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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

Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice  

PubMed Central

Background Brain edema as a result of secondary injury following traumatic brain injury (TBI) is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI) as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI). Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice. PMID:22269349

2012-01-01

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

Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury  

Microsoft Academic Search

The role of inducible nitric oxide synthase (iNOS) in cerebral edema and neurological deficit following traumatic brain injury (TBI) is not yet clear-cut. Therefore, the aim of this study was to investigate the effect of three different iNOS inhibitors on cerebral edema and functional outcome after TBI. First, the time courses of blood–brain barrier (BBB) breakdown, cerebral edema, and neurological

G. Louin; C. Marchand-Verrecchia; B. Palmier; M. Plotkine; M. Jafarian-Tehrani

2006-01-01

5

[Pharmacological correction of traumatic brain edema].  

PubMed

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

Novikov, V E; Iasnetsov, V S

1984-01-01

6

Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits  

PubMed Central

Background Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. Results The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5’-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH?+?saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. Conclusion The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH. PMID:22587664

2012-01-01

7

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

8

Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke  

Microsoft Academic Search

Increased transport of Na+ across an intact blood-brain barrier (BBB) participates in edema formation during the early hours of cerebral ischemia. In previous studies, the authors showed that the BBB Na-K-Cl cotransporter is stimulated by factors present during ischemia, suggesting that the cotrans-porter may contribute to the increased brain Na+ uptake in edema. The present study was conducted to determine

Lien Tran; Tina I. Lam; Xiao Bo Liu; Steven E. Anderson; Martha E O’Donnell

2004-01-01

9

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

Microsoft Academic Search

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

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

2006-01-01

10

Treatment of Brain Edema in Acute Liver Failure  

Microsoft Academic Search

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

Alejandro A. Rabinstein

2010-01-01

11

Evaluation of brain edema using magnetic resonance proton relaxation times.  

PubMed

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. PMID:2396512

Fu, Y; Tanaka, K; Nishimura, S

1990-01-01

12

Role of early edema in the development of regional seizure-related brain damage  

Microsoft Academic Search

Kainic acid-induced seizures produced early (2 hr) generalized edema and later (24 and 48 hr) necrotic edema in temporal cortex and hippocampus as measured by specific gravity changes. Mannitol given during the seizure partially protected against the early edema and prevented the necrotic edema indicating early edema may play a role in later brain damage. However, H2O intoxication, causing much

Stanley R. Nelson; John P. Olson

1987-01-01

13

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

PubMed Central

Objective: To investigate brain edema and protein expression of c-Fos and c-Jun in brain after diffuse brain injury, and to investigate the pathological change after brain injury, which may provide evidence for the clinical treatment of diffused brain injury. Methods: Marmarou method was used to establish the diffuse brain injury in rats. Results: After diffused brain injury, brain water content increased at 1 h, reached the peak at 1 d and remained at a high level at 7 d when compared with control group. One day after injury, diffuse subarachnoid hemorrhage was observed in the brain. HE staining showed vascular swelling and bleeding at the cortex and corpus callosum at 1 d. ?-APP expression was found at the brainstem, hippocampus, thalamus, corpus callosum and periventricular regions. Pathological examination of ultrathin sections showed evidence edema and fracture of axons at 3 d after brain injury. The brain injury caused severe cerebral ischemia. The c-Fos and c-Jun expression increased at 1 h. The c-Fos expression peaked at 3 h (P < 0.05), then reduced, reached a maximal level again at 3 d (P < 0.05), and reduced significantly at 7 d but remained at a higher level when compared with control group (P < 0.05). The number of c-Jun positive cells peaked at 6 h (P < 0.05), then reduced, reached a maximal level again at 3 d and reduced markedly but still remained at a higher level when compared with control group (P < 0.05). Conclusion: After diffuse brain injury, brain water content and c-Fos/c-Jun expression change over time. PMID:25031700

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

2014-01-01

14

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

PubMed Central

Background Surgical brain injury (SBI) is damage to functional brain tissue resulting from neurosurgical manipulations such as sharp dissection, electrocautery, retraction, and direct applied pressure. Brain edema is the major contributor to morbidity with inflammation, necrosis, oxidative stress and apoptosis likely playing smaller roles. Effective therapies for SBI may improve neurological outcomes and postoperative morbidities associated with brain surgery. Previous studies show an adrenergic correlation to blood-brain barrier control. The alpha-2 receptor agonist dexmedetomidine (DEX) has been shown to improve neurological outcomes in stroke models. We hypothesized that DEX may reduce brain edema and improve neurological outcomes in a rat model of SBI. Methods Male Sprague-Dawley rats (n=63) weighing 280–350g were randomly assigned to one of four intraperitoneal (IP) treatment groups: sham IP, vehicle IP, DEX 10 mg/kg, and DEX 30 mg/kg. Treatments were given 30 minutes before SBI. These treatment groups were repeated to observe the physiologic impact of DEX on mean arterial blood pressure (MAP), heart rate (HR), and blood glucose on SBI naïve animals. Rats were also assigned to four postinjury IV treatment groups: sham IV, vehicle IV, DEX 10/5, and DEX 30/15 (DEX group doses were 10 and 30 mg/kg/hr, with 5 and 15 mg/kg initial loading doses respectively). Initial loading doses began 20 minutes after SBI, followed by 2 hours of infusion. SBI animals were subjected to neurological testing 24 hours after brain injury by a blinded observer, promptly killed, and brain water content measured via the dry/wet weight method. Results All treatment groups showed a significant difference in ipsilateral frontal brain water content and neurological scores when compared with sham animals. However, there was no difference between DEX-treated and vehicle animals. Physiologic monitoring showed treatment with low or high doses of DEX significantly decreased MAP and HR, and briefly increased blood glucose compared with naïve or vehicle-treated animals. Conclusions DEX administration did not reduce brain edema or improve neurological function after SBI in this study. The statistical difference in brain water content and neurological scores when comparing sham treatment to vehicle and DEX treatments shows consistent reproduction of this model. Significant changes in MAP, HR, and blood glucose after DEX as compared to vehicle and sham treatments suggest appropriate delivery of drug. PMID:22584551

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

2012-01-01

15

Induced and sustained hypernatremia for the prevention and treatment of cerebral edema following brain injury.  

PubMed

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm. PMID:23468135

Ryu, Justine H; Walcott, Brian P; Kahle, Kristopher T; Sheth, Sameer A; Peterson, Randall T; Nahed, Brian V; Coumans, Jean-Valery C E; Simard, J Marc

2013-10-01

16

Acute Methamphetamine Intoxication: Brain Hyperthermia, Blood-Brain Barrier and Brain Edema  

PubMed Central

Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. PMID:19897075

Kiyatkin, Eugene A.; Sharma, Hari S.

2011-01-01

17

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats  

NASA Astrophysics Data System (ADS)

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

18

Edema  

MedlinePLUS

... you have edema of the legs, wear support stockings. You can buy these at most drugstores. Support stockings put pressure on your legs to keep fluid ... for me to exercise? Should I wear support stockings? What lifestyle changes should I make? Can you ...

19

Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.  

PubMed

Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on brain injury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-?B (NF-?B) protein expression was analyzed by western blotting. IL-1? and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reduced brain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-?B activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1? and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism. PMID:23974988

Zhou, Qing-Bo; Jin, Yun-Ling; Jia, Qing; Zhang, Yuan; Li, Lu-Yang; Liu, Ping; Liu, Yuan-Tao

2014-02-01

20

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

Microsoft Academic Search

Treatments for brain edema are important and one of the major options is corticosteroids. Cell membrane stabilization and prevention of formation of free radicals are the main mechanisms of action of steroids in edema treatment. As an alternative therapeutic agent, magnesium sulphate has been used for its neuroprotective effect in various injury models. In our animal model of brain injury,

Omer Faruk Turkoglu; Hakan Eroglu; Ozerk Okutan; M. Kagan Tun; Ebru Bodur; Mustafa F. Sargon; Levent Öner; Etem Beskonakl?

2008-01-01

21

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

PubMed

Abstract 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

22

Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats  

Microsoft Academic Search

BackgroundThis study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats.

Kazuhisa Doi; Takeshi Kawano; Yujiro Morioka; Yasutaka Fujita; Masuhiro Nishimura

2006-01-01

23

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

24

Expression of Aquaporin 4 and Breakdown of the Blood-Brain Barrier after Hypoglycemia-Induced Brain Edema in Rats  

PubMed Central

Background Hypoglycemia-induced brain edema is a severe clinical event that often results in death. The mechanisms by which hypoglycemia induces brain edema are unclear. Methods In a hypoglycemic injury model established in adult rats, brain edema was verified by measuring brain water content and visualizing water accumulation using hematoxylin and eosin staining. Temporal expression of aquaporin 4 (AQP4) and the integrity of the blood-brain barrier (BBB) were evaluated. We assessed the distribution and expression of AQP4 following glucose deprivation in astrocyte cultures. Results Brain edema was induced immediately after severe hypoglycemia but continued to progress even after recovery from hypoglycemia. Upregulation of AQP4 expression and moderate breakdown of the BBB were observed 24 h after recovery. In vitro, significant redistribution of AQP4 to the plasma membrane was induced following 6 h glucose deprivation. Conclusion Hypoglycemia-induced brain edema is caused by cytotoxic and vasogenic factors. Changes in AQP4 location and expression may play a protective role in edema resolution. PMID:25264602

Deng, Jiangshan; Zhao, Fei; Yu, Xiaoyan; Zhao, Yuwu; Li, Dawei; Shi, Hong; Sun, Yongning

2014-01-01

25

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

26

Predictors of Life-Threatening Brain Edema in Middle Cerebral Artery Infarction  

Microsoft Academic Search

Background: We performed a systematic review to identify predictors of the development of life-threatening brain edema in patients with middle cerebral artery infarction. Methods: We searched Medline from January 1966 and Embase from January 1974 to April 2007 for cohort and case-control studies on predictors of life-threatening edema in patients with middle cerebral artery infarction. Crude data were used to

Jeannette Hofmeijer; Ale Algra; L. Jaap Kappelle; H. Bart van der Worp

2008-01-01

27

Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.  

PubMed

Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 ?L) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. PMID:24518201

Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

2014-05-01

28

Dynamics of Rabbit Brain Edema in Focal Lesion and Perilesion Area after Traumatic Brain Injury: A MRI Study  

PubMed Central

Abstract To understand the dynamics of brain edema in different areas after traumatic brain injury (TBI) in rabbit, we used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to monitor blood–brain barrier (BBB) permeability and cytotoxic brain edema after weight drop-induced TBI in rabbit. The dynamics of BBB permeability and brain edema were quantified using Ktrans and apparent diffusion coefficient (ADC) in the focal and perifocal lesion areas, as well as the area contralateral to the lesion. In the focal lesion area, Ktrans began to increase at 3?h post-TBI, peaked at 3 days, and decreased gradually while remaining higher than sham injury animals at 7 and 30 days. ADC was more variable, increased slightly at 3?h, decreased to its lowest value at 7 days, then increased to a peak at 30 days. In the perifocal lesion area, Ktrans began to increase at 1 day, peaked at 3–7 days, and returned to control level by 30 days. ADC showed a trend to increase at 1 day, followed by a continuous increase thereafter. In the contralateral area, no changes in Ktrans and ADC were observed at any time-point. These data demonstrate that different types of brain edema predominate in the focal and perifocal lesion areas. Specifically cytotoxic edema was predominant in the focal lesion area while vasogenic edema predominated in the perifocal area in acute phase. Furthermore, secondary opening of the BBB after TBI may appear if secondary injury is not controlled. BBB damage may be a driving force for cytotoxic brain edema and could be a new target for TBI intervention. PMID:21675826

Wei, Xiao-Er; Zhang, Yu-Zhen; Li, Yue-Hua; Li, Ming-Hua

2012-01-01

29

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, Andre; Badaut, Jerome

2012-01-01

30

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

PubMed

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, AQP4, and AQP9) 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 7days 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 astrocyticAQP4 plays a more central role than AQP1 or AQP9 during the edema process in the young brain. PMID:22728101

