshu (BL23). Axin expression was lower, ?-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuroprotective effect of acupuncture and moxibustion in Alzheimer's disease is associated with axin and ?-catenin expression in the Wnt signal transduction pathway. PMID:25206919

Zhou, Hua; Sun, Guojie; Kong, Lihong; Du, Yanjun; Shen, Feng; Wang, Shuju; Chen, Bangguo; Zeng, Xiaoling

2014-01-01

29

Acupuncture and moxibustion reduces neuronal edema in Alzheimer's disease rats.  

PubMed

To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer's disease, we established a rat model of Alzheimer's disease and measured axin and ?-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacupuncture, or both, at Baihui (GV20) and Shenshu (BL23). Axin expression was lower, ?-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuroprotective effect of acupuncture and moxibustion in Alzheimer's disease is associated with axin and ?-catenin expression in the Wnt signal transduction pathway. PMID:25206919

Zhou, Hua; Sun, Guojie; Kong, Lihong; Du, Yanjun; Shen, Feng; Wang, Shuju; Chen, Bangguo; Zeng, Xiaoling

2014-05-01

30

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. PMID:23997917

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

2013-01-01

31

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions  

PubMed Central

We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na+,K+,2Cl? cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation. PMID:19889792

Paulson, Jennifer R.; Yang, Tianzhi; Selvaraj, Pradeep K.; Mdzinarishvili, Alexander; Van der Schyf, Cornelis J.; Klein, Jochen; Bickel, Ulrich

2010-01-01

32

Hyperbaric Oxygen in the Management of Brain Edema Associated with Stereotactic Radiosurgery  

Microsoft Academic Search

Background: Hyperbaric oxygenation therapy (HBOT) is a method rarely used for patients with complications associated with the management of inoperable arteriovenous malformations, such as brain edema, treated with stereotactic radiosurgery. We present a successful treatment protocol in a series of steroid-refractory patients. Methods: Five patients diagnosed with arteriovenous malformations and 1 patient diagnosed with cavernous malformation were irradiated using stereotactic

M. A. Celis López; S. Moreno Jiménez; G. A. Gutierrez Aceves; C. Tenorio Tellez; C. Sanchez; J. J. Suárez Campos

2010-01-01

33

Candesartan Attenuates Ischemic Brain Edema and Protects the Blood–Brain Barrier Integrity from Ischemia/Reperfusion Injury in Rats  

PubMed Central

Background: Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat. Methods: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion. Vehicle and non-hypotensive doses of candesartan (0.1 mg/kg) were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability. Results: The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption (Evans blue extravasation = 12.5 ± 1.94 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%). Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke. PMID:25326022

Panahpour, Hamdollah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-01-01

34

Effects of focal mild hypothermia on thrombin-induced brain edema formation and the expression of protease activated receptor-1, matrix metalloproteinase-9 and aquaporin 4 in rats.  

PubMed

Hypothermia is an effective neuroprotective treatment for brain injury caused by intracerebral hemorrhage (ICH). It is reported to reduce brain edema and neuronal cell death. Thrombin, a coagulation protease released from blood clots, is critical in brain edema formation following ICH. Protease activated receptor?1 (PAR?1), matrix metalloproteinase?9 (MMP?9) and aquaporin 4 (AQP4) are edema?associated mediators that have been implicated in ICH pathology. In the present study, thrombin was used to induce brain edema in adult male Sprague?Dawley rats. Differences between a focal mild hypothermic group (33±0.5?C) and a normothermic group (37?C) were investigated. Following hypothermia, brain water content and blood?brain barrier (BBB) disruption was assessed at 6, 24 and 48 h and subsequently at 3, 5 and 7 days. At the same time, the mRNA and protein expression of PAR?1, MMP?9 and AQP4 were also determined. It was identified that brain water content and BBB disruption increased at 6 h and reached a maximal level at 24 h in the normothermic group. The mRNA and protein expression levels of PAR?1, MMP?9 and AQP4 started to increase at 24 h and reached a maximal level at 48 h. Focal mild hypothermia tended to significantly reduce brain water content, BBB disruption and PAR?1, MMP?9 and AQP expression at 24 and 48 h. The present data suggest that focal mild hypothermia is an effective treatment for edema formation through moderation of the mRNA and protein expression of PAR?1, MMP?9 and AQP4. PMID:25523640

Gao, Dapeng; Ding, Feifan; Lei, Gongwen; Luan, Guohui; Zhang, Shibao; Li, Kesen; Wang, Desheng; Zhang, Liming; Dai, Dawei

2015-04-01

35

Brain expression of the water channels aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema.  

PubMed

Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and/or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and intravenous ammonia-acetate (NH(4)(+)), the GLN+LPS+NH(4)(+) group. The vehicle control group (CONTROL) was treated with NaCl and phosphate-buffered saline. The GLN+LPS+NH(4)(+) group showed significantly elevated p-alanine aminotransferase, p-INR and p-ammonium vs. CONTROL (p < 0.001). Cortical brain water content was significantly elevated in the GLN+LPS+NH(4)(+) group vs. CONTROL, mean (SEM) 80.8(0.3) vs 80.0(0.1) % (p < 0.05). Western blot of membrane enriched cortical brain tissue showed significantly upregulation of Aqp4 in the GLN+LPS+NH(4)(+) group vs. CONTROL, mean AU (SEM) 100775(14820) vs. 58857(6266) (p < 0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF. PMID:20938728

Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E; Vainer, Ben; Bisgaard, Hanne Cathrine; Larsen, Fin S

2010-09-01

36

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. PMID:22174658

Panickar, Kiran S.; Anderson, Richard A.

2011-01-01

37

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. PMID:22815977

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

2012-01-01

38

Therapeutic implications of melatonin in cerebral edema.  

PubMed

Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema. PMID:24876075

Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit

2014-12-01

39

Antagonists of the Vasopressin V1 Receptor and of the ?1-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes – but the Mechanisms Differ  

PubMed Central

Brain edema is a serious complication in ischemic stroke because even relatively small changes in brain volume can compromise cerebral blood flow or result in compression of vital brain structures on account of the fixed volume of the rigid skull. Literature data indicate that administration of either antagonists of the V1 vasopressin (AVP) receptor or the ?1-adrenergic receptor are able to reduce edema or infarct size when administered after the onset of ischemia, a key advantage for possible clinical use. The present review discusses possible mechanisms, focusing on the role of NKCC1, an astrocytic cotransporter of Na+, K+, 2Cl- and water and its activation by highly increased extracellular K+ concentrations in the development of cytotoxic cell swelling. However, it also mentions that due to a 3/2 ratio between Na+ release and K+ uptake by the Na+,K+-ATPase driving NKCC1 brain extracellular fluid can become hypertonic, which may facilitate water entry across the blood-brain barrier, essential for development of edema. It shows that brain edema does not develop until during reperfusion, which can be explained by lack of metabolic energy during ischemia. V1 antagonists are likely to protect against cytotoxic edema formation by inhibiting AVP enhancement of NKCC1-mediated uptake of ions and water, whereas ?1-adrenergic antagonists prevent edema formation because ?1-adrenergic stimulation alone is responsible for stimulation of the Na+,K+-ATPase driving NKCC1, first and foremost due to decrease in extracellular Ca2+ concentration. Inhibition of NKCC1 also has adverse effects, e.g. on memory and the treatment should probably be of shortest possible duration. PMID:25342939

Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting; Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting

2014-01-01

40

Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.  

PubMed

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus. PMID:24333865

Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

2014-03-01

41

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

42

Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases  

PubMed Central

Background Differentiation of tumor recurrence from radionecrosis is a critical step in the follow-up management of patients treated with stereotactic radiosurgery (SRS) for brain metastases. A method that can reliably differentiate tumor recurrence from radiation necrosis using standard MR sequences would be of significant value. Methods We analyzed the records of 49 patients with 52 brain metastases treated with SRS who subsequently underwent surgical resection of the same lesion. Forty-seven of the lesions had preoperative MRI available for review (90%), including T1 postcontrast, T2, and fluid attenuated inversion recovery sequences. Pre-SRS and preoperative lesion and edema volumes were manually contoured and measured in a blinded fashion using radiation treatment planning software. A neuropathologist analyzed samples for the presence of tumor and/or radiation necrosis. Results Longer time between SRS and resection (P < .001) and a larger edema/lesion volume ratio (high T2/T1c, P = .002) were found to be predictive of radionecrosis as opposed to tumor recurrence. Using a cutoff value of 10 for the edema/lesion volume ratio, we were able to predict the presence of tumor with a positive predictive value of 92%, which increased to 100% when looking only at patients who underwent resection <18 months following SRS. Conclusions On follow-up imaging, lesions with a high edema/lesion volume ratio and lesions that progress later after SRS are more likely to contain radionecrosis. These indices may help guide clinical decision making in the context of evolving lesions after SRS for brain metastases and thereby avoid unnecessary interventions. PMID:24243914

Leeman, Jonathan E.; Clump, David A.; Flickinger, John C.; Mintz, Arlan H.; Burton, Steven A.; Heron, Dwight E.

2013-01-01

43

[Topography and structure of secondary brain damage in edema associated with supratentorial foci of encephalomalacia].  

PubMed

The paper comprises 70 cases of extensive supratentorial infarctions. The topography and structure of secondary lesions occurring in the region of herniation and displacements caused by the coexisting brain edema were analysed. The extent of edema served as criterion in the division of the material into three groups in dependence on the occurrence of herniations and displacements. Most frequent was herniation of hippocampal uncus and most rare that of the cerebellar vermis. In group I showing no herniations selective necrosis was noted of neurons particularly sensitive to ischemia and anoxia, especially in Sommer's sector of the hippocampus. In group II secondary necrosis was visible in the regions of herniae, and in the group III also in the translocated deep brain structures in the hemisphere contralateral to the infarct and in the brain stem where, moreover, secondary hemorrhages were present. Supratentorial secondary hemorrhages were less frequent. They were noted in the thalamus both on the side of the infarct and in the contralateral hemisphere. Supratentorial necroses were more frequent. Their intensity varied from selective necrosis to Jacob's edematous necrosis. Severe displacement of deep structures and of the brain stem was associated with development of secondary internal hydrocephalus, especially in the hemisphere contralateral to the herniation. To the most important pathogenetic factors causing development of secondary morphological lesions belong disturbances of blood supply occurring as the result of pressure differences between the supra- and infratentorial space, resulting from pressure and displacement of arterial vessels, damage of their walls and distrubances of venous flow and also development of secondary internal hydrocephalus. Extensive necroses and hemorrhages increase the area of primary necrosis. Lesions resulting from herniation, displacement and compression of vessels were superposed on the picture of brain edema both present or passed. Secondary necroses damaging bilaterally structures belonging to the limbic system and reticular formation may be an additional factor in the development of edematous encephalopathy and the development of a psychoorganic syndrome after stroke. PMID:2626177

Szpakowa, G M

1989-01-01

44

Blood–brain barrier damage and brain penetration of antiepileptic drugs: Role of serum proteins and brain edema  

PubMed Central

SUMMARY Purpose: Increased blood–brain barrier (BBB) permeability is radiologically detectable in regions affected by drug-resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy-glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage. Methods: In vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3-sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively. Results: BBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain. Discussion: After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug-resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies. PMID:19175391

Marchi, Nicola; Betto, Giulia; Fazio, Vincent; Fan, Quinyuan; Ghosh, Chaitali; Machado, Andre; Janigro, Damir

2009-01-01

45

Near-infrared (NIR) spectroscopy for detection of water content in two in-vitro models of brain edema  

NASA Astrophysics Data System (ADS)

Currently, methods for the detection of brain edema in patients or laboratory experiments are invasive or inconvenient for continuous monitoring. We have performed experiments on two models of brain edema to determine the validity of differential near infrared spectroscopy (NIR) as a real-time, low cost and noninvasive method of monitoring brain edema. As a chemical in-vitro model, we prepared serial dilutions of Liposyn III, a fat emulsion, to simulate varying degrees of brain water content. NIR light at two wavelengths (703 nm and 957 nm) was used to assess water content of Liposyn solutions. We demonstrated a strong relation between wavelength specific light interactance and water content, for (n equals 4) serial dilutions from 97.6% to 80.0% water, R2 equals 0.985 plus or minus 0.017. Secondly an in vitro brain tissue model was developed to test the NIR method against wet-to-dry water content measurements. A total brain water content range of from 83.5 to 67.6 water was investigated (n equals 4). Using 695 nm and 957 nm NIR light, a correlation between NIR interactance and brain water content was again obtained, R2 equals 0.957 plus or minus 0.027. Our preliminary results suggest differential NIR spectroscopy may serve as an accurate and useful technique for monitoring surface brain edema in clinical and laboratory settings.

Johnson, Lee J.; Thakor, Nitish V.; Hanley, Daniel F.

1997-08-01

46

Norepinephrine and traumatic brain injury: a possible role in post-traumatic edema.  

PubMed

Unilateral cerebral contusion is associated with an early (30 min) increase in norepinephrine (NE) turnover followed by a later (6-24 h) depression of turnover which is bilateral and widespread throughout the brain. Blockade of NE function during the first few hours after traumatic brain injury (TBI) impedes subsequent recovery of function without enlarging the size of the lesion. The current studies were carried out to characterize further the timing of the switch from increased to decreased NE turnover and to investigate the pathogenesis of the delayed recovery of function associated with blocking NE function. Adult male rats had unilateral somatosensory cortex contusions made with a 5 mm diameter impact piston. They were killed after 2 h and their brains analyzed for NE turnover by HPLC with electrochemical detection. In general, NE turnover (the ratio of 3-methoxy-4-hyroxyphenylglycol to NE levels) had returned to sham-lesion control levels in most brain regions by 2 h after either left or right sided contusions. The only exceptions were a persistent 87% increase at the lesion site after right-sided contusions and 22% and 32% increases in the contralateral cerebellum after right- and left-sided contusions, respectively. Blockade of alpha1-adrenoceptors by treatment with prazosin (3 mg/ kg, i.p.) 30 min prior to TBI produced edema in the striatum and hippocampus at 24 h which was not seen saline-treated rats nor in rats where NE reuptake was blocked with desmethylimipramine (DMI; 10 mg/kg, i.p.). DMI increased edema at the lesion site at 24 h, however. These data suggest that the early increase in NE release following unilateral cerebral contusion is protective and that this may act to stabilize the blood-brain barrier in areas adjacent to the injury site. Drugs that interfere with this enhanced noradrenergic function might enhance the damage caused by TBI. PMID:9685666

Dunn-Meynell, A A; Hassanain, M; Levin, B E

1998-08-01

47

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.

2008-03-01

48

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

49

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

50

Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury.  

PubMed

Objective:Spinal cord edema contributes to the pathophysiological mechanisms underlying spinal cord injury (SCI) and is associated with functional recovery after SCI. Early myelotomy may be a promising surgical intervention for reducing SCI-induced edema. However, it remains unclear whether myelotomy can reduce SCI-induced edema. In addition, aquaporin-4 (AQP4) and aquaporin-9 (AQP9) have important roles in the regulation of water homeostasis. Here, we aimed to determine the effects of myelotomy on AQP4 and AQP9 expression and spinal cord edema in a rat model of moderate SCI.Methods:Rats were randomly assigned to three groups: the sham control group (n=22) receiving laminectomy alone; the contusion group (n=44) receiving laminectomy plus contusion; and the myelotomy group (n=44) receiving laminectomy plus contusion followed by myelotomy at 24?h. Functional recovery was estimated by the open-field and inclined plane tests. Spinal cord edema was determined by measuring the water content. The expression of AQP4 and AQP9 was determined by western blot.Results:Compared with the contusion group, myelotomy significantly improved the Basso, Beattie and Bresnahan scores in the open-field test and resulted in a higher mean angle value in the incline plane test. Myelotomy significantly reduced SCI-induced edema at 4 and 6 days after SCI, which was accompanied by downregulation of AQP4 and AQP9 expression.Conclusion:Myelotomy improves locomotor function, reduces edema in rats with SCI and is associated with decreased expression of AQP4 and AQP9.Spinal Cord advance online publication, 2 December 2014; doi:10.1038/sc.2014.209. PMID:25448191

Hu, A-M; Li, J-J; Sun, W; Yang, D-G; Yang, M-L; Du, L-J; Gu, R; Gao, F; Li, J; Chu, H-Y; Zhang, X; Gao, L-J

2014-12-01

51

Radiation brain injury is reduced by the polyamine inhibitor [alpha]-difluoromethylornithine  

SciTech Connect

[alpha]-difluoromethylornithine (DFMO) was used to reduce [sup 125]I-induced brain injury in normal beagle dogs. Different DFMO doses and administration schedules were used to determine if the reduction in brain injury was dependent on dose and/or dependent upon when the drug was administered relative to the radiation treatment. Doses of DMFO of 75 mg/kg/day and 37.5 mg/kg/day given 2 days before, during and for 14 days after irradiation reduced levels of putrescine (PU) in the cerebrospinal fluid relative to controls. Volume of edema was significantly reduced by 75 mg/kg/day of DFMO before, during and after irradiation and by the same dose when the drug was started immediately after irradiation. A reduction in edema volume after 37.5 mg/kg/day of DFMO before, during and after irradiation was very near significance. Ultrafast CT studies performed on dogs that received a DFMO dose of 75 mg/kg/day before, during and after irradiation suggested that the reduce edema volume was associated with reduced vascular permeability. Volume of necrosis and volume of contrast enhancement (breakdown of the blood-brain barrier) were significantly lower than controls only after a DFMO dose of 75 mg/kg/day before, during and after irradiation. These latter data, coupled with the findings relative to edema, suggest that different mechanisms may be involved with respect to the effects of DFMO on brain injury, or that the extents of edema, necrosis and breakdown of the blood-brain barrier may depend upon different levels of polyamine depletion. The precise mechanisms by which DFMO exerts the effects observed here need to be determined. 41 refs., 5 figs.

Fike, J.R.; Seilhan, T.M.; Gobbel, G.T. (Univ. of California, San Francisco, CA (United States)); Marton, L.J. (Univ. of Wisconsin, Madison, WI (United States))

1994-04-01

52

Activation of peroxisome proliferator-activated receptor gamma in brain inhibits inflammatory pain, dorsal horn expression of Fos, and local edema.  

PubMed

Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumably by acting at peroxisome proliferator-activated receptor gamma (PPARgamma) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARgamma actions, we postulated that brain PPARgamma modulates peripheral edema and the processing of inflammatory pain signals in the dorsal horn of the spinal cord. To test this in the plantar carrageenan model of inflammatory pain, we measured paw edema, heat hyperalgesia, and dorsal horn expression of the immediate-early gene c-fos after intracerebroventricular (ICV) administration of PPARgamma ligands or vehicle. We found that ICV rosiglitazone (0.5-50 microg) or 15d-PGJ(2) (50-200 microg), but not vehicle, dose-dependently reduced paw thickness, paw volume and behavioral withdrawal responses to noxious heat. These anti-inflammatory and anti-hyperalgesia effects result from direct actions in the brain and not diffusion to other sites, because intraperitoneal and intrathecal administration of rosiglitazone (50 microg) and 15d-PGJ(2) (200 microg) had no effect. PPARgamma agonists changed neither overt behavior nor motor coordination, indicating that non-specific behavioral effects do not contribute to PPAR ligand-induced anti-hyperalgesia. ICV administration of structurally dissimilar PPARgamma antagonists (either GW9662 or BADGE) reversed the anti-inflammatory and anti-hyperalgesic actions of both rosiglitazone and 15d-PGJ(2). To evaluate the effects of PPARgamma agonists on a classic marker of noxious stimulus-evoked gene expression, we quantified Fos protein expression in the dorsal horn. The number of carrageenan-induced Fos-like immunoreactive profiles was less in rosiglitazone-treated rats as compared to vehicle controls. We conclude that pharmacological activation of PPARgamma in the brain rapidly inhibits local edema and the spinal transmission of noxious inflammatory signals. PMID:19891980

Morgenweck, J; Abdel-Aleem, O S; McNamara, K C; Donahue, R R; Badr, M Z; Taylor, B K

2010-02-01

53

Lipophilic amino alcohols reduces carrageenan-induced paw edema and anti-OVA DTH in BALB/c mice.  

PubMed

The inflammation process is a coordinated response of the organism related to immune response with release of pro-inflammatory substances, as nitric oxide, TNF-? and IL-1?. In this work, a series of lipophilic amino alcohols were evaluated on RAW264.7 and primary macrophages for the modulation of nitric oxide and TNF-?. The most potent compounds were submitted to the treatment of BALB/c mice and evaluation of the carrageenan-induced paw edema and TNF-? and IL1-? release in the paws and anti-OVA delayed type hypersensitivity reaction. RAW264.7 and primary macrophages were incubated in the presence of amino alcohols at different concentrations (1, 0.5, 0.05 and 0.005 ?g mL(-1)). All tested compounds were not cytotoxic, however the inhibition of NO and TNF-? were observed only in RAW264.7 cultures. The NO production were reduced in 100% for all compounds, but only the compounds 4a and 4b expressively reduced the TNF-? release (67% and 92% respectively). On the carrageenan-induced paw edema, the compound 4b treatment showed reduction of edema, TNF-? and IL-1? as efficient as dexamethasone treatment. Meanwhile, the compound 4a treatment showed only slight reduction of paw edema. In the anti-OVA DTH reaction, both compounds showed reduction in the paw edema as effective as dexamethasone. In function of the observed results in vitro and in the acute and anti-OVA inflammation of mice paw edema compound 4b showed promissory anti-inflammatory properties. PMID:24035232

Reis, Elaine F C; Castro, Sandra B R; Alves, Caio Cesar S; Oliveira, Erick E; Corrêa, Tais A; Almeida, Mauro V; Ferreira, Ana Paula

2013-11-01

54

Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.  

PubMed

Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan. PMID:24072671

Zieli?ska, Magdalena; Popek, Mariusz; Albrecht, Jan

2014-01-01

55

The Protein Kinase C Activator Phorbol Myristate Acetate Decreases Brain Edema by Aquaporin 4 Downregulation after Middle Cerebral Artery Occlusion in the Rat  

PubMed Central

Abstract The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) is known to interact with aquaporin 4 (AQP 4), a water-selective transporting protein that is abundant in astrocytes, and has experimentally been found to decrease osmotically-induced cell swelling. The purpose of this study was to examine whether PMA reduces brain edema following focal ischemia induced by middle cerebral artery (MCA) occlusion by modulation of AQP4 expression. Male Sprague-Dawley rats were randomly assigned to either sham surgery (n?=?6), or a continuous intravenous infusion of vehicle (1% dimethylsulfoxide), followed by MCA occlusion (n?=?18), and administration of PMA at 50??g/kg (n?=?6) or at 200??g/kg (n?=?6) starting 60?min before or 30?min (200??g/kg; n?=?6) or 60?min (200??g/kg; n?=?6) after MCA occlusion. Cerebral blood flow was monitored with laser Doppler over the MCA territory, and confirmed a 70% reduction during occlusion. After a 2-h period of ischemia and 2?h of reperfusion, the animals were sacrificed for assessment of brain water content and sodium and potassium concentration. AQP4 expression was assessed by immunoblotting and quantified by densitometry (n?=?24). Statistical analysis was performed by ANOVA followed by Tukey's post-hoc test. PMA treatment at 200??g/kg significantly reduced brain water concentration in the infarcted area when started 60?min before or 30?min after occlusion (p?brain edema formation following PMA treatment suggests that the effect was mediated by AQP4 modulation. PMID:19831719

Fazzina, Giovanna; Amorini, Angela M.; Marmarou, Christina R.; Fukui, Shinji; Okuno, Kenji; Dunbar, Jana G.; Glisson, Renee; Kleindienst, Andrea

2010-01-01

56

The protein kinase C activator phorbol myristate acetate decreases brain edema by aquaporin 4 downregulation after middle cerebral artery occlusion in the rat.  

PubMed

The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) is known to interact with aquaporin 4 (AQP 4), a water-selective transporting protein that is abundant in astrocytes, and has experimentally been found to decrease osmotically-induced cell swelling. The purpose of this study was to examine whether PMA reduces brain edema following focal ischemia induced by middle cerebral artery (MCA) occlusion by modulation of AQP4 expression. Male Sprague-Dawley rats were randomly assigned to either sham surgery (n = 6), or a continuous intravenous infusion of vehicle (1% dimethylsulfoxide), followed by MCA occlusion (n = 18), and administration of PMA at 50 microg/kg (n = 6) or at 200 microg/kg (n = 6) starting 60 min before or 30 min (200 microg/kg; n = 6) or 60 min (200 microg/kg; n = 6) after MCA occlusion. Cerebral blood flow was monitored with laser Doppler over the MCA territory, and confirmed a 70% reduction during occlusion. After a 2-h period of ischemia and 2 h of reperfusion, the animals were sacrificed for assessment of brain water content and sodium and potassium concentration. AQP4 expression was assessed by immunoblotting and quantified by densitometry (n = 24). Statistical analysis was performed by ANOVA followed by Tukey's post-hoc test. PMA treatment at 200 microg/kg significantly reduced brain water concentration in the infarcted area when started 60 min before or 30 min after occlusion (p < 0.001 and p = 0.022, respectively), and prevented the subsequent sodium shift (p < 0.05). PMA normalized the AQP4 upregulation in ischemia (p = 0.021). A downregulation of AQP4 in the ischemic area paralleling the reduction in brain edema formation following PMA treatment suggests that the effect was mediated by AQP4 modulation. PMID:19831719

Fazzina, Giovanna; Amorini, Angela M; Marmarou, Christina R; Fukui, Shinji; Okuno, Kenji; Dunbar, Jana G; Glisson, Renee; Marmarou, Anthony; Kleindienst, Andrea

2010-02-01

57

Loss of AQP4 polarized localization with loss of ?-dystroglycan immunoreactivity may induce brain edema following intracerebral hemorrhage.  

PubMed

The aquaporin-4 (AQP4) water channel contributes to brain water homeostasis in perivascular and subpial membrane domains of astrocytes where it is concentrated. These membranes form the interface between the neuropil and the extracellular liquid spaces. The brain-selective deletion of the dystroglycan (DG) gene causes a disorganization of AQP4 on the astroglial endfeet. First, we analyzed the expression of AQP4, ?-DG in the brain following intracerebral hemorrhage (ICH) and correlated AQP4 expression with the expression pattern of the ?-DG, which is a component of dystrophin-dystroglycan complex (DDC). Besides, the vessels ultrastructure and brain water content were investigated at different time points post-ICH (day 1, day 3, day 7). We found that AQP4 polarity was disturbed in parallel with the loss of ?-DG in the perihematomal area post-ICH. At day 1 post-ICH, brain edema was obvious and the damage of vascular ultrastructure was the most severe. These results suggest a role for ?-DG in targeting and stabilizing AQP4 channel in astrocytic cells, which may be critical for water homeostasis in brain. PMID:25545558

Qiu, Guo-Ping; Xu, Jin; Zhuo, Fei; Sun, Shan-Quan; Liu, Hui; Yang, Mei; Huang, Juan; Lu, Wei-Tian; Huang, Si-Qin

2015-02-19

58

Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage  

PubMed Central

Subarachnoid hemorrhage (SAH) causes secondary brain injury due to vasospasm and inflammation. Here, we studied a rat model of mild-to-moderate SAH intended to minimize ischemia/hypoxia to examine the role of sulfonylurea receptor 1 (SUR1) in the inflammatory response induced by SAH. mRNA for Abcc8, which encodes SUR1, and SUR1 protein were abundantly upregulated in cortex adjacent to SAH, where tumor-necrosis factor-? (TNF?) and nuclear factor (NF)?B signaling were prominent. In vitro experiments confirmed that Abcc8 transcription is stimulated by TNF?. To investigate the functional consequences of SUR1 expression after SAH, we studied the effect of the potent, selective SUR1 inhibitor, glibenclamide. We examined barrier permeability (immunoglobulin G, IgG extravasation), and its correlate, the localization of the tight junction protein, zona occludens 1 (ZO-1). SAH caused a large increase in barrier permeability and disrupted the normal junctional localization of ZO-1, with glibenclamide significantly reducing both effects. In addition, SAH caused large increases in markers of inflammation, including TNF? and NF?B, and markers of cell injury or cell death, including IgG endocytosis and caspase-3 activation, with glibenclamide significantly reducing these effects. We conclude that block of SUR1 by glibenclamide may ameliorate several pathologic effects associated with inflammation that lead to cortical dysfunction after SAH. PMID:18854840

Simard, J Marc; Geng, Zhihua; Woo, S Kyoon; Ivanova, Svetlana; Tosun, Cigdem; Melnichenko, Ludmila; Gerzanich, Volodymyr

2009-01-01

59

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

60

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. PMID:17532882

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

2009-01-01

61

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. PMID:23469092

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

2013-01-01

62

Pulmonary edema  

MedlinePLUS

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

63

Massive cerebral edema resulting in brain death as a complication of Cryptococcus neoformans meningitis.  

PubMed

Despite the widespread use of highly active antiretroviral therapy, cryptococcal meningoencephalitis has emerged as the second leading cause of infectious morbidity and mortality in HIV-infected patients worldwide. It presents usually as subacute or chronic disease but occasionally may be fulminant. Common clinical presentations included headache, fever, and depressed level of consciousness. The infection affects both the subarachnoid space and brain parenchyma, and is characterized by a paucity of inflammation and a large fungal burden in the cerebrospinal fluid at the time of diagnosis. Infection is usually lethal without treatment, thus the prompt diagnosis and therapy might improve the outcome. We report a case of brain death caused by Cryptococcus neoformans meningitis that was diagnosed based on clinical neurological examinations and supported by the absence of cerebral blood flow on brain angiography. PMID:25656669

Orsini, Jose; Blaak, Christa; Mahmoud, Dalia; Young-Gwang, Jeong

2015-01-01

64

Radiation Exposure Prior to Ischemia Decreases Lesion Volume, Brain Edema and Cell Death  

Microsoft Academic Search

\\u000a \\u000a Purpose  To investigate the neuronal response to ischemic injury following exposure to whole brain proton irradiation.\\u000a \\u000a \\u000a \\u000a Methods  Brain only proton irradiation (8 Gy, 250 MeV) was performed ten days prior to middle cerebral artery occlusion (MCAO) in 1\\u000a year old male Sprague Dawley rats. MCAO was induced in two animal groups: proton irradiated (MCAO + Rad) and MCAO only. Magnetic\\u000a resonance imaging

E. Titova; A. Adami; R. Ostrowski; S. Lalas; R. Vlkolinsky; J. H. Zhang; G. Nelson; A. Obenaus

65

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

66

Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet.  

PubMed

Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ET(A) antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury. PMID:15815585

Lo, Amy C Y; Chen, Ann Y S; Hung, Victor K L; Yaw, Lai Ping; Fung, Maggie K L; Ho, Maggie C Y; Tsang, Margaret C S; Chung, Stephen S M; Chung, Sookja K

2005-08-01

67

Oxymatrine reduces neuroinflammation in rat brain  

PubMed Central

Cerebral neuroinflammation models were established by injecting 10 ?g lipopolysaccharide into the hippocampus of male Sprague-Dawley rats. The rats were treated with an intraperitoneal injection of 120, 90, or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection. Twenty-four hours after model induction, the hippocampus was analyzed by real-time quantitative PCR, and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay. The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1? and tumor necrosis factor-? were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine. Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine. Additionally, 120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-?B p65 in the nucleus and of phosphorylated I?B? in the cytoplasm of brain cells, as detected by western blot assay. Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-?B signaling pathway.

Mao, Jiahui; Hu, Yae; Zhou, Ailing; Zheng, Bing; Liu, Yi; Du, Yueming; Li, Jia; Lu, Jinyang; Zhou, Pengcheng

2012-01-01

68

Mild therapeutic hypothermia does not reduce thrombin-induced brain injury.  

PubMed

Secondary neurodegeneration occurs hours to days after an intracerebral hemorrhage (ICH). Thrombin, a protease important in clotting, is one of the causes of this injury. Presently, we evaluated whether hypothermia mitigates thrombin-induced cerebral edema, cell death, and behavioral impairment. Rats were given a striatal infusion of thrombin, which models thrombin-mediated injury occurring after ICH, followed an hour later by whole-body cooling (33°C), local brain hypothermia (?33°C), or normothermia. Thrombin caused significant edema at 24 hours (?5% increase in water) that was not mitigated by whole-body or brain-selective cooling. Other rats were infused with thrombin and systemically cooled for 72 hours. At a 14-day survival they had similar walking impairments and brain tissue loss (?45?mm(3)) as normothermic rats. However, cooled animals had significantly more degenerating neurons in the peri-lesion zone (p=0.035), which were rare in normothermic rats. Thus, it appears that some cell death was increased or delayed by hypothermia. In summary, we did not find that hypothermia reduced thrombin-induced neurotoxicity. This suggests that cooling does not effectively target thrombin-mediated secondary degeneration after ICH, which may partly explain why cooling is often not robustly neuroprotective in rodent ICH studies. These findings also indicate that therapeutic hypothermia could be improved by the addition of drugs to minimize thrombin toxicity. PMID:25144891

Wowk, Shannon; Ma, Yonglie; Colbourne, Frederick

2014-12-01

69

Octreotide and cholecystokinin antagonist reduce edema in obstruction-induced acute pancreatitis.  