Fukuda, A M; Pop, V; Spagnoli, D; Ashwal, S; Obenaus, A; Badaut, J

2012-10-11

31

Enhanced expression of aquaporin-9 in rat brain edema induced by bacterial lipopolysaccharides  

Microsoft Academic Search

Summary  To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the\\u000a injection of lipopolysaccharide (LPS) was examined. Immunohistochemistry and reverse transcription-polymerase chain reaction\\u000a (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly\\u000a increased in LPS-treated animals in comparison with the

Huaili Wang; Runming Jin; Peichao Tian; Zhihong Zhuo

2009-01-01

32

Inhibition of Myosin Light-Chain Kinase Attenuates Cerebral Edema after Traumatic Brain Injury in Postnatal Mice  

PubMed Central

Abstract Traumatic brain injury (TBI) in children less than 8 years of age leads to decline in intelligence and executive functioning. Neurological outcomes after TBI correlate to development of cerebral edema, which affect survival rates after TBI. It has been shown that myosin light-chain kinase (MLCK) increases cerebral edema and that pretreatment with an MLCK inhibitor (ML-7) reduces cerebral edema. The aim of this study was to determine whether inhibition of MLCK after TBI in postnatal day 24 (PND-24) mice would prevent breakdown of the blood–brain barrier (BBB) and development of cerebral edema and improve neurological outcome. We used a closed head injury model of TBI. ML-7 or saline treatment was administered at 4?h and every 24?h until sacrifice or 5 days after TBI. Mice were sacrificed at 24?h, 48?h, and 72?h and 7 days after impact. Mice treated with ML-7 after TBI had decreased levels of MLCK-expressing cells (20.7±4.8 vs. 149.3±40.6), less albumin extravasation (28.3±11.2 vs. 116.2±60.7?mm2) into surrounding parenchymal tissue, less Evans Blue extravasation (339±314 vs. 4017±560?ng/g), and showed a significant difference in wet/dry weight ratio (1.9±0.07 vs. 2.2±0.05?g), compared to saline-treated groups. Treatment with ML-7 also resulted in preserved neurological function measured by the wire hang test (57 vs. 21?sec) and two-object novel recognition test (old vs. new, 10.5 touches). We concluded that inhibition of MLCK reduces cerebral edema and preserves neurological function in PND-24 mice. PMID:23984869

Todd, Tracey; Bazan, Nicolas G.; Belayev, Ludmila

2013-01-01

33

Regional Differences in Cerebral Edema after Traumatic Brain Injury Identified by Impedance Analysis  

PubMed Central

Objective Cerebral edema is a common and potentially devastating sequel of traumatic brain injury. We developed and validated a system capable of tissue impedance analysis, which was found to correlate with cerebral edema. Design and Methods Constant sinusoidal current (50 ?A), at frequencies from 500 to 5000 Hz, was applied across a bipolar electrode unit superficially placed in a rat brain after traumatic brain injury. Rats were randomized to three groups: severe controlled cortical injury (CCI), mild CCI, or sham injury. At 60 hours post CCI, cerebral voltage and phase angle were measured at each frequency at the site of injury, at the penumbral region, at the ipsilateral frontal region, and in the contralateral hemisphere. Impedance measurements were also obtained in vivo. The electrical properties of varied injuries and specified locations were compared using a repeated measures analysis of variance (RMANOVA), were correlated with regional tissue water percentage using regression analyses, and were combined to generate polar coordinates. Results The measured voltage was significantly different at the site of injury (p<0.0001), in the penumbra (p=0.002), and in the contralateral hemisphere (p=0.005) when severe, mild, and sham CCI rats were compared. Severely injured rats had statistically different voltage measurements when the various sites were compared (p=0.002). The ex vivo measurements correlated with in vivo measurements. Further, the impedance measurements correlated with measured tissue water percentage at the site of injury (R2=0.69; p<0.0001). The creation of a polar coordinate graph, incorporating voltage and phase angle measurements, enabled the identification of impedance areas unique to normal, mild edema, and severe edema measurements in the rat brain. Conclusions Electrical measurements and tissue water percentages quantified regional and severity differences in rat brain edema after CCI. Impedance was inversely proportional to the tissue water percentage. Thus, impedance measurement can be used to quantify severity of cerebral edema in real time at specific sites. PMID:19181334

Harting, Matthew T.; Smith, Carter T.; Radhakrishnan, Ravi S.; Aroom, Kevin R.; Dash, Pramod K.; Gill, Brijesh; Cox, Charles S.

2013-01-01

34

21-Aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia.  

PubMed

U74006F is a member of a new family of steroid drugs called 21-aminosteroids, which are potent inhibitors of lipid peroxidation with little or no glucocorticoid or mineralocorticoid activity. We investigated the effects of U74006F on the early ionic edema produced by middle cerebral artery occlusion in rats. Intravenous doses of 3 mg/kg U74006F were given 10 minutes and 3 hours after occlusion. Tissue concentrations of Na+, K+, and water at and around the infarct site were measured by atomic absorption spectroscopy and by wet-dry weight measurements 24 hours after occlusion. Compared with vehicle treatment, U74006F treatment reduced brain water entry, Na+ accumulation, K+ loss, and net ion shift by 25-50% in most brain areas sampled in the frontal and parietal cortex. However, reductions of ionic edema were most prominent and reached significance (p less than 0.005, unpaired two-tailed t test) mostly in the frontoparietal and parietal cortex areas adjacent to the infarct site. Our findings suggest that a steroid drug without glucocorticoid or mineralocorticoid activity can reduce edema in cerebral ischemia but that the effects are largely limited to tissues in which collateral blood flow may be present. PMID:3400099

Young, W; Wojak, J C; DeCrescito, V

1988-08-01

35

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

PubMed Central

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

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

2012-01-01

36

Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711  

Microsoft Academic Search

Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg\\/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an

B. A. Faraj; E. J. Jr. Cragoe; R. Sarper; M. Camp; E. Malveaux

1988-01-01

37

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

38

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

39

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

PubMed Central

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema. PMID:24783201

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

2014-01-01

40

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

SciTech Connect

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

Datz, F.L.

1986-05-01

41

High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.  

PubMed

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI. PMID:24166800

Laird, Melissa D; Shields, Jessica S; Sukumari-Ramesh, Sangeetha; Kimbler, Donald E; Fessler, R David; Shakir, Basheer; Youssef, Patrick; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

2014-01-01

42

Electron microscopic study of perivascular structure associated with experimentally induced brain edema in cats.  

PubMed

The fine structural features and water content of white matter associated with the resolution process of brain edema were sequentially investigated in the model produced by infusion of autoserum, mock CSF, or ferritin into the centrum semiovale of cats. The correlation between water content and morphological features was good. Mock CSF-infused edema disappeared within 3 days, serum infused edema within 6 days. In a fine structural study of serum-infused white matter, the distended extracellular spaces were found to be occupied with electron-dense materials, active phagocytosis of the dense materials being observed in the macrophages. Around the postcapillary venules, edematous changes were characterized by wide expansion of the perivascular spaces between endothelial cells and astrocytic endfeet. In some instances, the dense materials in the cytoplasm or in the membrane-bound vacuoles of the astrocytic endfeet were continuous with those in the perivascular space, through the hiatuses of the perivascular astrocytic endfeet being separated at their margins. At 3 days after infusion, wide distension of the extracellular space persisted, but the dense materials had markedly diminished. These results strongly suggest that water clearance of vasogenic brain edema does not commence until proteinaceous macromolecules are degraded and removed from the extracellular space. Perivascular channels around the postcapillary venules might also have some role on the movement of edematous fluid. PMID:2396518

Ohata, K; Tanaka, K; Katsuyama, J; Nishimura, S

1990-01-01

43

Feasibility of using diffuse reflectance spectroscopy for the quantification of brain edema  

NASA Astrophysics Data System (ADS)

Many diseased states of the brain can result in the displacement of brain tissues and restrict cerebral blood flow, disrupting function in a life-threatening manner. Clinical examples where displacements are observed include venous thromboses, hematomas, strokes, tumors, abscesses, and, particularly, brain edema. For the latter, the brain tissue swells, displacing the cerebral spinal fluid (CSF) layer that surrounds it, eventually pressing itself against the skull. Under such conditions, catheters are often inserted into the brain's ventricles or the subarachnoid space to monitor increased pressure. These are invasive procedures that incur increased risk of infection and consequently are used reluctantly by clinicians. Recent studies in the field of biomedical optics have suggested that the presence or absence of the CSF layer can lead to dramatic changes in NIR signals obtained from diffuse reflectance measurements around the head. In this study, we consider how this sensitivity of NIR signals to CSF might be exploited to non-invasively monitor the onset and resolution of brain edema.

Rodriguez, Juan G.; Sisson, Cynthia; Hendricks, Chad; Pattillo, Chris; McWaters, Megan; Hardjasudarma, Mardjohan; Quarles, Chad; Yaroslavsky, Anna N.; Yaroslavsky, Ilya V.; Battarbee, Harold

2001-05-01

44

The role of p53 in brain edema after 24 h of experimental subarachnoid hemorrhage in a rat model.  

PubMed

Our previous study demonstrated that p53 plays an orchestrating role in the vasospasm and apoptotic cell death after subarachnoid hemorrhage (SAH). We now hypothesize that p53 also plays an important role in brain edema by up-regulating the expression of MMP-9 via the NF-kappaB molecular signaling pathway. Adult male rats (300-350 g) were divided into five groups (n=20 each): Sham, SAH treatment with DMSO or PFT-alpha (0.2 mg/kg and 2.0 mg/kg), intraperitoneally. The monofilament puncture model was used to induce SAH and animals were subsequently sacrificed at 24 h. The blood-brain barrier (BBB) disruption, brain water content, MMP-9 activity, immunohistochemistry, treble fluorescence labeling, Western blot, and ultra-structural observations were performed. Evans blue extravagation, BBB diffuse leakage of IgG protein and brain water content were significantly reduced by PFT-alpha treatment; and the expression of p53, NF-kappaB and MMP-9 were significantly increased. The tight junction protein (Occludin) in endothelia cells and Collage IV in basal lamina were decreased in the brain of SAH rats, and were also modified by PFT-alpha treatment. Ultra-structural changes included disruption of endothelial tight junction and widening of the inter-endothelial spaces. Treble labeling showed p53 colocalized with NF-kappaB and MMP-9 in cerebral endothelia cells. We thus conclude that the level of p53 in cerebral microvasculature significantly affects the BBB permeability and brain edema after 24 h of SAH in rats. This can be at least partially ascribed to p53 inducing a significant up-regulation of MMP-9 via NF-kappaB in the endothelium, which in turn opened the tight junction by degrading Occludin and disrupting the basal lamina by degrading collagen IV. PMID:18691572

Yan, Junhao; Chen, Chunhua; Hu, Qing; Yang, Xiaomei; Lei, Jiliang; Yang, Lei; Wang, Ke; Qin, Lihua; Huang, Hongyun; Zhou, Changman

2008-11-01

45

Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711  

SciTech Connect

Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an infusion of normal saline containing 6-7 mg/kg of the drug given over a period of 2 hr caused reversal of brain injury. This was accompanied by full recovery within a period of 24 hr of all the animals tested. A follow-up study revealed that 24 hr after treatment with L-644,711 CSF levels of catecholamines and brain images of Tc-99m-DTPA were indistinguishable from normal controls. Animals that received no drug died from unresolved coma within 4 to 24 hr. Animals that had recovered due to therapy with L-644,711 were given 10-14 days rest followed by a repetition of the phenelzine and tyramine treatment but denied L-644,711 therapy. These animals also died of unresolved coma within 24 hr. This preliminary study suggest that the use of L-644,711 may constitute an important advance in treatment of brain edema of a wide range of neurological disorders.

Faraj, B.A.; Cragoe, E.J. Jr.; Sarper, R.; Camp, M.; Malveaux, E.

1988-01-01

46

Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia.  

PubMed

After focal cerebral ischemia, tumor necrosis factor-alpha deteriorates cerebral edema and survival rate. Therefore, tumor necrosis factor-alpha neutralization could reduce cerebral microvascular permeability in acute cerebral ischemia. Left middle cerebral artery occlusion for 120 mins followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Antirat tumor necrosis factor-alpha neutralizing monoclonal antibody with a rat IgG Fc portion (15 mg/kg) was infused intravenously right after reperfusion. Stroke index score, infarct volume, cerebral specific gravity, and the endogenous expression of tumor necrosis factor-alpha, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in the brain tissue were quantified in the ischemic and matched contralateral nonischemic hemisphere. In the antitumor necrosis factor-alpha neutralizing antibody-treated rats, infarct volume was significantly reduced (P=0.014, n=7; respectively), and cerebral specific gravity was dramatically increased in the cortex and caudate putamen (P<0.001, n=7; respectively) in association with a reduction in MMP-9 and membrane type 1-MMP upregulation. Tumor necrosis factor-alpha in the brain tissue was significantly elevated in the ischemic hemisphere 6 h after reperfusion in the nonspecific IgG-treated rats (P=0.021, n=7) and was decreased in the antitumor necrosis factor-alpha neutralizing antibody-treated rats (P=0.001, n=7). Postreperfusion treatment with antirat tumor necrosis factor-alpha neutralizing antibody reduced brain infarct volume and cerebral edema, which is likely mediated by a reduction in MMP upregulation. PMID:15729288

Hosomi, Naohisa; Ban, Camelia R; Naya, Takayuki; Takahashi, Tsutomu; Guo, Peng; Song, Xiao-yu R; Kohno, Masakazu

2005-08-01

47

Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage.  

PubMed

Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation. PMID:24516353

Dong, Yu-shu; Wang, Ju-lei; Feng, Da-yun; Qin, Huai-zhou; Wen, Hua; Yin, Zhong-min; Gao, Guo-dong; Li, Chuan

2014-01-01

48

Protective Effect of Quercetin against Oxidative Stress and Brain Edema in an Experimental Rat Model of Subarachnoid Hemorrhage  

PubMed Central

Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation. PMID:24516353

Dong, Yu-shu; Wang, Ju-lei; Feng, Da-yun; Qin, Huai-zhou; Wen, Hua; Yin, Zhong-min; Gao, Guo-dong; Li, Chuan

2014-01-01

49

Experimental Study Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats  

Microsoft Academic Search

Summary Background. Volatile anesthetics reduce neuronal excitation and ce- rebral metabolism but can also increase intracellular water accumula- tion in normal and injured brains. While attenuation of neuronal excitation and glutamate release are beneficial under pathological con- ditions, any increase in edema formation should be avoided. In the present study we investigated duration-dependent effects of the com- monly used isoflurane=nitrous

J. F. Stover; O. W. Sakowitz; S. N. Kroppenstedt; U. W. Thomale; O. S. Kempski; G. Flugge; A. W. Unterberg

50

Volumetric Electromagnetic Phase-Shift Spectroscopy of Brain Edema and Hematoma  

PubMed Central

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

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

2013-01-01

51

Influence of isoflurane, fentanyl, thiopental, and alpha-chloralose on formation of brain edema resulting from a focal cryogenic lesion.  

PubMed

The objective of this study was to analyze the effects of various anesthetics on the formation of brain edema resulting from a focal cryogenic lesion. Thirty rabbits (six per group) were anesthetized with isoflurane (1 minimum alveolar anesthetic concentration [MAC] 2.1 vol%), fentanyl (bolus 5 micrograms/kg; infusion rate 1.0-0.5 micrograms.kg-1.min-1), thiopental (32.5 mg.kg-1.h-1), or alpha-chloralose (50 mg/kg). Control animals (sham operation, no lesion) received alpha-chloralose (50 mg/kg). Regional cerebral blood flow (rCBF) in perifocal brain tissue was measured by H2-clearance. Animals anesthetized with isoflurane required support of arterial pressure by angiotensin II (0.15 micrograms.kg-1.min-1). Six hours after trauma the animals were killed. Formation of brain edema was studied by specific gravity of cortical gray matter, white matter, hippocampus, caudate nucleus, putamen, and thalamus. Brain tissue samples were collected at multiple sites close to and distant from the lesion. Mean arterial pressure, arterial PCO2 and PO2, hematocrit, body temperature, and blood glucose were not different between groups during the posttraumatic course (except for an increased arterial pressure with alpha-chloralose compared to thiopental 4-6 h after trauma). The specific gravity of cortical gray matter was significantly reduced up to a distance of 6 mm from the center of the lesion in animals anesthetized with isoflurane, thiopental, or alpha-chloralose and up to 9 mm in animals given fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7762836

Murr, R; Berger, S; Schürer, L; Peter, K; Baethmann, A

1995-06-01

52

Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats.  

PubMed

Blood-brain barrier (BBB) disruption is a critical event leading to vasogenic brain edema and secondary brain damage after cold injury-induced brain trauma. Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which degrade the extracellular matrix, are implicated in BBB disruption in this model. The purpose of this study was to examine the effects of MMI270 (N-hydroxy-2(R)-[(4-methoxysulfony) (3-picolyl)-amino]-3-metylbutaneamide hydrochloride monohydrate), a synthetic nonspecific MMP inhibitor, on cold injury-induced brain edema in rats. Cold injury was induced by applying a copper probe cooled with liquid nitrogen on the parietal skull for 30 sec in 38 rats. Treatment with MMI270, a bolus injection at a dose of 30 mg/kg, was started immediately after the induction of cold injury and was continued for 24 h at a dose of 40 mg/kg/day using an intraperitoneal osmotic minipump (n = 7). In the untreated control group (n = 7), rats were administered a vehicle and implanted with a vehicle-containing osmotic pump. Two percent Evans Blue (EB) in saline (1 mL/kg) was administrated intravenously immediately after the cold injury in another group of rats, six of which were untreated and six of which were treated with MMI270 at the above dose. At 24 h after the cold injury, the brain water content and the BBB permeability to EB were determined. To assess the protective effect of MMI270 on secondary brain lesion after the cold injury, the MMI270-treated rats received a bolus injection at a dose of 30 mg/kg, followed by a continuous administration of MMI270 for 7 days at a dose of 40 mg/kg/day using an osmotic minipump (n = 6). In the untreated control group (n = 6), the rats were administered the vehicle and implanted with a vehicle-containing osmotic pump. At 7 days after cold injury, the secondary brain lesion was assessed using hematoxylin and eosin (H-E) staining. Compared with the untreated control group, treatment with MMI270 significantly reduced the brain water content in the ipsilateral core and intermediate areas (p < 0.05 and p < 0.01) and protected the BBB integrity to EB in the ipsilateral core area (p < 0.05) at 24 h after the cold injury. The secondary lesion was significantly smaller in the MMI270-treated animals compared with the untreated animals (p < 0.05) a 7 days after the cold injury. O kur results indicate that treatment with MMI270 in rats exhibits protection in acute brain edema formation and secondary brain damage by attenuating the BBB permeability after cold injury. PMID:12908926

Kawai, Nobuyuki; Kawanishi, Masahiko; Okada, Mikiko; Matsumoto, Yoshihito; Nagao, Seigo

2003-07-01

53

Association Between a Quantitative CT Scan Measure of Brain Edema and Outcome After Cardiac Arrest  

PubMed Central

Background Cerebral edema is one physical change associated with brain injury and decreased survival after cardiac arrest. Edema appears on computed tomography (CT) scan of the brain as decreased x-ray attenuation by gray matter. This study tested whether the gray matter attenuation to white matter attenuation ratio (GWR) was associated with survival and functional recovery. Methods Subjects were patients hospitalized after cardiac arrest at a single institution between 1/1/2005 and 7/30/2010. Subjects were included if they had non-traumatic cardiac arrest and a non-contrast CT scan within 24 hours after cardiac arrest. Attenuation (Hounsfield Units) was measured in gray matter (caudate nucleus, putamen, thalamus, and cortex) and in white matter (internal capsule, corpus callosum and centrum semiovale). The GWR was calculated for basal ganglia and cerebrum. Outcomes included survival and functional status at hospital discharge. Results For 680 patients, 258 CT scans were available, but 18 were excluded because of hemorrhage (10), intravenous contrast (3) or technical artifact (5), leaving 240 CT scans for analysis. Lower GWR values were associated with lower initial Glasgow Coma Scale motor score. Overall survival was 36%, but decreased with decreasing GWR. The average of basal ganglia and cerebrum GWR provided the best discrimination. Only 2/58 subjects with average GWR<1.20 survived and both were treated with hypothermia. The association of GWR with functional outcome was completely explained by mortality when GWR<1.20. Conclusions Subjects with severe cerebral edema, defined by GWR<1.20, have very low survival with conventional care, including hypothermia. GWR estimates pre-treatment likelihood of survival after cardiac arrest. PMID:21592642

Metter, Robert B.; Rittenberger, Jon C.; Guyette, Francis X.; Callaway, Clifton W.

2011-01-01

54

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

PubMed Central

Objective Treadmill pre-training can ameliorate blood brain barrier (BBB) dysfunction in ischemia-reperfusion injury, however, its role in ischemic brain edema remains unclear. This study assessed the neuroprotective effects induced by treadmill pre-training, particularly on brain edema in transient middle cerebral artery occluded model. Methods Transient middle cerebral artery occlusion to induce stroke was performed on rats after 2 weeks of treadmill pre-training. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after ischemia-reperfusion injury. In addition, measurements of wet and dry brain weight, Evans Blue assay and Garcia scores were performed to investigate the cerebral water content, BBB permeability and neurologic deficit, respectively. Moreover, during ischemia-reperfusion injury, the expression of Aquaporin 4 (AQP4) was detected using immunofluorescence and Western bloting analyses. Results Treadmill pre-training improved the relative apparent diffusion coefficient (rADC) loss in the ipsilateral cortex and striatum at 1 hour and 2.5 hours after cerebral ischemia. In the treadmill pre-training group, T2W1 values of the ipsilateral cortex and striatum increased less at 7.5 hours, 1 day, and 2 days after stroke while the brain water content decreased at 2 days after ischemia. Regarding the BBB permeability, the semi-quantitative amount of contrast agent leakage of treadmill pre-training group significantly decreased. Less Evans Blue exudation was also observed in treadmill pre-training group at 2 days after stroke. In addition, treadmill pre-training mitigated the Garcia score deficits at 2 days after stroke. Immunofluorescence staining and Western blotting results showed a significant decrease in the expression of AQP4 after treadmill ischemia following pre-training. Conclusions Treadmill pre-training may reduce cerebral edema and BBB dysfunction during cerebral ischemia/reperfusion injury via the down-regulation of AQP4. PMID:24416250

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

2014-01-01

55

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

Microsoft Academic Search

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

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

56

PGJ2 Provides Prolonged CNS Stroke Protection by Reducing White Matter Edema  

PubMed Central

Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NF?B-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-?12,14-prostaglandin J2 (PGJ2), an analog of the metabolically active PGD2 metabolite. We evaluated PGJ2's effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION); an in vivo white matter ischemia model. PGJ2 administration systemically administered either acutely or 5 hours post-insult results in significant neuroprotection, with stereologic evaluation showing improved neuronal survival 30 days post-infarct. Quantitative capillary vascular analysis reveals that PGJ2 improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ2 acts by reducing NF?B signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ2 showed no in vivo toxicity structurally as measured by optic nerve (ON) myelin thickness, functionally by ON-compound action potentials, on a cellular basis by oligodendrocyte precursor survival or changes in ON-myelin gene expression. PGJ2 may be a clinically useful neuroprotective agent for ON and other CNS infarcts involving white matter, with mechanisms of action enabling effective treatment beyond the currently considered maximal time for intervention. PMID:23284631

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

2012-01-01

57

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

PubMed Central

The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis. PMID:24966914

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

2014-01-01

58

Photobiostimulation reduces edema formation induced in mice by Lys-49 phospholipases A2 isolated from Bothrops moojeni venom.  