PubMed

Obstruction-induced acute pancreatitis in rats is associated with increased plasma cholecystokinin (CCK) levels. Duodenal replacement of bile reduces severity of pancreatitis and limits CCK increase. We investigated the role of CCK in the pathogenesis of obstruction-induced acute pancreatitis by pretreating rats with the somatostatin analog octreotide and the CCK antagonist L-364,718. Octreotide inhibits duodenal CCK release, and L-364,718 competitively blocks CCK receptors. We studied 31 rats after (1) sham operation (n = 7), (2) bile and pancreatic duct obstruction (BPDO) (n = 12), (3) BPDO plus octreotide (20 micrograms/kg IP and then 5 micrograms/kg/hr IV) (n = 6), and (4) BPDO plus L-364,718 (1 mg/kg IP and then 0.25 mg/kg/hr IV) (n = 6). Rats were killed after 18 hours. Pancreas weight, acute pancreatitis histology score, and plasma amylase and CCK levels were determined. Octreotide and L-364,718 limited the increase in pancreas weight. Octreotide also limited the rise in plasma CCK levels. These findings suggest that CCK may play a role in the pathogenesis of obstruction-induced acute pancreatitis. PMID:8228560

Toriumi, Y; Samuel, I; Wilcockson, D P; Turkelson, C M; Solomon, T E; Joehl, R J

1993-10-01

70

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

71

Aerobic Fitness Reduces Brain Tissue Loss in Aging Humans  

Microsoft Academic Search

Background. The human brain gradually loses tissue from the third decade of life onward, with concomitant declines in cognitive performance. Given the projected rapid growth in aged populations, and the staggering costs associated with geriatric care, identifying mechanisms that may reduce or reverse cerebral deterioration is rapidly emerging as an important public health goal. Previous research has demonstrated that aerobic

Kirk I. Erickson; Naftali Raz; Andrew G. Webb; Neal J. Cohen; Edward McAuley; Arthur F. Kramer

2003-01-01

72

Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery  

PubMed Central

Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood–brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site. PMID:23899928

Fukuda, Andrew M; Adami, Arash; Pop, Viorela; Bellone, John A; Coats, Jacqueline S; Hartman, Richard E; Ashwal, Stephen; Obenaus, Andre; Badaut, Jerome

2013-01-01

73

The effect of dexamethasone on serum protein extravasation and edema development in experimental brain tumors of cat  

Microsoft Academic Search

Experimental brain tumors were produced in 20 cats by stereotaxic xenotransplantation of a blastomatous glial cell clone into the internal capsule of the left hemisphere. Ten of these animals were treated after 2 weeks with a single injection of 10 mg dexamethasone in crystalline suspension. Three weeks after xenotransplantation vascular permeability was studied by electron microscopy with horseradish peroxidase as

K.-A. Hossmann; T. Hürter; U. Oschlies

1983-01-01

74

Drug That Crosses Blood-Brain Barrier Reduces Formation of Brain Metastases in Mice  

Cancer.gov

The drug vorinostat is able to cross the blood-brain barrier and reduce the development of large metastatic tumors in mice brains by 62 percent when compared to mice that did not receive the drug, according to a new study. In humans, the drug has been approved by the U.S. Food and Drug Administration for the treatment of a cancer called cutaneous T-cell lymphoma but can be used experimentally to study its effectiveness against other cancers.

75

C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation  

PubMed Central

Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 h. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 h after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted anti-inflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings. PMID:25249935

Albert-Weissenberger, Christiane; Mencl, Stine; Schuhmann, Michael K.; Salur, Irmak; Göb, Eva; Langhauser, Friederike; Hopp, Sarah; Hennig, Nelli; Meuth, Sven G.; Nolte, Marc W.; Sirén, Anna-Leena; Kleinschnitz, Christoph

2014-01-01

76

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

77

Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?  

PubMed Central

Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia–ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia–ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications. PMID:25346720

Li, Jingang; McDonald, Courtney A.; Fahey, Michael C.; Jenkin, Graham; Miller, Suzanne L.

2014-01-01

78

Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage.  

PubMed

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis. © 2014 Wiley Periodicals, Inc. PMID:25042403

Lee, I-Neng; Cheng, Wan-Chun; Chung, Chiu-Yen; Lee, Ming-Hsueh; Lin, Martin Hsiu-Chu; Kuo, Chia-Hui; Weng, Hsu-Huei; Yang, Jen-Tsung

2015-01-01

79

Release of bradykinin and expression of kinin B2 receptors in the brain: role for cell death and brain edema formation after focal cerebral ischemia in mice  

Microsoft Academic Search

Pharmacological studies using bradykinin B2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein–kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B2 receptors for brain damage after experimental stroke have not

Moritz Gröger; Diane Lebesgue; Didier Pruneau; Jane Relton; Seong-Woong Kim; Jürg Nussberger; Nikolaus Plesnila

2005-01-01

80

Acute nicotine reduces brain arachidonic acid signaling in unanesthetized rats  

PubMed Central

Nicotine exerts its central effects by activating pre- and post-synaptic nicotinic acetylcholine receptors (nAChRs). Pre-synaptic nAChRs modulate the release of many neurotransmitters that bind to post-synaptic receptors. These may be coupled to the activation of cytosolic phospholipase A2 (cPLA2), which hydrolyzes arachidonic acid (AA) from membrane phospholipids. We hypothesized that nicotine would modify brain signaling involving AA by binding to nAChRs. Nicotine (0.1 mg/kg s.c.) or saline was injected 2 or 10 min before infusing [1-14C]AA in unanesthetized rats. The AA incorporation coefficient k* (a marker of the AA signal) was measured in 80 brain regions by quantitative autoradiography. Nicotine, compared to saline, when given 2 min before [1-14C]AA, significantly decreased k* for AA in 26 regions, including cerebral cortex, thalamus and habenula-interpeduncular regions, by 13% to 45%. These decreases could be entirely prevented by pretreatment with mecamylamine (1.0 mg/kg s.c.). When given 10 min before [1-14C]AA, nicotine did not alter any value of k*. In summary, nicotine given to unanesthetized rats rapidly reduces signaling involving AA in brain regions containing nAChRs, likely by modulating pre-synaptic release of neurotransmitters. The effect shows rapid desensitization and is produced at a nicotine dose equivalent to smoking one cigarette in humans. PMID:19142197

Chang, Lisa; Rapoport, Stanley I.; Nguyen, Henry N.; Greenstein, Dede; Chen, Mei; Basselin, Mireille

2009-01-01

81

Continuous hyperosmolar therapy for traumatic brain injury-associated cerebral edema: as good as it gets, or an iatrogenic secondary insult?  

PubMed

Cerebral edema is a heterogeneous condition that is present in almost every type of neurological disease process--ranging from tumor, to cerebrovascular disease, to infection, to trauma, among others. It is associated with a high rate of morbidity and mortality. The pathophysiologic mechanisms of edema formation are distinct for the different conditions, thereby defining the various classifications. A relatively new treatment practice for cerebral edema is known as induced, sustained hypernatremia. This practice is highly controversial, is in widespread use, and lacks robust evidence for efficacy. Herein, we review details of the controversy regarding this practice. PMID:23200533

Kahle, Kristopher T; Walcott, Brian P; Simard, J Marc

2013-01-01

82

[Post-traumatic cerebral edema. Physiopathology and treatment].  

PubMed

Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. These are responsible for two types of edema: vasogenic edema, with outflow of molecules and fluid into the extracellular spaces by rupture of the blood-brain barrier and vasoplegia, and cytotoxic edema, with swelling of astrocytes due to membrane lesions. The connexions between these two types of edema are still obscure. Alterations in membrane phospholipids may impede function of Na-K pump enzymes, causing accumulation of water in the cell. Cerebral edema is responsible for intracranial hypertension and tentorial herniation, which in turn increase edema through venous compression, ischemia, and hypoxia. The least controversial anti-edema therapeutic measures include relative fluid and salt restriction, mannitol if called for, neuroplegia, in particular with diazepam and Gamma-OH, and assisted ventilation. PMID:6322313

Verier, A; Jomin, M; Lozes, G; Lesoin, F

1984-03-01

83

Hypnotic suggestion reduces conflict in the human brain  

PubMed Central

Many studies have suggested that conflict monitoring involves the anterior cingulate cortex (ACC). We previously showed that a specific hypnotic suggestion reduces involuntary conflict and alters information processing in highly hypnotizable individuals. Hypothesizing that such conflict reduction would be associated with decreased ACC activation, we combined neuroimaging methods to provide high temporal and spatial resolution and studied highly and less-hypnotizable participants both with and without a suggestion to interpret visual words as nonsense strings. Functional MRI data revealed that under posthypnotic suggestion, both ACC and visual areas presented reduced activity in highly hypnotizable persons compared with either no-suggestion or less-hypnotizable controls. Scalp electrode recordings in highly hypnotizable subjects also showed reductions in posterior activation under suggestion, indicating visual system alterations. Our findings illuminate how suggestion affects cognitive control by modulating activity in specific brain areas, including early visual modules, and provide a more scientific account relating the neural effects of suggestion to placebo. PMID:15994228

Raz, Amir; Fan, Jin; Posner, Michael I.

2005-01-01

84

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. PMID:24592235

Gómez, Carlos; Lizier, Joseph T.; Schaum, Michael; Wollstadt, Patricia; Grützner, Christine; Uhlhaas, Peter; Freitag, Christine M.; Schlitt, Sabine; Bölte, Sven; Hornero, Roberto; Wibral, Michael

2014-01-01

85

Reducing Calibration Time for the P300 Brain-Computer Interface H. Cecotti 1  

E-print Network

Reducing Calibration Time for the P300 Brain-Computer Interface Speller H. Cecotti 1 , G. Saint Interface (BCI), it is nowa- days possible to achieve a direct pathway between the brain and computers The goal of a Brain-Computer Interface (BCI) is to provide a direct communication pathway between the brain

Paris-Sud XI, Université de

86

Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation  

PubMed Central

Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng?/? mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng?/? mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases. PMID:22936662

Langhauser, Friederike; Göb, Eva; Kraft, Peter; Geis, Christian; Schmitt, Joachim; Brede, Marc; Göbel, Kerstin; Helluy, Xavier; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Stoll, Guido; Meuth, Sven G.; Nieswandt, Bernhard; McCrae, Keith R.

2012-01-01

87

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  

Microsoft Academic Search

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,

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

2011-01-01

88

Substance P Mediates Reduced Pneumonia Rates After Traumatic Brain Injury  

PubMed Central

Objectives Traumatic brain injury results in significant morbidity and mortality and is associated with infectious complications, particularly pneumonia. However, whether traumatic brain injury directly impacts the host response to pneumonia is unknown. The objective of this study was to determine the nature of the relationship between traumatic brain injury and the prevalence of pneumonia in trauma patients and investigate the mechanism of this relationship using a murine model of traumatic brain injury with pneumonia. Design Data from the National Trauma Data Bank and a murine model of traumatic brain injury with postinjury pneumonia. Setting Academic medical centers in Cincinnati, OH, and Boston, MA. Patients/Subjects Trauma patients in the National Trauma Data Bank with a hospital length of stay greater than 2 days, age of at least 18 years at admission, and a blunt mechanism of injury. Subjects were female ICR mice 8–10 weeks old. Interventions Administration of a substance P receptor antagonist in mice. Measurements and Main Results Pneumonia rates were measured in trauma patients before and after risk adjustment using propensity scoring. In addition, survival and pulmonary inflammation were measured in mice undergoing traumatic brain injury with or without pneumonia. After risk adjustment, we found that traumatic brain injury patients had significantly lower rates of pneumonia compared to blunt trauma patients without traumatic brain injury. A murine model of traumatic brain injury reproduced these clinical findings with mice subjected to traumatic brain injury demonstrating increased bacterial clearance and survival after induction of pneumonia. To determine the mechanisms responsible for this improvement, the substance P receptor was blocked in mice after traumatic brain injury. This treatment abrogated the traumatic brain injury–associated increases in bacterial clearance and survival. Conclusions The data demonstrate that patients with traumatic brain injury have lower rates of pneumonia compared to non–head-injured trauma patients and suggest that the mechanism of this effect occurs through traumatic brain injury–induced release of substance P, which improves innate immunity to decrease pneumonia. PMID:25014065

Yang, Sung; Stepien, David; Hanseman, Dennis; Robinson, Bryce; Goodman, Michael D.; Pritts, Timothy A.; Caldwell, Charles C.; Remick, Daniel G.; Lentsch, Alex B.

2014-01-01

89

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

90

Melatonin lowers edema after spinal cord injury  

PubMed Central

Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein.

Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

2014-01-01

91

Lymphangiogenesis-independent resolution of experimental edema  

PubMed Central

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis, and excess VEGF-C has been shown to be ameliorative for edema produced by lymphatic obstruction in experimental models. However, it has recently been shown that edema can resolve in the mouse tail even in the complete absence of capillary lymphangiogenesis when distal lymph fluid crosses the regenerating wound site interstitially. This finding has raised questions about the action of VEGF-C/VEGF receptor (VEGFR) signaling during the resolution of experimental edema. Here, the roles of VEGFR-2 and VEGFR-3 signaling in edema resolution were explored. It was found that edema resolved following neutralization of either VEGFR-2 or VEGFR-3 in the mouse tail skin, which inhibited lymphangiogenesis. Neutralization of either VEGFR-2 or VEGFR-3 reduced angiogenesis at the site of obstruction at day 10 (9.2 ± 1.2% and 11.5 ± 1.0% blood capillary coverage, respectively) relative to controls (14.3 ± 1.5% blood capillary coverage). Combined VEGFR-2/-3 neutralization more strongly inhibited angiogenesis (6.9 ± 1.5% blood capillary coverage), leading to a reduced wound repair of the lymphatic obstruction and extended edema in the tail skin. In contrast, improved tissue repair of the obstruction site increased edema resolution. Macrophages in the swollen tissue were excluded as contributing factors in the VEGFR-dependent extended edema. These results support a role for VEGFR-2/-3-combined signaling in the resolution of experimental edema that is lymphangiogenesis independent. PMID:20207821

Ongstad, Emily L.; Bouta, Echoe M.; Roberts, Jaclynn E.; Uzarski, Joseph S.; Gibbs, Sara E.; Sabel, Michael S.; Cimmino, Vincent M.; Roberts, Melissa A.

2010-01-01

92

Bone marrow edema syndrome  

Microsoft Academic Search

Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient\\u000a osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily\\u000a characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged\\u000a males. Many hypotheses have been proposed

Anastasios V. Korompilias; Apostolos H. Karantanas; Marios G. Lykissas; Alexandros E. Beris

2009-01-01

93

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

E-print Network

with communicating hydrocephalus. Mathematical brain models were created using the MRI images of normal subjects­structure interaction, Communicating hydrocephalus, Intracranial pressure. INTRODUCTION A more complete understandingNormal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption

Linninger, Andreas A.

94

Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine  

E-print Network

Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine States of America Abstract Objective: Gender differences in vulnerability for cocaine addiction have been brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers

Homes, Christopher C.

95

The antioxidative, non-psychoactive tricyclic phenothiazine reduces brain damage after experimental traumatic brain injury in mice.  

PubMed

Oxidative stress due to free radical formation is an important mechanism of secondary brain damage following traumatic brain injury (TBI). Phenothiazine has been found to be a strong antioxidant in eukaryotic cells in vitro and in invertebrates in vivo. The present study was designed to determine the neuroprotective potency of unsubstituted phenothiazine in a paradigm of acute brain injury. Thirty minutes after pneumatic, controlled cortical impact (CCI) injury, C57BI6 mice were randomly assigned to "low dose" (3mg/kg, LD) or "high dose" (30mg/kg, HD) s.c. phenothiazine or vehicle treatment. Brain lesion, neurofunctional impairment, body weight, and markers of cerebral inflammation were determined 24h after the insult. Phenothiazine treatment dose-dependently reduced brain lesion volume (LD: -19.8%; HD: -26.1%) and posttraumatic body weight loss. There were no significant differences in the neurological function score and in markers of cerebral inflammation (Iba-1 positive cells, TNF? expression), whereas iNOS expression was significantly lower compared to vehicle-treated animals. Phenothiazine appears to modify in a post-treatment protocol certain aspects of secondary brain damage in vivo at unusually low concentrations, in particular the cortical contusion volume after TBI. The potential role of the reduced iNOS expression is unclear at present. PMID:25449871

Songarj, Phuriphong; Luh, Clara; Staib-Lasarzik, Irina; Engelhard, Kristin; Moosmann, Bernd; Thal, Serge C

2015-01-01

96

TPI-287, a new taxane family member, reduces the brain metastatic colonization of breast cancer cells.  

PubMed

Brain metastases of breast and other cancers remain resistant to chemotherapeutic regimens that are effective systemically, in part due to the blood-brain barrier. We report that TPI-287, a new microtubule-stabilizing agent, displays in vitro cytotoxic activity similar to taxanes and epothilones. Unlike the taxanes, TPI-287 is permeable through the blood-brain barrier. Brain-to-plasma ratios of TPI-287 after a single injection typically exceeded one and were as high as 63.8 in the rat and 14.1 in the mouse. A brain-tropic derivative of the MDA-MB-231 triple-negative breast cancer cell line, 231-BR, was used to test whether TPI-287 may be efficacious at preventing or treating brain metastases. TPI-287 had growth inhibitory effects comparable with paclitaxel when 231-BR tumor cells were injected into the mammary fat pad. Brain metastatic colonization was determined by intracardiac injection of 231-BR cells, with treatment beginning on day 3 to 4 postinjection, culminating in a histologic count of brain metastases in brains necropsied days 25 to 28 postinjection. In this assay, paclitaxel, ixabepilone, and nab paclitaxel did not have significant inhibitory activity. TPI-287 was ineffective in the same assay using a 6 mg/kg every week schedule; however an 18 mg/kg dose delivered on days 3, 7, and 11 significantly reduced the outgrowth of brain metastases (55% reduction, P = 0.028) and reduced proliferation in brain metastases (16% reduction, P = 0.008). When TPI-287 treatment was delayed until days 18, 22, and 26 postinjection, efficacy was reduced (17% reduction, not significant). These data suggest that TPI-287 may have efficacy when administered early in the course of the disease. PMID:22622283

Fitzgerald, Daniel P; Emerson, David L; Qian, Yongzhen; Anwar, Talha; Liewehr, David J; Steinberg, Seth M; Silberman, Sandra; Palmieri, Diane; Steeg, Patricia S

2012-09-01

97

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. PMID:24346174

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

2014-01-01

98

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

99

Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy  

Microsoft Academic Search

Cerebral edema is one of the main acute complications arising after irradiation of brain tumors. Microbeam radiation therapy (MRT), an innovative experimental radiotherapy technique using spatially fractionated synchrotron x-rays, has been shown to spare radiosensitive tissues such as mammal brains. The aim of this study was to determine if cerebral edema occurs after MRT using diffusion-weighted MRI and microgravimetry. Prone

Raphaël Serduc; Yohan van de Looij; Gilles Francony; Olivier Verdonck; Boudewijn van der Sanden; Jean Laissue; Régine Farion; Elke Bräuer-Krisch; Erik Albert Siegbahn; Alberto Bravin; Yolanda Prezado; Christoph Segebarth; Chantal Rémy; Hana Lahrech

2008-01-01

100

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

101

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. PMID:24428713

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

2014-05-01

102

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

103

Minocycline-induced attenuation of iron overload and brain injury following experimental intracerebral hemorrhage  

PubMed Central

Background and Purpose Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo. Methods This study was divided into four parts. (1) Rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination. (2) Rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured. (3) Rats had an intracaudate injection of either saline, iron, iron+minocycline or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements. (4) Rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement. Results After ICH, serum total iron and brain non-heme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage and brain cell death, all of which were significantly reduced by co-injection with minocycline. Conclusions The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for ICH patients because both iron accumulation and microglia activation contribute to brain damage following ICH. PMID:21998050

Zhao, Fan; Hua, Ya; He, Yangdong; Keep, Richard F; Xi, Guohua

2011-01-01

104

Multifunctional Liposomes Reduce Brain ?-Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models  

PubMed Central

Alzheimer's disease is characterized by the accumulation and deposition of plaques of ?-amyloid (A?) peptide in the brain. Given its pivotal role, new therapies targeting A? are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of A? assemblies and evaluated their efficiency in reducing the A? burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood–brain barrier targeting and with phosphatidic acid for A? binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, A? assemblies in vitro (EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble A?1–42 (?33%), assessed by ELISA, and the number and total area of plaques (?34%) detected histologically. Also, brain A? oligomers were reduced (?70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [11C]Pittsburgh compound B (PIB). The reduction of brain A? was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain A? aggregates and promote peptide removal across the blood–brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease. PMID:25319699

Balducci, Claudia; Mancini, Simona; Minniti, Stefania; La Vitola, Pietro; Zotti, Margherita; Sancini, Giulio; Mauri, Mario; Cagnotto, Alfredo; Colombo, Laura; Fiordaliso, Fabio; Grigoli, Emanuele; Salmona, Mario; Snellman, Anniina; Haaparanta-Solin, Merja; Forloni, Gianluigi; Re, Francesca

2014-01-01

105

Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice.  

PubMed

BackgroundTraumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury.MethodsHere we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 ¿mol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days.ResultsResults revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI.ConclusionsThese data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process. PMID:25472548

Campolo, Michela; Esposito, Emanuela; Ahmad, Akbar; Di Paola, Rosanna; Paterniti, Irene; Cordaro, Marika; Bruschetta, Giuseppe; Wallace, John L; Cuzzocrea, Salvatore

2014-12-01

106

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. PMID:24179791

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

107

Caffeic acid reduces cutaneous tumor necrosis factor alpha (TNF-?), IL-6 and IL-1? levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice.  

PubMed

Caffeic acid (3,4-dihydroxycinnamic acid, CA) has been reported to have anti-inflammatory activity in animal models. However, the mechanisms underlying the anti-inflammatory effects of CA in skin inflammation are only partially understood. The present study was designed to investigate the effects and mechanisms of CA on acute and chronic skin inflammation in mice and the effect of CA in keratinocytes in vitro. The results showed that topical treatment with CA inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced skin edema in a dose-dependent manner, leading to substantial reductions in skin thickness and tissue weight, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. The CA treatment also significantly reduced the mRNA and protein levels of tumor necrosis factor alpha (TNF-?), interleukin-6 (IL-6) and IL-1? at the application site, and the TNF-? production, the TNF-?-induced IL-6 and IL-1? production, and TNF-?-induced nuclear factor-kappa B (NF-?B) activation in human keratinocytes in vitro. Furthermore, CA was effective at reducing inflammatory damage induced by chronic TPA exposure. These results demonstrate that CA has anti-inflammatory activities in both acute and chronic contact dermatitis models via blockade of the mRNA and protein synthesis of these cytokines and neutrophil-mediated myeloperoxidase activity, and can target inflammatory mediators specifically in the keratinocytes. Taken together, the present results suggest that CA might be a therapeutic agent against inflammatory skin diseases. PMID:24583856

Zhang, Mengjun; Zhou, Juan; Wang, Li; Li, Bin; Guo, Jiawei; Guan, Xiao; Han, Qingjuan; Zhang, Huijing

2014-01-01

108

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. PMID:23956805

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

2013-01-01

109

Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function  

Microsoft Academic Search

A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting from developmental NMDA receptor hypofunction, regional brain

Gary E Duncan; Seiya Miyamoto; Hongbin Gu; Jeffrey A Lieberman; Beverly H Koller; John N Snouwaert

2002-01-01

110

Decreased brain zinc availability reduces hippocampal neurogenesis in mice and rats  

Microsoft Academic Search

In the adult brain, neurogenesis occurs in the subgranular zone of the dentate gyrus (DG), where high levels of vesicular zinc are localized in the presynaptic terminals. To determine whether zinc has a role in modulating hippocampal neurogenesis under normal or pathologic conditions, we manipulated the level of vesicular zinc experimentally. To reduce hippocampal vesicular zinc, rats were either fed

Sang Won Suh; Seok Joon Won; Aaron M Hamby; Byung Hoon Yoo; Yang Fan; Christian T Sheline; Haruna Tamano; Atsushi Takeda; Jialing Liu

2009-01-01

111

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

112

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

113

Candesartan, an angiotensin II AT?-receptor blocker and PPAR-? agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT?R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5?h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGF?1 while increasing expression of TGF?3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPAR?) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPAR? activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT?R-blocking and PPAR? activation properties may have therapeutic value in treating TBI. PMID:22892395

Villapol, Sonia; Yaszemski, Alexandra K; Logan, Trevor T; Sánchez-Lemus, Enrique; Saavedra, Juan M; Symes, Aviva J

2012-12-01

114

Candesartan, an Angiotensin II AT1-Receptor Blocker and PPAR-? Agonist, Reduces Lesion Volume and Improves Motor and Memory Function After Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT1R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5?h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGF?1 while increasing expression of TGF?3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPAR?) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPAR? activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT1R-blocking and PPAR? activation properties may have therapeutic value in treating TBI. PMID:22892395

Villapol, Sonia; Yaszemski, Alexandra K; Logan, Trevor T; Sánchez-Lemus, Enrique; Saavedra, Juan M; Symes, Aviva J

2012-01-01

115

Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury  

PubMed Central

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury. PMID:25546517

Xiao, Ai-Jiao; Chen, Wenliang; Xu, Baofeng; Liu, Rui; Turlova, Ekaterina; Barszczyk, Andrew; Sun, Christopher Lf; Liu, Ling; Deurloo, Marielle; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

2014-01-01

116

Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.  

PubMed

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury. PMID:25546517

Xiao, Ai-Jiao; Chen, Wenliang; Xu, Baofeng; Liu, Rui; Turlova, Ekaterina; Barszczyk, Andrew; Sun, Christopher Lf; Liu, Ling; Deurloo, Marielle; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

2014-01-01

117

Early cortical cytotoxic edema in meningococcal meningitis.  

PubMed

Meningococcal disease frequently presents neurologic sequels via vascular, metabolic, or inflammatory processes. Understanding the underlying pathogenic mechanisms may influence both treatment and outcome. We present a 2-year-old child affected by Neisseria meningitidis sepsis, who on the second day from clinical onset manifested recurrent partial motor seizures and focal neurologic signs. An early magnetic resonance angiography of the circle of Willis produced normal results, whereas magnetic resonance imaging of the brain disclosed cortical signal abnormalities consistent with cytotoxic edema, without involvement of the adjacent white matter. Six-month follow-up magnetic resonance imaging of the brain indicated faint cortical atrophy in the same regions, although the neurologic picture had resolved. The literature contains few data on early magnetic resonance parenchymal changes, and their pathogenic mechanism is controversial. Diffusion-weighted images may contribute to an understanding of the mechanisms of such brain damage. PMID:19589467

Citton, Valentina; Toldo, Irene; Calderone, Milena; Sartori, Stefano; Manara, Renzo

2009-08-01

118

Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury  

PubMed Central

Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema. PMID:23251381

Schaible, Eva-Verena; Timaru-Kast, Ralph; Hedrich, Jana; Luhmann, Heiko J.; Engelhard, Kristin

2012-01-01

119

Carvacrol alleviates cerebral edema by modulating AQP4 expression after intracerebral hemorrhage in mice.  

PubMed

Carvacrol is a natural compound extracted from many plants of the family Lamiaceae. Previous studies have demonstrated that carvacrol has potential neuroprotective effects in central nervous system diseases such as Alzheimer's disease and cerebral ischemia. In this study, we investigated the preclinical effect of carvacrol on cerebral edema after intracerebral hemorrhage (ICH) using a bacterial collagenase-induced ICH mouse model. Mice were randomly divided into sham (n=43), vehicle-treated (n=51), and carvacrol-treated groups (n=101). In carvacrol-treated group, carvacrol was administrated to mice at 0h, 1h, or 3h after ICH induction. Carvacrol was injected intraperitoneally with single doses of 10, 25, 50, or 100mg/kg. Neurologic dysfunctions, brain water content, aquaporins (AQPs) mRNAs level and AQP4 protein expression in the perihematomal area were evaluated post ICH. Our results showed that carvacrol administration improved neurological deficits after day 3 following ICH (p<0.05). Carvacrol reduced cerebral edema and Evans Blue leakage at day 3 (p<0.05). We also found that carvacrol treatment decreased AQP4 mRNA in a dose-dependent manner at 24h. Furthermore, AQP4 protein expression in the perihematomal area was reduced by carvacrol significantly at day 3 after ICH (p<0.05). Our findings suggest that carvacrol may exert its protective effect on ICH injury by ameliorating AQP4-mediated cerebral edema. PMID:24051341

Zhong, Zhihong; Wang, Baofeng; Dai, Minchao; Sun, Yuhao; Sun, Qingfang; Yang, Guoyuan; Bian, Liuguan

2013-10-25

120

Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice  

PubMed Central

Alpha-synuclein (?-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that ?-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing ?-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used ?-Syn small interfering RNA (siRNA) to reduce total and aggregated ?-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease ?-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D ?-Syn, which exhibits aggregation. In normal mice we detected significantly reduced ?-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to ?-Syn. In S129D ?-Syn transgenic mice we found a decreased ?-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain ?-Syn pathological conditions. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:25112864

Cooper, J Mark; Wiklander, PB Oscar; Nordin, Joel Z; Al-Shawi, Raya; Wood, Matthew J; Vithlani, Mansi; Schapira, Anthony H V; Simons, J Paul; El-Andaloussi, Samir; Alvarez-Erviti, Lydia

2014-01-01

121

Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats.  

PubMed

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction. PMID:20204486

Tu, Xian-kun; Yang, Wei-zhong; Wang, Chun-hua; Shi, Song-sheng; Zhang, Yong-liang; Chen, Chun-mei; Yang, Yi-kun; Jin, Chang-dan; Wen, Shuai

2010-10-01

122

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. PMID:24684749

2014-01-01

123

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.  

PubMed

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ? 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity. PMID:25558242

Kozi?, Duško B; Petrovi?, Igor; Svetel, Marina; Pekmezovi?, Tatjana; Ragaji, Aleksandar; Kosti?, Vladimir S

2014-11-01

124

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain  

PubMed Central

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ? 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity. PMID:25558242

Kozi?, Duško B.; Petrovi?, Igor; Svetel, Marina; Pekmezovi?, Tatjana; Ragaji, Aleksandar; Kosti?, Vladimir S.

2014-01-01

125

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

126

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. PMID:23313314

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

2013-01-01

127

Role of histamine in brain protection in surgical brain injury in mice.  

PubMed

Surgical resection of brain tissue is associated with tissue damage at the resection margin. Studies of ischemic brain injury in rodents have shown that administration of L-histidine and thioperamide reduces ischemic tissue loss, in part by inhibition of apoptotic cell death. In this study we tested administration of L-histidine and thioperamide in surgical brain injury in mice. Mice were randomized to one of three groups: Sham surgery (n=18), surgical brain injury without treatment (SBI) (n=33), and surgical brain injury with combined l-histidine and thioperamide treatment (SBI+H) (n=29). Surgical brain injury was induced via right frontal craniotomy with resection of the right frontal lobe. L-histidine (1000 mg/kg) and thioperamide (5 mg/kg) were administered to the SBI+H group immediately following surgical resection. Postoperative assessment included neurobehavioral scores, Evans blue measurement of blood-brain barrier breakdown, brain water content, Nissl histology, and immunohistochemistry for IgG and cleaved caspase 3. Postoperative findings included equivalent neurobehavioral outcomes at 24 and 72 h in the SBI and SBI+H groups, similar histological outcomes between SBI and SBI+H, and similar qualitative staining for cleaved caspase 3. SBI+H had increased BBB breakdown on Evans blue analysis and a trend towards increased brain edema which was significant at 72 h. We conclude that combined treatment with l-histidine and thioperamide leads to increased BBB breakdown and brain edema in surgical brain injury. PMID:18343355

Bravo, Thomas P; Matchett, Gerald A; Jadhav, Vikram; Martin, Robert D; Jourdain, Aliiah; Colohan, Austin; Zhang, John H; Tang, Jiping

2008-04-18

128

Multiple actions of the coumarine derivative cloricromene and its protective effects on ischemic brain injury  

Microsoft Academic Search

The effects of different doses (0.25, 0.5, 1 and 2 mg\\/kg\\/i.p.) of cloricromene, a coumarine derivative, have been investigated on brain malondialdehyde levels, brain edema, myeloperoxidase activity, survival, locomotor hyperactivity and hippocampal neuronal loss following transient cerebral ischemia induced by temporary bilateral carotid occlusion in the Mongolian gerbil. Cloricromene reduced brain lipid peroxidation, measured through the evaluation of malondialdehyde (-82.9%

Gioacchino Calapai; Francesco Squadrito; Antonio Rizzo; Maria C. Marciano; Giuseppe M. Campo; Achille P. Caputi

1995-01-01

129

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

130

Angioneurotic Edema Associated with Haloperidol  

PubMed Central

Background. Angioneurotic edema is a life-threatening medical emergency that requires urgent diagnosis and treatment. Haloperidol is in the butyrophenone class of antipsychotic medications. Acute anaphylaxis to Haloperidol is very rare and no cases have been reported in literature. Objective. To report the association of life-threatening angioneurotic edema with intramuscular Haloperidol. Case Report. We present a case of an adult with no known allergies in whom angioneurotic edema with tongue swelling and protrusion developed after the administration of a single IM dose of Haloperidol. Conclusion. We propose angioneurotic edema in a rare side effect of Haloperidol. The onset of the symptoms is abrupt, but it may take 12–36 hours to resolve completely. Therefore patient should be monitored for 12–36?hrs. PMID:23326722

Kahlon, Samrina; Lee, Cathy; Chirurgi, Roger; Worku Hassen, Getaw

2012-01-01

131

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the  

E-print Network

with reduced brain volume in the healthy elderlyQ:1 April J. Hoa,1 , Jason L. Steina,1 , Xue Huaa , Suh Leea maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI to differences in cholesterol levels, hypertension, or the vol- ume of white matter hyperintensities; theseQ:3

Thompson, Paul

132

Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function.  

PubMed

A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting from developmental NMDA receptor hypofunction, regional brain metabolic activity was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, ligand binding to NMDA, AMPA, and kainate receptors was measured by quantitative autoradiography. MK-801 binding to NMDA receptors was reduced markedly throughout the brain of the NR1 hypomorphic mice. However, no alteration in 3H-AMPA or 3H-kainate binding was apparent in any region examined. Neuroanatomically specific alterations in regional 2-DG uptake were observed in the NR1 hypomorphic animals. Reduced relative 2-DG uptake was observed in the medial prefrontal and anterior cingulate cortices. Altered patterns of 2-DG uptake were also found in neocortical regions, with selective reductions of uptake in layer 6 in frontal regions of somatosensory and motor cortices. These data indicate alterations in cortical circuitry in the NR1 hypomorphic animals and are consistent with functional imaging studies in chronic schizophrenia patients which typically show reduced frontal cortical metabolic activity. Reduced relative 2-DG uptake was also found in the caudate, accumbens, hippocampus, and select thalamic regions in the NR1-deficient mice. However, in many other brain regions no alteration in 2-DG uptake was observed. The alterations in 2-DG uptake in the NR1 hypomorphic mice were distinctly different compared to those observed after acute challenge with the selective NMDA antagonist MK-801 in wild-type mice. The altered patterns of brain 2-DG uptake in the NR1 hypomorphic mice found in the present work, together with the altered behavioral phenotypes previously described, suggest that the mice may provide a valuable model to study novel therapeutic strategies to counteract the neurobiological consequences of chronic developmental NMDA receptor hypofunction. PMID:12270494

Duncan, Gary; Miyamoto, Seiya; Gu, Hongbin; Lieberman, Jeffrey; Koller, Beverly; Snouwaert, John

2002-10-01

133

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. PMID:24829832

Anand, Uttara Swati; Arulneyam, Jayanthi

2013-01-01

134

Prenatal alcohol exposure reduces magnetic susceptibility contrast and anisotropy in the white matter of mouse brains.  

PubMed

Prenatal alcohol exposure can result in long-term cognitive and behavioral deficits. Fetal alcohol spectrum disorder (FASD) refers to a range of permanent birth defects caused by prenatal alcohol exposure, and is the most common neurodevelopmental disorder in the US. Studies by autopsy and conventional structural MRI indicate that the midline structures of the brain are particularly vulnerable to prenatal alcohol exposure. Diffusion tensor imaging (DTI) has shown that abnormalities in brain white matter especially the corpus callosum are very common in FASD. Quantitative susceptibility mapping (QSM) is a novel technique that measures tissue's magnetic property. Such magnetic property is affected by tissue microstructure and molecular composition including that of myelin in the white matter. In this work, we studied three major white matter fiber bundles of a mouse model of FASD and compared it to control mice using both QSM and DTI. QSM revealed clear and significant abnormalities in anterior commissure, corpus callosum, and hippocampal commissure, which were likely due to reduced myelination. Our data also suggested that QSM may be even more sensitive than DTI for examining changes due to prenatal alcohol exposure. Although this is a preclinical study, the technique of QSM is readily translatable to human brain. PMID:25175539

Cao, Wei; Li, Wei; Han, Hui; O'Leary-Moore, Shonagh K; Sulik, Kathleen K; Allan Johnson, G; Liu, Chunlei

2014-11-15

135

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. PMID:24121737

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.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

136

Reduced brain cortical folding in schizophrenia revealed in two independent samples.  

PubMed

The cerebral cortex is highly convoluted, and principal folding patterns are determined early in life. Degree of cortical folding in adult life may index aberrations in brain development. Results from previous studies of cortical folding in schizophrenia are inconsistent. Here we investigated cortical folding patterns in the hitherto largest sample of patients with schizophrenia drawn from two independent cohorts. Magnetic resonance imaging scans were acquired from 207 patients and 206 healthy subjects recruited to two separate research projects in Sweden and Norway. Local gyrification index (lGI) was estimated continuously across the cortex using automated methods. Group differences in lGI were analyzed using general linear models. Patients had lower lGI in three large clusters of the cortex with peak differences found in the left precentral gyrus, right middle temporal gyrus, and right precuneus. Similar, although not completely overlapping results were found when the two cohorts were analyzed separately. There were no significant interaction effects between age and diagnosis and gender and diagnosis. The finding of reduced degree of folding in large regions of the cerebral cortex across two independent samples indicates that reduced gyrification is an inherent feature of the brain pathology in schizophrenia. PMID:24365403

Nesvåg, Ragnar; Schaer, Marie; Haukvik, Unn K; Westlye, Lars T; Rimol, Lars M; Lange, Elisabeth H; Hartberg, Cecilie B; Ottet, Marie-Christine; Melle, Ingrid; Andreassen, Ole A; Jönsson, Erik G; Agartz, Ingrid; Eliez, Stephan

2014-02-01

137

Decreased light attenuation in cerebral cortex during cerebral edema detected using optical coherence tomography  

PubMed Central

Cerebral edema develops in response to a variety of conditions, including traumatic brain injury and stroke, and contributes to the poor prognosis associated with these injuries. This study examines the use of optical coherence tomography (OCT) for detecting cerebral edema in vivo. Three-dimensional imaging of an in vivo water intoxication model in mice was performed using a spectral-domain OCT system centered at 1300 nm. The change in attenuation coefficient was calculated and cerebral blood flow was analyzed using Doppler OCT techniques. We found that the average attenuation coefficient in the cerebral cortex decreased over time as edema progressed. The initial decrease began within minutes of inducing cerebral edema and a maximum decrease of 8% was observed by the end of the experiment. Additionally, cerebral blood flow slowed during late-stage edema. Analysis of local regions revealed the same trend at various locations in the brain, consistent with the global nature of the cerebral edema model used in this study. These results demonstrate that OCT is capable of detecting in vivo optical changes occurring due to cerebral edema and highlights the potential of OCT for precise spatiotemporal detection of cerebral edema.

Rodriguez, Carissa L. R.; Szu, Jenny I.; Eberle, Melissa M.; Wang, Yan; Hsu, Mike S.; Binder, Devin K.; Park, B. Hyle

2015-01-01

138

CT imaging and spontaneous behavior analysis after osmotic blood-brain barrier opening in Wistar rat.  

PubMed

In our previous experiments we demonstrated that osmotic opening of the blood brain barrier (BBB) in rats by administration of mannitol into the internal carotid artery leads to cerebral edema. The aim of this study was to confirm objectively the development of brain edema and determine whether it affects spontaneous locomotor activity in rats (SLA). Brain edema was verified by computer tomography (CT) examination of the brain and SLA was observed during open field test. Twenty four adult male rats were divided into four groups of six: (1) control animals (C), (2) controls with anesthesia (CA), (3) controls with sham surgery (CS), (4) experimental - osmotic opening of the BBB (MA). Osmotic BBB disruption manifested by reducing the density of brain tissue (hypodensity), suggesting a higher water content in the brain tissue. SLA was compared between C, CA, CS and MA groups and between MA and CA groups. Significant difference was found only between the control group and MA group. In the first 30 min of the examination, rats after the mannitol administration revealed a marked limitation of spontaneous locomotor activity. Experimental results demonstrated reduction of spontaneous locomotor activity in rats with induced brain edema. PMID:25669684

Kozler, P; Riljak, V; Jandová, K; Pokorný, J

2015-02-10

139

Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury  

PubMed Central

Background Burn survivors develop long-term cognitive impairment with increased inflammation and apoptosis in the brain. Gelsolin, an actin-binding protein with capping and severing activities, plays a crucial role in the septic response. We investigated if gelsolin infusion could attenuate neural damage in burned mice. Methods Mice with 15% total body surface area burns were injected intravenously with bovine serum albumin as placebo (2 mg/kg), or with low (2 mg/kg) or high doses (20 mg/kg) of gelsolin. Samples were harvested at 8, 24, 48 and 72 hours postburn. The immune function of splenic T cells was analyzed. Cerebral pathology was examined by hematoxylin/eosin staining, while activated glial cells and infiltrating leukocytes were detected by immunohistochemistry. Cerebral cytokine mRNAs were further assessed by quantitative real-time PCR, while apoptosis was evaluated by caspase-3. Neural damage was determined using enzyme-linked immunosorbent assay of neuron-specific enolase (NSE) and soluble protein-100 (S-100). Finally, cerebral phospho-ERK expression was measured by western blot. Results Gelsolin significantly improved the outcomes of mice following major burns in a dose-dependent manner. The survival rate was improved by high dose gelsolin treatment compared with the placebo group (56.67% vs. 30%). Although there was no significant improvement in outcome in mice receiving low dose gelsolin (30%), survival time was prolonged against the placebo control (43.1 ± 4.5 h vs. 35.5 ± 5.0 h; P < 0.05). Burn-induced T cell suppression was greatly alleviated by high dose gelsolin treatment. Concurrently, cerebral abnormalities were greatly ameliorated as shown by reduced NSE and S-100 content of brain, decreased cytokine mRNA expressions, suppressed microglial activation, and enhanced infiltration of CD11b+ and CD45+ cells into the brain. Furthermore, the elevated caspase-3 activity seen following burn injury was remarkably reduced by high dose gelsolin treatment along with down-regulation of phospho-ERK expression. Conclusion Exogenous gelsolin infusion improves survival of mice following major burn injury by partially attenuating inflammation and apoptosis in brain, and by enhancing peripheral T lymphocyte function as well. These data suggest a novel and effective strategy to combat excessive neuroinflammation and to preserve cognition in the setting of major burns. PMID:21936896

2011-01-01

140

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

PubMed Central

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 studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13?Kcal?day?1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers. British Journal of Cancer (2002) 86, 1615–1621. DOI: 10.1038/sj/bjc/6600298 www.bjcancer.com © 2002 Cancer Research UK PMID:12085212

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

2002-01-01

141

[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

142

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

143

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury  

PubMed Central

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-?, interleukin-1? and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-? and interleukin-1? concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-?, interleukin-1? and interleukin-10 in the serum and brain tissue. PMID:25368644

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

144

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain.  

PubMed

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia. PMID:7860651

Hasegawa, Y; Latour, L L; Formato, J E; Sotak, C H; Fisher, M

1995-03-01

145

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 brainÂ?s 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

146

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study  

SciTech Connect

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

1987-01-01

147

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. PMID:22321027

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

2012-01-01

148

[Hereditary angioneurotic edema (author's transl)].  

PubMed

Hereditary angioneurotic edema is a rare autosomally-inherited disease, which is caused by a deficiency or functional inactivation of C-1 inactivator in the complement system. The poor prognosis of the disease mandates that an early diagnosis be made and drug therapy begun to prevent a lethal outcome. The pathogenesis, clinical course and therapies available are detailed. PMID:7462039

Löhle, E; Mann, W

1980-01-01

149

Evaluation of Peritumoral Edema in the Delineation of Radiotherapy Clinical Target Volumes for Glioblastoma  

SciTech Connect

Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r {sup 2} 0.0007; p = 0.3). For patients with edema >75 cm{sup 3}, the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm{sup 3}, using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema.

Chang, Eric L. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States)]. E-mail: echang@mdanderson.org; Akyurek, Serap [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Avalos, Tedde C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Rebueno, Neal C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Spicer, Chris C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Garcia, John C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Famiglietti, Robin [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Chao, K.S. Clifford [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Mahajan, Anita [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Woo, Shiao Y. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Maor, Moshe H. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States)

2007-05-01

150

Imatinib preserves blood-brain barrier integrity following experimental subarachnoid hemorrhage in rats.  

PubMed

Blood-brain barrier (BBB) disruption and consequent edema formation contribute to the development of early brain injury following subarachnoid hemorrhage (SAH). Various cerebrovascular insults result in increased platelet-derived growth factor receptor (PDGFR)-? stimulation, which has been linked to BBB breakdown and edema formation. This study examines whether imatinib, a PDGFR inhibitor, can preserve BBB integrity in a rat endovascular perforation SAH model. Imatinib (40 or 120 mg/kg) or a vehicle was administered intraperitoneally at 1 hr after SAH induction. BBB leakage, brain edema, and neurological deficits were evaluated. Total and phosphorylated protein expressions of PDGFR-?, c-Src, c-Jun N-terminal kinase (JNK), and c-Jun were measured, and enzymatic activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined in the injured brain. Imatinib treatment significantly ameliorated BBB leakage and edema formation 24 hr after SAH, which was paralleled by improved neurological functions. Decreased brain expressions of phosphorylated PDGFR-?, c-Src, JNK, and c-Jun as well as reduced MMP-9 activities were found in treated animals. PDGFR-? inhibition preserved BBB integrity following experimental SAH; however, the protective mechanisms remain to be elucidated. Targeting PDGFR-? signaling might be advantageous to ameliorate early brain injury following SAH. © 2014 Wiley Periodicals, Inc. PMID:25196554

Zhan, Yan; Krafft, Paul R; Lekic, Tim; Ma, Qingyi; Souvenir, Rhonda; Zhang, John H; Tang, Jiping

2015-01-01

151

Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production.  

PubMed

A recent epidemiological study suggested that higher caffeine intake over decades reduces the risk of Alzheimer's disease (AD). The present study sought to determine any long-term protective effects of dietary caffeine intake in a controlled longitudinal study involving AD transgenic mice. Caffeine (an adenosine receptor antagonist) was added to the drinking water of amyloid precursor protein, Swedish mutation (APPsw) transgenic (Tg) mice between 4 and 9 months of age, with behavioral testing done during the final 6 weeks of treatment. The average daily intake of caffeine per mouse (1.5 mg) was the human equivalent of 500 mg caffeine, the amount typically found in five cups of coffee per day. Across multiple cognitive tasks of spatial learning/reference memory, working memory, and recognition/identification, Tg mice given caffeine performed significantly better than Tg control mice and similar to non-transgenic controls. In both behaviorally-tested and aged Tg mice, long-term caffeine administration resulted in lower hippocampal beta-amyloid (Abeta) levels. Expression of both Presenilin 1 (PS1) and beta-secretase (BACE) was reduced in caffeine-treated Tg mice, indicating decreased Abeta production as a likely mechanism of caffeine's cognitive protection. The ability of caffeine to reduce Abeta production was confirmed in SweAPP N2a neuronal cultures, wherein concentration-dependent decreases in both Abeta1-40 and Abeta1-42 were observed. Although adenosine A(1) or A(2A) receptor densities in cortex or hippocampus were not affected by caffeine treatment, brain adenosine levels in Tg mice were restored back to normal by dietary caffeine and could be involved in the cognitive protection provided by caffeine. Our data demonstrate that moderate daily intake of caffeine may delay or reduce the risk of AD. PMID:16938404

Arendash, G W; Schleif, W; Rezai-Zadeh, K; Jackson, E K; Zacharia, L C; Cracchiolo, J R; Shippy, D; Tan, J

2006-11-01

152

Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury  

PubMed Central

OBJECTIVE Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3–immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3–immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuro-protective endocannabinoid, in the injured brain. CONCLUSION These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials. PMID:15730585

Gopez, Jonas J.; Yue, Hongfei; Vasudevan, Ram; Malik, Amir S.; Fogelsanger, Lester N.; Lewis, Shawn; Panikashvili, David; Shohami, Esther; Jansen, Susan A.; Narayan, Raj K.; Strauss, Kenneth I.

2006-01-01

153

Omega3 Fatty Acid Deficiency during Brain Maturation Reduces Neuronal and Behavioral Plasticity in Adulthood  

Microsoft Academic Search

Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3

Harsharan Singh Bhatia; Rahul Agrawal; Sandeep Sharma; Yi-Xin Huo; Zhe Ying; Fernando Gomez-Pinilla

2011-01-01

154

Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis  

Microsoft Academic Search

Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. We therefore

Sarah Cader; Alberto Cifelli; Yasir Abu-Omar; Jacqueline Palace; Paul M. Matthews

2006-01-01

155

Prohibitin reduces mitochondrial free radical production and protects brain cells from different injury modalities  

PubMed Central

Prohibitin is an essential mitochondrial protein that has been implicated in a wide variety of functions in many cell types, but its role in neurons remains unclear. In a proteomic screen of rat brains in which ischemic tolerance was induced by electrical stimulation of the cerebellar fastigial nucleus, we found that prohibitin is upregulated in mitochondria. This observation prompted us to investigate the role of prohibitin in neuronal death and survival. We found that prohibitin is upregulated also in the ischemic tolerance induced by transient ischemia in vivo, or oxygen-glucose deprivation in neuronal cultures. Cell fractionation and electron microscopic immunolabeling studies demonstrated that prohibitin is localized to neuronal mitochondria. Upregulation of prohibitin in neuronal cultures or hippocampal slices was markedly neuroprotective, whereas prohibitin gene-silencing increased neuronal vulnerability, an effect associated with loss of mitochondrial membrane potential and increased mitochondrial production of reactive oxygen species. Prohibitin upregulation was associated with reduced production of reactive oxygen species in mitochondria exposed to the complex I inhibitor rotenone. In addition, prohibitin protected complex I activity from the inhibitory effects of rotenone. These observations, collectively, establish prohibitin as an endogenous neuroprotective protein involved in ischemic tolerance. Prohibitin exerts beneficial effects on neurons by reducing mitochondrial free radical production. The data with complex I activity suggest that prohibitin may stabilize the function of complex I. The protective effect of prohibitin has potential translational relevance in diseases of the nervous system associated with mitochondrial dysfunction and oxidative stress. PMID:22238093

Zhou, Ping; Qian, Liping; D’Aurelio, Marilena; Cho, Sunghee; Wang, Gang; Manfredi, Giovanni; Pickel, Virginia; Iadecola, Costantino

2012-01-01

156

Cerebellar haemorrhage as a cause of neurogenic pulmonary edema-case report  

Microsoft Academic Search

The neurogenic pulmonary edema is a rare clinical situation caused by an imbalance characterized by an excessive sympathetic\\u000a outflow. It is observed mostly in young patients, is associated with brain or spinal cord haemorrhage, trauma, tumours or\\u000a infections and is usually fatal. A case of neurogenic pulmonary edema in a 27-year-old woman is presented, caused by a cerebellar\\u000a haemorrhage due

Victor Gonçalves; Lu’is Silva-Carvalho; Isabel Rocha

2005-01-01

157

Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients  

PubMed Central

Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress. Materials and Methods: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days. Results: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004). Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients. PMID:25535502

Mojtahedzadeh, Mojtaba; Ahmadi, Arezoo; Mahmoodpoor, Ata; Beigmohammadi, Mohammad Taghi; Abdollahi, Mohammad; Khazaeipour, Zahra; Shaki, Fatemeh; Kuochaki, Bizhan; Hendouei, Narjes

2014-01-01

158

Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease.  

PubMed

A report of cell loss in the nucleus basalis of Meynert in patients with Wernicke-Korsakoff disease prompted the examination of thiamine pyrophosphate (TPP)-dependent enzymes in the brain and peripheral tissues of patients with Alzheimer's disease. In these brains, the activities of the 2-ketoglutarate dehydrogenase complex were reduced more than 75% and those of transketolase more than 45%. Decreases occurred in histologically damaged and in relatively undamaged areas. Small but statistically significant abnormalities of transketolase, but not of 2-ketoglutarate dehydrogenase complex, were identified in red blood cells and cultured fibroblasts. Previous studies have shown deficiencies in the brain and variable effects in peripheral tissues on another TPP-dependent enzyme--the pyruvate dehydrogenase complex. Activities of TPP-dependent enzymes appear to be deficient in the brain and perhaps in some peripheral tissues in patients with Alzheimer's disease. PMID:3395256

Gibson, G E; Sheu, K F; Blass, J P; Baker, A; Carlson, K C; Harding, B; Perrino, P

1988-08-01

159

COG1410 improves cognitive performance and reduces cortical neuronal loss in the traumatically injured brain.  

PubMed

We have previously shown that a single dose of COG1410, a small molecule ApoE-mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region, improves sensorimotor and motor outcome following cortical contusion injury (CCI). The present study evaluated a regimen of COG1410 following frontal CCI in order to examine its preclinical efficacy on cognitive recovery. Animals were prepared with a bilateral CCI of the frontal cortex. A regimen of COG1410 (0.8mg/kg intravenously [IV]) was administered twice, at 30min and again at 24h post-CCI. Starting on day 11, the animals were tested for their acquisition of a reference memory task in the Morris water maze (MWM), followed by a working memory task in the MWM on day 15. Following CCI, the animals were also tested on the bilateral tactile adhesive removal test to measure sensorimotor dysfunction. On all of the behavioral tests the COG1410 group was no different from the uninjured sham group. Administration of the regimen of COG1410 significantly improved recovery on the reference and working memory tests, as well as on the sensorimotor test. Lesion analysis revealed that COG1410 significantly reduced the size of the injury cavity. Administration of COG1410 also reduced the number of degenerating neurons, as measured by Fluoro-Jade C staining, in the frontal cortex at 48h post-CCI. These results suggest that a regimen of COG1410 appeared to block the development of significant behavioral deficits and reduced tissue loss. These combined findings suggest that COG1410 appears to have strong preclinical efficacy when administered following traumatic brain injury (TBI). PMID:19119914

Hoane, Michael R; Kaufman, Nicholas; Vitek, Michael P; McKenna, Suzanne E

2009-01-01

160

Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage.  

PubMed

Germinal matrix hemorrhage (GMH) is the most important adverse neurologic event during the newborn period. Evidence has shown that neonates with GMH and hydrocephalus have more severe damage compared to those with GMH alone. Our preliminary study demonstrated the role of iron in hydrocephalus and brain damage in adult rats following intraventricular hemorrhage. Therefore, the aim of the current study was to investigate iron accumulation and iron-handling proteins in a rat model of GMH and whether minocycline reduces iron overload after GMH and iron-induced brain injury in vivo. This study was divided into two parts. In the first part, rats received either a needle insertion or an intracerebral injection of 0.3 U of clostridial collagenase VII-S. Brain iron and brain iron handling proteins (heme oxygenase-1 and ferritin) were measured. In the second part, rats with a GMH were treated with minocycline or vehicle. Brain edema, brain cell death, hydrocephalus, iron-handling proteins and long-term motor function were examined. The result showed iron accumulation and upregulation of iron-handling proteins after GMH. Minocycline treatment significantly reduced GMH-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH. In conclusion, the current study found that iron plays a role in brain injury following GMH and that minocycline reduces iron overload after GMH and iron-induced brain injury. PMID:25451129

Guo, Jing; Chen, Qianwei; Tang, Jun; Zhang, Jianbo; Tao, Yihao; Li, Lin; Zhu, Gang; Feng, Hua; Chen, Zhi

2015-01-12

161

Association of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain Infarction.  

PubMed

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099

Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

2015-01-01

162

Association of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain Infarction  

PubMed Central

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099

Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

2015-01-01

163

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. PMID:15784740

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

164

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke  

PubMed Central

Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (?13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially in the small-vessel occlusion strokes. PMID:21447190

2011-01-01

165

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. PMID:23321384

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

2013-01-01

166

Treatment with Ginsenoside Rb1, A Component of Panax Ginseng , Provides Neuroprotection in Rats Subjected to Subarachnoid Hemorrhage-Induced Brain Injury  

Microsoft Academic Search

\\u000a \\u000a Objective: Recent trials have shown Ginsenoside Rb1 (GRb1), an active component of a well known Chinese medicine Panax Ginseng, plays a significant role in improving the complications seen after an ischemic brain event. In the present study, we investigated\\u000a the use of GRb1 as a treatment modality to reduce brain edema, reduce arterial vasospasm, and improve neurobehavioral function\\u000a after subarachnoid

Yingbo Li; Jiping Tang; Nikan H. Khatibi; Mei Zhu; Di Chen; Liu Tu; Li Chen; Shali Wang

167

The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.  

PubMed

Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia. PMID:25446452

Song, Juhyun; Cheon, So Yeong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-01-21

168

Catalpol Increases Brain Angiogenesis and Up-Regulates VEGF and EPO in the Rat after Permanent Middle Cerebral Artery Occlusion  

PubMed Central

To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately. PMID:20827397

Zhu, Hui-Feng; Wan, Dong; Luo, Yong; Zhou, Jia-Li; Chen, Li; Xu, Xiao-Yu

2010-01-01

169

Ranibizumab in diabetic macular edema  

PubMed Central

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

2013-01-01

170

Reduced serum brain-derived neurotrophic factor in patients with first onset vitiligo  

PubMed Central

Purpose Vitiligo is an acquired pigmentary skin disease that can cause serious cosmetic problems. There have been numerous and well established studies that have demonstrated the comorbidity of various psychiatric disorders in patients with vitiligo. However, to our knowledge, there have been no studies investigating whether a psychiatric biomarker, such as brain-derived neurotrophic factor (BDNF), is associated with vitiligo. Patients and methods This study was conducted in Nam?k Kemal University Medical Faculty, Departments of Dermatology and Psychiatry between January 2013 and September 2014. After meeting inclusion and exclusion criteria, serum BDNF levels were assayed in 57 patients with first onset vitiligo and no known current or past psychiatric disorder and compared with BDNF levels in 58 age and sex matched healthy subjects. Results The age and female/male ratios were similar between groups. The mean values of serum BDNF were 1.57±0.97 ng/dL and 2.37±1.73 ng/dL in the vitiligo group and in the healthy control group, respectively. The mean BDNF level was significantly higher in the healthy control group compared with the vitiligo group (t=2.76, P=0.007). Conclusion This is the first study to compare serum BDNF levels between patients with vitiligo and healthy subjects. The reduced level of serum BDNF in patients with vitiligo may be directly related to the etiology of vitiligo or associated with the high percentage of psychiatric disorders in that patient population. Further studies are needed to support our preliminary results. PMID:25540586

Yanik, M Emin; Erfan, Gamze; Albayrak, Yakup; Aydin, Murat; Kulac, Mustafa; Kuloglu, Murat

2014-01-01

171

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. PMID:24286024

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

2013-01-01

172

Progesterone protects blood-brain barrier function and improves neurological outcome following traumatic brain injury in rats  

PubMed Central

Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction and neurological deficits following traumatic brain injury (TBI). The aim of the present study was to investigate the effects of progesterone on the expression of the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nuclear factor ?B (NF-?B) and tumor necrosis factor-? (TNF-?) in the brain, BBB permeability, cerebral edema and neurological outcome, as well as to explore the mechanism of its neuroprotective effect. In this study, male rats were randomly divided into three groups: a sham-operated group (SHAM), a TBI group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was established using a modified Feeney’s weight-dropping method. Brain samples were extracted 24 h following injury. The expression levels of COX-2 and NF-?B were examined using immunohistochemistry, whilst the expression levels of PGE2 and TNF-? were detected by enzyme-linked immunosorbent assay. BBB permeability was analyzed using Evans blue and cerebral edema was determined using the dry-wet method. The neurological outcome was evaluated using the modified neurological severity score test. The results revealed that progesterone treatment significantly reduced post-injury inflammatory response, brain edema and Evans blue dye extravasation, and improved neurological scores compared with those in the TBI group. In conclusion, the inhibition of inflammation may be an important mechanism by which progesterone protects the BBB and improves neurological outcome. PMID:25120639

SI, DAOWEN; LI, JUAN; LIU, JIANG; WANG, XIAOYIN; WEI, ZIFENG; TIAN, QINGYOU; WANG, HAITAO; LIU, GANG

2014-01-01

173

Bilateral ankle edema with bilateral iritis  

Microsoft Academic Search

I report two patient presented to me with bilateral symmetrical ankle edema and bilateral acute iritis. A 42-year-old female\\u000a of Indian origin and 30-year-old female from Somalia both presented with bilateral acute iritis. In the first patient, bilateral\\u000a ankle edema preceded the onset of bilateral acute iritis. Bilateral ankle edema developed during the course of disease after\\u000a onset of ocular

Sunil Kumar

2007-01-01

174

Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain  

PubMed Central

Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

2011-01-01

175

Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.  

PubMed

Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

2011-11-01

176

THYROID HORMONE INSUFFICIENCY DURING BRAIN DEVELOPMENT REDUCES PARVALBUMIN IMMUNOREACTIVITY AND INHIBITORY FUNCTION IN THE HIPPOCAMPUS.  

EPA Science Inventory

The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

177

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 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. 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 3 dpf. 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

178

A strategy to passively reduce neuroinflammation surrounding devices implanted chronically in brain tissue by manipulating device surface permeability.  

PubMed

Available evidence indicates that pro-inflammatory cytokines produced by immune cells are likely responsible for the negative sequela associated with the foreign body response (FBR) to chronic indwelling implants in brain tissue. In this study a computational modeling approach was used to design a diffusion sink placed at the device surface that would retain pro-inflammatory cytokines for sufficient time to passively antagonize their impact on the FBR. Using quantitative immunohistochemistry, we examined the FBR to such engineered devices after a 16-week implantation period in the cortex of adult male Sprague-Dawley rats. Our results indicate that thick permeable surface coatings, which served as diffusion sinks, significantly reduced the FBR compared to implants either with no coating or with a thinner coating. The results suggest that increasing surface permeability of solid implanted devices to create a diffusion sink can be used to reduce the FBR and improve biocompatibility of chronic indwelling devices in brain tissue. PMID:25310936

Skousen, John L; Bridge, Michael J; Tresco, Patrick A

2015-01-01

179

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. PMID:23444303

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

2013-01-01

180

Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study.  

PubMed

Substantial evidence suggests that nonpsychotic relatives of schizophrenia patients manifest subtle abnormalities in communication, eye movements, event-related potentials, and neuropsychological processes of attention, reasoning, and memory. We sought to determine whether adult relatives without psychosis or schizophrenia spectrum diagnoses might also have structural brain abnormalities, particularly in subcortical regions found to be impaired in patients with schizophrenia itself. Subjects were six sisters of schizophrenic patients and eleven normal female controls. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images (MRI) of the entire brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter was segmented using a semiautomated intensity contour mapping algorithm. Volumes were adjusted for total brain volumes. Adjusted gray matter subcortical volumes were significantly smaller in relatives than in controls in total hippocampus, right amygdala, right putamen, left thalamus, and brainstem. Relatives had significantly enlarged left and total inferior lateral ventricles. These results, though preliminary, suggest that some never-psychotic relatives of schizophrenic patients have abnormal brain structure. If replicated in a larger sample including both sexes, these results would suggest that the genetic liability to schizophrenia is also expressed as structural brain abnormalities. PMID:9342202

Seidman, L J; Faraone, S V; Goldstein, J M; Goodman, J M; Kremen, W S; Matsuda, G; Hoge, E A; Kennedy, D; Makris, N; Caviness, V S; Tsuang, M T

1997-09-19

181

The effect of inhaled nitric oxide on the carrageenan-induced paw edema.  