PubMed

The prominent local myotoxic effects induced by Bothrops snake venom are due, in part, to myotoxins. This effect is not neutralized by antivenom, which is the main therapy for victims of snakebite. Two basic myotoxins named MjTX-I and MjTX-II were isolated from Bothrops moojeni venom. Both myotoxins have a Lys-49 phospholipase A2 structure devoid of enzymatic activity, but are highly myonecrotic and edema-inducing. In this study, we analyzed the effect of a low-level laser (LLL) at 685 nm, an energy density of 2.2 J cm(-2), and the irradiation time of 15 s, and a light emitting diode (LED) at 635 or 945 nm at energy densities of 4 and 3.8 J cm(-2), and irradiation times of 41 and 38 s, respectively, applied 30 min and 3 h after edema formation in mice caused by MjTX-I or MjTX-II. MjTX-I or MjTX-II caused a significant edema formation in envenomed paws. LLL and LED irradiation significantly reduced the edema formation by both myotoxins from 1 up to 6 hours after the injection. Both LLL and LEDs were similar in reducing the edema formation induced by myotoxins. The combined photobiostimulation with antivenom had the same effect in reducing edema as treatment with the LLL or LEDs alone. In conclusion, the results of this study indicate that photobiostimulation could be used in association with antivenom therapy for treatment of local effects of Bothrops species venom. PMID:25232894

Nadur-Andrade, Nikele; Dale, Camila Squarzone; Santos, Adriano Silvio Dos; Soares, Andreimar M; de Lima, Carlos J; Zamuner, Stella Regina

2014-10-15

59

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

PubMed

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

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

2009-04-01

60

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

61

[Ultrastructure of capillary permeability in human brain tumors. Part 1: Gliomas associated with cerebral edema (low density area)].  

PubMed

In order to elucidate pathogenesis of perifocal edema in the human brain tumors, we observed the alteration of capillary permeability between the glioblastomas with remarkable edema (4 cases) and astrocytoma with slight edema (3 cases). Specimens were studied by conventional ultrathin section and freeze-fracture replica technique. In ultrathin sections of capillaries in glioblastomas, some of these cell junctions were tortuous, elongated, in fact, open. Other capillary abnormalities included endothelial hyperplasia with extensive vesicular formation, surface infolding of endothelial cells, irregularity of the basal lamina and the presence of a large collagen filled extracellular space. In freeze-fracture replicas of capillary endothelium, pinocytotic vesicles markedly increased and were an average fo 52 per micron. Tight junction in one area was seen as network of 6 strands composed of about 100A particles, but in the other areas as one or two strands. In ultrathin sections of astrocytoma, yet there were blood vessels appeared relatively normal. In freeze-fracture replicas, pinocytotic vesicles markedly increased and were an average of 34 per micron. Tight junction was seen as network of 7 strands. We concluded that fewer strands of the tight junction play an important role in increasing the permeability in the vessels of glioblastomas with severe perifocal edema, in addition to increasing the pinocytotic vesicles. PMID:2989720

Shibata, S; Fukushima, M; Inoue, M; Tsutsumi, K; Mori, K

1985-03-01

62

Radiation necrosis and brain edema association with CyberKnife treatment.  

PubMed

The CyberKnife (CK) is a frameless and image guided robotic controlled instrument for stereotactic irradiation. The authors studied CK treatment of glioma and glioblastoma, and analyzed frequency and risk factors of radiation necrosis. Of 61 patients with glioma and glioblastoma treated with CyberKnife, four patients showed symptomatic radiation necrosis. All of these patients were treated with stereotactic radiotherapy, varying from 3 to 6 fractions without previous radiation therapy. Two patients required necrotomy through craniotomy. Two patients were treated conservatively. Our four patients with radiation necrosis were not specific in terms of tumor volume and dose delivery. Glioma cells invade the normal brain tissue and over-radiation to this intermingling area is one of the risk factors for injury to normal endothelial cells. The homogeneity of the maximum dose area is an important factor to reduce over radiation to the normal brain parenchyma. The dose volume effect has been discussed in terms of risk factor; however, the number of fractions and dose per fraction should be considered to avoid radiation necrosis. We consider that conformal treatment with inverse algorism, fractionated stereotactic radiotherapy and precise anatomic targeting reduce the risk of radiation necrosis. PMID:14753497

Sato, K; Baba, Y; Inoue, M; Omori, R

2003-01-01

63

690. Angiopoietin-1 Reduces Lung Edema and Mortality Induced by Bacterial Endotoxin  

Microsoft Academic Search

Acute lung injury (ALI) is a frequent cause of morbidity and mortality in patients with bacterial sepsis. Capillary leakage together with interstitial and alveolar edema are the hallmarks of this condition. The loss of integrity in the endothelial barrier is a prerequisite for development of ALI. Angiopoietin-1 (Ang-1) binds to the Tie2 receptor. This interaction activates the phosphatidylinositol 3?-kinase\\/Akt survival

Yao Qi Huang; Harald Sauthoff; Teona Pipiya; Shu Chen; William N. Rom; John G. Hay

2004-01-01

64

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

PubMed

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-alpha (TNFalpha) and nuclear factor (NF)kappaB signaling were prominent. In vitro experiments confirmed that Abcc8 transcription is stimulated by TNFalpha. 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 TNFalpha and NFkappaB, 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

2009-02-01

65

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

PubMed Central

Purpose To evaluate patients' self-recognition of reduced visual acuity due to recurring macular edema in retinal vein occlusion. Methods A retrospective review of medical records of patients who were diagnosed with recurring macular edema secondary to retinal vein occlusion was performed. The proportion of patients who recognized reduced visual acuity due to the recurrence of macular edema and who visited the hospital before the scheduled follow-up date was determined. Parameters including age, sex, diagnosis, visual acuity before recurrence of macular edema, and extent of visual acuity reduction due to recurrence of macular edema were compared in patients who recognized a reduction in visual acuity and those who did not. The proportion of patients who visited the hospital promptly was also determined. Results Forty eyes of 40 patients were included in the analysis. Sixteen and 24 patients were diagnosed with central retinal vein occlusion and branch retinal vein occlusion, respectively. Twenty-one patients (52.5%) recognized reduced visual acuity due to recurring macular edema. These patients were younger (59.2 ± 7.6 vs. 64.8 ± 9.4 years, p = 0.046), had better visual acuity before recurrence of macular edema (0.52 ± 0.48 vs. 1.02 ± 0.46, p = 0.002), and exhibited a greater reduction in visual acuity after recurrence of macular edema (0.34 ± 0.24 vs. 0.14 ± 0.13, p = 0.003). Only four patients visited the hospital before the scheduled follow-up date, and all of these patients lived relatively close to the hospital. Conclusions For prompt treatment of recurring macular edema, more intensive education about the self-estimation of visual acuity is necessary, particularly for elderly patients who have relatively poor visual acuity. In addition, a simple and easy way to identify the recurrence of macular edema at the local clinic should be established for patients who live relatively far from the hospital. PMID:24882954

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

2014-01-01

66

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

67

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

PubMed

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

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

2014-03-01

68

Does steroid medication reduce facial edema following face lift surgery? A prospective, randomized study of 30 consecutive patients.  

PubMed

A prospective, double-blinded study of 30 consecutive face lift patients was conducted to determine if the administration of corticosteroid medication would reduce postoperative facial edema. Half the patients received steroid medications in a random fashion. Three independent plastic surgeons who were blinded to the study rated facial swelling by comparing preoperative and postoperative photographs using a scale of 1 to 4. The data were tabulated and subjected to statistical analysis. There were no significant differences in facial swelling between the steroid-treated group and the untreated patients on any occasion. PMID:8657760

Owsley, J Q; Weibel, T J; Adams, W A

1996-07-01

69

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

PubMed Central

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

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

2014-01-01

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

Reducing Test Anxiety: A Right Brain Approach.  

ERIC Educational Resources Information Center

Methods of helping students reduce test anxiety are discussed, including guided fantasy which leads students to imagine a setting in which they feel competent and relaxed. Catastrophic-anastrophic expectations teach that different expectations create different feelings and make students aware that they are in charge of their own attitudes. Anxiety…

Cohen, Ruth I.

72

Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema.  

PubMed

The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema. PMID:201954

P?u?escu, E; Chirvasie, R; Popescu, M V; Teodosiu, T

1977-01-01

73

Influence of engineered nanoparticles from metals on the blood-brain barrier permeability, cerebral blood flow, brain edema and neurotoxicity. An experimental study in the rat and mice using biochemical and morphological approaches.  

PubMed

Influence of nanoparticles on brain function following in vivo exposures is not well known. Depending on the magnitude and intensity of nanoparticle exposure from the environment, food and/or water source, neuronal function could be affected and may lead to neurotoxicity and neuropathology. This hypothesis was examined in present investigation using systemic or intracerebroventricular administration of engineered nanoparticles from metals, i.e., Al, Ag and Cu (approximately equal to 50 to 60 nm) on neurotoxicity in rats and mice. Intraperitoneal (50 mg/kg), intravenous (30 mg/kg), intracarotid (2.5 mg/kg) or intracerebroventricular administration (20 microg) of nanoparticles significantly altered the blood-brain barrier (BBB) function to Evans blue and radioiodine in several regions of the brain and spinal cord at 24 h after their administration. Marked decreases in local cerebral blood flow (CBF) and pronounced brain edema was seen in regional areas associated with BBB leakage. Neuronal cell injuries, glial cell activation, heat shock protein (HSP) upregulation and loss of myelinated fibers are quite common in effected brain areas. The observed pathological changes were most pronounced in mice compared to rats. Exposures to Cu and Ag nanoparticles showed most marked effects on brain pathology when administered into systemic circulation or into the brain ventricular spaces as compared to Al nanoparticles. Our results are the first to show that nanoparticles from metals are able to induce selective and specific neurotoxicity that depends on the type of metals, route of administration and the species used. PMID:19928185

Sharma, Hari S; Ali, Syed F; Hussain, Saber M; Schlager, John J; Sharma, Aruna

2009-08-01

74

Caveolin-1 Deletion Reduces Early Brain Injury after Experimental Intracerebral Hemorrhage  

PubMed Central

Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of morbidity and mortality. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in regulating signal transduction and cholesterol trafficking in cells. Although a recent study suggests a protective role of Cav-1 in cerebral ischemia, its function in ICH remains unknown. In this study, we examined the role of Cav-1 and in a model of collagenase-induced ICH and in neuronal cultures. Our results indicate that Cav-1 was up-regulated in the perihematomal area predominantly in endothelial cells. Cav-1 knockout mice had smaller injury volumes, milder neurologic deficits, less brain edema, and neuronal death 1 day after ICH than wild-type mice. The protective mechanism in Cav-1 knockout mice was associated with marked reduction in leukocyte infiltration, decreased expression of inflammatory mediators, including macrophage inflammatory protein (MIP)-2 and cyclooxygenase (COX)-2, and reduced matrix metalloproteinase-9 activity. Deletion of Cav-1 also suppressed heme oxygenase-1 expression and attenuated reactive oxygen species production after ICH. Moreover, deletion or knockdown of Cav-1 decreased neuronal vulnerability to hemin-induced toxicity and reduced heme oxygenase (HO)-1 induction in vitro. These data suggest that Cav-1 plays a deleterious role in early brain injury after ICH. Inhibition of Cav-1 may provide a novel therapeutic approach for the treatment of hemorrhagic stroke. PMID:21435456

Chang, Che-Feng; Chen, Shu-Fen; Lee, Tzong-Shyuan; Lee, Hung-Fu; Chen, Szu-Fu; Shyue, Song-Kun

2011-01-01

75

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

PubMed Central

Chronic administration of mood stabilizers to rats downregulates the brain arachidonic acid (AA) cascade. This downregulation may explain their efficacy against bipolar disorder (BD), in which brain AA cascade markers are elevated. The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act against BD. When given to rats, both reduce brain cyclooxygenase activity and prostaglandin E2 concentration; OLZ also reduces rat plasma unesterified and esterified AA concentrations, and AA incorporation and turnover in brain phospholipid. To test whether CLZ produces similar changes, we used our in vivo fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days; or 1 day after CLZ washout. [1-14C]AA was infused intravenously for 5 min, arterial plasma was collected and microwaved brain was analyzed. CLZ increased incorporation coefficients ki? and rates Jin,i of plasma unesterified AA into brain phospholipids i, while decreasing plasma unesterified but not esterified AA. These effects disappeared after washout. Thus, CLZ and OLZ similarly downregulated kinetics and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma unesterified AA availability. Atypical antipsychotics and mood stabilizers may be therapeutic in BD by downregulating, indirectly or directly respectively, the elevated brain AA cascade of that disease. PMID:23121637

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

2012-01-01

76

Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis  

PubMed Central

Background In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synthesis. In this study, we investigated the hypothesis that impaired LNAA influx relates to reduced cerebral protein synthesis. Methods Using positron emission tomography, L-[1-11C]-tyrosine (11C-Tyr) brain influx and incorporation into cerebral protein were studied in 16 PKU patients (median age 24, range 16 – 47 years), most of whom were early and continuously treated. Data were analyzed by regression analyses, using either 11C-Tyr brain influx or 11C-Tyr cerebral protein incorporation as outcome variable. Predictor variables were baseline plasma Phe concentration, Phe tolerance, age, and 11C-Tyr brain efflux. For the modelling of cerebral protein incorporation, 11C-Tyr brain influx was added as a predictor variable. Results 11C-Tyr brain influx was inversely associated with plasma Phe concentrations (median 512, range 233 – 1362 ?mol/L; delta adjusted R2=0.571, p=0.013). In addition, 11C-Tyr brain influx was positively associated with 11C-Tyr brain efflux (delta adjusted R2=0.098, p=0.041). Cerebral protein incorporation was positively associated with 11C-Tyr brain influx (adjusted R2=0.567, p<0.001). All additional associations between predictor and outcome variables were statistically nonsignificant. Conclusions Our data favour the hypothesis that an elevated concentration of Phe in blood reduces cerebral protein synthesis by impairing LNAA transport from blood to brain. Considering the importance of cerebral protein synthesis for adequate brain development and functioning, our results support the notion that PKU treatment be continued in adulthood. Future studies investigating the effects of impaired LNAA transport on cerebral protein synthesis in more detail are indicated. PMID:24007597

2013-01-01

77

Astaxanthin reduces ischemic brain injury in adult rats.  