PubMed

Inhaled nitric oxide therapy reaches not only pulmonary vessels, but also other vasculatures, presenting anti-inflammatory effects. Therefore, this study investigated the effects of inhaled nitric oxide on a mice model of carrageenan-induced paw edema. Paw edema was induced in male Swiss mice (20-30 g) by subplantar injection of carrageenan (0.05 ml of a 1% suspension in 0.9% saline). The evaluation of time-course edema (mililiter) was measured by plethysmometry until 12 h following carrageenan administration. Thirty minutes after carrageenan injection, some groups received inhaled nitric oxide (300 ppm at variable doses and times) or Indometacin (INDO 5 mg/Kg, v.o), while others received sildenafil (1 mg/Kg, i.p) or rolipram (3 mg/Kg, i.p.) with or without inhaled nitric oxide. Paws were assessed for edema levels by plethysmometry, mieloperoxidase activity and histological analysis. Inhaled nitric oxide significantly reduced carrageenan-induced paw edema, mieloperoxidase activity and inflammatory infiltrate, although similar results were also observed in sildenafil and rolipram treated groups. In addition, significant effects between inhaled nitric oxide with pharmacological therapy was observed. Inhaled nitric oxide presents anti-inflammatory effects on carrageenan-induce paw edema, as observed through reduced edema, mieloperoxidase activity and neutrophil infiltration, indicating that inhaled nitric oxide therapy goes beyond lung vascular effects. PMID:25070733

Coelho, Carly Faria; Vieira, Rodolfo P; Lopes-Martins, Patrícia Sardinha Leonardo; Teixeira, Simone Aparecida; Borbely, Alexandre Urban; Gouvea, Irene Maria; Frigo, Lucio; Lopes-Martins, Rodrigo Álvaro Brandão

2015-01-01

182

Reduced resting-state brain activity in the default mode network in children with (central) auditory processing disorders  

PubMed Central

Background In recent years, there has been a growing interest in Central Auditory Processing Disorder (C)APD. However, the neural correlates of (C)APD are poorly understood. Previous neuroimaging experiments have shown changes in the intrinsic activity of the brain in various cognitive deficits and brain disorders. The present study investigated the spontaneous brain activity in (C)APD subjects with resting-state fMRI (rs-fMRI). Methods Thirteen children diagnosed with (C)APD and fifteen age and gender-matched controls participated in a rs-fMRI study during which they were asked to relax keeping their eyes open. Two different techniques of the rs-fMRI data analysis were used: Regional Homogeneity (ReHo) and Independent Component Analysis (ICA), which approach is rare. Results Both methods of data analysis showed comparable results in the pattern of DMN activity within groups. Additionally, ReHo analysis revealed increased co-activation of the superior frontal gyrus, the posterior cingulate cortex/the precuneus in controls, compared to the (C)APD group. ICA yielded inconsistent results across groups. Conclusions Our ReHo results suggest that (C)APD children seem to present reduced regional homogeneity in brain regions considered a part of the default mode network (DMN). These findings might contribute to a better understanding of neural mechanisms of (C)APD. PMID:25261349

2014-01-01

183

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

PubMed

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 D(3) (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. PMID:19482377

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

2011-05-01

184

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. PMID:19482377

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

2013-01-01

185

Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts...

186

Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells.  

PubMed

Brain damage around birth may cause lifelong neurodevelopmental deficits. We examined the therapeutic potential of human umbilical cord blood-derived mononuclear cells containing multipotent stem cells to facilitate motor recovery after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d 7, succeeded by intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells on postnatal d 8 in a sham-controlled design. Histologic and immunohistochemical analysis on postnatal d 21 revealed that neonates developed severe cerebral damage after the hypoxic-ischemic insult. These animals also suffered from contralateral spastic paresis, as evidenced by their locomotor behavior. After transplantation of human umbilical cord blood-derived mononuclear cells, spastic paresis was largely alleviated, resulting in a normal walking behavior. This "therapeutic" effect was accompanied by the fact that mononuclear cells had entered the brain and were incorporated around the lesion without obvious signs of transdifferentiation. This study demonstrates that intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells in a rat model of perinatal brain damage leads to both incorporation of these cells in the lesioned brain area and to an alleviation of the neurologic effects of cerebral palsy as assessed by footprint and walking pattern analysis. PMID:16439586

Meier, Carola; Middelanis, Johannes; Wasielewski, Bianca; Neuhoff, Sandra; Roth-Haerer, Astrid; Gantert, Markus; Dinse, Hubert R; Dermietzel, Rolf; Jensen, Arne

2006-02-01

187

Caffeic Acid Phenethyl Ester Protects Blood–Brain Barrier Integrity and Reduces Contusion Volume in Rodent Models of Traumatic Brain Injury  

PubMed Central

Abstract 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.

2012-01-01

188

Neuroprotective effects of erythropoietin in focal brain ischemia in rats.  

PubMed

Neuroprotective effect of erythropoietin administered before ischemia has been previously demonstrated. The efficiency of erythropoietin administration after ischemia was not studied, though in case of success these protocols would be applied in clinical neurology. In our experiments on the model of transitory focal ischemia, erythropoietin was injected intraperitoneally during the early and delayed postischemic period (3 and 12 h). The size of the necrotic zone, neurological deficit, and the severity of brain edema were evaluated in 48 h. Injection of erythropoietin in 3 and 12 h after ischemia significantly reduced the size of necrosis (p = 0.0007 and p=0.0016, respectively), neurological deficit (p=0.0013 and p=0.0062, respectively), and brain edema (p=0.02 and p=0.0186, respectively). Injection of erythropoietin after transitory focal cerebral ischemia produced a pronounced neuroprotective effect. PMID:24770748

Prosvirnina, M S; Shmonin, A A; Mel'nikova, E V; Vlasov, T D

2014-03-01

189

Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.  

PubMed

Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier. PMID:19812973

Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

2010-01-01

190

Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation  

NASA Astrophysics Data System (ADS)

This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications.

Jeon, Myounggun; Cho, Jeiwon; Kim, Yun Kyung; Jung, Dahee; Yoon, Eui-Sung; Shin, Sehyun; Cho, Il-Joo

2014-02-01

191

Low-Power 2MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats  

Microsoft Academic Search

It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was\\u000a to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long–Evans rats with\\u000a permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power\\u000a (128 or 10 mW) or no ultrasound

Andrei V. Alexandrov; Kristian Barlinn; Roger Strong; Anne W. Alexandrov; Jaroslaw Aronowski

192

Serum brain-derived neurotrophic factor is associated with reduced appetite in healthy older adults  

Microsoft Academic Search

Objective: Loss of appetite and body mass are common in older adults and are associated with negative consequences. Research indicates\\u000a that these processes likely involve increases in serum brain-derived neurotrophic factor (BDNF). Animal and human models demonstrate\\u000a that BDNF may serve a regulatory function in food intake, but no study has addressed the possibility that BDNF may be involved\\u000a in

K. Stanek; J. Gunstad; T. Leahey; E. Glickman; T. Alexander; M. B. Spitznagel; J. Juvancic-Heltzel; L. Murray

2008-01-01

193

Reduced Metabolsim in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers  

SciTech Connect

Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and {sup 18}FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% {+-} 10) whereas males tended to increase it (+5.5% {+-} 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

2011-03-01

194

Cross-sex hormone treatment in male-to-female transsexual persons reduces serum brain-derived neurotrophic factor (BDNF).  

PubMed

Serum levels of brain-derived neurotrophic factor (BDNF) are reduced in male-to-female transsexual persons (MtF) compared to male controls. It was hypothesized before that this might reflect either an involvement of BDNF in a biomechanism of transsexualism or to be the result of persistent social stress due to the condition. Here, we demonstrate that 12 month of cross-sex hormone treatment reduces serum BDNF levels in male-to-female transsexual persons independent of anthropometric measures. Participants were acquired through the European Network for the Investigation of Gender Incongruence (ENIGI). Reduced serum BDNF in MtF thus seems to be a result of hormonal treatment rather than a consequence or risk factor of transsexualism. PMID:25498415

Fuss, Johannes; Hellweg, Rainer; Van Caenegem, Eva; Briken, Peer; Stalla, Günter K; T'Sjoen, Guy; Auer, Matthias K

2015-01-01

195

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. PMID:24191011

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; Göring, 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

196

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. PMID:22253429

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

2012-01-01

197

Low-power hardware implementation of movement decoding for brain computer interface with reduced-resolution discrete cosine transform.  

PubMed

This paper describes a low-power hardware implementation for movement decoding of brain computer interface. Our proposed hardware design is facilitated by two novel ideas: (i) an efficient feature extraction method based on reduced-resolution discrete cosine transform (DCT), and (ii) a new hardware architecture of dual look-up table to perform discrete cosine transform without explicit multiplication. The proposed hardware implementation has been validated for movement decoding of electrocorticography (ECoG) signal by using a Xilinx FPGA Zynq-7000 board. It achieves more than 56× energy reduction over a reference design using band-pass filters for feature extraction. PMID:25570284

Minho Won; Albalawi, Hassan; Xin Li; Thomas, Donald E

2014-08-01

198

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. PMID:24131855

2013-01-01

199

Ceftriaxone Treatment after Traumatic Brain Injury Restores Expression of the Glutamate Transporter, GLT-1, Reduces Regional Gliosis, and Reduces Post-Traumatic Seizures in the Rat  

PubMed Central

Abstract Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely to post-traumatic epilepsy. Glutamate transport is the only known mechanism of extracellular glutamate clearance, and glutamate transporter 1 (GLT-1) is the major glutamate transporter of the mammalian brain. We tested, by immunoblot, in the rat lateral fluid percussion injury TBI model whether GLT-1 expression is depressed in the cortex after TBI, and whether GLT-1 expression after TBI is restored after treatment with ceftriaxone, a well-tolerated ?-lactam antibiotic previously shown to enhance GLT-1 expression in noninjured animals. We then tested whether treatment with ceftriaxone mitigates the associated regional astrogliosis, as reflected by glial fibrillary acid protein (GFAP) expression, and also whether ceftriaxone treatment mitigates the severity of post-traumatic epilepsy. We found that 7 days after TBI, GLT-1 expression in the ipsilesional cortex was reduced by 29% (n=7/group; p<0.01), relative to the contralesional cortex. However, the loss of GLT-1 expression was reversed by treatment with ceftriaxone (200?mg/kg, daily, intraperitoneally). We found that ceftriaxone treatment also decreased the level of regional GFAP expression by 43% in the lesioned cortex, relative to control treatment with saline (n=7 per group; p<0.05), and, 12 weeks after injury, reduced cumulative post-traumatic seizure duration (n=6 rats in the ceftriaxone treatment group and n=5 rats in the saline control group; p<0.001). We cautiously conclude that our data suggest a potential role for ceftriaxone in treatment of epileptogenic TBI. PMID:23510201

Goodrich, Grant S.; Kabakov, Anatoli Y.; Hameed, Mustafa Q.; Dhamne, Sameer C.; Rosenberg, Paul A.

2013-01-01

200

Testicular edema is associated with spermatogonial arrest in irradiated rats.  

PubMed

Irradiation of LBNF1 rat testes induces arrest of spermatogonial differentiation, which can be reversed by suppression of testosterone with GnRH antagonist treatment. The cause of the arrest is unknown. We investigated the time course and hormonal effects on radiation-induced arrest and changes in interstitial fluid volume. We postulated that the edema evident in irradiated testes caused the differentiation blockade. Rat testes were irradiated with 3.5 or 6 Gy. Interstitial fluid testosterone (IFT) increased between 2 and 6 wk after irradiation, followed by increased interstitial fluid volume at 6 wk and spermatogonial blockade at 8 wk. Additional rats irradiated with 6 Gy were given GnRH antagonist, alone or with exogenous testosterone, for 8 wk starting at 15 wk after irradiation. In rats treated with GnRH antagonist, IFT started falling within 1 wk of treatment, followed by interstitial fluid volume decreases at wk 2 and 3, with recovery of spermatogenesis starting at wk 4. Addition of exogenous testosterone largely blocked the effects of GnRH antagonist on IFT, interstitial fluid volume, and spermatogenesis. Thus the testicular edema was largely modulated by intratesticular testosterone levels. The time course of changes in the spermatogonial blockade more closely followed that of the testicular edema than of IFT, indicating that testosterone may block spermatogonial differentiation indirectly by producing edema. This conclusion was further supported by an experiment in which irradiated rats were treated with GnRH antagonist plus estrogen; the treatment further reduced IFT and interstitial fluid volume and reduced the time to initiation of recovery of spermatogonial differentiation. These results suggest that studies of the edematous process or composition of the fluid would help elucidate the mechanism of spermatogonial arrest in toxicant-treated rats. PMID:16306082

Porter, Karen L; Shetty, Gunapala; Meistrich, Marvin L

2006-03-01

201

MAGNESIUM SULFATE REDUCES INFLAMMATION-ASSOCIATED BRAIN INJURY IN FETAL MICE  

PubMed Central

OBJECTIVE To investigate whether magnesium sulfate (MgSO4) prevents fetal brain injury in inflammation-associated preterm birth (PTB). STUDY DESIGN Utilising a mouse model of PTB, LPS or normal saline (NS)-exposed mice via intrauterine injection, were randomized to intraperitoneal treatment with MgSO4 or NS. From the 4 treatment groups, 1)NS+NS; 2)LPS+NS; 3)LPS+MgSO4; and 4)NS+MgSO4, fetal brains were collected for QPCR studies and primary neuronal cultures. mRNA expression of cytokines, cell death, and markers of neuronal and glial differentiation were assessed. Immunocytochemistry and confocal microscopy were performed. RESULTS There was no difference between LPS+NS and LPS+MgSO4 groups in expression of pro-inflammatory cytokines, cell death markers as well markers of pro-oligodendrocyte and astrocyte development (P>0.05 for all). Neuronal cultures from LPS+NS demonstrated morphological changes and this neuronal injury was prevented by MgSO4 (P<0.001). CONCLUSION Amelioration of neuronal injury in inflammation-associated PTB may be a key mechanism by which MgSO4 prevents cerebral palsy. PMID:20207246

Burd, Irina; Breen, Kelsey; Friedman, Alexander; Chai, Jinghua; Elovitz, Michal A.

2010-01-01

202

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. PMID:24058344

Lin, Li-Chun; Sibille, Etienne

2013-01-01

203

Blood-brain barrier in acute liver failure  

PubMed Central

Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF. PMID:22100566

Nguyen, Justin H.

2011-01-01

204

Disruption of Ion Homeostasis in the Neurogliovascular Unit Underlies the Pathogenesis of Ischemic Cerebral Edema  

PubMed Central

Cerebral edema is a major cause of morbidity and mortality following ischemic stroke, but its underlying molecular pathophysiology is incompletely understood. Recent data have revealed the importance of ion flux via channels and transporters expressed in the neurogliovascular unit in the development of ischemia-triggered cytotoxic edema, vasogenic edema, and hemorrhagic conversion. Disruption of homeostatic mechanisms governing cell volume regulation and epithelial/endothelial ion transport due to ischemia-associated energy failure results in the thermodynamically driven re-equilibration of solutes and water across the CSF–blood and blood–brain barriers that ultimately increases the brain’s extravascular volume. Additionally, hypoxia, inflammation, and other stress-triggered increases in the functional expression of ion channels and transporters normally expressed at low levels in the neurogliovascular unit cause disruptions in ion homeostasis that contribute to ischemic cerebral edema. Here, we review the pathophysiological significance of several molecular mediators of ion transport expressed in the neurogliovascular unit, including targets of existing FDA-approved drugs, which might be potential nodes for therapeutic intervention. PMID:24323726

Khanna, Arjun; Kahle, Kristopher T.; Gerzanich, Volodymyr

2014-01-01

205

Cystoid macular edema associated with acitretin  

PubMed Central

Summary Cystoid macular edema represents a “final common pathway” response of the retina to a variety of insults. It has been reported in association with vascular problems, inflammatory conditions, inherited diseases, tractional problems, intraocular surgery and medications. We report a case of cystoid macular edema associated with acitretin in a 65-year-old woman and document its resolution with optical coherence tomography (OCT). PMID:24459457

Yap, Joel; Buller, Alex

2013-01-01

206

Transient Corneal Edema is a Predictive Factor for Pseudophakic Cystoid Macular Edema after Uncomplicated Cataract Surgery  

PubMed Central

Purpose To report transient corneal edema after phacoemulsification as a predictive factor for the development of pseudophakic cystoid macular edema (PCME). Methods A total of 150 eyes from 150 patients (59 men and 91 women; mean age, 68.0 ± 10.15 years) were analyzed using spectral domain optical coherence tomography 1 week and 5 weeks after routine phacoemulsification cataract surgery. Transient corneal edema detected 1 week after surgery was analyzed to reveal any significant relationship with the development of PCME 5 weeks after surgery. Results Transient corneal edema developed in 17 (11.3%) of 150 eyes 1 week after surgery. A history of diabetes mellitus was significantly associated with development of transient corneal edema (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.41 to 11.54; p = 0.011). Both diabetes mellitus and transient corneal edema were significantly associated with PCME development 5 weeks after surgery (OR, 4.58; 95% CI, 1.56 to 13.43; p = 0.007; and OR, 6.71; CI, 2.05 to 21.95; p = 0.003, respectively). In the 8 eyes with both diabetes mellitus and transient corneal edema, 4 (50%) developed PCME 5 weeks after surgery. Conclusions Transient corneal edema detected 1 week after routine cataract surgery is a predictive factor for development of PCME. Close postoperative observation and intervention is recommended in patients with transient corneal edema. PMID:25646056

Do, Jae Rock; Oh, Jong-Hyun; Chuck, Roy S.

2015-01-01

207

The impact of dietary isoflavonoids on malignant brain tumors  

PubMed Central

Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose–response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach. PMID:24898306

Sehm, Tina; Fan, Zheng; Weiss, Ruth; Schwarz, Marc; Engelhorn, Tobias; Hore, Nirjhar; Doerfler, Arnd; Buchfelder, Michael; Eyüpoglu, IIker Y; Savaskan, Nic E

2014-01-01

208

Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania.  

PubMed

Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice. PMID:25035188

Arunagiri, Pandiyan; Rajeshwaran, Krishnamoorthy; Shanthakumar, Janakiraman; Tamilselvan, Thangavel; Balamurugan, Elumalai

2014-09-01

209

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. PMID:24280275

2013-01-01

210

Gravity-induced hyperventilation is caused by a reduced brain perfusion.  

PubMed

The suggestion that hyperventilation caused by increased gravity is mediated by a decrease in brain perfusion has led us to propose a mathematical model based on: (1) the CO2 balance equation for the respiratory center (RC), and (2) the relationship between RC blood flow (QRC), foot-to-head acceleration (Gz) and PRCCO2, namely, QRC = [1 - a(Gz - 1)](b X PRCCO2 + c), where the coefficients a, b and c can be calculated from data in the literature. QRC is significantly affected by + GZ only at high PaCO2. The model can be used to calculate oxygen pressure in the RC; the numbers so obtained are in good agreement with measurements of jugular vein PO2 obtained by others. PMID:3114853

Arieli, R; Farhi, L E

1987-08-01

211

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. PMID:22295102

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

2012-01-01

212

Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice  

PubMed Central

Abstract Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15–30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1?d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1?, tumor necrosis factor ?) in enriched microglia/macrophages 1?d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1? and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1–7?d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7?d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. PMID:25070744

Fenn, Ashley M.; Skendelas, John P.; Moussa, Daniel N.; Muccigrosso, Megan M.; Popovich, Phillip G.; Lifshitz, Jonathan

2015-01-01

213

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.  

PubMed

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1?d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1?, tumor necrosis factor ?) in enriched microglia/macrophages 1?d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1? and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7?d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7?d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. PMID:25070744

Fenn, Ashley M; Skendelas, John P; Moussa, Daniel N; Muccigrosso, Megan M; Popovich, Phillip G; Lifshitz, Jonathan; Eiferman, Daniel S; Godbout, Jonathan P

2015-01-15

214

Lithium Reduces BACE1 Overexpression, Beta Amyloid Accumulation, and Spatial Learning Deficits in Mice with Traumatic Brain Injury  

PubMed Central

Abstract Traumatic brain injury (TBI) leads to both acute injury and long-term neurodegeneration, and is a major risk factor for developing Alzheimer's disease (AD). Beta amyloid (A?) peptide deposits in the brain are one of the pathological hallmarks of AD. A? levels increase after TBI in animal models and in patients with head trauma, and reducing A? levels after TBI has beneficial effects. Lithium is known to be neuroprotective in various models of neurodegenerative disease, and can reduce A? generation by modulating glycogen synthase kinase-3 (GSK-3) activity. In this study we explored whether lithium would reduce A? load after TBI, and improve learning and memory in a mouse TBI model. Lithium chloride (1.5?mEq/kg, IP) was administered 15?min after TBI, and once daily thereafter for up to 3 weeks. At 3 days after injury, lithium attenuated TBI-induced A? load increases, amyloid precursor protein (APP) accumulation, and ?-APP-cleaving enzyme-1 (BACE1) overexpression in the corpus callosum and hippocampus. Increased Tau protein phosphorylation in the thalamus was also attenuated after lithium treatment following TBI at the same time point. Notably, lithium treatment significantly improved spatial learning and memory in the Y-maze test conducted 10 days after TBI, and in the Morris water maze test performed 17–20 days post-TBI, in association with increased hippocampal preservation. Thus post-insult treatment with lithium appears to alleviate the TBI-induced A? load and consequently improves spatial memory. Our findings suggest that lithium is a potentially useful agent for managing memory impairments after TBI or other head trauma. PMID:22583494

Yu, Fengshan; Zhang, Yumin

2012-01-01

215

Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain ?-amyloid production  

Microsoft Academic Search

A recent epidemiological study suggested that higher caffeine intake over decades reduces the risk of Alzheimer’s disease (AD). The present study sought to determine any long-term protective effects of dietary caffeine intake in a controlled longitudinal study involving AD transgenic mice. Caffeine (an adenosine receptor antagonist) was added to the drinking water of amyloid precursor protein, Swedish mutation (APPsw) transgenic

G. W. Arendash; W. Schleif; K. Rezai-Zadeh; E. K. Jackson; L. C. Zacharia; J. R. Cracchiolo; D. Shippy; J. Tan

2006-01-01

216

Immunization reverses memory deficits without reducing brain A? burden in Alzheimer's disease model  

Microsoft Academic Search

We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid ?-peptide (A?), increases plasma concentrations of A? and reduces A? 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

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

2002-01-01

217

Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans  

PubMed Central

Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate to the ability to generate a maximal voluntary contraction and to the transcranial magnetic stimulated force generation. To determine the role of a reduced OCI and in central fatigue, 16 males performed low intensity, maximal intensity and hypoxic cycling exercise. Exercise fatigue was evaluated by ratings of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia ( 0.10) reduced cerebral oxygen delivery ?25% and decreased 11 ± 4 mmHg (P < 0.001) together with OCI (6.2 ± 0.7 to 4.8 ± 0.5, P < 0.001). RPE increased while MVC and voluntary activation were reduced (P < 0.05). During maximal exercise declined 8 ± 4 mmHg (P < 0.05) and OCI to 3.8 ± 0.5 (P < 0.001). RPE was 18.5, and MVC and voluntary activation were reduced (P < 0.05). We observed no signs of muscular fatigue in the elbow flexors and all control MVCs were similar to resting values. Exhaustive exercise provoked cerebral deoxygenation, metabolic changes and indices of fatigue similar to those observed during exercise in hypoxia indicating that reduced cerebral oxygenation may play a role in the development of central fatigue and may be an exercise capacity limiting factor. PMID:20403976

Rasmussen, P; Nielsen, J; Overgaard, M; Krogh-Madsen, R; Gjedde, A; Secher, N H; Petersen, N C

2010-01-01

218

Reduced brain resting-state network specificity in infants compared with adults  

PubMed Central

Purpose Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. Patients and methods Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. Results Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. Conclusion We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience. PMID:25092980

Wylie, Korey P; Rojas, Donald C; Ross, Randal G; Hunter, Sharon K; Maharajh, Keeran; Cornier, Marc-Andre; Tregellas, Jason R

2014-01-01

219

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. 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

220

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. PMID:22792343

Liu, Jiang-Qin; Chaudhary, Hetal; Brocks, Dion R.; Bigam, David L.; Cheung, Po-Yin

2012-01-01

221

Cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets.  

PubMed

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 (H(2)O(2)) 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 H(2)O(2) 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 H(2)O(2) 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 H(2)O(2) production and minimizes oxidative stress in newborn piglets following hypoxia-reoxygenation. PMID:22792343

Gill, Richdeep S; Lee, Tze-Fun; Liu, Jiang-Qin; Chaudhary, Hetal; Brocks, Dion R; Bigam, David L; Cheung, Po-Yin

2012-01-01

222

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

223

Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain ?-amyloid through PPAR? activation  

PubMed Central

Aim: To examine the effects of pioglitazone, a PPAR? agonist, on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice. Methods: ICR male mice were injected with STZ (150 mg/kg, iv) to induce experimental diabetes. Pioglitazone (9 and 18 mg·kg-1·d-1, po) was administered for 6 weeks. Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function. The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay, respectively. ?-amyloid (A?), ?-amyloid precursor protein (APP), ?-amyloid precursor protein cleaving enzyme 1 (BACE1), NF-?B p65, the receptor for advanced glycation end products (RAGE) and PPAR? in the brains were analyzed using Western blotting assays. Results: The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests, accompanied by increased A?1–40/A?1–42, APP, BACE1, NF-?B p65 and RAGE levels and decreased PPAR? level in the hippocampus and cortex. Chronic pioglitazone treatment significantly ameliorated the memory deficits and amyloidogenesis of STZ-induced diabetic mice, and suppressed expression of APP, BACE1, RAGE and NF-?B p65, and activated PPAR? in the hippocampus and cortex. However, pioglitazone did not significantly affect blood glucose and insulin levels. Conclusion: Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain A? level via activation of PPAR?, which is independent of its effects on blood glucose and insulin levels. The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus. PMID:23524568

Liu, Li-ping; Yan, Tian-hua; Jiang, Li-ying; Hu, Wei; Hu, Meng; Wang, Chao; Zhang, Qian; Long, Yan; Wang, Jiang-qing; Li, Yong-qi; Hu, Mei; Hong, Hao

2013-01-01

224

A3 Adenosine Receptor Agonist Reduces Brain Ischemic Injury and Inhibits Inflammatory Cell Migration in Rats  

PubMed Central

A3 adenosine receptor (A3AR) is recognized as a novel therapeutic target for ischemic injury; however, the mechanism underlying anti-ischemic protection by the A3AR agonist remains unclear. Here, we report that 2-chloro-N6-(3-iodobenzyl)-5?-N-methylcarbamoyl-4?-thioadenosine (LJ529), a selective A3AR agonist, reduces inflammatory responses that may contribute to ischemic cerebral injury. Postischemic treatment with LJ529 markedly reduced cerebral ischemic injury caused by 1.5-hour middle cerebral artery occlusion, followed by 24-hour reperfusion in rats. This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. LJ529 prevented the infiltration/migration of microglia and monocytes occurring after middle cerebral artery occlusion and reperfusion, and also after injection of lipopolysaccharides into the corpus callosum. The reduced migration of microglia by LJ529 could be related with direct inhibition of chemotaxis and down-regulation of spatiotemporal expression of Rho GTPases (including Rac, Cdc42, and Rho), rather than by biologically relevant inhibition of inflammatory cytokine/chemokine release (eg, IL-1?, TNF-?, and MCP-1) or by direct inhibition of excitotoxicity/oxidative stress (not affected by LJ529). The present findings indicate that postischemic activation of A3AR and the resultant reduction of inflammatory response should provide a promising therapeutic strategy for the treatment of ischemic stroke. PMID:21854743

Choi, In-Young; Lee, Jae-Chul; Ju, Chung; Hwang, Sunyoung; Cho, Geum-Sil; Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin; Kim, Won-Ki

2011-01-01

225

Multimodal MR imaging of acute and subacute experimental traumatic brain injury: Time course and correlation with cerebral energy metabolites  

PubMed Central

Background Traumatic brain injury (TBI) is one of the leading causes of death and permanent disability world-wide. The predominant cause of death after TBI is brain edema which can be quantified by non-invasive diffusion-weighted magnetic resonance imaging (DWI). Purpose To provide a better understanding of the early onset, time course, spatial development, and type of brain edema after TBI and to correlate MRI data and the cerebral energy state reflected by the metabolite adenosine triphosphate (ATP). Material and Methods The spontaneous development of lateral fluid percussion-induced TBI was investigated in the acute (6?h), subacute (48?h), and chronic (7 days) phase in rats by MRI of quantitative T2 and apparent diffusion coefficient (ADC) mapping as well as perfusion was combined with ATP-specific bioluminescence imaging and histology. Results An induced TBI led to moderate to mild brain damages, reflected by transient, pronounced development of vasogenic edema and perfusion reduction. Heterogeneous ADC patterns indicated a parallel, but mixed expression of vasogenic and cytotoxic edema. Cortical ATP levels were reduced in the acute and subacute phase by 13% and 27%, respectively, but were completely normalized at 7 days after injury. Conclusion The partial ATP reduction was interpreted to be partially caused by a loss of neurons in parallel with transient dilution of the regional ATP concentration by pronounced vasogenic edema. The normalization of energy metabolism after 7 days was likely due to infiltrating glia and not to recovery. The MRI combined with metabolite measurement further improves the understanding and evaluation of brain damages after TBI. PMID:25610615

Maegele, Marc; Hoeffgen, Alexander; Uhlenkueken, Ulla; Mautes, Angelika; Schaefer, Nadine; Lippert-Gruener, Marcela; Schaefer, Ute; Hoehn, Mathias

2015-01-01

226

Reduced glucose uptake and A? in brain regions with hyperintensities in connected white matter.  

PubMed

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (? = 0.045) and FDG-PET (? = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition. PMID:24999038

Glodzik, L; Kuceyeski, A; Rusinek, H; Tsui, W; Mosconi, L; Li, Y; Osorio, R S; Williams, S; Randall, C; Spector, N; McHugh, P; Murray, J; Pirraglia, E; Vallabhajosula, S; Raj, A; de Leon, M J

2014-10-15

227

Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus  

PubMed Central

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (?30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy. PMID:21519387

Stefani, Alessandro; Fedele, Ernesto; Pierantozzi, Mariangela; Galati, Salvatore; Marzetti, Francesco; Peppe, Antonella; Pastore, Francesco Saverio; Bernardi, Giorgio; Stanzione, Paolo

2011-01-01

228

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers  

NASA Astrophysics Data System (ADS)

Previous studies have shown that 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 strongly depends 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 (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, 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 appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon 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.

(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-08-01

229

Effectiveness of CPAP by mask for pulmonary edema associated with hypercarbia  

Microsoft Academic Search

We describe continuous positive airway pressure (CPAP) by mask to reduce hypercarbia in two patients who had pulmonary edema due to congestive heart failure. In such patients, beside reducing venous return and filling pressures, CPAP improves compliance and decreases the work of breathing, thereby improving effective ventilation. Hence, CPAP may be useful to combat not only hypoxemia but also hypercarbia

A. Perel; D. C. Williamson; J. H. Modell

1983-01-01

230

Vaccination with genetically modified Shiga-like toxin IIe prevents edema disease in swine.  

PubMed Central

Escherichia coli strains producing Shiga-like toxin II variant (SLT-IIe, formerly called SLT-IIv) cause edema disease in weaned pigs. Vaccination of pigs with a genetically modified form of Shiga-like toxin IIe, SLT-IIe(E167Q), has been previously shown to be nontoxic and to induce antibodies to SLT-IIe (V.M. Gordon. S.C. Whipp, H.W. Moon, A.D. O'Brien, and J.E. Samuel, Infect, Immun. 60:485-502, 1992). Fifty micrograms of SLT-IIe(E167Q) toxin was used to vaccinate suckling pigs at 1 and 2 weeks of age. Both vaccinated and nonvaccinated pigs were orally inoculated with an SLT-IIe-producing strain of E. coli after weaning (3 to 4 weeks of age). Pigs fed a low-protein diet that were not vaccinated with SLT-IIe(E167Q) developed subclinical edema disease, histologically evident as vascular necrosis. Pigs fed a high-protein diet that were not vaccinated with SLT-IIe(E167Q) developed clinical edema disease manifested as vascular necrosis, reduced weight gain, ataxia, palpebral edema, lateral recumbency, and death. Pigs vaccinated with SLT-IIe(E167Q) had a reduction in the incidence of subclinical edema disease and never developed clinical edema disease. These data demonstrate that vaccination with a genetically modified form of SLT-IIe prevents edema disease and are consistent with the notion that diet influences susceptibility to edema disease. PMID:8557374

Bosworth, B T; Samuel, J E; Moon, H W; O'Brien, A D; Gordon, V M; Whipp, S C

1996-01-01

231

Traumatic Brain Injury During Development Reduces Minimal Clonic Seizure Thresholds At Maturity  

PubMed Central

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. naive). 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

2008-01-01

232

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

233

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

234

Bilateral ankle edema with bilateral iritis.  

PubMed

I report two patient presented to me with bilateral symmetrical ankle edema and bilateral acute iritis. A 42-year-old female of Indian origin and 30-year-old female from Somalia both presented with bilateral acute iritis. In the first patient, bilateral ankle edema preceded the onset of bilateral acute iritis. Bilateral ankle edema developed during the course of disease after onset of ocular symptoms in the second patient. Both patients did not suffer any significant ocular problem in the past, and on systemic examination, all clinical parameters were within normal limit. Lacrimal gland and conjunctival nodule biopsy established the final diagnosis of sarcoidosis in both cases, although the chest x-rays were normal. PMID:16633708

Kumar, Sunil

2007-07-01

235

Diabetic macular edema: New promising therapies  

PubMed Central

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

2013-01-01

236

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. PMID:24227908

Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

2013-01-01

237

Simvastatin attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury.  

E-print Network

??Purpose: Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration.… (more)

Wang, Kuo-wei

2011-01-01

238

Deep Brain Stimulation Reduces Neuronal Entropy in the MPTP-Primate Model of Parkinson's Disease  

PubMed Central

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n ? 18 and P ? 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n ? 24 and P ? 10?4 in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit. PMID:18784271

Dorval, Alan D.; Russo, Gary S.; Hashimoto, Takao; Xu, Weidong; Grill, Warren M.; Vitek, Jerrold L.

2008-01-01

239

Emotional graphic cigarette warning labels reduce the electrophysiological brain response to smoking cues.  

PubMed

There is an ongoing public debate about the new graphic warning labels (GWLs) that the Food and Drug Administration (FDA) proposes to place on cigarette packs. Tobacco companies argued that the strongly emotional images FDA proposed to include in the GWLs encroached on their constitutional rights. The court ruled that FDA did not provide sufficient scientific evidence of compelling public interest in such encroachment. This study's objectives were to examine the effects of the GWLs on the electrophysiological and behavioral correlates of smoking addiction and to determine whether labels rated higher on the emotional reaction (ER) scale are associated with greater effects. We studied 25 non-treatment-seeking smokers. Event-related potentials (ERPs) were recorded while participants viewed a random sequence of paired images, in which visual smoking (Cues) or non-smoking (non-Cues) images were preceded by GWLs or neutral images. Participants reported their cigarette craving after viewing each pair. Dependent variables were magnitude of P300 ERPs and self-reported cigarette craving in response to Cues. We found that subjective craving response to Cues was significantly reduced by preceding GWLs, whereas the P300 amplitude response to Cues was reduced only by preceding GWLs rated high on the ER scale. In conclusion, our study provides experimental neuroscience evidence that weighs in on the ongoing public and legal debate about how to balance the constitutional and public health aspects of the FDA-proposed GWLs. The high toll of smoking-related illness and death adds urgency to the debate and prompts consideration of our findings while longitudinal studies of GWLs are underway. PMID:24330194

Wang, An-Li; Romer, Dan; Elman, Igor; Strasser, Andrew A; Turetsky, Bruce I; Gur, Ruben C; Langleben, Daniel D

2015-03-01

240

Tumefactive perivascular spaces mimicking cerebral edema in a patient with diabetic hyperglycemic hyperosmolar syndrome: a case report  

PubMed Central

Introduction Acute cerebral edema is a significant cause of death in patients treated for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Case presentation We present the case of a 44-year-old African American woman admitted with acute severe headache and diagnosed with diabetic hyperglycemic hyperosmolar syndrome. Computed tomography of the head showed diffuse leukoencephalopathy, but sparing of the cortex. We were concerned for acute cerebral edema secondary to hyperglycemic hyperosmolar syndrome. Magnetic resonance imaging of the brain showed numerous collections of cystic spaces in the white matter of both hemispheres representing tumefactive perivascular spaces. Her headache improved with correction of the hyperglycemic hyperosmolar state. Conclusion Although the clinical presentation and head computed tomography were concerning for cerebral edema, the distinctive features on brain magnetic resonance imaging helped to clarify the diagnosis and differentiate it from other processes. PMID:23432798

2013-01-01

241

Cytokine production in the brain following closed head injury: dexanabinol (HU211) is a novel TNF ? inhibitor and an effective neuroprotectant  

Microsoft Academic Search

Traumatic brain injury triggers a cascade of events resulting in delayed edema, necrosis and impaired function. Harmful mediators are accumulating in the brain after injury and recently, the role of cytokines in the pathophysiology of brain injury has been suggested. We have developed an experimental model for closed head injury (CHI), in which edema, blood–brain-barrier disruption, motor and memory dysfunctions

E Shohami; R Gallily; R Mechoulam; R Bass; T Ben-Hur

1997-01-01

242

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. PMID:2466516

Sharp, T.; Bramwell, S. R.; Grahame-Smith, D. G.

1989-01-01

243

Tumor necrosis factor-? reduces beta-amyloid accumulation primarily by lowering cellular prion protein levels in a brain endothelial cell line.  

PubMed

Disruption of beta-amyloid (A?) transport across the blood-brain barrier is thought to cause A? accumulation in the brain, thus leading to the development of Alzheimer's disease (AD). As AD patients show increased serum tumor necrosis factor-? (TNF?) levels, we examined the effect of TNF? on the function and expression of A? transport-related proteins including cellular prion protein (PrP(C)) in the mouse brain microvascular endothelial cell line MBEC4. TNF? decreased PrP(C) levels and intracellular radiolabeled A?. Similarly, anti-prion protein antibody also decreased radiolabeled A?. These results suggest that TNF? lowers PrP(C) levels, which in turn, reduces A? in the brain endothelium. PMID:25497018

Yasutaka, Yuki; Watanabe, Takuya; Nakashima, Akio; Matsumoto, Junichi; Futagami, Koujiro; Yamauchi, Atsushi; Kataoka, Yasufumi

2015-01-16

244

Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood–brain barrier and reduces atrophy volume  

PubMed Central

Vascular endothelial growth factor (VEGF)-induced neovasculature is immature and leaky. We tested if coexpression of angiopoietin-1 (ANG1) with VEGF improves blood–brain barrier (BBB) integrity and VEGF neuroprotective and neurorestorative effects using a permanent distal middle cerebral artery occlusion (pMCAO) model. Adult CD-1 mice were injected with 2 × 109 virus genomes of adeno-associated viral vectors expressing VEGF (AAV-VEGF) or ANG1 (AAV-ANG1) individually or together in a 1:1 ratio into the ischemic penumbra 1?hour after pMCAO. AAV-LacZ was used as vector control. Samples were collected 3 weeks later. Compared with AAV-LacZ, coinjection of AAV-VEGF and AAV-ANG1 reduced atrophy volume (46%, P=0.004); injection of AAV-VEGF or AAV-ANG1 individually reduced atrophy volume slightly (36%, P=0.08 and 33%, P=0.09, respectively). Overexpression of VEGF reduced tight junction protein expression and increased Evans blue extravasation. Compared with VEGF expression alone, coexpression of ANG1 with VEGF resulted in upregulation of tight junction protein expression and reduction of Evans blue leakage (AAV-ANG1/AAV-VEGF: 1.4±0.3 versus AAV-VEGF: 2.8±0.7, P=0.001). Coinjection of AAV-VEGF and AAV-ANG1 induced a similar degree of angiogenesis as injection of AAV-VEGF alone (P=0.85). Thus, coexpression of ANG1 with VEGF improved BBB integrity and resulted in better neuroprotection compared with VEGF expression alone. PMID:21772310

Shen, Fanxia; Walker, Espen J; Jiang, Lidan; Degos, Vincent; Li, Jianping; Sun, Baoliang; Heriyanto, Fransisca; Young, William L; Su, Hua

2011-01-01

245

Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy  

NASA Astrophysics Data System (ADS)

Cerebral edema is one of the main acute complications arising after irradiation of brain tumors. Microbeam radiation therapy (MRT), an innovative experimental radiotherapy technique using spatially fractionated synchrotron x-rays, has been shown to spare radiosensitive tissues such as mammal brains. The aim of this study was to determine if cerebral edema occurs after MRT using diffusion-weighted MRI and microgravimetry. Prone Swiss nude mice's heads were positioned horizontally in the synchrotron x-ray beam and the upper part of the left hemisphere was irradiated in the antero-posterior direction by an array of 18 planar microbeams (25 mm wide, on-center spacing 211 mm, height 4 mm, entrance dose 312 Gy or 1000 Gy). An apparent diffusion coefficient (ADC) was measured at 7 T 1, 7, 14, 21 and 28 days after irradiation. Eventually, the cerebral water content (CWC) was determined by microgravimetry. The ADC and CWC in the irradiated (312 Gy or 1000 Gy) and in the contralateral non-irradiated hemispheres were not significantly different at all measurement times, with two exceptions: (1) a 9% ADC decrease (p < 0.05) was observed in the irradiated cortex 1 day after exposure to 312 Gy, (2) a 0.7% increase (p < 0.05) in the CWC was measured in the irradiated hemispheres 1 day after exposure to 1000 Gy. The results demonstrate the presence of a minor and transient cellular edema (ADC decrease) at 1 day after a 312 Gy exposure, without a significant CWC increase. One day after a 1000 Gy exposure, the CWC increased, while the ADC remained unchanged and may reflect the simultaneous presence of cellular and vasogenic edema. Both types of edema disappear within a week after microbeam exposure which may confirm the normal tissue sparing effect of MRT. For more information on this article, see medicalphysicsweb.org

Serduc, Raphaël; van de Looij, Yohan; Francony, Gilles; Verdonck, Olivier; van der Sanden, Boudewijn; Laissue, Jean; Farion, Régine; Bräuer-Krisch, Elke; Siegbahn, Erik Albert; Bravin, Alberto; Prezado, Yolanda; Segebarth, Christoph; Rémy, Chantal; Lahrech, Hana

2008-03-01

246

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

247

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

248

Angular Impact Mitigation System for Bicycle Helmets to Reduce Head Acceleration and Risk of Traumatic Brain Injury  

PubMed Central

Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p < 0.001), a 34% reduction in peak angular acceleration (p < 0.001), and a 22% to 32% reduction in neck loading (p < 0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required. PMID:23770518

Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M.; Bottlang, Michael

2013-01-01

249

3-Nitropropionic acid-induced ischemia tolerance in the rat brain is mediated by reduced metabolic activity and cerebral blood flow.  

PubMed

Tissue tolerance to ischemia can be achieved by noxious stimuli that are below a threshold to cause irreversible damage ('preconditioning'). Understanding the mechanisms underlying preconditioning may lead to the identification of novel therapeutic targets for diseases such as stroke. We here used the oxidative chain inhibitor 3-nitropropionic acid (NPA) to induce ischemia tolerance in a rat middle cerebral artery occlusion (MCAO) stroke model. Cerebral blood flow (CBF) and structural integrity were characterized by longitudinal magnetic resonance imaging (MRI) in combination with behavioral, histologic, and biochemical assessment of NPA-preconditioned animals and controls. Using this approach we show that the ischemia-tolerant state is characterized by a lower energy charge potential and lower CBF, indicating a reduced baseline metabolic demand, and therefore a cellular mechanism of neural protection. Blood vessel density and structural integrity were not altered by NPA treatment. When subjected to MCAO, preconditioned animals had a characteristic MRI signature consisting of enhanced CBF maintenance within the ischemic territory and intraischemic reversal of the initial cytotoxic edema, resulting in reduced infarct volumes. Thus, our data show that tissue protection through preconditioning occurs early during ischemia and indicate that a reduced cellular metabolism is associated with tissue tolerance to ischemia. PMID:24938399

Bracko, Oliver; Di Pietro, Valentina; Lazzarino, Giacomo; Amorini, Angela M; Tavazzi, Barbara; Artmann, Judith; Wong, Eric C; Buxton, Richard B; Weller, Michael; Luft, Andreas R; Wegener, Susanne

2014-09-01

250

Hypertonic/hyperoncotic solution attenuate blood-brain barrier breakdown and brain pathology in whole body hyperthermia rats  

PubMed Central

This study was designed to investigate the effects of hypertonic/hyperoncotic solution on blood-brain barrier damage, brain edema and morphological changes of rats during whole body hyperthermia. 90 adult male Sprague-Dawley rats were randomized into 5 groups: Control group (a room temperature for 4 hours); Whole body hyperthermia group without solution treatment; Whole body hyperthermia group with Ringer's solution treatment; Whole body hyperthermia group with hydroxyethyl starch and Ringer's solution treatment; Whole body hyperthermia group with Hypertonic/hyperoncotic solution treatment. All rats except those of control group were housed in a heated container and maintained at 36°C for 3 hours until the rectal temperature reached 41-42°C. Corresponding solutions were administered intravenously at the beginning of whole body hyperthermia within 30 minutes as designed. Following whole body hyperthermia, rats were subsequently cooled down for 1h. Evans blue was administered intravenously when the rectal temperature was cooled down to 37°C. The leakage of Evans blue-albumin and water content of brain were calculated and morphological changes were investigated. In group with hypertonic/hyperoncotic solution treatment, brain water content and the leakage of Evans blue-albumin were the lowest among the four whole body hyperthermia groups. Compared with the other three whole body hyperthermia groups, in which profound to moderate damages to blood-brain barrier and brain tissue and cells were found, there were only slight morphological changes in the group with hypertonic/hyperoncotic solutionon treatment. Treatment with hypertonic/hyperoncotic solution appeared to attenuate the injury to blood-brain barrier and reduce brain edema and cell morphological changes in whole body hyperthermia rats. PMID:22140599

Liu, Youtan; Tang, Jing; Ye, Jionxian; Zhan, Lifang; Huang, Shaonong; Wang, Tingting; Gu, Miaoning

2011-01-01

251

Treatment and functional outcome of patients with cystoid macular edema: a single-center experience.  

PubMed

The aim of this study was to describe a single-center experience in the treatment and follow-up of cystoid macular edema patients. Clinical records of all patients with cystoid macular edema followed up in the Rheumatologic and Ophthalmological Unit of our center between 1993 and 2013 were retrospectively evaluated. The outcome was assessed by visual acuity and optical coherence tomography status during follow-up. Comparisons were made by Fisher's exact test (p?reducing macular edema. At the end of follow-up, 50 % of patients showed a significant visual loss, while 88 % did not present macular edema. In our small cohort, interferon-? is the most promising drug in contrasting visual acuity loss in cystoid macular edema. Visual prognosis remains severe in these patients. PMID:25028250

Taraborelli, Mara; Cavazzana, Ilaria; Fredi, Micaela; Airò, Paolo; Nascimbeni, Giuseppe; Tincani, Angela; Franceschini, Franco

2014-06-11

252

Impact of clipping versus coiling on postoperative hemodynamics and pulmonary edema after subarachnoid hemorrhage.  

PubMed

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. PMID:24818154

Horie, Nobutaka; Iwaasa, Mitsutoshi; Isotani, Eiji; Ishizaka, Shunsuke; Inoue, Tooru; Nagata, Izumi

2014-01-01

253

Evolution of cerebral edema and its relationship with power in the theta band.  

PubMed

In previous papers we have proposed that in patients with space-occupying lesions, delta power was related with the volume of the lesion and theta power with the volume of the edema. In this report we analyze the evolution of 10 patients with space-occupying lesions in whom we measured the volume of the lesion and of the edema before and after treatment that produced changes in these volumes. EEGs were recorded in the leads of the 10-20 system referenced to linked earlobes. Delta and theta powers were calculated for voltage and current source densities (CSD) and compared with age-norms to compute conventional Z-maps. These maps provide probability statements about the deviation of observed values from the norm. Rank correlations between the change in the volume of the lesion before and after treatment and the change in Z-values before and after treatment were significant only in the delta band. However, rank correlations between the change in the volume of the edema and the change in EEG Z-values were only significant in the theta band. These correlations were higher for CSD than for voltage estimates. We also observed that the site of the lesion and of the edema was better represented by CSD maps than by voltage maps. These results are also in agreement with our previous reports, in which we observed more precise localization of brain lesions by CSD than by voltage estimates. PMID:9146487

Fernández-Bouzas, A; Harmony, T; Marosi, E; Fernández, T; Silva, J; Rodríguez, M; Bernal, J; Reyes, A; Casián, G

1997-04-01

254

[Epidemiology and development of macular edema in the diabetic].  

PubMed

Macular edema is the first cause of blindness in diabetics. Macular edema is defined by macular thickening or deposits of hard exudates. On 1000 diabetics examined over 2 years, 60 patients had a macular edema of which we retained 38 cases(54 eyes). All the patients had an ophthalmologic examination with a retinal angiography. Laser photocoagulation with green Argon laser was instituted in 50 eyes. 63% had background rethinopathy. Total or partial regression of the edema happened in 84.4%. Laser photocoagulation decrease by the half vision loss risk. Interest of early detection and treatment to decrease blindness incidence of macular edema in diabetics. PMID:11892440

Zghal-Mokni, I; Jeddi, A; Boujemaa, C; Ben Hadj Alouane, W; Gaigi, S; Ayed, S

2001-12-01

255

Management of pseudophakic cystoid macular edema.  

PubMed

Pseudophakic cystoid macular edema (PCME) is a common complication following cataract surgery. Acute PCME may resolve spontaneously, but some patients will develop chronic macular edema that affects vision and is difficult to treat. This disease was described more than 50 years ago, and there are multiple options for clinical management. We discuss mechanisms, clinical efficacy, and adverse effects of these treatment modalities. Topical non-steroidal anti-inflammatory agents and corticosteroids are widely used and, when combined, may have a synergistic effect. Intravitreal corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) agents have shown promise when topical medications either fail or have had limited effects. Randomized clinical studies evaluating anti-VEGF agents are needed to fully evaluate benefits and risks. When PCME is either refractory to medical therapy or is associated with significant vitreous involvement, pars plana vitrectomy has been shown to improve outcomes, though it is associated with additional risks. PMID:25438734

Guo, Suqin; Patel, Shriji; Baumrind, Ben; Johnson, Keegan; Levinsohn, Daniel; Marcus, Edward; Tannen, Brad; Roy, Monique; Bhagat, Neelakshi; Zarbin, Marco

2014-09-01

256

[Transient bone marrow edema of the hip].  

PubMed

Transient bone marrow edema of the hip is characterized by moderate homogeneous low MR signal intensity with ill-defined margins that involves at least a portion of the femoral head. Spin echo T1-weighted images are helpful to exclude other underlying diseases (tumor, infection, necrosis from systemic origin…), for which marrow edema is secondary or no epiphyseal in location. High-resolution fat-suppressed T2-weighted or proton density images allow evaluation of the articular cartilage, subchondral bone and subchondal marrow: if the articular cartilage is abnormal, the lesion is irreversible (arthrosis or necrosis); if the subchondral bone is focally interrupted and/or if the femoral is no longer spherical, the lesion is irreversible (necrosis); if a focal linear fluid collection is present under the subchondral bone, the lesion is irreversible (necrosis). Finally, subchondral changes may provide useful prognostic information: the absence of any abnormality other than marrow edema typically indicates that complete resolution is likely; the presence of a focal T2-weighted hypointense lesion immediately next to the subchondral bone suggests an irreversible lesion, especially if it is equal to or thicker than 4mm or the joint space. In some instances, prognosis cannot be reliably determined requiring the need for follow-up imaging. PMID:21704251

Vande Berg, B; Lecouvet, F; Koutaïssoff, S; Simoni, P; Maldague, B; Malghem, J

2011-06-01

257

Use of Electrical Impedance Tomography to Monitor Regional Cerebral Edema during Clinical Dehydration Treatment  

PubMed Central

Objective Variations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content. Design a prospective study. Setting In this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank. Patients 23 patients with brain edema. Interventions The patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes. Measurement and Main Results Overall impedance across the brain increased significantly before and after mannitol dehydration treatment (p?=?0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment. Conclusions EIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients. PMID:25474474

Hu, Shi-Jie; Li, Xia; Xu, Can-Hua; Wang, Bing; Yang, Bin; Tang, Meng-Xing; Dong, Xiu-Zhen; Fei, Zhou; Shi, Xue-Tao

2014-01-01

258

Progesterone improves acute recovery after traumatic brain injury in the aged rat.  

PubMed

Recent evidence has demonstrated that treatment with progesterone can attenuate many of the pathophysiological events following traumatic brain injury (TBI) in young adult rats, but this effect has not been investigated in aged animals. In this study, 20-month-old male Fischer 344 rats with bilateral contusions of the frontal cortex (n = 4 per group) or sham operations received 8, 16, or 32 mg/kg of progesterone or vehicle. Locomotor activity was measured at 72 h to assess behavioral recovery. Brain tissue was harvested at 24, 48, and 72 h, and Western blotting was performed for inflammatory and apoptotic factors. Edema was assessed at 48 h by measuring brain water content. Injured animals treated with 8 and 16 mg/kg progesterone showed decreased expression of COX-2, IL-6, and NFkappaB at all time points, indicating a reduction in the acute inflammatory process compared to vehicle. The 16 mg/kg group also showed reduced apoptosis at all time points as well as decreased edema and improved locomotor outcomes. Thus, in aged male rats, treatment with 16 mg/kg progesterone improves short-term motor recovery and attenuates edema, secondary inflammation, and cell death after TBI. PMID:17892409

Cutler, Sarah M; Cekic, Milos; Miller, Darren M; Wali, Bushra; VanLandingham, Jacob W; Stein, Donald G

2007-09-01

259

Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier  

PubMed Central

The blood-brain barrier (BBB) is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules into brain, and preserves ionic homeostasis within the brain microenvironment. BBB properties are primarily determined by junctional complexes between the cerebral endothelial cells. These complexes are comprised of tight and adherens junctions. Such restrictive angioarchitecture at the BBB reduces paracellular diffusion, while minimal vesicle transport activity in brain endothelial cells limits transcellular transport. Under normal conditions, this largely prevents the extravasation of large and small solutes (unless specific transporters are present) and prevents migration of any type of blood-borne cell. However, this is changed in many pathological conditions. There, BBB disruption (“opening”) can lead to increased paracellular permeability, allowing entry of leukocytes into brain tissue, but also contributing to edema formation. In parallel, there are changes in the endothelial pinocytotic vesicular system resulting in the uptake and transfer of fluid and macromolecules into brain parenchyma. This review highlights the route and possible factors involved in BBB disruption in a variety of neuropathological disorders (e.g. CNS inflammation, Alzheimer’s disease, Parkinson’s disease, epilepsy). It also summarizes proposed signal transduction pathways that may be involved in BBB “opening”. PMID:19506719

Stamatovic, Svetlana M; Keep, Richard F; Andjelkovic, Anuska V

2008-01-01

260

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. PMID:22262924

Le Naour, M.; Harmon, T. M.; Tucker, A. M.; Portoghese, P. S.; Pentel, P. R.

2012-01-01

261

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. PMID:22583811

Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

2012-01-01

262

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

263

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. PMID:25047645

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

264

Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging.  

PubMed

The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction. PMID:12686405

Sakamaki, Masanori; Igarashi, Hironaka; Nishiyama, Yutaka; Hagiwara, Hiroshi; Ando, Jun; Chishiki, Tetsurou; Curran, Brian C; Katayama, Yasuo

2003-05-15

265

A Prospective, Observational Clinical Trial of Fever Reduction to Reduce Systemic Oxygen Consumption in the Setting of Acute Brain Injury  

Microsoft Academic Search

Introduction  Fever after acute brain injury appears to be a detrimental factor, associated with impaired neurological outcomes. This study\\u000a assessed physiological changes in systemic oxygen consumption (VO2) during cutaneous cooling after severe brain injury.\\u000a \\u000a \\u000a \\u000a Methods  This prospective, observational, clinical study evaluated ten, critically ill, brain-injured patients requiring mechanical\\u000a ventilation with a core body temperature of greater or equal to 38°C.\\u000a \\u000a Febrile patients

J. Steven Hata; Constance R. Shelsky; Bradley J. Hindman; Thomas C. Smith; Jonathan S. Simmons; Michael M. Todd

2008-01-01

266

The inhibitory effect of S-nitrosoglutathione on blood-brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke  

PubMed Central

The hallmark of stroke injury is endothelial dysfunction leading to blood brain barrier (BBB) leakage and edema. Among the causative factors of BBB disruption are accelerating peroxynitrite formation and the resultant decreased bioavailability of nitric oxide (NO). S-nitrosoglutathione (GSNO), an S-nitrosylating agent, was found not only to reduce the levels of peroxynitrite but also to protect the integrity of BBB in a rat model of cerebral ischemia and reperfusion (IR). A treatment with GSNO (3 ?mol/kg) after IR reduced 3-nitrotyrosine levels in and around vessels and maintained NO levels in brain. This mechanism protected endothelial function by reducing BBB leakage, increasing the expression of Zonula occludens-1 (ZO-1), decreasing edema, and reducing the expression of MMP-9 and E-selectin in the neurovascular unit. An administration of the peroxynitrite-forming agent 3-morpholino sydnonimine (3 ?mol/kg) at reperfusion increased BBB leakage and decreased the expression of ZO-1, supporting the involvement of peroxynitrite in BBB disruption and edema. Mechanistically, the endothelium-protecting action of GSNO was invoked by reducing the activity of NF-?B and increasing the expression of S-nitrosylated proteins. Taken together, the results support the ability of GSNO to improve endothelial function by reducing nitroxidative stress in stroke. PMID:23050646

Khan, Mushfiquddin; Dhammu, Tajinder S; Sakakima, Harutoshi; Shunmugavel, Anadakumar; Gilg, Anne G; Singh, Avtar K.; Singh, Inderjit

2012-01-01

267

Intercorrelations of Glucose Metabolic Rates Between Brain Regions: Application to Healthy Males in a State of Reduced Sensory Input  

Microsoft Academic Search

Summary: We use a correlational analysis of regional metabolic rates to characterize relations among different brain regions. Starting with rates of local glucose metabolism (rCMRglc) obtained by positron emission tomography using [18F]fluorodeoxyglucose, we propose that pairs of brain regions whose rCMRglc values are significantly correlated are functionally associated, and that the strength of the association is proportional to the magnitude

Barry Horwitz; Ranjan Duara; Stanley I. Rapoport

1984-01-01

268

Augmentation of M-Type (KCNQ) Potassium Channels as a Novel Strategy to Reduce Stroke-Induced Brain Injury.  

PubMed

Cerebral ischemic stroke is a worldwide cause of mortality/morbidity and thus an important focus of research to decrease the severity of brain injury. Therapeutic options for acute stroke are still limited. In neurons throughout the brain, "M-type" K(+) currents, underlain by KCNQ subunits 2-5, play dominant roles in control over excitability, and are thus implicated in myriad neurological and psychiatric disorders. Although KCNQ channel openers, such as retigabine, have emerged as anti-epilepsy drugs, their effects on ischemic injury remain unknown. Here, we investigated the protective effects of M-channel openers on stroke-induced brain injury in mouse photothrombotic and middle cerebral artery occlusion (MCAo) models. Both photothrombosis and MCAo led to rapid, predictable, and consistently sized necrotic brain lesions, inflammatory responses, and behavioral deficits. Administration of three distinct M-channel openers at 0-6 h after ischemic injury significantly decreased brain infarct size and inflammation, and prevented neurological dysfunction, although they were more effective when administered 0-3 h poststroke. Thus, we show beneficial effects against stroke-induced brain injury and neuronal death through pharmacological regulation of ion channels that control neuronal excitability. PMID:25653366

Bierbower, Sonya M; Choveau, Frank S; Lechleiter, James D; Shapiro, Mark S

2015-02-01

269

Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration.  

PubMed

The clinical development of neuropeptides has been limited by a combination of the short plasma half-life of these drugs and their ultimate failure to permeate the blood brain barrier. Peptide nanofibres have been used to deliver peptides across the blood brain barrier and in this work we demonstrate that the polymer coating of peptide nanofibres further enhances peptide delivery to the brain via the intravenous route. Leucine(5)-enkephalin (LENK) nanofibres formed from the LENK ester prodrug - tyrosinyl(1)palmitate-leucine(5)-enkephalin (TPLENK) were coated with the polymer - N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) and injected intravenously. Peptide brain delivery was enhanced because the GCPQ coating on the peptide prodrug nanofibres, specifically enables the peptide prodrug to escape liver uptake, avoid enzymatic degradation to non-active sequences and thus enjoy a longer plasma half life. Plasma half-life is increased 520%, liver AUC0-4 decreased by 54% and brain AUC0-4 increased by 47% as a result of the GCPQ coating. The increased brain levels of the GCPQ coated peptide prodrug nanofibres result in the pharmacological activity of the parent drug (LENK) being significantly increased. LENK itself is inactive on intravenous injection. PMID:25449808

Lalatsa, A; Schätzlein, A G; Garrett, N L; Moger, J; Briggs, Michael; Godfrey, Lisa; Iannitelli, Antonio; Freeman, Jay; Uchegbu, I F

2015-01-10

270

Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema  

PubMed Central

To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 ?L shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25–6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5–4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = ?0.806, P < 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong

2012-01-01

271

Reduced immune cell infiltration and increased pro-inflammatory mediators in the brain of Type 2 diabetic mouse model infected with West Nile virus  

PubMed Central

Background Diabetes is a significant risk factor for developing West Nile virus (WNV)-associated encephalitis (WNVE) in humans, the leading cause of arboviral encephalitis in the United States. Using a diabetic mouse model (db/db), we recently demonstrated that diabetes enhanced WNV replication and the susceptibility of mice to WNVE. Herein, we have examined immunological events in the brain of wild type (WT) and db/db mice after WNV infection. We hypothesized that WNV-induced migration of protective leukocytes into the brain is attenuated in the presence of diabetes, leading to a high viral load in the brain and severe disease in diabetic mice. Methods Nine-week old C57BL/6 WT and db/db mice were infected with WNV. Leukocyte infiltration, expression of cell adhesion molecules (CAM), neuroinflammatory responses, activation of astrocytes, and neuronal death were analyzed using immunohistochemistry, qRT-PCR, flow cytometry, and western blot. Results We demonstrate that infiltration of CD45+ leukocytes and CD8+T cells was significantly reduced in the brains of db/db mice, which was correlated with attenuated expression of CAM such as E-selectin and ICAM-1. WNV infection in db/db mice was associated with an enhanced inflammatory response in the brain. mRNA and protein levels of key chemokines such as CXCL10, CXCL1, CCL2, CCL5, CCL3, and G-CSF, and cytokines such as IL-1?, TNF, IL-6, IFN?, and IL-1? were significantly elevated in the brains of db/db mice compared to WT mice. Elevated levels of cytokines also correlated with increased astrocytes activation and neuronal damage in the brains of db/db mice. Conclusion These data suggest that reduced leukocytes recruitment, in part, due to lower levels of CAM results in failure to clear WNV infection from the brain leading to increased production of inflammatory molecules, which mediates increased neuronal death and mortality in db/db mice. This is the first study to elucidate the expression of CAM and their correlation with the migration of leukocytes, specifically cytotoxic CD8+ T cells, in increasing disease severity in the diabetic mouse model. PMID:24750819

2014-01-01

272

Interleukin-2 induces early multisystem organ edema mediated by neutrophils.  