PubMed

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

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

2009-06-01

78

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.

79

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

80

Could cord blood cell therapy reduce preterm brain injury?  

PubMed

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

81

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

82

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

PubMed

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

2013-10-01

83

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

84

Continuous Hyperosmolar Therapy for Traumatic Brain Injury-Associated Cerebral Edema: As Good as It Gets, or an Iatrogenic Secondary Insult?  

PubMed Central

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

2012-01-01

85

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

86

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

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

2014-01-01

87

Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing  

PubMed Central

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

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

2013-01-01

88

Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) is a major cause of preventable death and morbidity in young adults. This complex condition is characterized by significant blood brain barrier leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Recovery of function after TBI is partly through neuronal plasticity. In order to test whether treatments that enhance plasticity might improve functional recovery, a controlled cortical impact (CCI) in adult mice, as a model of TBI, in which a controlled cortical impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex, was performed. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family that maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether PEA shows efficacy in a mice model of experimental TBI. PEA treatment is able to reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level further support the efficacy of PEA therapy. The PEA treatment blocked infiltration of astrocytes and restored CCI-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, CD11b and GFAP. PEA inhibited the TBI-mediated decrease in the expression of pJNK and NF-?B. PEA-treated injured animals improved neurobehavioral functions as evaluated by behavioral tests. PMID:22884901

Ahmad, Akbar; Crupi, Rosalia; Impellizzeri, Daniela; Campolo, Michela; Marino, Angela; Esposito, Emanuela; Cuzzocrea, Salvatore

2012-11-01

89

Cilnidipine induced ankle edema.  

PubMed

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

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

2014-01-01

90

Cilnidipine induced ankle edema  

PubMed Central

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

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

2014-01-01

91

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

PubMed Central

Acute amyloid-? peptide (A?) deposition has been observed in young traumatic brain injury (TBI) patients, leading to the hypothesis that elevated extracellular A? levels could underlie the increased risk of dementia following TBI. However, a recent microdialysis-based study in human brain injury patients found that extracellular A? dynamics correlate with changes in neurological status. Because neurological status is generally diminished following injury, this correlation suggested the alternative hypothesis that soluble extracellular A? levels may instead be reduced after TBI relative to baseline. We have developed a methodologically novel mouse model that combines experimental controlled cortical impact TBI with intracerebral microdialysis. In this model, we found that A? levels in microdialysates were immediately decreased by 25–50% in the ipsilateral hippocampus following TBI. This result was found in PDAPP, Tg2576, and Tg2576-ApoE2 transgenic mice producing human A? plus wild-type animals. Changes were not due to altered probe function, edema, changes in APP levels, or A? deposition. Similar decreases in A? were observed in phosphate buffered saline-soluble tissue extracts. Hippocampal electroencephalographic activity was also decreased up to 40% following TBI, and correlated with reduced microdialysate A? levels. These results support the alternative hypothesis that post-injury extracellular soluble A? levels are acutely decreased relative to baseline. Reduced neuronal activity may contribute, though the underlying mechanisms have not been definitively determined. Further work will be needed to assess the dynamics of insoluble and oligomeric A? after TBI. PMID:20682338

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

2010-01-01

92

A new model of spinal cord edema.  

PubMed

Edema of the spinal cord has not been well understood. Brain edema produced by Marmarou's infusion method is essentially similar to vasogenic edema. This infusion method for producing edema was applied to a cat spinal cord. After laminectomy, a 30-gauge needle was inserted into the intumescentia cervicalis. A total amount of 10 microliters of 2% Evans' blue or autoserum were infused using an infusion pump at a rate of 5 microliters/hr. Macroscopally, Evans' blue was observed in the vicinity of infused site at the same level of the needle insertion and was seen spreading mainly longitudinally in the lateral column for a certain distance. The extracellular space was markedly distended in the in fused white mater and filled with electron-dense materials which were thought to be proteins in the electron microscopic study. The fine structural features were similar to the findings which were seen in Marmarou's infusion type of brain edema. Using this model, it seems to be feasible to produce reproducible spinal cord edema at any location in order to investigate not only the morphological aspect but also physiological aspect of the edema. PMID:9416351

Naruse, H; Tanaka, K; Kim, A; Hakuba, A

1997-01-01

93

Diagnostic and Prognostic Utility of Brain Natriuretic Peptide in Subjects Admitted to the ICU With Hypoxic Respiratory Failure Due to Noncardiogenic and Cardiogenic Pulmonary Edema  

PubMed Central

Background Brain natriuretic peptide (BNP) is useful in diagnosing congestive heart failure (CHF) in patients presenting in the emergency department with acute dyspnea. We prospectively tested the utility of BNP for discriminating ARDS vs cardiogenic pulmonary edema (CPE). Methods We enrolled ICU patients with acute hypoxemic respiratory failure and bilateral pulmonary infiltrates who were undergoing right-heart catheterization (RHC) to aid in diagnosis. Patients with acute coronary syndrome, end-stage renal disease, recent coronary artery bypass graft surgery, or preexisting left ventricular ejection fraction ? 30% were excluded. BNP was measured at RHC. Two intensivists independently reviewed the records to determine the final diagnosis. Results Eighty patients were enrolled. Median BNP was 325 pg/mL (interquartile range [IQR], 82 to 767 pg/mL) in acute lung injury/ARDS patients, vs 1,260 pg/mL (IQR, 541 to 2,020 pg/mL) in CPE patients (p = 0.0001). The correlation between BNP and pulmonary capillary wedge pressure was modest (r = 0.27, p = 0.02). BNP offered good discriminatory performance for the final diagnosis (C-statistic, 0.80). At a cut point ? 200 pg/mL, BNP provided specificity of 91% for ARDS. At a cut point ? 1,200 pg/mL, BNP had a specificity of 92% for CPE. Higher levels of BNP were associated with a decreased odds for ARDS (odds ratio, 0.4 per log increase; p = 0.007) after adjustment for age, history of CHF, and right atrial pressure. BNP was associated with in-hospital mortality (p = 0.03) irrespective of the final diagnosis and independent of APACHE (acute physiology and chronic health evaluation) II score. Conclusion In ICU patients with hypoxemic respiratory failure, BNP appears useful in excluding CPE and identifying patients with a high probability of ARDS, and was associated with mortality in patients with both ARDS and CPE. Larger studies are necessary to validate these findings. PMID:17426196

Karmpaliotis, Dimitri; Kirtane, Ajay J.; Ruisi, Christopher P.; Polonsky, Tamar; Malhotra, Atul; Talmor, Daniel; Kosmidou, Ioanna; Jarolim, Petr; de Lemos, James A.; Sabatine, Marc S.; Gibson, C. Michael; Morrow, David

2008-01-01

94

Changes in brain morphology in albinism reflect reduced visual acuity.  

PubMed

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

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

2014-07-01

95

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

96

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

PubMed

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

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

2013-11-01

97

Acute Blast Injury Reduces Brain Abeta in Two Rodent Species  

PubMed Central

Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The ?-amyloid (A?) peptide associated with the development of Alzheimer’s disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain A? following experimental blast injury using enzyme-linked immunosorbent assays for A? 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain A? levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the ?-secretase, ?-site APP cleaving enzyme 1, and the ?-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering A? production may not be effective for treating acute blast injury to the brain. PMID:23267342

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

2012-01-01

98

Etanercept Attenuates Traumatic Brain Injury in Rats by Reducing Brain TNF-? Contents and by Stimulating Newly Formed Neurogenesis  

PubMed Central

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF-? and/or stimulating newly formed neurogenesis. Rats that sustained TBI are immediately treated with etanercept. Acute neurological and motor injury is assessed in all rats the day prior to and 7 days after surgery. The numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain injury that occurred during TBI were counted by immunofluorescence staining. Enzyme immunoassay for quantitative determination of TNF-? or etanercept in brain tissues is also performed. Seven days after systemic administration of etanercept, levels of etanercept can be detected in the contused brain tissues. In addition, neurological and motor deficits, cerebral contusion, and increased brain TNF-? contents caused by TBI can be attenuated by etanercept therapy. Furthermore, the increased numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain tissues caused by TBI can be potentiated by etanercept therapy. These findings indicate that systemically administered etanercept may penetrate directly into the contused brain tissues and may improve outcomes of TBI by reducing brain contents of TNF-? and by stimulating newly formed neurogenesis. PMID:23710117

Cheong, Chong-Un; Chao, Chien-Ming; Cheng, Bor-Chih; Yang, Chung-Zhing; Chio, Chung-Ching

2013-01-01

99

STUDIES ON PULMONARY EDEMA  

PubMed Central

1. Bilateral cervical vagotomy in rabbits soon leads to death, usually within 8 to 24 hours. 2. Gradually increasing dyspnea, crises with expulsion of frothy, serous or sanguineous fluid from the mouth and nose, and terminal asphyxia are the important clinical features. 3. Postmortem examination reveals severe acute pulmonary edema and congestion, variable amounts of bronchopneumonia, and evidences of aspiration of food and secretions. This picture is similar to that found in the lungs in the bulbar form of poliomyelitis. 4. These changes are brought about by a combination of factors secondary to bilateral vagotomy: laryngeal paralysis (aspiration of food, slow asphyxia); loss of the vagal innervation of the lungs. 5. Laryngeal paralysis is not an essential factor in the production of severe pulmonary edema and death following bilateral cervical vagotomy. 6. To denote the pathogenesis of this type of edema, the term neuropathic pulmonary edema is employed. PMID:19870671

Farber, Sidney

1937-01-01

100

Ischemic Edema and Necrosis  

Microsoft Academic Search

Animal studies have substantially added to our understanding of the creation and development of vasogenic edema and necrosis\\u000a after stroke onset. T2 has emerged as the most commonly applied MR parameter to study this aspect of infarct evolution in\\u000a animal as well as in human stroke (Warach 2001). Although MRI monitoring of vasogenic edema is possible, there are still open

Susanne Wegener; Mathias Hoehn; Tobias Back

101

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

PubMed Central

Introduction Clinical and preclinical studies have shown that supplementation with ?-3 polyunsaturated fatty acids (?-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ?-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ?-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis. Methods Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 ?g/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection. Results The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA. Conclusions To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and anti-inflammatory effects as individual ?-3 PUFAs following sustained systemic and intraarticular administration in a mouse model of CFA-induced knee arthritis. The results suggest that DHA treatment may offer a new therapeutic approach to alleviate inflammation as well as a beneficial effect on pain-related functional disabilities in RA patients. PMID:24612981

2014-01-01

102

[Edema and the tropics].  

PubMed

People visiting or living in tropical or subtropical regions are exposed to various factors, which can lead to edema. Tourists staying for only a short time in the tropics are exposed to different risks, with other disease patterns, than people living in the tropics or immigrants from tropical regions. The differential diagnosis of edema and swelling is extensive and it can sometimes be difficult to distinguish classical edema with fluid retention in the extravascular interstitial space, from lymphedema or swelling due to other aetiologies. The patients often connect the edema to their stay in the tropics although it may have been pre-existing with no obvious relation to their travels. Already the long trip in the plane can lead to an "economy class syndrome" due to deep venous thrombosis. Contacts with animal or plant toxins, parasites or parasitic larvae can produce peripheral edema. The diagnosis can often only be made by taking a meticulous history, checking for eosinophilia and with the help of serological investigations. Chronic lymphedema or elephantiasis of the limbs is often due to blocked lymph vessels by filarial worms. It has to be distinguished from other forms as e.g. podoconiosis due to blockage by mineral particles in barefoot walking people. The trend to book adventure and trekking holidays at high altitude leads to high altitude peripheral edema or non-freezing cold injuries such as frostbites and trench foot. Edema can be an unwanted side effect of a range of drugs e.g. nifedipine, which is used to prevent and treat high altitude pulmonary edema. Protein malnutrition, (Kwashiorkor), and vitamin B6 deficiency, (Beri-Beri) are very rarely observed in immigrants and almost never in tourists. A very painful swelling of fingers and hands in children and young adults of African origin can be observed during a sickle cell crisis. Many protein loosing nephropathies connected with plant and animal toxins but also bacterial, viral or parasitic agents, can lead to edema. But very often edema in tourists or immigrants from the tropics is not related to their stay abroad. To take an accurate history of the itinerary, eating habits and exposure to water etc. is very important. Knowledge of the precise epidemiology and geographic distribution of diseases are essential. PMID:15605460

Holzer, B R

2004-11-01

103

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

Microsoft Academic Search

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

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

2008-01-01

104

Reduced Metabolic Response of the Aged Rat Brain to Haloperidol  

Microsoft Academic Search

Local cerebral glucose utilization (LCGU) was determined in 49 brain regions of 3-, 12-, 24-, and 33-month-old awake Fischer-344 rats, at 30 to 120 min after administration of the dopaminergic antagonist haloperidol (HAL) at 1 mg\\/kg (i.p.). The quantitative autoradiographic ('4C)-2-deoxyglucose technique was employed. In 3-month rats, HAL produced statistically significant (p c 0.05) reductions in LCGU in 63% of

TIMOTHY T. SONCRANT; HAROLD W. HOLLOWAY; STANLEY I. RAPOPORT

105

Immunization of rats reduces nicotine distribution to brain  

Microsoft Academic Search

The effect of active immunization against nicotine on the initial distribution of nicotine to brain was studied in anesthetized\\u000a rats. Animals received nicotine 0.03?mg\\/kg nicotine (equivalent to the nicotine dose absorbed by a human smoking two cigarettes)\\u000a as a rapid injection in the jugular vein. In control animals, the arterial serum nicotine concentration initially exceeded\\u000a the venous concentration 4.6-fold, similar

Yoko Hieda; Dan E. Keyler; John T. VanDeVoort; R. Sam Niedbala; Donna E. Raphael; Cathy A. Ross; Paul R. Pentel

1999-01-01

106

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.

107

Cystoid macular edema  

PubMed Central

We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME). Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin), ranibizumab (Lucentis), pegaptamid (Macugen), and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice. PMID:19668445

Rotsos, Tryfon G; Moschos, Marilita M

2008-01-01

108

Monthly Blood Transfusions Reduce Sickle Cell Anemia-Related Brain Injury in Children  

MedlinePLUS

... M. EDT Monthly blood transfusions reduce sickle cell anemia-related brain injury in children NIH-funded study ... in one third of children with sickle cell anemia, according to a study funded by the National ...

109

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

110

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

111

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

PubMed

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

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

2014-01-01

112

Chronic carbamazepine administration reduces NMDA receptor-initiated signaling via arachidonic acid in rat brain  

PubMed Central

Background Lithium and carbamazepine (CBZ) are used to treat mania in bipolar disorder. When given chronically to rats, both agents reduce brain arachidonic acid (AA) turnover in brain phospholipids and downstream AA metabolism. Lithium administration to rats also attenuates N-methyl-D-aspartic acid receptor (NMDAR) signaling via AA. Hypothesis Chronic CBZ administration to rats, like chronic lithium, will reduce NMDAR-mediated signaling via AA. Methods We used our fatty acid method with quantitative autoradiography to image the regional brain incorporation coefficient k* of AA, a marker of AA signaling, in unanesthetized rats that had been given 25 mg/kg/day i.p. CBZ or vehicle for 30 days, then injected with NMDA (25 mg/kg i.p.) or saline. We also measured brain concentration of two AA metabolites, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Results In chronic vehicle-treated rats, NMDA compared with saline increased k* significantly in 69 of 82 brain regions examined, but did not change k* significantly in any region in the CBZ-treated rats. In vehicle- but not CBZ-treated rats, NMDA also increased brain concentration of PGE2 and TXB2. Conclusions Chronic CBZ administration to rats blocks the brain NMDAR-mediated AA signal k* and the increments in PGE2 and TXB2 that are seen in vehicle-treated rats. The clinical action of antimanic drugs may involve inhibition of brain NMDAR-mediated signaling involving AA and its metabolites. PMID:17628508

Basselin, Mireille; Villacreses, Nelly E.; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.

2007-01-01

113

Disk Edema and Cranial MRI Optic Nerve Enhancement  

Microsoft Academic Search

A 43-year-old woman presented with painful visual loss and optic disk edema in the right eye (OD) diagnosed as optic neuritis. Initial non–gadolinium-enhanced fat suppressed cranial magnetic resonance imaging (MRI) was normal. Three months later, the disk edema persisted and a gadolinium-enhanced MRI scan of the brain and orbits with fat suppression showed enhancement of the optic nerve OD, most

Michael S Vaphiades

2001-01-01

114

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

115

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

PubMed

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 [(11)C]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; Masserini, Massimo; Re, Francesca

2014-10-15

116

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

117

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

118

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

119

Normal brain development in PS1 hypomorphic mice with markedly reduced ?-secretase cleavage of ?APP  

Microsoft Academic Search

Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced ?-secretase cleavage of ?APP. The assumption has been that facilitation of Notch signaling and ?APP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels (?1%

R Rozmahel; J Huang; F Chen; Y Liang; V Nguyen; M Ikeda; G Levesque; G Yu; M Nishimura; P Mathews; S. D Schmidt; M Mercken; C Bergeron; D Westaway; P St George-Hyslop

2002-01-01

120

Chronic administration of valproic acid reduces brain NMDA signaling via arachidonic acid in unanesthetized rats  

PubMed Central

Evidence that brain glutamatergic activity is pathologically elevated in bipolar disorder suggests that mood stabilizers are therapeutic in the disease in part by downregulating glutamatergic activity. Such activity can involve the second messenger, arachidonic acid (AA, 20:4n-6). We tested this hypothesis with regard to valproic acid (VPA), when stimulating glutamatergic N-methyl-D-aspartate (NMDA) receptors in rat brain and measuring AA and related responses. An acute subconvulsant dose of NMDA (25 mg/kg i.p.) or saline was administered to unanesthetized rats that had been treated i.p. daily with VPA (200 mg/kg) or vehicle for 30 days. Quantitative autoradiography following intravenous [1-14C]AA infusion was used to image regional brain AA incorporation coefficients k*, markers of AA signaling. In chronic vehicle-pretreated rats, NMDA compared with saline significantly increased k* in 41 of 82 examined brain regions, many of which have high NMDA receptor densities, and also increased brain concentrations of the AA metabolites, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). VPA pretreatment reduced baseline concentrations of PGE2 and TXB2, and blocked the NMDA induced increases in k* and in eicosanoid concentrations. These results, taken with evidence that carbamazepine and lithium also block k* responses to NMDA in rat brain, suggest that mood stabilizers act in bipolar disorder in part by downregulating glutamatergic signaling involving AA. PMID:18461450

Basselin, Mireille; Chang, Lisa; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.

2008-01-01

121

Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-?  

PubMed Central

Background Tumor necrosis factor-alpha (TNF-?) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-? antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-?. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-? expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-? was measured by Immunofluorescence staining. In addition, TNF? contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits. Results In addition to inducing brain ischemia as well as neurological and motor deficits, TBI caused significantly higher numbers of microglia-TNF-? double positive cells, but not neurons-TNF-? or astrocytes-TNF-? double positive cells in the injured brain areas than did the sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral ischemia, neurological motor deficits, and increased numbers of microglia-TNF-? double positive cells and increased TNF-? levels in the injured brain were all significantly attenuated by etanercept therapy. Conclusion This finding indicates that early microglia overproduction of TNF-? in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients. PMID:23496862

2013-01-01

122

Electroacupuncture reduces injury to the blood-brain barrier following cerebral ischemia/ reperfusion injury?  

PubMed Central

This study used electroacupuncture at Renzhong (DU26) and Baihui (DU20) in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results demonstrated that electroacupuncture markedly reduced neurological deficits, decreased corpus striatum aquaporin-4 protein and mRNA expression, and relieved damage to the blood-brain barrier in a rat model of cerebral ischemia/reperfusion injury. These results suggest that electroacupuncture most likely protects the blood-brain barrier by regulating aquaporin-4 expression following cerebral ischemia/reperfusion injury.

Peng, Yongjun; Wang, Hesheng; Sun, Jianhua; Chen, Li; Xu, Meijuan; Chu, Jihong

2012-01-01

123

Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.  

PubMed

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia. PMID:9700666

Schwab, M; Antonow-Schlorke, I; Zwiener, U; Bauer, R

1998-01-01

124

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

PubMed

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, P B 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

2014-10-01

125

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

PubMed Central

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA. PMID:21836043

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

2011-01-01

126

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

127

A microstructural study of spinal cord edema.  

PubMed

The experimental spinal cord edema was produced in a cat by the infusion method of Marmarou. Horseradish peroxidase (HRP) dissolved in autoserum of a cat was used as a tracer. After laminectomy, a 30-gauge needle was inserted into the intumescentia cervicalis. A total amount of 20 microliters of a tracer was infused at a rate of 10 microliters/hr. The structural features were studied immediately and 3 days after infusion. Immediately after infusion, HRP was noted in the infused white and gray matters. Though the perivascular space in the white matter at the infused site was widely distended and filled with HRP, the space in the gray matter was not distended but filled with HRP. HRP which was observed along vessels led to the surface of the spinal cord. Swelling of astrocyte was not observed. Three days after infusion, the extracellular space and the perivascular space in the infused white matter were still expanded but were not filled with HRP. The fine structural features were similar to the findings as seen in Marmarou's infusion type of brain edema. Using this model, it seems to be feasible to study the resolution process of spinal cord edema. PMID:11449985

Naruse, H; Tanaka, K; Kim, A

2000-01-01

128

Cerebral ischemia reduces expression of Hs1-associated protein X-1 (Hax-1) in mouse brain.  