PubMed Central

Interleukin-2 (IL-2), an agent known to activate neutrophils (PMN) with thromboxane (Tx)B2 release, produces pulmonary edema within 6 hours of intravenous infusion. This study tests the role of PMN in mediating the edema. Anesthetized rats received 10(6)U recombinant human IL-2 (n = 15) or vehicle (n = 14) as a constant intravenous infusion during a period of 1 hour. At this time there was leukopenia 3.63 +/- 0.43 (x10(3)/mm3) relative to vehicle-infused control rats 6.12 +/- 0.86 and a decline in PMN, 2.19 +/- 0.14 relative to control value of 3.33 +/- 0.05 (both p less than 0.05). After 6 hours edema, as measured by increase in the wet to dry weight (W/d) ratio, was present in the lungs (4.93 +/- 0.20 relative to control 4.06 +/- 0.10), heart (4.09 +/- 0.11 versus 3.76 +/- 0.08), liver (3.50 +/- 0.10 versus 3.18 +/- 0.10), and kidney (4.25 +/- 0.07 versus 4.00 +/- 0.07) (all p less than 0.05). There was increased lung permeability demonstrated by bronchoalveolar lavage fluid protein concentration of 1970 +/- 210 micrograms/mL relative to control 460 +/- 90 micrograms/mL (p less than 0.05). Interleukin-2 resulted in lung PMN sequestration of 53 +/- 7 PMN/10 high-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05) and increased plasma TxB2 levels to 1290 +/- 245 pg/mL relative to control 481 +/- 93 pg/mL (p less than 0.05). Pretreatment of other rats (n = 8) with selective anti-rat neutrophil antiserum 18 hours before the experiment led to a peripheral PMN count 10% of baseline and prevented edema in the lungs (W/d ratio 4.20 +/- 0.16) and heart (3.67 +/- 0.07) (both p less than 0.05) but not liver or kidney. Protein in lung lavage was reduced to 760 +/- 220 micrograms/mL (p less than 0.05). The protection afforded by leukopenia was associated with lack of PMN sequestration and prevention of the increase in plasma Tx levels (484 +/- 120 pg/mL, p less than 0.05). These data indicate that the rapid induction of lung and heart edema with a 1-hour infusion of IL-2 in the rat is mediated, in large part, by activated PMNs. PMID:1867524

Welbourn, R; Goldman, G; Kobzik, L; Paterson, I; Shepro, D; Hechtman, H B

1991-01-01

273

Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) is the leading cause of disability and death in young adults. The secondary neuroinflammation and neuronal damage that follows the primary mechanical injury is an important cause of disability in affected people. The membrane attack complex (MAC) of the complement system is detected in the traumatized brain early after TBI; however, its role in the pathology and neurologic outcome of TBI has not yet been investigated. We generated a C6 antisense oligonucleotide that blocks MAC formation by inhibiting C6, and we compared its therapeutic effect to that of Ornithodoros moubata complement inhibitor (OmCI), a known inhibitor of C5 activation that blocks generation of the anaphylatoxin C5a and C5b, an essential component of MAC. Severe closed head injury in mice induced abundant MAC deposition in the brain. Treatment with C6 antisense reduced C6 synthesis (85%) and serum levels (90%), and inhibited MAC deposition in the injured brain (91-96%). Treatment also reduced accumulation of microglia/macrophages (50-88%), neuronal apoptosis, axonal loss and weight loss (54-93%), and enhanced neurologic performance (84-92%) compared with placebo-treated controls after injury. These data provide the first evidence, to our knowledge, that inhibition of MAC formation in otherwise complement-sufficient animals reduces neuropathology and promotes neurologic recovery after TBI. Given the importance of maintaining a functional complement opsonization system to fight infections, a critical complication in TBI patients, inhibition of the MAC should be considered to reduce posttraumatic neurologic damage. This work identifies a novel therapeutic target for TBI and will guide the development of new therapy for patients. PMID:24489093

Fluiter, Kees; Opperhuizen, Anne Loes; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2014-03-01

274

Adrenalectomy reduces FGF1 and FGF2 gene expression in specific rat brain regions and differently affects their induction by seizures  

Microsoft Academic Search

We have previously reported that limbic seizures regulate the gene expression of fibroblast growth factor-2 (basic, FGF-2) according to a specific spatio-temporal pattern. In the present paper we have investigated the role of adrenal hormones on seizure-induced elevation of fibroblast growth factor-1 (acidic, FGF-1) and FGF-2 gene expression. Adrenalectomy reduces FGF-2 mRNA expression in specific brain regions, such as frontal

Marco A. Riva; Fabio Fumagalli; Joan M. C. Blom; Eugenio Donati; Giorgio Racagni

1995-01-01

275

Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model  

Microsoft Academic Search

Corneal neovascularization, which occurs in many pathologic states of the cornea, reduces the visual acuity. Recently, we found that the extracellular region of brain-specific angiogenesis inhibitor 1 (BAI1-ECR) has antiproliferative activity through functional blocking of ?v?5 integrin in endothelial cells. In this study, we investigated the effects of lipid-mediated subconjunctival injection of the BAI1-ECR gene on corneal angiogenesis induced by

K C Yoon; K Y Ahn; J H Lee; B J Chun; S W Park; M S Seo; Y-G Park; K K Kim

2005-01-01

276

[ 123I]-?-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder  

Microsoft Academic Search

Background: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [123I]-2-?-carbomethoxy-3-?-(4-iodophenyl)-tropane ([123I]-?-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [123I]-?-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [123I]-?-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients.Methods: Depressed SAD patients and healthy control subjects were investigated using

Matthäus Willeit; Nicole Praschak-Rieder; Alexander Neumeister; Walter Pirker; Susanne Asenbaum; Oliver Vitouch; Johannes Tauscher; Eva Hilger; Jürgen Stastny; Thomas Brücke; Siegfried Kasper

2000-01-01

277

A Type-II Positive Allosteric Modulator of ?7 nAChRs Reduces Brain Injury and Improves Neurological Function after Focal Cerebral Ischemia in Rats  

PubMed Central

In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of ?7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous ?7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

Sun, Fen; Jin, Kunlin; Uteshev, Victor V.

2013-01-01

278

Pathophysiology of brain dysfunction in hyperammonemic syndromes: The many faces of glutamine.  

PubMed

Ineffective hepatic clearance of excess ammonia in the form of urea, as occurs in urea cycle enzymopathies (UCDs) and in liver failure, leads to increases in circulating and tissue concentrations of glutamine and a positive correlation between brain glutamine and the severity of neurological symptoms. Studies using 1H/13C Nuclear Magnetic Resonance (NMR) spectroscopy reveal increased de novo synthesis of glutamine in the brain in acute liver failure (ALF) but increases of synthesis rates per se do not correlate with either the severity of encephalopathy or brain edema. Skeletal muscle becomes primarily responsible for removal of excess ammonia in liver failure and in UCDs, an adaptation that results from a post-translational induction of the glutamine synthetase (GS) gene. The importance of muscle in ammonia removal in hyperammonemia accounts for the resurgence of interest in maintaining adequate dietary protein and the use of agents aimed at the stimulation of muscle GS. Alternative or additional metabolic and regulatory pathways that impact on brain glutamine homeostasis in hyperammonemia include (i) glutamine deamination by the two isoforms of glutaminase, (ii) glutamine transamination leading to the production of the putative neurotoxin alpha-ketoglutaramate and (iii) alterations of high affinity astrocytic glutamine transporters (SNATs). Findings of reduced expression of the glutamine transporter SNAT-5 (responsible for glutamine clearance from the astrocyte) in ALF raise the possibility of "glutamine trapping" within these cells. Such a trapping mechanism could contribute to cytotoxic brain edema and to the imbalance between excitatory and inhibitory neurotransmission in this disorder. PMID:25034052

Butterworth, Roger F

2014-01-01

279

The Curious Question of Exercise-Induced Pulmonary Edema  

PubMed Central

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

2011-01-01

280

Avascular necrosis and bone marrow edema syndrome.  

PubMed

MR imaging is the most accurate modality for the diagnosis of AVN, bone marrow edema syndrome, and femoral head insufficiency fractures. When the particular demographics of the patient are considered, the specificity of this examination is high. The reported success rates of joint-sparing operative intervention are variable. When compared with conservative management, the outcome of joint-sparing operative intervention in patients who have early (stage I, II) AVN lesions is improved. This is impetus for screening programs for patients who are known to be at high risk for AVN, such as patients who have undergone renal transplants and others who are on long-term, high-dose corticosteroid treatment. There is strong evidence that bone marrow edema syndrome (TO) is a distinct entity with demonstrable unique histopathology and well-defined demographics. Increased spatial resolution revealed typical subchondral findings of AVN in lesions that were once believed to represent irreversible TO. SIF of the femoral head is a new concept with a seemingly distinct population and with clinical presentation and imaging characteristics that should permit its differentiation from AVN. PMID:15049532

Watson, Rohan M; Roach, Neil A; Dalinka, Murray K

2004-01-01

281

New Compton densitometer for measuring pulmonary edema  

SciTech Connect

Pulmonary edema is the pathological increase of extravascular lung water found most often in patients with congestive heart failure and other critically ill patients who suffer from intravenous fluid overload. A non-invasive lung density monitor that is accurate, easily portable, safe and inexpensive is needed for clinical evaluation of pulmonary edema. Other researchers who have employed Compton scattering techniques generally used systems of extended size and detectors with poor energy resolution. This has resulted in significant systematic biases from multiply-scattered photons and larger errors in counting statistics at a given radiation dose to the patient. We are proposing a patented approach in which only backscattered photons are measured with a high-resolution HPGe detector in a compact system geometry. By proper design and a unique data extraction scheme, effects of the variable chest wall on lung density measurements are minimized. Preliminary test results indicate that with a radioactive source of under 30 GBq, it should be possible to make an accurate lung density measurement in one minute, with a risk of radiation exposure to the patient a thousand times smaller than that from a typical chest x-ray. The ability to make safe, frequent lung density measurements could be very helpful for monitoring the course of P.E. at the hospital bedside or outpatient clinics, and for evaluating the efficacy of therapy in clinical research. 6 refs., 5 figs.

Loo, B.W.; Goulding, F.S.; Simon, D.S.

1985-10-01

282

Objectification of the severity of Reinke's edema.  

PubMed

According to the severity, Reinke's edema (RE) of the vocal folds can be divided into three stages as classified by Yonekawa. We evaluated open and closed quotients of vocal folds vibratory cycles using Videostrobokymography (VSK) in a cohort of patients with RE. Parameters were measured from the anterior, medial and posterior third of the vocal folds. Mean values from RE group were OQ (0.44; 0.46; 0.52); CQ (0.56; 0.54; 0.48). Results from the whole glottis OQ and CQ in RE were: OQ=0.48 and CQ=0.52. Significant differences were found for OQ and CQ mean values as well as values measured from each third of the glottis between the control group and patients with RE. In the first Yonekawa group no statistically significant differences were found compared to the control group, but there were significant differences in the remaining two groups. The correlation between the stage of edema on the Yonekawa classification and the mean values of OQ and CQ was 70%. PMID:25173824

Szkie?kowska, Agata; Mia?kiewicz, Beata; Krasnod?bska, Paulina; Skar?y?ski, Henryk

2014-01-01

283

[Pulmonary edemas due to acute heroin poisoning].  

PubMed

Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics. PMID:9875

Francois, G; Faizende, J; Reboul, J

1975-01-01

284

Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates  

EPA Science Inventory

Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

285

Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism  

PubMed Central

Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. PMID:24451134

Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

2014-01-01

286

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the  

E-print Network

in the healthy elderly April J. Hoa,1 , Jason L. Steina,1 , Xue Huaa , Suh Leea , Derrek P. Hibara , Alex D structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly not attrib- utable to differences in cholesterol levels, hypertension, or the vol- ume of white matter

Thompson, Paul

287

Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke  

PubMed Central

Pathological conditions in the central nervous system, including stroke and trauma, are often exacerbated by cerebral edema. We recently identified a nonselective cation channel, the NCCa-ATP channel, in ischemic astrocytes that is regulated by sulfonylurea receptor 1 (SUR1), is opened by depletion of ATP and, when opened, causes cytotoxic edema. Here, we evaluated involvement of this channel in rodent models of stroke. SUR1 protein and mRNA were newly expressed in ischemic neurons, astrocytes and capillaries. Upregulation of SUR1 was linked to activation of the transcription factor Sp1 and was associated with expression of functional NCCa-ATP but not KATP channels. Block of SUR1 with low-dose glibenclamide reduced cerebral edema, infarct volume and mortality by 50%, with the reduction in infarct volume being associated with cortical sparing. Our findings indicate that the NCCa-ATP channel is crucially involved in development of cerebral edema, and that targeting SUR1 may provide a new therapeutic approach to stroke. PMID:16550187

Simard, J Marc; Chen, Mingkui; Tarasov, Kirill V; Bhatta, Sergei; Ivanova, Svetlana; Melnitchenko, Ludmila; Tsymbalyuk, Natalya; West, G Alexander; Gerzanich, Volodymyr

2009-01-01

288

Cost-Effectiveness of Treatment of Diabetic Macular Edema  

PubMed Central

Background Macular edema is the most common cause of visual loss among patients with diabetes. Objective To determine the cost-effectiveness of different treatments of diabetic macular edema (DME). Design Markov model. Data Sources Published literature and expert opinion. Target Population Patients with clinically significant DME. Time Horizon Lifetime. Perspective Societal. Intervention Laser treatment, intraocular injections of triamcinolone or a vascular endothelial growth factor (VEGF) inhibitor, or a combination of both. Outcome Measures Discounted costs, gains in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis All treatments except laser monotherapy substantially reduced costs, and all treatments except triamcinolone monotherapy increased QALYs. Laser treatment plus a VEGF inhibitor achieved the greatest benefit, gaining 0.56 QALYs at a cost of $6975 for an ICER of $12 410 per QALY compared with laser treatment plus triamcinolone. Monotherapy with a VEGF inhibitor achieved similar outcomes to combination therapy with laser treatment plus a VEGF inhibitor. Laser monotherapy and triamcinolone monotherapy were less effective and more costly than combination therapy. Results of Sensitivity Analysis VEGF inhibitor monotherapy was sometimes preferred over laser treatment plus a VEGF inhibitor, depending on the reduction in quality of life with loss of visual acuity. When the VEGF inhibitor bevacizumab was as effective as ranibizumab, it was preferable to because of its lower cost. Limitation Long-term outcome data for treated and untreated diseases are limited. Conclusion The most effective treatment of DME is VEGF inhibitor injections with or without laser treatment. This therapy compares favorably with cost-effective interventions for other conditions. Primary Funding Source Agency for Healthcare Research and Quality. PMID:24573663

Pershing, Suzann; Enns, Eva A.; Matesic, Brian; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.

2014-01-01

289

Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage  

Microsoft Academic Search

Intracerebral infusion of lysed erythrocytes causes brain edema without inducing ischemic cerebral blood flow. Reports have indicated that oxidative damage contributes to secondary brain injury in stroke. In the present study, we investigated whether erythrocyte lysis after intracerebral hemorrhage (ICH) might result in oxidative brain damage. This study had four parts. Male Sprague–Dawley rats received an infusion of autologous lysed

Jimin Wu; Ya Hua; Richard F Keep; Timothy Schallert; Julian T Hoff; Guohua Xi

2002-01-01

290

Pediatric cerebral stroke: susceptibility-weighted imaging may predict post-ischemic malignant edema.  

PubMed

Susceptibility-weighted imaging (SWI) is an advanced MRI technique providing information on the blood oxygenation level. Deoxyhemoglobin is increased in hypoperfused tissue characterized by SWI-hypointensity, while high oxyhemoglobin concentration within hyperperfused tissue results in a SWI iso- or hyperintensity compared to healthy brain tissue. We describe a child with a stroke, where SWI in addition to excluding hemorrhage and delineating the thrombus proved invaluable in determining regions of hyperperfusion or luxury perfusion, which contributed further to the prognosis including an increased risk of developing post-ischemic malignant edema. PMID:24199819

Bosemani, Thangamadhan; Poretti, Andrea; Orman, Gunes; Meoded, Avner; Huisman, Thierry A G M

2013-10-01

291

Noncardiac Pulmonary Edema induced by Sitagliptin Treatment  

PubMed Central

A 74-year-old male patient with type 2 diabetes mellitus admitted to the emergency department with the complaints of progressive breathlessness, dry cough, and swollen lower extremities. Our patient had type 2 diabetes mellitus and hypertension for 3 years. His HbA1c was not within the target range so sitagliptin was added to on-going therapy. After 1 week of starting sitagliptin therapy, even though the patient had not heart failure he applied to the emergency department with a complaint of dyspnea. The cardiovascular safety and efficacy of many anti-hyperglycemic agents such as sitagliptin, saxagliptin are unclear. Our case has shown that dipeptidyl peptidase 4 inhibitors may cause pulmonary edema. Hence, it should be used with cautious, especially in patients with heart failure.

Belice, Tahir; Yuce, Suleyman; Kizilkaya, Bayram; Kurt, Aysel; Cure, Erkan

2014-01-01

292

Massive vulvar edema in 2 prepartum dairy cows  

PubMed Central

Two late gestation Holstein cows about to begin the third lactation developed massive vulvar edema. These were the only affected animals in the herd of 500 milking cows. The vulvar edema spontaneously regressed postpartum for both cows. Massive vulvar swelling is seldom observed in dairy cows in advanced pregnancy and is not described in the literature. PMID:24790232

Cheong, Soon Hon; Gilbert, Robert O.

2014-01-01

293

Oxygen-deficient metabolism and corneal edema  

PubMed Central

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

Leung, B.K.; Bonanno, J.A.; Radke, C.J.

2014-01-01

294

[ 123I] ?-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa  

Microsoft Academic Search

Background: Impaired serotonin transmission has been implicated in the pathophysiology of eating disorders. We investigated the in vivo availability of brain serotonin transporters and dopamine transporters in bulimia nervosa patients.Methods: Approximately 24 hours after injection of [123I]-2?-carbomethoxy-3?-(4-iodophenyl)tropane ([123I] ?-CIT), single photon emission computed tomography scans were performed in 10 medication-free, female bulimic patients and 10 age-matched, healthy females. For quantification

Johannes Tauscher; Walter Pirker; Matthäus Willeit; Martina de Zwaan; Ursula Bailer; Alexander Neumeister; Susanne Asenbaum; Claudia Lennkh; Nicole Praschak-Rieder; Thomas Brücke; Siegfried Kasper

2001-01-01

295

Cannabinoid receptor agonists reduce the short-term mitochondrial dysfunction and oxidative stress linked to excitotoxicity in the rat brain.  

PubMed

The endocannabinoid system (ECS) is involved in a considerable number of physiological processes in the Central Nervous System. Recently, a modulatory role of cannabinoid receptors (CBr) and CBr agonists on the reduction of the N-methyl-d-aspartate receptor (NMDAr) activation has been demonstrated. Quinolinic acid (QUIN), an endogenous analog of glutamate and excitotoxic metabolite produced in the kynurenine pathway (KP), selectively activates NMDAr and has been shown to participate in different neurodegenerative disorders. Since the early pattern of toxicity exerted by this metabolite is relevant to explain the extent of damage that it can produce in the brain, in this work we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) and other agonists (anandamide or AEA, and CP 55,940 or CP) on early markers of QUIN-induced toxicity in rat striatal cultured cells and rat brain synaptosomes. WIN, AEA and CP exerted protective effects on the QUIN-induced loss of cell viability. WIN also preserved the immunofluorescent signals for neurons and CBr labeling that were decreased by QUIN. The QUIN-induced early mitochondrial dysfunction, lipid peroxidation and reactive oxygen species (ROS) formation were also partially or completely prevented by WIN pretreatment, but not when this CBr agonist was added simultaneously with QUIN to brain synaptosomes. These findings support a neuroprotective and modulatory role of cannabinoids in the early toxic events elicited by agents inducing excitotoxic processes. PMID:25446347

Rangel-López, E; Colín-González, A L; Paz-Loyola, A L; Pinzón, E; Torres, I; Serratos, I N; Castellanos, P; Wajner, M; Souza, D O; Santamaría, A

2015-01-29

296

The cysteine protease inhibitor, E64d, reduces brain amyloid-? and improves memory deficits in Alzheimer’s disease animal models by inhibiting cathepsin B, but not BACE1, ?-secretase activity  

PubMed Central

The cysteine protease cathepsin B is a potential drug target for reducing brain amyloid-? peptides (A?) and improving memory in Alzheimer’s disease (AD), because reduction of cathepsin B in transgenic mice expressing human wild-type amyloid-? protein precursor (A?PP) results in significantly decreased brain A?. Cathepsin B cleaves the wild-type ?-secretase site sequence in A?PP to produce A? and cathepsin B inhibitors administered to animal models expressing A?PP containing the wild-type ?-secretase site sequence reduce brain A? in a manner consistent with ?-secretase inhibition. But such inhibitors could act either by direct inhibition of cathepsin B ?-secretase activity or by off-target inhibition of the other ?-secretase, the aspartyl protease BACE1. To evaluate that issue, we orally administered a cysteine protease inhibitor, E64d, to normal guinea pigs or transgenic mice expressing human A?PP, both of which express the human wild-type ?-secretase site sequence. In guinea pigs, oral E64d administration caused a dose-dependent reduction of up to 92% in brain, CSF and plasma of A?(40) and A?(42), a reduction of up to 50% in the C-terminal ?-secretase fragment (CTF?), and a 91% reduction in brain cathepsin B activity but increased brain BACE1 activity by 20%. In transgenic AD mice, oral E64d administration improved memory deficits and reduced brain A?(40) and A?(42), amyloid plaque, brain CTF?, and brain cathepsin B activity but increased brain BACE1 activity. We conclude that E64d likely reduces brain A? by inhibiting cathepsin B and not BACE1 ?-secretase activity and that E64d therefore may have potential for treating AD patients. PMID:21613740

Hook, Gregory; Hook, Vivian; Kindy, Mark

2015-01-01

297

Comparison of diffusion-weighted with T2-weighted imaging for detection of edema in acute myocardial infarction  

PubMed Central

Background Recent studies, performed with the use of a commercially available diffusion weighted imaging (DWI) sequence, showed that they are sensitive to the increase of water content in the myocardium and may be used as an alternative to the standard T2-weighted sequences. The aim of this study was to compare two methods of myocardial edema imaging: DWI and T2-TIRM. Methods The study included 91 acute and post STEMI patients. We applied a qualitative and quantitative image analysis. The qualitative analysis consisted of evaluation of the quality of blood suppression, presence of artifacts and occurrence of high signal (edema) areas. On the basis of edema detection in AMI and control (post STEMI) group, the sensitivity and specificity of TIRM and DWI were determined. Two contrast to noise ratios (CNR) were calculated: CNR1 - the contrast between edema and healthy myocardium and CNR2 - the contrast between edema and intraventricular blood pool. The area of edema was measured for both TIRM and DWI sequences and compared with the infarct size in LGE images. Results Edema occurred more frequently in the DWI sequence. A major difference was observed in the inferior wall, where an edema-high signal was observed in 46% in T2-TIRM, whereas in the DWI sequence in 85%. An analysis of the image quality parameters showed that the use of DWI sequence allows complete blood signal suppression in the left ventricular cavity and reduces the occurrence of motion artifacts. However, it is connected with a higher incidence of magnetic susceptibility artifacts and image distortion. An analysis of the CNRs showed that CNR1 in T2-TIRM sequence depends on the infarct location and has the lowest value for the inferior wall. The area of edema measured on DWI images was significantly larger than in T2-TIRM. Conclusions DWI is a new technique for edema detection in patients with acute myocardial infarction which may be recommended for the diagnosis of acute injuries, especially in patients with slow-flow artifacts in TIRM images. PMID:24098944

2013-01-01

298

Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer  

ClinicalTrials.gov

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal

2014-04-21

299

History of mild traumatic brain injury is associated with deficits in relational memory, reduced hippocampal volume, and less neural activity later in life  

PubMed Central

Evidence suggests that a history of head trauma is associated with memory deficits later in life. The majority of previous research has focused on moderate-to-severe traumatic brain injury (TBI), but recent evidence suggests that even a mild TBI (mTBI) can interact with the aging process and produce reductions in memory performance. This study examined the association of mTBI with memory and the brain by comparing young and middle-aged adults who have had mTBI in their recent (several years ago) and remote (several decades ago) past, respectively, with control subjects on a face-scene relational memory paradigm while they underwent functional magnetic resonance imaging (fMRI). Hippocampal volumes were also examined from high-resolution structural images. Results indicated middle-aged adults with a head injury in their remote past had impaired memory compared to gender, age, and education matched control participants, consistent with previous results in the study of memory, aging, and TBI. The present findings extended previous results by demonstrating that these individuals also had smaller bilateral hippocampi, and had reduced neural activity during memory performance in cortical regions important for memory retrieval. These results indicate that a history of mTBI may be one of the many factors that negatively influence cognitive and brain health in aging. PMID:23986698

Monti, Jim M.; Voss, Michelle W.; Pence, Ari; McAuley, Edward; Kramer, Arthur F.; Cohen, Neal J.

2013-01-01

300

Early methyl donor deficiency may induce persistent brain defects by reducing Stat3 signaling targeted by miR-124  

PubMed Central

The methyl donors folate (vitamin B9) and vitamin B12 are centrepieces of the one-carbon metabolism that has a key role in transmethylation reactions, and thus in epigenetic and epigenomic regulations. Low dietary intakes of folate and vitamin B12 are frequent, especially in pregnant women and in the elderly, and deficiency constitutes a risk factor for various diseases, including neurological and developmental disorders. In this respect, both vitamins are essential for normal brain development, and have a role in neuroplasticity and in the maintenance of neuronal integrity. The consequences of a methyl donor deficiency (MDD) were studied both in vivo in rats exposed in utero, and in vitro in hippocampal progenitors (H19-7 cell line). Deficiency was associated with growth retardation at embryonic day 20 (E20) and postnatally with long-term brain defects in selective areas. mRNA and protein levels of the transcription factor Stat3 were found to be decreased in the brains of deprived fetuses and in differentiating progenitors (62 and 48% for total Stat3 protein, respectively), along with a strong reduction in its phosphorylation at both Tyr705 and Ser727 residues. Vitamin shortage also affected upstream kinases of Stat3 signaling pathway (phospho-Erk1/2, phospho-Src, phospho-JNK, and phospho-p38) as well as downstream target gene products (Bcl-2 and Bcl-xL), thus promoting apoptosis. Conversely, the expression of the Stat3 regulator miR-124 was upregulated in deficiency conditions (?65%), and its silencing by using siRNA partly restored Stat3 signaling in hippocampal neurons by increasing specifically the phosphorylation of Erk1/2 and Src kinases. Furthermore, miR-124 siRNA improved the phenotype of deprived cells, with enhanced neurite outgrowth. Taken together, our data suggest that downregulation of Stat3 signaling by miR-124 would be a key factor in the deleterious effects of MDD on brain development. PMID:23928694

Kerek, R; Geoffroy, A; Bison, A; Martin, N; Akchiche, N; Pourié, G; Helle, D; Guéant, J-L; Bossenmeyer-Pourié, C; Daval, J-L

2013-01-01

301

Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targetting and results in a verotoxin 1-like disease in pigs  

PubMed Central

All members of the verotoxin (VT) family specifically recognize globo- series glycolipids on the surface of susceptible cells. Those toxins that are associated with human disease, VT1, VT2, and VT2c, bind to globotriaosyl ceramide (Gb3) while VT2e, which is associated with edema disease of swine, binds preferentially to globotetraosyl ceramide (Gb4). We were recently able to identify, using site-directed mutagenesis, amino acids in the binding subunit of these toxins that are important in defining their glycosphingolipid (GSL) binding specificity (Tyrrell, G. J., K. Ramotar, B. Boyd, B. W. Toye, C. A. Lingwood, and J. L. Brunton. 1992. Proc. Natl. Acad. Sci. USA. 89:524). The concomitant mutation of Gln64 and Lys66 in the VT2e binding subunit to the corresponding residues (Glu and Gln, respectively) found in VT2 effectively converted the GSL binding specificity of the mutant toxin from Gb4 to Gb3 in vitro. We now report that the altered carbohydrate recognition of the mutant toxin (termed GT3) has biological significance, resulting in a unique disease after intravascular injection into pigs as compared with classical VT2e-induced edema disease. The tissue localization of radiolabeled GT3 after intravascular injection was elevated in neural tissues compared with VT2e accumulation, while localization of GT3 to the gastrointestinal tract was relatively reduced. Accordingly, the pathological lesions after challenge with GT3 involved gross edema of the cerebrum, cerebellum, and brain stem, while purified VT2e caused hemorrhage and edema of the cerebellum, and submucosa of the stomach and large intestine. In addition, both radiolabeled toxins bound extensively to tissues not directly involved in the pathology of disease. VT2e, unlike GT3 or VT1, bound extensively to red cells, which have high levels of Gb4. The overall tissue distribution of VT2e was thus found to be influenced by regional blood flow to each organ and not solely by the Gb4 levels of these tissues. Conversely, the distribution of GT3 (and VT1), which cleared more rapidly from the circulation, correlated with respective tissue Gb3 levels rather than blood flow. These studies indicate the primary role of carbohydrate binding specificity in determining systemic pathology, suggest that the red cells act as a toxin carrier in edema disease, and indicate that red cell binding does not protect against the pathology of systemic verotoxemia. PMID:8496689

1993-01-01

302

A Data-Driven Method to Reduce the Impact of Region Size on Degree Metrics in Voxel-Wise Functional Brain Networks  

PubMed Central

Degree, which is the number of connections incident upon a node, measures the relative importance of the node within a network. By computing degree metrics in voxel-wise functional brain networks, many studies performed high-resolution mapping of brain network hubs using resting-state functional magnetic resonance imaging. Despite its extensive applications, defining nodes as voxels without considering the different sizes of brain regions may result in a network where the degree cannot accurately represent the importance of nodes. In this study, we designed a data-driven method to reduce this impact of the region size in degree metrics by (1) disregarding all self-connections among voxels within the same region and (2) regulating connections from voxels of other regions by the sizes of those regions. The modified method that we proposed allowed direct evaluation of the impact of the region size, showing that traditional degree metrics overestimated the degree of previous identified hubs in humans, including the visual cortex, precuneus/posterior cingulate cortex, and posterior parietal cortex, and underestimated the degree of regions including the insular cortex, anterior cingulate cortex, parahippocampus, sensory and motor cortex, and supplementary motor area. However, the locations of prominent hubs were stable even after correcting the impact. These findings were robust under different connectivity thresholds, degree metrics, data-preprocessing procedures, and datasets. In addition, our modified method improved test–retest reliability of degree metrics as well as the sensitivity in group-statistic comparisons. As a promising new tool, our method may reveal network properties that better represent true brain architecture without compromising its data-driven advantage. PMID:25352826

Liu, Cirong; Tian, Xiaoguang

2014-01-01

303

Extremely Low Frequency Magnetic Field (50 Hz, 0.5 mT) Reduces Oxidative Stress in the Brain of Gerbils Submitted to Global Cerebral Ischemia  

PubMed Central

Magnetic field as ecological factor has influence on all living beings. The aim of this study was to determine if extremely low frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) affects oxidative stress in the brain of gerbils submitted to 10-min global cerebral ischemia. After occlusion of both carotid arteries, 3-month-old gerbils were continuously exposed to ELF-MF for 7 days. Nitric oxide and superoxide anion production, superoxide dismutase activity and index of lipid peroxidation were examined in the forebrain cortex, striatum and hippocampus on the 7th (immediate effect of ELF-MF) and 14th day after reperfusion (delayed effect of ELF-MF). Ischemia per se increased oxidative stress in the brain on the 7th and 14th day after reperfusion. ELF-MF also increased oxidative stress, but to a greater extent than ischemia, only immediately after cessation of exposure. Ischemic gerbils exposed to ELF-MF had increased oxidative stress parameters on the 7th day after reperfusion, but to a lesser extent than ischemic or ELF-MF-exposed animals. On the 14th day after reperfusion, oxidative stress parameters in the brain of these gerbils were mostly at the control levels. Applied ELF-MF decreases oxidative stress induced by global cerebral ischemia and thereby reduces possible negative consequences which free radical species could have in the brain. The results presented here indicate a beneficial effect of ELF-MF (50 Hz, 0.5 mT) in the model of global cerebral ischemia. PMID:24586442

Rauš Balind, Snežana; Selakovi?, Vesna; Radenovi?, Lidija; Proli?, Zlatko; Jana?, Branka

2014-01-01

304

Painless transient bone marrow edema syndrome in a pediatric patient.  

PubMed

Transient regional migratory osteoporosis, considered to be part of the spectrum of bone marrow edema syndrome, is a rare condition with an unknown etiology. Patients usually present with lower extremity pain, most commonly in the 4th-5th decades of life. We describe a 15-year-old male patient with type 1 Gaucher disease who presented with transient bone marrow edema syndrome with features most closely resembling regional migratory osteoporosis. The patient presented with bone marrow edema of the lateral tibial epiphysis of his right knee that was incidentally seen on routine surveillance MRI that was performed as protocol for patients with type 1 Gaucher disease on enzyme replacement therapy. At this time, the patient had no pain and physical examination was normal. Follow-up MRI of the right knee 4 months afterward showed complete resolution of the signal abnormality in the right tibial epiphysis, and repeat study 8 months later displayed a new focus of painless migratory edema of the medial tibial epiphysis of the same knee. These changes completely resolved as well. Marrow signal abnormalities in children with Gaucher disease can have a broad differential, including infection, marrow infiltration, trauma, osteonecrosis, and bone marrow edema syndrome, amongst others. Correct diagnosis of bone marrow edema syndrome is critical, as this disease process most often resolves on conservative measures. The unusual presentation of transient bone marrow edema syndrome with regional migratory osteoporosis features in a young patient with Gaucher disease is described. PMID:24893724

Joshi, Vivek; Hermann, George; Balwani, Manisha; Simpson, William L

2014-11-01

305

Different expressions of AQP1, AQP4, eNOS, and VEGF proteins in ischemic versus non-ischemic cerebropathy in rats: potential roles of AQP1 and eNOS in hydrocephalic and vasogenic edema formation.  