PubMed

Hax-1, a multi-functional protein, recently was found to be involved in apoptosis and nerve system development. The purpose of this study was to detect the effect of cerebral ischemia on Hax-1 expression. We have detected the expression of Hax-1 in normal brain tissue and in ischemic brain tissue. Hax-1 was expressed in all brain regions detected with a level similar to the level of ?-actin. There were no differences in the expression of Hax-1 in different brain regions detected. The confocal images confirmed that neurons expressed Hax-1. The results of ischemic stroke in vivo indicated that Hax-1 level was significantly reduced at 24h after ischemia in the ischemic hemisphere, which was only 37%±4.8 of healthy hemisphere (p<0.05), and there was a strong reverse correlation between the level of Hax-1 and infarct size indicated by the regress analysis (R(2)=0.84). The expression of Hax-1 was also reduced in the cells subjected to oxygen/glucose deprivation (OGD) (p<0.01). The expression of Hax-1 was 87%±4.6, 78%±4.9 and 54%±8.2 of control in the murine brain endothelial cell (bEND5 cell) at 1h, 2h and 16h OGD, respectively. The Hax-1 level was 82%±7.3 and 61%±8.1 of control in neuronal cell line (neuro-2a cells) at 5h and 12h OGD, respectively. The percentage of neuro-2a cell death was 40%±11 induced by a 5h of OGD compared to only 10%±4.2 cell death in the control group (p<0.01). Our present study provides preliminary evidence of the effect of cerebral ischemia on Hax-1 expression. The expression of Hax-1 in normal brain tissue and reduction of Hax-1 in ischemic brain tissue indicate its possible involvement in pathophysiological functions in the brain. PMID:23262083

Hu, Jing; Mu, Chaofeng; Hao, Jiukuan

2013-02-01

129

Preischemic induction of TNF-? by physical exercise reduces blood–brain barrier dysfunction in stroke  

Microsoft Academic Search

This study explores the neuroprotective action of tumor necrosis factor-? (TNF-?) induced during physical exercise, which, consequently, reduces matrix metalloproteinase-9 (MMP-9) activity and ameliorates blood–brain barrier (BBB) dysfunction in association with extracellular signal-regulated kinase 1 and 2 (ERK1\\/2) phosphorylation. Adult male Sprague–Dawley rats were subjected to exercise on a treadmill for 3 weeks. A 2-h middle cerebral artery occlusion and

Miao Guo; Victoria Lin; William Davis; Tao Huang; Aaron Carranza; Shane Sprague; Raul Reyes; David Jimenez; Yuchuan Ding

2008-01-01

130

J Neurotrauma . Author manuscript Perfusional deficit and the dynamics of cerebral edemas in experimental  

E-print Network

was to characterize edema dynamics, cerebral blood volume and flow alterations in an experimental model of brainJ Neurotrauma . Author manuscript Page /1 9 Perfusional deficit and the dynamics of cerebral edemas, a 70 80 reduction in cerebral blood flow is% ­ % measured within the lesioned region. Transient

Paris-Sud XI, Université de

131

Hipertensión endocraneana secundaria a edema cerebral y la utilización de soluciones salinas hipertónicas y manitol en su tratamiento  

Microsoft Academic Search

SUMMARY: During the last years, the intracranial hypertension and brain edema has been studied in detail. Research drives us to find new and better treatments. We have made a short review about the classic definitions that are necessary to understand the physiology, physiopathology and treatment of the brain edema. We also compare the advantage and disadvantage between the traditional and

Susan Soto Pernudi; Jorge Fernández Alpízar

132

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

PubMed

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 have asked whether altered functional interactions between regions normally recruited provide an alternative adaptive mechanism with multiple sclerosis pathology. We used a version of the n-back task to probe working memory in patients with early multiple sclerosis. We applied a functional connectivity analysis to test whether relationships between relative activations in different brain regions change in potentially adaptive ways with multiple sclerosis. We studied 21 patients with relapsing-remitting multiple sclerosis and 16 age- and sex-matched healthy controls with 3T functional MRI. The two groups performed equally well on the task. Task-related activations were found in similar regions for patients and controls. However, patients showed relatively reduced activation in the superior frontal and anterior cingulate gyri (P > 0.01). Patients also showed a variable, but generally substantially smaller increase in activation than healthy controls with greater task complexity, depending on the specific brain region assessed (P < 0.001). Functional connectivity analysis defined further differences not apparent from the univariate contrast of the task-associated activation patterns. Control subjects showed significantly greater correlations between right dorsolateral prefrontal and superior frontal/anterior cingulate activations (P < 0.05). Patients showed correlations between activations in the right and left prefrontal cortices, although this relationship was not significant in healthy controls (P < 0.05). We interpret these results as showing that, while cognitive processing in the task appears to be performed using similar brain regions in patients and controls, the patients have reduced functional reserve for cognition relevant to memory. Functional connectivity analysis suggests that altered inter-hemispheric interactions between dorsal and lateral prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. Together, these results suggest that therapeutic enhancement of the coherence of interactions between brain regions normally recruited (functional enhancement), as well as recruitment of alternative areas or use of complementary cognitive strategies (both forms of adaptive functional change), may limit expression of cognitive impairments in multiple sclerosis. PMID:16251214

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

2006-02-01

133

Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.  

PubMed

Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1?, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor ?B nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis. PMID:25027327

Wilkins, Heather M; Harris, Janna L; Carl, Steven M; E, Lezi; Lu, Jianghua; Eva Selfridge, J; Roy, Nairita; Hutfles, Lewis; Koppel, Scott; Morris, Jill; Burns, Jeffrey M; Michaelis, Mary L; Michaelis, Elias K; Brooks, William M; Swerdlow, Russell H

2014-12-15

134

Postextubation pulmonary edema: an unusual cause of transient pulmonary edema.  

PubMed

We report a case of sudden onset of respiratory distress caused by pulmonary edema due to laryngospasm. The diagnosis was established by the clinical context and chest X-ray. A CT-scan was performed to narrow down the differential diagnosis and to confirm the diagnosis. Postextubation pulmonary edema due to laryngospasm is a rare entity with a typical clinical and radiographic presentation. PMID:23610874

Carels, K; Herpels, V; Cardoen, L; Lecluyse, C; Traen, S; Verschakelen, J

2013-01-01

135

Evaluation & design of a novel drug delivery device for treating tumor-related cerebral edema  

E-print Network

Tumor-related cerebral edema is a debilitating medical condition that afflicts tens of thousands of newly diagnosed brain cancer patients in the U.S. each year, where the standard care of treatment indicates the systemic ...

Shair, Kamal A. (Kamal Abdo)

2010-01-01

136

Limb remote ischemic post-conditioning reduces brain reperfusion injury by reversing eNOS uncoupling.  

PubMed

Limb remote ischemic postconditioning (LRIP) can reduce ischemia-reperfusion injury (IRI), but its mechanisms are still unclear. We hypothesize that LRIP reduces IRI by reversing eNOS uncoupling. Focal ischemia was induced in Sprague-Dawley rats by middle cerebral artery occlusion for 2 h followed by a 24 h reperfusion. Before this surgery, folic acid (FA) was administered to the drug treatment group by gavage for 11 days. After a 24 h reperfusion, behavioural testing, vascular function, NO concentration and superoxide dismutase activity in the serum were determined. In addition, the infarct size of the brain was also detected. The mRNA of eNOS, nNOS, GTP cyclohydrolase I (GTPCH), P22(phox) and xanthine oxidase (XO) in the ischemic region were detected by RT-PCR, and nitrotyrosine (Tyr-NO2) was detected using Western blot analysis. The results showed that LRIP, FA and FA+LRIP all could improve behavioural score, and increase NO-mediated endothelium-dependent vasomotor responses, reduce infarction of rats subjected to IRI. Western blot and RT-PCR analyses showed that the Tyr-NO2 levels and the mRNA expression of NADPH oxidase catalytic subunit P22(phox) and XO were up-regulated in the ischemic brain, which was significantly inhibited by LRIP, FA and FA+LRIP. The mRNA expression of the rate-limiting enzyme in BH4 synthesis, GTPCH, was down-regulated in the ischemic brain, which could be significantly augmented by LRIP and FA+LRIP. It can be concluded that IRI induces eNOS uncoupling in the cerebral ischemic region and LRIP partially reverses the eNOS uncoupling induced by IRI. PMID:24956890

Chen, Gangling; Yang, Jie; Lu, Guoxun; Guo, Jiaomei; Dou, Yannong

2014-06-01

137

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

Microsoft Academic Search

Background  Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical\\u000a scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more\\u000a than one year to evaluate the effect of edaravone which might reduce ischemic damage.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We sequentially enrolled acute

Taizen Nakase; Shotaroh Yoshioka; Akifumi Suzuki

2011-01-01

138

Glucose transport is reduced in the blood-brain barrier of aged rats.  

PubMed

To determine the biochemical basis of decreased brain uptake of glucose with age, the brain influx of 3-O-methylglucose (3-O-MG) was measured in male Fischer 344 rats at various ages using the arterial injection-tissue sampling technique of Oldendorf. The Vmax of 3-O-MG transport in the 24-month-old rats (0.22 +/- 0.14 mumol/min/g) was significantly lower than that in 3-month-old rats (0.88 +/- 0.18 mumol/min/g) (P less than 0.05). The Km of transport in aged rats (10.1 +/- 4.8 mM) was not different from that in young rats (8.1 +/- 2.5 mM). The cytochalasin B binding sites in cerebral microvessels isolated from aged rats (13.9 +/- 0.9 pmol/mg) compared to the binding sites in cerebral microvessels of young rats (21.9 +/- 1.4 pmol/mg) were significantly reduced (P less than 0.001). However, the immunoreactive mass of glucose transporter of cerebral microvessels was not altered with age. The enrichment of capillary preparations with gamma-glutamyl transpeptidase activity, a marker of endothelial cells, was not altered in aged rats, suggesting that the reduced blood-brain barrier transport of glucose is due to specific reduction in glucose binding sites of the transporter rather than secondary to a non-specific age-related effect of endothelial cell drop-out. PMID:1913147

Mooradian, A D; Morin, A M; Cipp, L J; Haspel, H C

1991-06-14

139

Reducing human error in P300 speller paradigm for brain-computer interface.  

PubMed

Since the brain-computer interface (BCI) speller paradigm was first introduced by Farwell and Donchin in 1988, there have been many visual modifications to the paradigm. Most of these changes involve the original matrix format such as changes in the number of rows and columns, font size and color, flash time vs. dark time, and flash order. However, recent studies show that there is human error in generating P300 based on this paradigm that none of these changes can help to reduce it. In this study, we analyze this type of error among three paradigms, two based on the matrix structure and one region-based paradigm. It is shown that the human error is reduced significantly in the region-based paradigm. PMID:23366523

Gavett, Scott; Wygant, Zachary; Amiri, Setare; Fazel-Rezai, Reza

2012-01-01

140

Blood-brain barrier transport of choline is reduced in the aged rat.  

PubMed

An age-related impairment in choline transport across the blood-brain barrier (BBB) may contribute to the cholinergic mechanisms of geriatric memory dysfunction. To test this hypothesis, the brain choline uptake in male Fisher 344 rats at 2, 18 and 24 months of age was studied using the Oldendorf technique. The Vmax of choline transport in the 24-month-old rats (0.05 +/- 0.04 nmol/min/g) was significantly lower than that in the 2-month-old rat (2.5 +/- 1.0 nmol/min/g) (P less than 0.05). The Km of transport in old rats (13 +/- 35 microM) was also significantly smaller than the value in 24-month-old rats (450 +/- 195 microM), while the constant of the non-saturable component of the transport, Kd, was not significantly different in older rats (1.2 +/- 0.3 vs 0.6 +/- 0.1 microliter/min/g). These results indicate that the carrier in old rats has reduced capacity and increased affinity to choline. The reduced choline carrier capacity explains the significant decrease in BBB choline transport in aged rats. PMID:3359216

Mooradian, A D

1988-02-01

141

Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats.  