PubMed

In this study, expressions of aquaporin (AQP) 1, AQP4, endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor in blood-cerebrospinal fluid (CSF) barrier and blood-brain barrier (BBB) are examined in rat choroid plexus and peri-infarcted hippocampal formation (HF) following systemic hyponatremia (SH) and permanent middle cerebral artery occlusion (pMCAO). These events are thought to cause the development of hydrocephalic and vasogenic edemas. The importance of CSF overproduction and intact blood-CSF barrier during hydrocephalic edema formation is demonstrated by the high expression of AQP1 (329.86±10.2%, n=4 , P<0.01) and trapped plasma immunoglobulin G (IgG) in choroid plexus epithelium after 24 hours of SH. However, the increased eNOS expression in peri-infarcted HF (130±3%, n=4, P<0.01) and extravasation of plasma IgG into the extravascular compartment after 24 hours of pMCAO suggest that increased microvascular permeability, probably due to elevated levels of nitric oxide, leads to development of vasogenic brain edema via BBB breakdown. Based on these findings, the authors suggest that modulation of different protein expression, dependent on the type of brain edema, is required for primary (pMCAO) and secondary (SH) brain injuries to attenuate brain edema and neuronal degeneration. PMID:22254158

Kim, Jaehyun; Jung, Yongwook

2011-12-01

306

Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: Possible involvement of TLR4/NF-?B-mediated inflammatory pathway.  

PubMed

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes. Hence, effective therapeutic strategies targeting on EBI have recently become a major goal in the treatment of SAH patients. Baicalein is a flavonoid that has been shown to offer neuroprotection in kinds of brain injury models. This study investigated the effects of baicalein on EBI in rats following SAH. SAH was inducted in male Sprauge-Dawley rats by injection of fresh non-heparinized arterial blood into the prechiasmatic cistern. Baicalein (30 or 100mg/kg) or vehicle were administrated 30min after injury. Neurological deficit, brain edema, blood-brain barrier (BBB) permeability and neural cell apoptosis were assessed. To explore the further mechanisms, the change of toll-like receptor 4 (TLR4) and nuclear factor-?B (NF-?B) signaling pathway and the levels of apoptosis associated proteins were also examined. Our study showed that treatment with baicalein (30mg/kg) significantly improved neurological function at 24h after SAH and reduced brain edema at both 24h and 72h after SAH. Baicalein also significantly reduced neural cell death, BBB permeability. These changes were associated with the remarkable reductions of TLR4 expression, I?B-? degradation, NF-?B translocation to nucleus, as well as the expressions of matrix metalloproteinase-9, tight junctions protein, interleukin-1? and tumor necrosis factor- ?. These findings suggest that baicalein may ameliorate EBI after SAH potentially via inhibition of inflammation-related pathway. PMID:25451085

Wang, Chun-Xi; Xie, Guang-Bin; Zhou, Chen-Hui; Zhang, Xiang-Sheng; Li, Tao; Xu, Jian-Guo; Li, Ning; Ding, Ke; Hang, Chun-Hua; Shi, Ji-Xin; Zhou, Meng-Liang

2015-01-12

307

Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia.  

PubMed

Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine] or mGluR1 antagonist LY367385 by intraperitoneal injection at 3 h after PT decreased brain infarct volume evaluated one day after ischaemia. Additive effects on infarct volume were observed upon co-injection with MPEP and LY367385. These antagonists also significantly alleviated neurodegeneration and apoptosis in the penumbra. In addition, when evaluated 2 weeks after PT, they reduced infarct volume and tissue loss, attenuated glial scar formation, and inhibited cell proliferation in the penumbra. Importantly, co-injection with MPEP and LY367385 reduced the expression levels of calpain, a Ca2+-activated protease known to mediate ischaemia-induced neuronal death. Injection of calpeptin, a calpain inhibitor, could inhibit neuronal death and brain damage after PT but injection of calpeptin together with MPEP and LY367385 did not further improve the protective effects mediated by MPEP and LY367385. These results suggest that inhibition of group I mGluRs is sufficient to protect ischaemic damage through the calpain pathway. Taken together, our results demonstrate that inhibition of group I mGluRs can mitigate PT-induced brain damage through attenuating the effects of calpain, and improve long-term histological outcomes. PMID:23772679

Li, Hailong; Zhang, Nannan; Sun, Grace; Ding, Shinghua

2013-01-01

308

Fibroblast Growth Factor-19 Action in the Brain Reduces Food Intake and Body Weight and Improves Glucose Tolerance in Male Rats  

PubMed Central

Fibroblast growth factor-19 (FGF19) and its rodent ortholog, FGF15, are hormones produced in the distal small intestine and secreted into the circulation after a meal. In addition to controlling the enterohepatic circulation of bile acids, FGF15/19 also regulates systemic lipid and glucose metabolism. In these experiments we investigated the hypothesis that, like other gut-derived postprandial hormones, FGF15/19 can act in the central nervous system to elicit its metabolic effects. We found that FGF-receptors 1 and 4 are present in rat hypothalamus, and that their expression was reduced by up to 60% in high-fat fed rats relative to lean controls. Consistent with a potential role for brain FGF15/19 signaling to regulate energy and glucose homeostasis, and with a previous report that intracerebroventricular (i.c.v.) administration of FGF19 increases energy expenditure, we report that acute i.c.v. FGF19 reduces 24-h food intake and body weight, and acutely improves glucose tolerance. Conversely, i.c.v. administration of an FGF-receptor inhibitor increases food intake and impairs glucose tolerance, suggesting a physiological role for brain FGF receptor signaling. Together, these findings identify the central nervous system as a potentially important target for the beneficial effects of FGF19 in the treatment of obesity and diabetes. PMID:23183168

Kohli, Rohit; Gutierrez-Aguilar, Ruth; Gaitonde, Shrawan G.; Woods, Stephen C.; Seeley, Randy J.

2013-01-01

309

Economic Considerations of Macular Edema Therapies  

PubMed Central

Purpose To relate costs and treatment benefits for macular edema due to diabetes (DME) and branch and central retinal vein occlusion (BRVO, CRVO). Design A model of resource utilization, outcomes, and cost effectiveness and utility. Participants none Methods Results from published clinical trials (index studies) of laser, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and vitrectomy trials were used to ascertain visual benefit and clinical protocols. Calculations followed from the costs of one year of treatment for each treatment modality and the visual benefits as ascertained. Main Outcome measures Visual acuity (VA) saved, cost of therapy, cost per line saved, cost per line-year saved, and costs per quality adjusted life years (QALYs). Results The lines saved for DME (0.26 to 2.02), BRVO (0.74 to 4.92), and CRVO (1.2 to 3.75) yielded calculations of costs/line of saved VA for DME ($1329 to 11609), BRVO ($494 to 13039), and CRVO ($704 to 7611), costs/line-year for DME ($60 to 561), BRVO ($25 to 754), and CRVO ($45 to 473), and costs/QALY of $824 to $25566. Conclusion Relative costs and benefits should be considered in perspective when applying and developing treatment strategies. PMID:21507488

Smiddy, William E.

2012-01-01

310

[Intestinal edema caused by ingested formalin].  

PubMed

A 65-yr-old man treated for depression was transferred to our hospital. He ingested over 150 ml of formalin for suicidal attempt. On admission, he was hypotensive, developing acute renal failure and liver dysfunction. During first 36 hours, he needed 21 l of lactate Ringer solutions to maintain enough urination. The abdominal computed tomography showed obvious edema of intestine and endoscopic findings of the upper digestive tract were corrosive erosions. We started proton pump inhibiter on the first day. After a week, they changed in many ulcers with smooth-surfaced elevation on the greater curvature of the stomach. On the 15th hospitalized day, he was discharged from our hospital without sequelae. Formalin consists of forty percent solution of formaldehyde and methanol. Ingestion of formaldehyde may cause burning in the digestive systems and harmful effect to major organ such as kidney or liver. Although previous reports said that formalin has direct toxicity to major organs, we could discharge him without sequelae by treatment with large amount of fluid resuscitation. PMID:14740567

Shimizu, Keiki; Sugita, Manabu; Yokote, Ryo; Sekii, Hajime; Miyake, Yasufumi; Kiyota, Kazuya

2003-10-01

311

A clinical overview of bone marrow edema.  

PubMed

Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities, which are often characterized by pain as their main symptom, but show significant differences in terms of histopathological findings, causal mechanisms and prognosis. Bone marrow lesions in the subchondral bone of subjects with knee osteoarthritis (OA) seem to be associated with pain and progression of cartilage damage over time. Some histopathological studies of advanced OA have shown a prevalent fibrosis and bone marrow necrosis. BME of the subchondral bone in rheumatoid arthritis is associated with an infiltrate of inflammatory cells and osteoclasts and has a predictive value of further development of erosions. In spondyloarthritis, BME of the sacroiliac joints identifies an active sacroiliitis and is associated with histological inflammation and radiographic progression, whereas the relationship between BME lesions of the spine and syndesmophyte development is still controversial. BME syndromes (BMES), such as transient osteoporosis of the hip, regional migratory osteoporosis, and transient post-traumatic BMES, are characterized by a BME pattern on MRI and a self-limiting course. The potential evolution of BMES toward osteonecrosis is still controversial. PMID:25069499

Manara, M; Varenna, M

2014-01-01

312

Role of mouthguards in reducing mild traumatic brain injury/concussion incidence in high school football athletes.  

PubMed

There is continued speculation on the value of mouthguards (MGs) in preventing mild traumatic brain injury (MTBI)/concussion injuries. The purpose of this randomized prospective study was to compare the impact of pressure-laminated (LM), custom-made, properly fitted MGs to over-the-counter (OTC) MGs on the MTBI/concussion incidence in high school football athletes over a season of play. Four hundred twelve players from 6 high school football teams were included in the study. Twenty-four MTBI/concussion injuries (5.8%) were recorded. When examining the MTBI/concussion injury rate by MG type, there was a significant difference (P = 0.0423) with incidence rates of 3.6% and 8.3% in the LM MG and OTC MG groups, respectively. PMID:24784512

Winters, Jackson; DeMont, Richard

2014-01-01

313

[The suppressive effect of melilotus extract on the thermal edema of rats].  

PubMed

The effect of melilotus extract (ME) and Esberiven (ES) which contain coumarin on the thermal edema, which is one of high protein edema, was evaluated by both quantitative and qualitative assays. The intraperitoneal injection of ME immediately after burn greatly reduced the amount of swelling and effectively inhibited the occurrence of necrosis and induration in the injured leg-skin as compared with the saline controls in which a 3rd degree of thermal injury was observed. Administration of ES also induced a similar suppressive effect. Furthermore, either intraperitoneal or subcutaneous local injection of ME 4 hr before burn was effective in reducing the edema and thermal injury. No increase of the lymph flow and output of lymphocytes and protein from the thoracic duct lymph was observed in thermally injured rats given an injection of ME. The massive infiltration of neutrophils and macrophages 6 to 24 hr after the subcutaneous injection of ME was histologically observed in the dermal lesion of normal rats. Twenty-four hr later, macrophages, fibroblasts, and lymphocytes became predominant. The present data taken together suggest that ME exerts the suppressive effect on thermal injury by either prior or post administration, and these effects might be induced in an indirect manner, through the action of phagocytic cells accumulated in the injured lesion, not via lymphatic drainages of excess fluid and protein. PMID:6862319

Nishikawa, M; Yamashita, A; Ando, K; Mitsuhiro, S

1983-03-01

314

Bilateral upper lobe pulmonary edema during gynecologic laparoscopic surgery in the Trendelenberg position -A case report-.  

PubMed

A 25-year-old woman was diagnosed with a ruptured ectopic pregnancy. During laparoscopic surgery, the patient was in the Trendelenberg position (20° degrees). Massive froth in the endotracheal tube was observed at the end of surgery. A portable chest x-ray, checked at the end of the operation, showed diffuse haziness in both upper lung fields. After one hour of aggressive treatment with drugs and positive mechanical ventilation, the amount of froth in the endotracheal tube was reduced considerably. Considering the symptom and radiologic findings, we concluded that diffuse bilateral upper lung field haziness was due to atypical pulmonary edema. We speculated that the rapid improvement of pulmonary edema was due to redistribution of fluid to the lowest part of lung by immediate reversing the patient's Trendelenberg position, along with aggressive treatment. PMID:21286430

Shim, Jae-Hang; Shin, Woo Jong; Lee, Sang Hoon

2010-12-01

315

Anthrax Lethal and Edema Toxins Fail to Directly Impair Human Platelet Function  

PubMed Central

Hemorrhage is a prominent clinical manifestation of systemic anthrax. Therefore, we have examined the effects of anthrax lethal and edema toxins on human platelets. We find that anthrax lethal toxin fails to cleave its target, mitogen-activated protein kinase 1, and anthrax edema toxin fails to increase intracellular cyclic adenosine monophosphate. Surface expression of toxin receptors tumor endothelial marker 8 and capillary morphogenesis gene 2, as well as coreceptor low density lipoprotein receptor-related protein 6 (LRP6), are markedly reduced, preventing toxin binding to platelets. Our studies suggest that the hemorrhagic clinical manifestations of systemic anthrax are unlikely to be caused by the direct binding and entry of anthrax toxins into human platelets. PMID:22158563

Chauncey, Kassidy M.; Szarowicz, Sarah E.; Sidhu, Gurjit S.; During, Russell L.

2012-01-01

316

IMAGING OF PULMONARY EDEMA WITH ELECTRICAL IMPEDANCE TOMOGRAPHY  

E-print Network

IMAGING OF PULMONARY EDEMA WITH ELECTRICAL IMPEDANCE TOMOGRAPHY Andy ADLER , Yves BERTHIAUME=?J - Electrical Impedance Tomography (EIT) uses electrical measurements at electrodes placed on the thorax Electrical Impedance Tomography (EIT) is an imaging technique which calculates the electrical conductivity

Adler, Andy

317

Anti-VEGF for the Management of Diabetic Macular Edema  

PubMed Central

Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME. PMID:24741610

Stefanini, Francisco Rosa; Badaró, Emmerson; Falabella, Paulo; Koss, Michael; Farah, Michel Eid; Maia, Maurício

2014-01-01

318

Local fluid shifts and edema in humans during simulated microgravity  

NASA Technical Reports Server (NTRS)

Local fluid shifts and edema in humans during simulated microgravity is studied. Recent results and significance and future plans on the following research topics are discussed: mechanisms of headward edema formation during head-down tilt; postural responses of head and foot microcirculations and their sensitivity to bed rest; and transcapillary fluid transport associated with lower body negative pressure (LBNP) with and without saline ingestion.

Hargens, Alan R.

1991-01-01

319

Angioneurotic edema: a rare case of hypersensitivity to metoclopramide  

PubMed Central

The case of a 30-year-old woman who had already experienced two incidents of angioneurotic edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found. PMID:24278059

Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

2013-01-01

320

Negative pressure pulmonary edema after acute upper airway obstruction  

Microsoft Academic Search

Study Objectives: To review the clinical characteristics and the pathogenesis of negative pressure pulmonary edema, and to determine its incidence in surgical patients.Design: Retrospective case-report study.Setting: Operating room, postanesthesia care unit and surgical intensive care of a teaching hospital.Patients: 30 surgical adult ASA physical status I, II, III, IV, and V patients who suffered from negative pressure pulmonary edema during

Krishnaprasad Deepika; Charbel A. Kenaan; Alex M. Barrocas; Janett J. Fonseca; George B. Bikazi

1997-01-01

321

Acute, transient hemorrhagic hypotension does not aggravate structural damage or neurologic motor deficits but delays the long-term cognitive recovery following mild to moderate traumatic brain injury  

PubMed Central

Objectives Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury. Design Experimental prospective, randomized study in rodents. Setting Experimental laboratory at a university hospital. Subjects One hundred nineteen male Sprague-Dawley rats weighing 350-385 g. Interventions Experimental traumatic brain injury of mild to moderate severity was induced using the lateral fluid percussion brain injury model in anesthetized rats (n = 89). Following traumatic brain injury, in surviving animals one group of animals was subjected to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently either resuscitated with lactated Ringer’s solution (three times shed blood volume, n = 18) or left uncompensated (n = 29). Other groups of animals included those with isolated traumatic brain injury (n = 34), those with isolated hemorrhagic hypotension (n = 8), and sham-injured control animals receiving anesthesia and surgery alone (n = 22). Measurements and Main Results The withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood pressure by 50% without decreasing arterial oxygen saturation or Pao2. Brain injury induced significant cerebral edema (p < .001) in vulnerable brain regions and cortical tissue loss (p < .01) compared with sham-injured animals. Neither regional brain edema formation at 24 hrs postinjury nor the extent of cortical tissue loss assessed at 7 days postinjury was significantly aggravated by superimposed hemorrhagic hypotension. Brain injury-induced neurologic deficits persisted up to 20 wks after injury and were also not aggravated by the hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks postinjury. The superimposition of hemorrhagic hypotension significantly delayed the time course of cognitive recovery. Conclusions A single, acute hypotensive event lasting 30 mins did not aggravate the short- and long-term structural and motor deficits but delayed the speed of recovery of cognitive function associated with experimental traumatic brain injury. PMID:16424733

Schütz, Christian; Stover, John F.; Thompson, Hilaire J.; Hoover, Rachel C.; Morales, Diego M.; Schouten, Joost W.; McMillan, Asenia; Soltesz, Kristie; Motta, Melissa; Spangler, Zachery; Neugebauer, Edmund; McIntosh, Tracy K.

2008-01-01

322

In aging, the vulnerability of rat brain mitochondria is enhanced due to reduced level of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) and subsequently increased permeability transition in brain mitochondria in old animals.  

PubMed

Aging is accompanied by progressive dysfunction of mitochondria associated with a continuous decrease of their capacity to produce ATP. Mitochondria isolated from brain of aged animals show an increased mitochondrial permeability transition pore (mPTP) opening. We recently detected new regulators of mPTP function in brain mitochondria, the enzyme 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and its substrates 2', 3'-cAMP and 2', 3'-cNADP, and the neuronal protein p42(IP4). Here, we compared parameters of mPTP opening in non-synaptic brain mitochondria isolated from young and old rats. In mitochondria from old rats (>18 months), mPTP opening occurred at a lower threshold of Ca(2+) concentration than in mitochondria from young rats (<3 months). mPTP opening in mitochondria from old rats was accelerated by 2', 3'-cAMP, which further lowered the threshold Ca(2+) concentration. In non-synaptic mitochondria from old rats, the CNP level was decreased by 34%. Lowering of the CNP level in non-synaptic mitochondria with aging was accompanied by decreased levels of voltage-dependent anion channel (VDAC; by 69%) and of p42(IP4) (by 59%). Thus, reduced levels of CNP in mitochondria could lead to a rise in the concentration of the mPTP promoter 2', 3'-cAMP. The level of CNP and p42(IP4) and, probably VDAC, might be essential for myelination and electrical activity of axons. We propose that in aging the reduction in the level of these proteins leads to mitochondrial dysfunction, in particular, to a decreased threshold Ca(2+) concentration to induce mPTP opening. This might represent initial steps of age-related mitochondrial dysfunction, resulting in myelin and axonal pathology. PMID:25277077

Krestinina, Olga; Azarashvili, Tamara; Baburina, Yulia; Galvita, Anastasia; Grachev, Dmitry; Stricker, Rolf; Reiser, Georg

2015-01-01

323

Human platelets modulate edema formation in isolated rabbit lungs.  

PubMed Central

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products. PMID:2527253

Heffner, J E; Cook, J A; Halushka, P V

1989-01-01

324

Acute repeated intracerebroventricular injections of angiotensin II reduce agonist and antagonist radioligand binding in the paraventricular nucleus of the hypothalamus and median preoptic nucleus in the rat brain.  

PubMed

Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To test this hypothesis, we examined the binding of a radiolabeled agonist ((125)I-sarcosine(1) Ang II) and a radiolabeled antagonist ((125)I-sarcosine(1), isoleucine(8) Ang II) in brain homogenates and tissue sections prepared from rats given repeated injections of Ang II or vehicle. Although no treatment-related differences were found in hypothalamic homogenates, a focus on specific brain structures using receptor autoradiography, found that the desensitization treatment reduced binding of both radioligands in the paraventricular nucleus of the hypothalamus (PVN) and median preoptic nucleus (MnPO), but not in the subfornical organ (SFO). Because G protein coupling is reported to have a selective effect on agonist binding without affecting antagonist binding, these findings do not support a G protein uncoupling treatment effect. This suggests that receptor number is more critical to the water intake response than the saline intake response, or that pathways downstream from the G protein mediate desensitization of the water intake response. PMID:25108041

Speth, Robert C; Vento, Peter J; Carrera, Eduardo J; Gonzalez-Reily, Luz; Linares, Andrea; Santos, Kira; Swindle, Jamala D; Daniels, Derek

2014-10-01

325

beta Adrenergic Receptors in Aged Rat Brain: Reduced Number and Capacity of Pineal Gland to Develop Supersensitivity  

Microsoft Academic Search

The density but not the affinity of beta -adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be

Louise H. Greenberg; Benjamin Weiss

1978-01-01

326

Reduced Levels of NR1 and NR2A with Depression-Like Behavior in Different Brain Regions in Prenatally Stressed Juvenile Offspring  

PubMed Central

Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes. Juvenile rats repeatedly exposed to prenatal stress (PS) exhibit behavioral features often observed in neuropsychiatric disorders including depression. However, to date the underlying neurological mechanisms are still unclear. In the current study, juvenile offspring rats whose mothers were exposed to PS were evaluated for depression-related behaviors in open field and sucrose preference test. NMDA receptor subunits NR1 and NR2A in the hippocampus, frontal cortex and striatum were assayed by western blotting. The results indicated that PS resulted in several behavioral anomalies in the OFT and sucrose preference test. Moreover, reduced levels of NMDA receptor subunits NR1 and NR2A in the hippocampus, and NR1 in prefrontal cortex and striatum of prenatally stressed juvenile offspring were found. Treatment with MK-801 to pregnant dams could prevent all those changes in the juvenile offspring. Collectivity, these data support the argument that PS to pregnant dams could induce depression-like behavior, which may be involved with abnormal expression of NR1 and NR2A in specific brain regions, and MK-801 may have antidepressant-like effects on the juvenile offspring. PMID:24278457

Sun, Hongli; Guan, Lixia; Zhu, Zhongliang; Li, Hui

2013-01-01

327

Protective effects of dl-3n-butylphthalide against diffuse brain injury  

PubMed Central

Dl-3n-butylphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. Dl-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es-timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier age and cerebral edema. PMID:25206572

Zhao, Yaning; Li, Jianmin; Zhang, Pan; Chen, Changxiang; Li, Shuxing

2013-01-01

328

Protective effects of dl-3n-butylphthalide against diffuse brain injury.  

PubMed

Dl-3n-butylphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. Dl-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es-timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier age and cerebral edema. PMID:25206572

Zhao, Yaning; Li, Jianmin; Zhang, Pan; Chen, Changxiang; Li, Shuxing

2013-10-01

329

Effectiveness of extracorporeal shock wave therapy in bone marrow edema syndrome of the hip.  

PubMed

There is no gold standard for treatment of bone marrow edema syndrome of the hip (BMESH). Usually, treatment is conservative, owing to the favorable and self limiting prognosis. In musculoskeletal disorders, the effectiveness of extracorporeal shock wave therapy (ESWT) has been widely recognized and recent research supports its use in the treatment of the first stages of avascular osteonecrosis of the proximal femur and in other conditions where bone marrow edema is present. On this basis, we performed a prospective study to evaluate the effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH. Twenty consecutive symptomatic patients underwent two treatments of high-energy ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up at mean 15.52 ± 1.91 months. Patients underwent magnetic resonance imaging of the hip and were evaluated according to the Harris hip score. The mean improvement in HHS over the course of the study was of 58.5 ± 14.9 points (p < 0.0001), and the mean edema area reduced from 981.9 ± 453.2 mm(2) pre-treatment to 107.8 ± 248.1 mm(2) at 6 months. ESWT seems to be a powerful, non-pharmacological tool that produces rapid pain relief and functional improvement and aids the normalization of the vascular and metabolic impairments which characterize BMESH. PMID:24658812

d'Agostino, Cristina; Romeo, Pietro; Lavanga, Vito; Pisani, Salvatore; Sansone, Valerio

2014-11-01

330

High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment  

PubMed Central

High altitude pulmonary edema (HAPE) is a noncardiogenic pulmonary edema which typically occurs in lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. Early symptoms of HAPE include a nonproductive cough, dyspnoea on exertion and reduced exercise performance. Later, dyspnoea occurs at rest. Clinical features are cyanosis, tachycardia, tachypnoea and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields. HAPE mainly occurs due to exaggerated hypoxic pulmonary vasoconstriction and elevated pulmonary artery pressure. It has been observed that HAPE is a high permeability type of edema occurring also due to leaks in the capillary wall (‘stress failure’). Slow descent is the most effective method for prevention; in addition, graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise are the key to preventing HAPE. Treatment of HAPE consists of immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent. PMID:23580834

Paralikar, Swapnil J.

2012-01-01

331

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.  

PubMed

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. PMID:23800689

Chen, Jing; Mo, Yiqun; Schlueter, Connie F; Hoyle, Gary W

2013-10-15

332

Periodic lateralized epileptiform discharges (PLEDs) in cerebral lupus correlated with white-matter lesions in brain MRI and reduced cerebral blood flow in SPECT.  

PubMed

This is a case report on an uncommon correlation between periodic lateralized epileptiform discharges (PLEDs) and white-matter lesions in cerebral lupus, and with a reduced cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). A 47-year-old woman with a long-term history of systemic lupus erythematosus (SLE) presented with a seizure followed by frontal lobe dysfunction clinically. An electroencephalogram (EEG) showed bilateral independent PLEDs in the frontal region. A magnetic resonance image of the brain showed white-matter changes in the frontal periventricular region. Cerebral angiogram did not reveal any evidence of vasculitis. A cerebral SPECT with tracer injected during the EEG showing PLEDs showed a reduction in CBF in the frontal regions. Clinical recovery was observed with intravenous immunoglobulin. This case shows that PLEDs can be seen with white-matter changes in SLE. PMID:23358870

Aye, S M M; Lim, K S; Ramli, N M; Tan, C T

2013-04-01

333

Selective antegrade cerebral perfusion reduces brain injury following deep hypothermic circulatory arrest in the piglets’ model by decreasing the levels of protein SUMO2/3-ylation  

PubMed Central

Selective antegrade cerebral perfusion (SACP), which was adopted by many surgical groups for complex neonatal cardiac surgery, especially aortic arch repair, is a proven adjunct for neuroprotection during deep hypothermic circulatory arrest (DHCA). Several recent studies suggest that SUMO2/3 modification of proteins is markedly activated during deep hypothermia and believed to be an endogenous neuroprotective stress response. Here, we report that SACP reduces the increasing degree of SUMO2/3 conjugation following DHCA. Piglets were subjected to 1 h SACP and/or 1 h DHCA. DHCA was sufficient to markedly increase in protein SUMOylation by SUMO2/3 both in the hippocampus and cerebral cortex. SACP, especially at flow rate of 50 ml/kg/min, reduces the increasing degree of SUMO2/3 conjugation and also reduces levels of pro-apoptotic factors, Bax and Caspase 3, and increases levels of antiapoptotic factors, Bcl-2, following DHCA both in the hippocampus and cerebral cortex. This suggests that SACP at flow rate of 50 ml/kg/min is more appropriate for neuroprotection during DHCA in the pig model and level of protein SUMO2/3-ylation maybe an indicator of the degree of brain injury. PMID:25550987

Li, Bin; Zhu, Yaobin; Liu, Aijun; Lu, Wei; Su, Junwu; Zhang, Jing; Li, Zhiqiang; Fan, Xiangming; Liu, Yinglong

2014-01-01

334

Brain, Behavior, and Immunity: Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors  

Cancer.gov

Brain, Behavior, and Immunity 30 (2013) S109–S116 Contents lists available at SciVerse ScienceDirect Brain, Behavior, and Immunity j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y b r b i Reduced hippocampal volume

335

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide  

SciTech Connect

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

2013-10-15

336

Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors  

PubMed Central

Cerebral edema is a serious side effect of malignant stroke. On average 70,000 patients are diagnosed with malignant cerebral edema every year, of those patients, approximately 60-80% results in fatalities. The treatment of cerebral edema includes multimodality approaches. In this article, we discuss our experience with glibenclamide in the treatment for malignant cerebral edema. Our study indicates that glibenclamide may decrease cerebral edema by blocking SUR1 receptors in ischemic stroke and non-ischemic etiologies. PMID:25422710

Ahmed, Iftekhar

2014-01-01

337

Factors Affecting Reading Speed in Patients with Diabetic Macular Edema Treated with Laser Photocoagulation  

PubMed Central

Purpose To study the factors that may affect reading speed in patients with diabetic macular edema previously treated with laser photocoagulation. Methods Consecutive patients with type II diabetes treated with laser photocoagulation for diabetic macular edema (DME) at least twelve months previously, with best corrected visual acuity of better than 65 letters (approximately 20/40) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts were included in this study. Patients previously treated with pan-retinal photocoagulation, vitrectomy, intravitreal steroid or anti-VEGF therapy were excluded. Any other ocular co-morbidities that may influence reading ability such as cataract, glaucoma or macular degeneration were also excluded. All patients were refracted by a certified examiner, the following measurements were collected: best corrected visual acuity (BCVA), contrast sensitivity with Pelli-Robson chart, reading speed with MNREAD chart, microperimetry with Nidek MP1, and central subfield thickness with Zeiss spectral domain optical coherent topography. Results The slow reading group had poorer contrast sensitivity (p?=?0.001), reduced retinal sensitivity (p?=?0.027) and less stable fixation (p?=?0.013). Most interestingly the reduced retinal sensitivity findings were driven by the microperimetry value on the right subfield (p?=?0.033), (nasal to the fovea in the right eye and temporal to the fovea in the left eye). Multiple linear regression analysis showed that contrast sensitivity is probably the most important factor that affects reading speed (p?=?0.001). Conclusion Reduced retinal sensitivity after laser treatment is associated with reduced reading speed in patients with diabetic macular edema. PMID:25265280

Pearce, Elizabeth; Sivaprasad, Sobha; Chong, Ngaihang V.

2014-01-01

338

Ginsenoside Rbeta1 reduces neurologic damage, is anti-apoptotic, and down-regulates p53 and BAX in subarachnoid hemorrhage.  

PubMed

Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent. PMID:20353383

Li, Yingbo; Tang, Jiping; Khatibi, Nikan H; Zhu, Mei; Chen, Di; Zheng, Weiping; Wang, Shali

2010-05-01

339

Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage  

PubMed Central

Background Endothelin-1 (ET-1) is a potent vasoconstrictor, and astrocytic ET-1 is reported to play a role in the pathogenesis of cerebral ischemic injury and cytotoxic edema. However, it is still unknown whether astrocytic ET-1 also contributes to vasogenic edema and vasospasm during subarachnoid hemorrhage (SAH). In the present study, transgenic mice with astrocytic endothelin-1 over-expression (GET-1 mice) were used to investigate the pathophysiological role of ET-1 in SAH pathogenesis. Results The GET-1 mice experienced a higher mortality rate and significantly more severe neurological deficits, blood–brain barrier breakdown and vasogenic edema compared to the non-transgenic (Ntg) mice following SAH. Oral administration of vasopressin V1a receptor antagonist, SR 49059, significantly reduced the cerebral water content in the GET-1 mice. Furthermore, the GET-1 mice showed significantly more pronounced middle cerebral arterial (MCA) constriction after SAH. Immunocytochemical analysis showed that the calcium-activated potassium channels and the phospho-eNOS were significantly downregulated, whereas PKC-? expression was significantly upregulated in the MCA of the GET-1 mice when compared to Ntg mice after SAH. Administration of ABT-627 (ETA receptor antagonist) significantly down-regulated PKC-? expression in the MCA of the GET-1 mice following SAH. Conclusions The present study suggests that astrocytic ET-1 involves in SAH-induced cerebral injury, edema and vasospasm, through ETA receptor and PKC-mediated potassium channel dysfunction. Administration of ABT-627 (ETA receptor antagonist) and SR 49059 (vasopressin V1a receptor antagonist) resulted in amelioration of edema and vasospasm in mice following SAH. These data provide a strong rationale to investigate SR 49059 and ABT-627 as therapeutic drugs for the treatment of SAH patients. PMID:24156724

2013-01-01

340

Nonlethal aluminum maltolate can reduce brain-derived neurotrophic factor-induced Arc expression through interrupting the ERK signaling in SH-SY5Y neuroblastoma cells.  

PubMed

Although many studies have demonstrated that aluminum (Al) exposure impairs learning and memory, its underlying mechanism is still uncertain. Long-lasting forms of synaptic plasticity that underlie memory are dependent on new protein synthesis. In particular, activity-regulated cytoskeleton-associated protein (Arc) has a versatile role in synaptic plasticity, and its synthesis can be induced by brain-derived neurotrophic factor (BDNF). BDNF-induced Arc expression has been suggested to play a fundamental role in the stabilization of synaptic plasticity. In the present study, the pretreatment of Al(malt)? at nonlethal level (200 ?M, 24 h) significantly reduced BDNF (10 ng/ml, 1h)-induced Arc expression in SH-SY5Y human neuroblastoma cells. BDNF-induced activation of ERK but not PI3K signaling pathway was interfered with the Al(malt)? pretreatment, resulting in the subsequent reduction of BDNF-induced phosphorylation of 4EBP1, p70S6K, and eIF4E. Reduced phospho-4EBP1 and phospho-eIF4E hindered the initiation step of translation, which may lead to a reduction in BDNF-induced Arc expression. However, reduced phospho-p70S6K did not influence the phosphorylation of eEF2K and eEF2, indicating no significant effect on BDNF-enhanced translation elongation. Therefore, even at nonlethal level, Al(malt)? pretreatment reduced BDNF-induced Arc expression, which was caused by interrupting the ERK signaling pathway as well as the subsequent translation initiation. PMID:21040763

Chen, Tsan-Ju; Cheng, Hsiu-Min; Wang, Dean-Chuan; Hung, Hui-Shan

2011-01-15

341

Edema can be a handicap in treatment of anorexia nervosa.  

PubMed

Anorexia and bulimia nervosa are common in western civilized countries. They are among the psychiatric disorders in that they are often accompanied by a variety of life-threatening physical abnormalities. These patients need a close follow-up of the pediatrician in collaboration with the psychiatrist since the changes in bodily functions affect the psychiatric therapy. The challenge to the physician is to use the traditional tools of medicine to diagnose and treat these physical abnormalities using careful medical history, a complete physical examination and appropriate laboratory testing. Peripheral edema is seen as a physical finding in anorexia nervosa (AN) and it is not rare. The estimated frequency is up to 20% among adolescent patients. Peripheral edema in this setting can be easily confused as weight gain. There are five possible mechanisms for its occurrence: hypoproteinemia, electrolyte imbalance, hormonal changes, rapid refeedings, and abuse of laxative, diuretics and diet pills. Patients with eating disorders may ingest a large number of drugs in an attempt to control their weight. We present a case of a female adolescent with AN and peripheral edema who terminated her psychiatric treatment during the refeeding phase because of the unbearable anxiety caused by this edema that affected her body image dramatically. With this case study, we point out the importance of assessing peripheral edema and discriminating it from true weight gain. PMID:20196395

Derman, Orhan; Kiliç, Emine Zinnur

2009-01-01

342

Photoacoustic diagnosis of edema in rat burned skin  

NASA Astrophysics Data System (ADS)

Diagnosis of edema, abnormal accumulation of water in tissue, is important for managing various traumatic injuries and diseases. However, there is no established method for real-time, noninvasive monitoring of edema. In severe extensive burn injuries, edema develops both topically and systemically due to the increased permeability of blood vessels. In this study, we examined photoacoustic (PA) monitoring of edema formed in rat burn models. Deep dermal burn with a 20% total body surface area was made in the dorsal skin of rats. Burn and its adjacent nonburn tissues were irradiated with 6-ns light pulses at 1430 nm, which is one of the absorption peak wavelengths of water in the near infrared. The PA signal amplitude increased until 12 - 24 hr postburn, and thereafter it gradually decreased to its initial level; the latter phase (after 24 hr postburn) coincided with a diuretic phase in the rats. There was a significant correlation between the PA signal amplitudes and water contents in the tissue measured by wet/dry weight method. These findings demonstrate the validity of PA measurement for real-time, noninvasive monitoring of edema.

Yoshida, Ken; Sato, Shunichi; Hatanaka, Kosuke; Saitoh, Daizoh; Ashida, Hiroshi; Sakamoto, Toshihisa; Obara, Minoru

2010-02-01

343

Adipose-derived mesenchymal stem cells reduce neuronal death after transient global cerebral ischemia through prevention of blood-brain barrier disruption and endothelial damage.  

PubMed

Global cerebral ischemia (GCI) is the leading cause of a poor prognosis even after successful resuscitation from cardiac arrest. Therapeutic induction of hypothermia (TH) is the only proven therapy-and current standard care-for GCI after cardiac arrest; however, its application has been significantly limited owing to technical difficulties. Mesenchymal stem cells (MSCs) are known to suppress neuronal death after cerebral ischemia. The prevention of blood-brain barrier (BBB) disruption has not been suggested as a mechanism of MSC treatment but has for TH. We evaluated the therapeutic effect of MSC administration on BBB disruption and neutrophil infiltration after GCI. To evaluate the therapeutic effects of MSC treatment, rats were subjected to 7 minutes of transient GCI and treated with MSCs immediately after reperfusion. Hippocampal neuronal death was evaluated at 7 days after ischemia using Fluoro-Jade B (FJB). BBB disruption, endothelial damage, and neutrophil infiltration were evaluated at 7 days after ischemia by immunostaining for IgG leakage, Rat endothelial antigen-1, and myeloperoxidase (MPO). Rats treated with MSCs showed a significantly reduced FJB(+) neuron count compared with the control group. They also showed reduced IgG leakage, endothelial damage, and MPO(+) cell counts. The present study demonstrated that administration of MSCs after transient GCI provides a dramatic protective effect against hippocampal neuronal death. We hypothesized that the neuroprotective effects of MSC treatment might be associated with the prevention of BBB disruption and endothelial damage and a decrease in neutrophil infiltration. PMID:25548390

Chung, Tae Nyoung; Kim, Jin Hee; Choi, Bo Young; Chung, Sung Phil; Kwon, Sung Won; Suh, Sang Won

2015-02-01

344

Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage  

PubMed Central

T-lymphocytes promote cerebral inflammation, thus aggravating neuronal injury after stroke. Fingolimod, a sphingosine 1-phosphate receptor analog, prevents the egress of lymphocytes from primary and secondary lymphoid organs. Based on these findings, we hypothesized fingolimod treatment would reduce the number of T-lymphocytes migrating into the brain, thereby ameliorating cerebral inflammation following experimental intracerebral hemorrhage (ICH). We investigated the effects of fingolimod in two well-established murine models of ICH, implementing intrastriatal infusions of either bacterial collagenase (cICH) or autologous blood (bICH). Furthermore, we tested the long term neurological improvements by Fingolimod in a collagenase-induced rat model of ICH. Fingolimod, in contrast to vehicle administration alone, improved neurological functions and reduced brain edema at 24 and 72 hours following experimental ICH in CD-1 mice (n=103; p<0.05). Significantly fewer lymphocytes were found in blood and brain samples of treated animals when compared to the vehicle group (p<0.05). Moreover, fingolimod treatment significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1), interferon-? (INF-?), and interleukin-17 (IL-17) in the mouse brain at 72 hours post-cICH (p<0.05 compared to vehicle). Long-term neurocognitive performance and histopathological analysis were evaluated in Sprague-Dawley rats between 8 and 10 weeks post-cICH (n=28). Treated rats showed reduced spatial and motor learning deficits, along with significantly reduced brain atrophy and neuronal cell loss within the basal ganglia (p<0.05 compared to vehicle). We conclude that fingolimod treatment ameliorated cerebral inflammation, at least to some extent, by reducing the availability and subsequent brain infiltration of T-lymphocytes, which improved the short and long-term sequelae after experimental ICH in rodents. PMID:23261767

Rolland, William B.; Lekic, Tim; Krafft, Paul R.; Hasegawa, Yu; Altay, Orhan; Hartman, Richard; Ostrowski, Robert; Manaenko, Anatol; Tang, Jiping; Zhang, John H.

2013-01-01

345

Link between D sub 1 and D sub 2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain  

SciTech Connect

Dopamine receptor types D{sub 1} and D{sub 2} can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D{sub 1}-D{sub 2} interaction in homogenized tissue as revealed by ligand binding. D{sub 2} agonists lowered the binding of ({sup 3}H)raclopride to D{sub 2} receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D{sub 1}-selective antagonist SCH 23390 prevented the agonist-induced decrease in ({sup 3}H)raclopride binding to D{sub 2} sites in the striatum but not in the anterior pituitary, which has no D{sub 1} receptors. Conversely, a dopamine-induced reduction in the binding of ({sup 3}H)SCH 23390 to D{sub 1} receptors could be prevented by the D{sub 2}-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D{sub 1}-D{sub 2} interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D{sub 2} receptors in the high-affinity state. Thus, the D{sub 1}-D{sub 2} link may be mediated by guanine nucleotide-binding protein components. The link may underlie D{sub 1}-D{sub 2} interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.

Seeman, P.; Niznik, H.B.; Guan, H.C.; Booth, G.; Ulpian, C. (Univ. of Toronto (Canada))

1989-12-01

346

Effects of Cold and Compression on Edema.  

ERIC Educational Resources Information Center

Investigation of ways to treat artificially induced acute inflammatory reactions in human tissue found that neither cooling or pressure alone reduced the swelling, while a combination of the two methods produced a significant reduction in swelling. (Author/CB)

Sloan, J. P.; And Others

1988-01-01

347

Amlodipine, enalapril, and dependent leg edema in essential hypertension.  

PubMed

Calcium channel blockers (CCBs) blunt postural skin vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. To evaluate the dose-response relation between this pharmacological interference and dependent edema, a frequent side effect of CCBs during antihypertensive treatment, skin blood flow (laser Doppler flowmetry) at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, and leg weight (Archimedes principle) were measured at baseline, during increasing doses of the dihydropyridine amlodipine (5 and 10 mg UID each for 2 weeks), and after drug withdrawal in 10 hypertensive men. Because angiotensin-converting enzyme inhibitors may attenuate ankle swelling by CCBs, those parameters were evaluated according to a similar design during amlodipine (10 mg UID) and enalapril (20 mg UID) combined (n=10). As a control, the effect of enalapril monotherapy (10 and 20 mg UID for 2 weeks each) was evaluated in a third series of patients (n=8). Amlodipine (5 mg UID) increased leg weight without modifying postural vasoconstriction (the percent skin blood flow decrease from horizontal to dependent position), which indicates that extravascular fluid shift was independent of postural skin vasoconstriction. At 10 mg UID, however, amlodipine blunted postural vasoconstriction and increased leg weight further, which suggests that skin blood flow autoregulation limited additional fluid transfer. Both parameters normalized after drug withdrawal. Enalapril per se did not affect cutaneous vasomotion or leg weight but reduced the amount of dependent fluid extravasation by the CCB despite a persistent antagonism for postural vasoconstrictor responses. PMID:10679507

Pedrinelli, R; Dell'Omo, G; Melillo, E; Mariani, M

2000-02-01

348

Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?  

PubMed Central

Background Both active and passive tobacco smoke (TS) potentially impair the vascular endothelial function in a causative and dose-dependent manner, largely related to the content of reactive oxygen species (ROS), nicotine, and pro-inflammatory activity. Together these factors can compromise the restrictive properties of the blood–brain barrier (BBB) and trigger the pathogenesis/progression of several neurological disorders including silent cerebral infarction, stroke, multiple sclerosis and Alzheimer’s disease. Based on these premises, we analyzed and assessed the toxic impact of smoke extract from a range of tobacco products (with varying levels of nicotine) on brain microvascular endothelial cell line (hCMEC/D3), a well characterized human BBB model. Results Initial profiling of TS showed a significant release of reactive oxygen (ROS) and reactive nitrogen species (RNS) in full flavor, nicotine-free (NF, “reduced-exposure” brand) and ultralow nicotine products. This release correlated with increased oxidative cell damage. In parallel, membrane expression of endothelial tight junction proteins ZO-1 and occludin were significantly down-regulated suggesting the impairment of barrier function. Expression of VE-cadherin and claudin-5 were also increased by the ultralow or nicotine free tobacco smoke extract. TS extract from these cigarettes also induced an inflammatory response in BBB ECs as demonstrated by increased IL-6 and MMP-2 levels and up-regulation of vascular adhesion molecules, such as VCAM-1 and PECAM-1. Conclusions In summary, our results indicate that NF and ultralow nicotine cigarettes are potentially more harmful to the BBB endothelium than regular tobacco products. In addition, this study demonstrates that the TS-induced toxicity at BBB ECs is strongly correlated to the TAR and NO levels in the cigarettes rather than the nicotine content. PMID:24755281

2014-01-01

349

Exendin-4 reduces ischemic brain injury in normal and aged type 2 diabetic mice and promotes microglial M2 polarization.  

PubMed

Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed. Finally, the cellular mechanisms behind the efficacy of Exendin-4 have been only partially studied. The main objective of this study was to determine the neuroprotective efficacy of Exendin-4 in normal and aged type 2 diabetic mice if the treatment started after stroke in a clinically relevant setting. Furthermore we characterized the Exendin-4 effects on stroke-induced neuroinflammation. Two-month-old healthy and 14-month-old type 2 diabetic/obese mice were subjected to middle cerebral artery occlusion. 5 or 50 µg/kg Exendin-4 was administered intraperitoneally at 1.5, 3 or 4.5 hours thereafter. The treatment was continued (0.2 µg/kg/day) for 1 week. The neuroprotective efficacy was assessed by stroke volume measurement and stereological counting of NeuN-positive neurons. Neuroinflammation was determined by gene expression analysis of M1/M2 microglia subtypes and pro-inflammatory cytokines. We show neuroprotective efficacy of 50 µg/kg Exendin-4 at 1.5 and 3 hours after stroke in both young healthy and aged diabetic/obese mice. The 5 µg/kg dose was neuroprotective at 1.5 hour only. Proinflammatory markers and M1 phenotype were not impacted by Exendin-4 treatment while M2 markers were significantly up regulated. Our results support the use of Exendin-4 to reduce stroke-damage in the prehospital/early hospitalization setting irrespectively of age/diabetes. The results indicate the polarization of microglia/macrophages towards the M2 reparative phenotype as a potential mechanism of neuroprotection. PMID:25101679

Darsalia, Vladimer; Hua, Sansan; Larsson, Martin; Mallard, Carina; Nathanson, David; Nyström, Thomas; Sjöholm, Åke; Johansson, Maria E; Patrone, Cesare

2014-01-01

350

Inflammatory optic disc edema due to Sarcoidosis mimicking malignant hypertension.  

PubMed

A common ocular manifestation of sarcoidosis is anterior uveitis. Posterior uveitis is uncommon and optic disc edema is rare. We report one such case in which the initial presentation was mimicking malignant hypertension as the patient had a recent record of high blood pressure. However, the painful progressive vision loss due to optic disc edema, along with anterior uveitis, and histological proof of non-caseating granulomas on transbronchial lung biopsy clinched the diagnosis of ocular sarcoidosis. There was complete resolution of signs and symptoms with institution of steroids. There was also probable cardiac involvement. This case highlights the fact that all disc edemas in a diabetic and hypertensive patients is not just due to malignant hypertension, even if there is a recent history of elevated blood pressure. PMID:25351429

Sharma, Aman; Sagar, Vinay; Singla, Veenu; Sharma, Kusum; Singh, Ramandeep; Singh, Surjit; Gupta, Amod

2014-10-28

351

Kawasaki Disease with Retropharyngeal Edema following a Blackfly Bite  

PubMed Central

We describe a patient with Kawasaki disease (KD) and retropharyngeal edema following a blackfly bite. An 8-year-old boy was referred to our hospital because of a 3-day-history of fever and left neck swelling and redness after a blackfly bite. Computed tomography of the neck revealed left cervical lymph nodes swelling with edema, increased density of the adjacent subcutaneous tissue layer, and low density of the retropharyngeum. The patient was initially presumed to have cervical cellulitis, lymphadenitis, and retropharyngeal abscess. He was administered antibiotics intravenously, which did not improve his condition. The patient subsequently exhibited other signs of KD and was diagnosed with KD and retropharyngeal edema. Intravenous immunoglobulin therapy and oral flurbiprofen completely resolved the symptoms and signs. A blackfly bite sometimes incites a systemic reaction in humans due to a hypersensitive reaction to salivary secretions, which may have contributed to the development of KD in our patient. PMID:25349761

Watanabe, Toru

2014-01-01

352

Epiretinal macular edema associated with thick epiretinal membranes.  

PubMed

High-resolution imaging with spectral-domain optical coherence tomography has identified an unusual group of epiretinal membranes (ERMs) in the presence of lamellar macular holes. These ERMs are unusually thick. The authors present the case of a patient with age-related macular degeneration who developed edema within a thickened ERM in both eyes after cataract surgery. The edema resolved with anti-vascular endothelial growth factor (VEGF) therapy. The authors propose that the VEGF-responsive fluid within these thick ERMs arose from fibrovascular tissue derived from the retina. Further studies with histopathology will be required to determine whether neovascular tissue is present in all cases of thickened ERMs with epiretinal edema. PMID:24044720

Doshi, Rishi R; Lowrance, Matthew D; Kim, Brian T; Davis, Janet L; Rosenfeld, Philip J

2013-01-01

353

Pathophysiological Response to Experimental Diffuse Brain Trauma Differs as a Function of Developmental Age  

Microsoft Academic Search

The purpose of experimental models of traumatic brain injury (TBI) is to reproduce selected aspects of human head injury such as brain edema, contusion or concussion, and functional deficits, among others. As the immature brain may be particularly vulnerable to injury during critical periods of development, and pediatric TBI may cause neurobehavioral deficits, our aim was to develop and characterize

Ibolja Cernak; Taeun Chang; Farid A. Ahmed; Maria I. Cruz; Robert Vink; Bogdan Stoica; Alan I. Faden

2010-01-01

354

Enhancement of subsurface brain shift model accuracy: a preliminary Ishita Garga  

E-print Network

recently which allow for uncertainty yet still capture the first order effects associated with brain the procedure for modeling the dural septa and study the effect of those membranes on subsurface brain shift-rigid deformation of brain tissue caused by gravity, edema, hyperosmotic drugs administered prior to surgery

Miga, Michael I.

355

Brain investigation and brain conceptualization  

PubMed Central

Summary The brain of a patient with Alzheimer’s disease (AD) undergoes changes starting many years before the development of the first clinical symptoms. The recent availability of large prospective datasets makes it possible to create sophisticated brain models of healthy subjects and patients with AD, showing pathophysiological changes occurring over time. However, these models are still inadequate; representations are mainly single-scale and they do not account for the complexity and interdependence of brain changes. Brain changes in AD patients occur at different levels and for different reasons: at the molecular level, changes are due to amyloid deposition; at cellular level, to loss of neuron synapses, and at tissue level, to connectivity disruption. All cause extensive atrophy of the whole brain organ. Initiatives aiming to model the whole human brain have been launched in Europe and the US with the goal of reducing the burden of brain diseases. In this work, we describe a new approach to earlier diagnosis based on a multimodal and multiscale brain concept, built upon existing and well-characterized single modalities. PMID:24139654

Redolfi, Alberto; Bosco, Paolo; Manset, David; Frisoni, Giovanni B.

356

Effect of Peripheral Edema on Oscillometric Blood Pressure Measurement  

PubMed Central

Introduction: Blood pressure (BP) measurement is essential for epidemiological studies and clinical decisions. It seems that tissue characteristics can affect BP results and we try to find edema effect on BP results taken by different methods. Methods: BP of 55 children before open heart surgery were measured and compared according to three methods: Arterial as standard and reference, oscillometric and auscultatory methods. Peripheral edema as a tissue characteristic was defined in higher than +2 as marked edema and in equal or lower than +2 as no edema. Statistical analyses: data was expressed as Mean and 95% of confidence interval (CI 95%). Comparison of two groups was performed by T independent test and of more than two groups by ANOVA test. Mann–Whitney U and paired T-test were used for serially comparisons of changes. P less than 0.05 was considered significant. Results: Fifty five children aged 29.4±3.9 months were divided into two groups: 10 children with peripheral edema beyond +2 and 45 cases without edema. Oscillometric method overestimated systolic BP and the Mean (CI 95%) difference of oscillometric to arterial was 4.8 (8/-1, P=0.02) in edematous and 4.2 (7/1, p=0.004) in non edematous. Oscillometric method underestimated diastolic BP as -9 (-1.8/-16.5, P=0.03) in edematous group and 2.6 (-0.7/+5, P= 0.2) in non edematous compared to arterial method. Conclusion: Oscillometric device standards cannot cover all specific clinical conditions. It underestimates diastolic BP significantly in edematous children, which was 9.2 mmHg in average beyond the acceptable standards. PMID:25610552

Ghaffari, Shamsi; Malaki, Majid; Rezaeifar, Afshin; Abdollahi Fakhim, Shahin

2014-01-01

357

Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia.  

PubMed

Intracerebral hemorrhage (ICH) is a devastating stroke with no proven treatment to reduce brain injury. In this study we modeled ICH by injecting 100 microL of autologous blood into the striatum of rats. We then tested whether hypothermia would reduce brain injury and improve recovery as has been repeatedly observed for ischemic and traumatic brain damage. Aside from reducing blood-brain barrier disruption, inflammation and edema, hypothermia has not consistently improved behavioral or histological outcome after ICH in animal studies. As this might relate to the choice of cooling method and the duration of hypothermia, we used a system that selectively cooled the injured hemisphere to approximately 32 degrees C (striatum) while the body remained normothermic. Cooling (vs. normothermia) started 1 h after ICH and lasted for 12 h, 3 days or 6 days followed by slow re-warming (approximately 1 degrees C/h). Functional impairment was evaluated from 2 to 3 weeks post-ICH at which time brain injury was determined. The ICH caused significant impairment on a neurological deficit scale and in tests of walking (horizontal ladder), skilled reaching (tray task) and spontaneous limb usage (cylinder test). Only the limb use asymmetry deficit was significantly mitigated by hypothermia, and then only by the longest treatment. Lesion volume, which averaged 16.9 mm3, was not affected. These results, in conjunction with earlier studies, suggest that prolonged mild hypothermia will not be a profound neuroprotectant for patients with striatal ICH, but it may nonetheless improve functional recovery in addition to its use for treating cerebral edema. PMID:19445934

Fingas, Matthew; Penner, Mark; Silasi, Gergely; Colbourne, Frederick

2009-09-01

358

Imaging of diabetic retinopathy and diabetic macular edema.  

PubMed

Imaging of the retinal complications of diabetes mellitus is rapidly changing from the emergence of new technology such as optical coherence tomography. In particular, the characterization of diabetic macular edema is much easier for the clinician and there are new, more sensitive clinical research end points. However, our understanding of structure-functional relationships remains suboptimal and the classification of macular edema by optical coherence tomography continues to evolve. The classification of diabetic retinopathy severity continues to rely upon fundus photography, although the transition from film to digital photography presents both challenges and advantages. PMID:21607565

Danis, Ronald P; Hubbard, Larry D

2011-08-01

359

Perihematomal edema as predictor of outcome in spontaneous intracerebral hemorrhage  

PubMed Central

Background: Spontaneous intracerebral hemorrhage (SICH) is a form of cerebrovascular accident with a very high rate of morbidity and mortality. The determinants of prognosis include the demographic, clinical, laboratory, and radiologic factors. It is long known that the hematoma size has a negative impact on the outcome in SICH. The influence of perihematomal edema (PHE) is not established to the extent same as that of hematoma volume. Hence, we planned this study to determine as to what role does PHE plays in the outcome in SICH. Aim of the Study: To evaluate the prognostic influence of absolute and relative edema (ratio of absolute edema to hematoma volume) in the patients of SICH. Materials and Methods: This is a prospective case-controlled study. A total of 44 patients were enrolled after excluding the confounding factors. The patients were evaluated and their disability was assessed using modified Rankin scale (MRS). The imaging was done in the interval between 24 and 72 h and the hematoma volume, absolute edema volume, and the relative edema were calculated. The outcome was reassessed at 12 weeks and defined as favorable if MRS < 3. Results: A total of 69 patients were found to be having SICH on imaging; however, 25 patients were excluded as they had one of the criterion for exclusion. Hence, only 44 patients were included in the study. On univariate analysis, none of the demographic characteristics of the patients, vascular risk factors, presenting complaints, blood pressure, Glasgow coma scale, and MRS at admission, laboratory parameters were not significantly different in the two outcome groups. The hematoma volume was significantly higher in the poor outcome group (P < 0.0001) and the relative edema was associated with a favorable outcome at 12 weeks (P < 0.0001). On multivariate logistic regression, the hematoma volume and relative edema were found to have effect on the outcome similar to that seen on univariate analysis. Conclusion: In SICH, a larger hematoma volume is a predictor of poor outcome and a relative edema is associated with a better functional status. PMID:24741251

Gupta, Mani; Verma, Rajesh; Parihar, Anit; Garg, Ravindra K.; Singh, Maneesh K.; Malhotra, Hardeep S.

2014-01-01

360

Resolution of macular edema in idiopathic juxtafoveal telangiectasis using PDT.  

PubMed

A 57-year-old woman was treated by photodynamic therapy for macular edema due to idiopathic juxtafoveal telangiectasis (presumed type 1A) without subretinal neovascularization. Initial visual acuity of the treated eye was 20/200 and it improved to 20/40 by 3 months after the photodynamic therapy session. Visual acuity remained stable 32 months after the treatment. Color photographs and fundus fluorescein angiography before and after photodynamic therapy revealed regression of hemorrhages, exudates, and fluorescein leakage. Photodynamic therapy has long-term benefits for the patient with idiopathic juxtafoveal telangiectasis, presumed type 1A, because it can improve visual acuity and macular edema. PMID:19205501

Kotoula, Maria G; Chatzoulis, Dimitrios Z; Karabatsas, Constantinos H; Tsiloulis, Aristoteles; Tsironi, Evangelia E

2009-01-01

361

Comparison of reduction of edema after rest and after muscle exercises in treatment of chronic venous insufficiency  

PubMed Central

Aim The aim of this work was to compare the reduction in edema obtained in the conservative treatment of phlebopathies after resting and after performing a muscle exercise program in the Trendelenburg position. Methods Twenty-eight limbs of 24 patients with venous edema of distinct etiologies and classified as between C3 and C5 using CEAP classification. Volumetric evaluation by water displacement was carried out before and after resting in the Trendelenburg position and after performing programmed muscle exercises 24 hours later under identical conditions of time, position and temperature. For the statistical analysis the paired t-test was used with an alpha error of 5% being considered acceptable. Results The average total volume of the lower limbs was 3,967.46 mL. The mean reduction in edema obtained after resting was 92.9 mL, and after exercises it was 135.4 mL, giving a statistically significant difference (p-value = 0.0007). Conclusion In conclusion, exercises are more efficient to reduce the edema of lower limbs than resting in the Trendelenburg position. PMID:19602249

Quilici, Belczak Cleusa Ema; Gildo, Cavalheri; de Godoy, Jose Maria Pereira; Quilici, Belczak Sergio; Augusto, Caffaro Roberto

2009-01-01

362

Kallikrein-kinin system activation by Lonomia obliqua caterpillar bristles: involvement in edema and hypotension responses to envenomation.  

PubMed

Lonomia obliqua envenomation induces an intense burning sensation at the site of contact and severe hemorrhage followed by edema and hypotension, and after few days death can occur usually due to acute renal failure. In order to understand more about the envenomation syndrome, the present study investigates the role played by kallikrein-kinin system (KKS) in edematogenic and hypotensive responses to the envenomation by L. obliqua. The incubation of L. obliqua caterpillar bristles extract (LOCBE) with plasma results in kallikrein activation, measured by cromogenic assay using the kallikrein synthetic substrate S-2302 (H-D-Pro-Phe-Arg-pNA). It was also showed that LOCBE was able to release kinins from low-molecular weight kininogen (LMWK). Moreover, it was demonstrated that previous administration of a kallikrein inhibitor (aprotinin) or bradykinin B2 receptor antagonist (HOE-140) significantly reduces the edema and hypotension in response to LOCBE, using mouse paw edema bioassay and mean arterial blood pressure analysis, respectively. The results demonstrate a direct involvement of the KKS in the edema formation and in the fall of arterial pressure that occur in the L. obliqua envenomation syndrome. PMID:17188732

Bohrer, C B; Reck Junior, J; Fernandes, D; Sordi, R; Guimarães, J A; Assreuy, J; Termignoni, C

2007-04-01

363

Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF) poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB) and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of motor function accompanied the combined therapy, which was either moderately or short-lived in the monotherapy conditions. These results suggest that combined treatment rather than monotherapy appears optimal for abrogating histophalogical and motor impairments in chronic TBI. PMID:24621603

Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Sanberg, Paul R.; Sanchez-Ramos, Juan; Song, Shijie; Kaneko, Yuji; Borlongan, Cesar V.

2014-01-01

364

Transplantation of olfactory ensheathing cells attenuates acute carbon monoxide poisoning-induced brain damages in rats.  

PubMed

In this study, the therapeutic effect of olfactory ensheathing cells (OEC) transplantation on brain damage was evaluated on acute carbon monoxide (CO) poisoning rat model. Two weeks after primary culture, OECs were microinjected into hippocampus of CO poisoning rats. Survival of OECs in the host was observed and quantified. OECs survived at 2 weeks, but surviving cell number was found sharply decreased at 6 weeks and reduced to less than 10(3) at 8 weeks after transplantation. At 2 weeks after transplantation, motor function test and cerebral edema assay were performed and followed by pathological examination including hematoxylin and eosin and immunohistochemistry staining to observe the neuron injury and synapsin I and growth associated protein-43 (GAP-43) expression. Furthermore, biomarkers of oxidative stress and apoptosis related proteins in the hippocampus were detected. The results showed that CO exposure led to neurological dysfunction and cerebral edema in rats. After OEC transplantation, neurological function was significantly improved and the cerebral edema was alleviated. In addition, the numbers of neurons and Nissl bodies were increased and synapsin I and GAP-43 protein expressions were upregulated in the hippocampus. Compared with CO poisoned rats, superoxide dismutase activity and glutathione content were both increased and methane dicarboxylic aldehyde level was decreased in the hippocampus of OEC transplanted rats. Moreover, OEC transplantation reduced apoptosis induced by CO exposure. The Bcl-2 expression was significantly upregulated and Bax expression was significantly downregulated. The activity of caspase-3 and the cleaved-poly ADP-ribose polymerase expression were decreased. Taken together, our data suggest that OEC attenuates brain damages induced by acute CO poisoning within 2 weeks after transplantation. PMID:25370793

Liu, Wei; Zheng, Qiang; Wang, Yu; Han, Xinfei; Yuan, Li; Zhao, Min

2015-01-01

365

Corticosteroids in brain cancer patients: benefits and pitfalls  

PubMed Central

Glucocorticoids have been used for decades in the treatment of brain tumor patients and belong to the most powerful class of agents in reducing tumor-associated edema and minimizing side effects and the risk of encephalopathy in patients undergoing radiation therapy. Unfortunately, corticosteroids are associated with numerous and well-characterized adverse effects, constituting a major challenge in patients requiring long-term application of corticosteroids. Novel anti-angiogenic agents, such as bevacizumab (Avastin®), which have been increasingly used in cancer patients, are associated with significant steroid-sparing effects, allowing neuro-oncologists to reduce the overall use of corticosteroids in patients with progressive malignant brain tumors. Recent experimental studies have revealed novel insights into the mechanisms and effects of corticosteroids in cancer patients, including modulation of tumor biology, angiogenesis and steroid-associated neurotoxicity. This article summarizes current concepts of using corticosteroids in brain cancer patients and highlights potential pitfalls in their effects on both tumor and neural progenitor cells. PMID:21666852

Dietrich, Jörg; Rao, Krithika; Pastorino, Sandra; Kesari, Santosh

2011-01-01

366

Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?  

PubMed Central

There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neuroprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inflammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphorylation of Akt via its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvested at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a significant decrease in Akt phosphorylation compared to sham operation. However, mice treated with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our findings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

Garling, Richard Justin; Watts, Lora Talley; Sprague, Shane; Fletcher, Lauren; Jimenez, David F.; Digicaylioglu, Murat

2014-01-01

367

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice  

PubMed Central

Blood–brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ?-gulono-?-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66?g/l) or high (3.3?g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies. PMID:24577081

Kook, S-Y; Lee, K-M; Kim, Y; Cha, M-Y; Kang, S; Baik, S H; Lee, H; Park, R; Mook-Jung, I

2014-01-01

368

Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions  

PubMed Central

Image segmentation has become a vital and often rate limiting step in modern radiotherapy treatment planning. In recent years the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumors in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: STAPLE and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers’ segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy. PMID:23685866

Deeley, MA; Chen, A; Datteri, R; Noble, J; Cmelak, A; Donnelly, EF; Malcolm, A; Moretti, L; Jaboin, J; Niermann, K; Yang, Eddy S; Yu, David S; Dawant, BM

2013-01-01

369

Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions  

NASA Astrophysics Data System (ADS)

Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers’ segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.

Deeley, M. A.; Chen, A.; Datteri, R. D.; Noble, J.; Cmelak, A.; Donnelly, E.; Malcolm, A.; Moretti, L.; Jaboin, J.; Niermann, K.; Yang, Eddy S.; Yu, David S.; Dawant, B. M.

2013-06-01

370