PubMed

Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to determine whether DBS delivered to either the shell or core of the NAcc would reduce ETOH intake in rats using a two-bottle choice limited access procedure. Long Evans rats were induced to drink a 10% ethanol solution using a saccharin fading procedure. Bipolar electrodes were implanted bilaterally into either the core or shell of the NAcc. During testing animals received DBS 5 min prior to and during a 30-minute test session in which both ETOH and water bottles were accessible. Current was delivered at amplitudes ranging from 0 to 150 microA. ETOH consumption was significantly reduced from baseline levels at the 150 microA current for both shell and core electrode placements. A significant current effect was not found for water consumption for either site. These results provide evidence that DBS delivered either to the nucleus accumbens core or shell subregions can significantly reduce ethanol intake in the rat. PMID:19463262

Knapp, Clifford M; Tozier, Lisa; Pak, Arlene; Ciraulo, Domenic A; Kornetsky, Conan

2009-05-01

142

Recurrent Negative Pressure Pulmonary Edema  

PubMed Central

An African-American man, aged 34 years, underwent an elective uncomplicated right wrist laceration repair while under general anesthesia. Following extubation, the patient developed hypoxemia, tachypnea, shortness of breath, pulmonary rales, frothy sputum, decreased oxygen saturation, and evidence of upper airway obstruction. Chest radiograph showed pulmonary edema. The patient was diagnosed with post-extubation pulmonary edema (aka. negative pressure pulmonary edema [NPPE]) and was treated with intravenous furosemide and oxygen therapy; he improved remarkably within a few hours. Once stabilized, the patient described a similar episode 10 years earlier following surgery for multiple gunshot wounds. Negative pressure pulmonary edema following tracheal extubation is an uncommon (0.1%) and life-threatening complication of patients undergoing endotracheal intubation and general anesthesia for surgical procedures. The common pattern in these cases is the occurrence of an episode of airway obstruction upon emergence from general anesthesia, usually caused by laryngospasm. Patients who are predisposed to airway obstruction may have an increased risk of airway complications upon extubation after general anesthesia. Prevention and early relief of upper airway obstruction should decrease incidence. Recurrent NPPE has not been previously described in the literature. Herein, we describe the first case of recurrent NPPE in the same patient following extubation. PMID:20852091

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

2011-01-01

143

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

144

A?1-42 reduces P-glycoprotein in the blood-brain barrier through RAGE-NF-?B signaling.  

PubMed

The reduced clearance of amyloid-? peptide (A?) from the brain partly accounts for the neurotoxic accumulation of A? in Alzheimer's disease (AD). Recently, it has been suggested that P-glycoprotein (P-gp), which is an efflux transporter expressed on the luminal membrane of the brain capillary endothelium, is capable of transporting A? out of the brain. Although evidence has shown that restoring P-gp reduces brain A? in a mouse model of AD, the molecular mechanisms underlying the decrease in P-gp expression in AD is largely unknown. We found that A?1-42 reduced P-gp expression in the murine brain endothelial cell line bEnd.3, which was consistent with our in vivo data that P-gp expression was significantly reduced, especially near amyloid plaques in the brains of five familial AD mutations (5XFAD) mice that are used as an animal model for AD. A neutralizing antibody against the receptor for advanced glycation end products (RAGE) and an inhibitor of nuclear factor-kappa B (NF-?B) signaling prevented the decrease in A?1-42-induced P-gp expression, suggesting that A? reduced P-gp expression through NF-?B signaling by interacting with RAGE. In addition, we observed that the P-gp reduction by A? was rescued in bEnd.3 cells receiving inductive signals or factors from astrocytes making contacts with endothelial cells (ECs). These results support that alterations of astrocyte-EC contacts were closely associated with P-gp expression. This suggestion was further supported by the observation of a loss of astrocyte polarity in the brains of 5XFAD mice. Taken together, we found that P-gp downregulation by A? was mediated through RAGE-NF-?B signaling pathway in ECs and that the contact between astrocytes and ECs was an important factor in the regulation of P-gp expression. PMID:24967961

Park, R; Kook, S-Y; Park, J-C; Mook-Jung, I

2014-01-01

145

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

146

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

147

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

148

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

149

Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum.  

PubMed

Brain cells expend large amounts of energy sequestering calcium (Ca(2+)), while loss of Ca(2+) compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum (ER) to sequester Ca(2+). This led to the hypothesis that G6P regulates Ca(2+) accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA). Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, (45)Ca(2+) accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi) coupled with Ca(2+) accumulation was quantified. Addition of G6P significantly and decreased Ca(2+) accumulation in a dose-dependent fashion (1-10 mM). The reduction in Ca(2+) accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca(2+) accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca(2+) uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca(2+) dystasis caused by altered G6P regulation of SERCA activity. PMID:22529775

Cole, Jeffrey T; Kean, William S; Pollard, Harvey B; Verma, Ajay; Watson, William D

2012-01-01

150

Hypothermia modulates cytokine responses after neonatal rat hypoxic-ischemic injury and reduces brain damage.  

PubMed

While hypothermia (HT) is the standard-of-care for neonates with hypoxic ischemic injury (HII), the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24?hr after HII with HT (32?; n?=?18) or normothermia (NT, 35?; n?=?15). Outcomes included magnetic resonance imaging (MRI), neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72?hr post-HII). Lesion volumes (24?hr) were reduced in HT pups (total 74%, p?reduced interleukin-1? (IL-1?) at all time points (p?reduces total and penumbral lesion volumes (at 24 and 48?hr), potentially by decreasing IL-1? without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72?hr post-HII when IL-1? levels remained low suggests that after rewarming, mechanisms unrelated to IL-1? expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury. PMID:25424430

Yuan, Xiangpeng; Ghosh, Nirmalya; McFadden, Brian; Tone, Beatriz; Bellinger, Denise L; Obenaus, Andre; Ashwal, Stephen

2014-10-01

151

Connectivity of Default-Mode Network Is Associated with Cerebral Edema in Hepatic Encephalopathy  

Microsoft Academic Search

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt

Wei-Che Lin; Tun-Wei Hsu; Chao-Long Chen; Changwei W. Wu; Cheng-Hsien Lu; Hsiu-Ling Chen; Shau-Hsuan Li; Pin-Yang Yeh; Yu-Fan Cheng; Ching-Po Lin

2012-01-01

152

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

153

Melatonin reduces phosphine-induced lipid and DNA oxidation in vitro and in vivo in rat brain.  

PubMed

Phosphine (PH(3)), a widely used pesticide, was found in our recent study to induce oxidative damage in the brain, liver and lung of rats. We also observed that melatonin significantly blocked this action. The present study focused on brain and the magnitude and mechanism of protection of PH(3)-induced oxidative damage by melatonin in vitro and in vivo. PH(3) in whole brain homogenate (3 mg protein/mL Tris-HCl pH 7.4 buffer) induced increasing lipid peroxidation [as malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] dependent on concentration (0.25-2 mM) and time (30-150 min), reaching a maximum level of 2.9-fold at 90 min after PH(3) at 1 mM. Elevation of MDA + 4-HDA levels by PH(3) at 1 mM was also observed in homogenates of cerebral cortex, cerebellum, hippocampus and hypothalamus examined individually. Melatonin at 0.1-2 mM progressively inhibited PH(3)-induced lipid peroxidation in brain and regions thereof. Additionally, PH(3) induced brain DNA oxidation in vitro and in vivo determined as 8-hydroxyguanosine (8-OH-dG). Melatonin at 1 mM significantly suppressed PH(3)-induced brain DNA oxidation in vitro. PH(3) at 4 mg/kg i.p. significantly elevated 8-OH-dG in frontal cortex and melatonin prevented it. PH(3) in vivo marginally lowered brain glutathione peroxidase activity and melatonin restored it completely. In contrast, PH(3) and melatonin both stimulated superoxide dismutase production. Brain glutathione (GSH) levels in PH(3)-treated rats were significantly reduced at 30 min and recovered gradually. It is concluded that melatonin, probably because of its free radical scavenging ability, confers marked protection against PH(3)-induced oxidative toxicity in brain. PMID:11841601

Hsu, Ching-Hung; Chi, Bei-Ching; Casida, John E

2002-01-01

154

Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain  

PubMed Central

Objective: HIV-associated neurocognitive deficits remain a challenge despite suppressive combined antiretroviral therapy. Given the association between HIV-induced central nervous system (CNS) disease and replication of HIV in immune-activated macrophages, CCR5 antagonists may attenuate CNS disease by modulating inflammatory signaling and by limiting viral replication. Design: To establish whether initiating CCR5 inhibition during early infection altered CNS disease progression, outcomes were compared between simian immunodeficiency virus (SIV)-infected macaques treated with maraviroc (MVC) versus untreated SIV-infected macaques. Methods: Six SIV-infected rhesus macaques were treated with MVC monotherapy for 5 months beginning 24 days postinoculation; 22 SIV-infected animals served as untreated controls. SIV RNA levels in plasma, cerobrospinal fluid, and brain, and CNS expression of TNF? and CCL2 were measured by qRT-PCR. Immunostaining for CD68 and amyloid precursor protein in the brain was measured by image analysis. Plasma sCD163 was measured by ELISA. Results: SIV RNA and proviral DNA levels in brain were markedly lower with MVC treatment, demonstrating CCR5 inhibition reduces CNS replication of SIV and may reduce the CNS latent viral reservoir. MVC treatment also lowered monocyte and macrophage activation, represented by CNS CD68 immunostaining and plasma sCD163 levels, and reduced both TNF? and CCL2 RNA expression in brain. Treatment also reduced axonal amyloid precursor protein immunostaining to levels present in uninfected animals, consistent with neuroprotection. Conclusion: CCR5 inhibitors may prevent neurologic disorders in HIV-infected individuals by reducing inflammation and by limiting viral replication in the brain. Furthermore, CCR5 inhibitors may reduce the latent viral reservoir in the CNS. Adding CCR5 inhibitors to combined antiretroviral regimens may offer multiple neuroprotective benefits. PMID:24051706

Kelly, Kathleen M.; Beck, Sarah E.; Pate, Kelly A. Metcalf; Queen, Suzanne E.; Dorsey, Jamie L.; Adams, Robert J.; Avery, Lindsay B.; Hubbard, Walter; Tarwater, Patrick M.; Mankowski, Joseph L.

2013-01-01

155

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

156

Radiosurgery Facilitates Resection of Brain Arteriovenous Malformations and Reduces Surgical Morbidity  

PubMed Central

OBJECTIVE Stereotactic radiosurgery makes brain arteriovenous malformations (AVM) more manageable during their microsurgical resection. To better characterize these effects, we compared results of microsurgical resection of radiated (RS+) and non-radiated (RS?) AVMs to demonstrate that prior radiosurgery facilitates surgery and decreases operative morbidity. METHODS From of series of 344 patients who had AVM resections at the University of California, San Francisco (1997–2007), 21 RS+ patients were matched with 21 RS? patients based on pre-treatment clinical and AVM characteristics. Matching was blinded to outcomes, which were assessed with the modified Rankin Scale (mRS). RESULTS Mean AVM volume was reduced by 78% (P<0.01) and Spetzler-Martin grades were reduced in 52% of RS+ patients (P < 0.001). Preoperative embolization was used less in RS+ than in RS? patients (P< 0.001). Mean operative time (P< 0.01), blood loss (P < 0.05), and length of hospital stay (P< 0.05) were lower in the RS+ group. Surgical morbidity was 14% higher in RS? patients, and they had significant worsening in mRS scores after surgery while RS+ patients did not (P<0.01). RS+ patients deteriorated between AVM diagnosis and surgery due to hemorrhages during the latency period (P< 0.05). CONCLUSION Prior radiosurgery facilitates AVM microsurgery and decreases operative morbidity. Radiosurgery is recommended for unruptured AVMs that are not favorable for microsurgical resection. Microsurgical resection is recommended for radiated AVMs that are not completely obliterated after the 3-year latency period, but altered favorably for surgery, even in asymptomatic patients. Prompt resection of persistent AVMs should be considered to avoid the risk of post-latency hemorrhage and to optimize patient outcomes. PMID:19057424

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

2010-01-01

157

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

PubMed

Niemann-Pick Type C (NPC) disease is a devastating developmental disorder with progressive and fatal neurodegeneration. Previous work has shown that a single injection of the neurosteroid allopregnanolone at postnatal day 7 significantly prolonged lifespan of Npc1-/- mice. However, the cellular/molecular basis for this beneficial effect remains undefined. Here, we further characterized the effect of allopregnanolone treatment on cholesterol accumulation, a pathological hallmark of NPC, as well as on autophagic/lysosomal dysfunction, myelination and inflammation in Npc1-/- mouse brains. At 1 month postnatal, accumulation of filipin-labeled unesterified cholesterol was clearly evident not only in neurons but also in microglia in untreated mutant mice, but was mostly absent in allopregnanolone-treated animals. Brain levels of the lysosomal enzymes cathepsins B and D were significantly higher in Npc1-/- than in wild-type mice. Levels of LC3-II, an autophagy marker, were also increased in mutant mouse brain as compared to wild-type mouse brain. Both changes were significantly reduced by allopregnanolone treatment. Injection of the neurosteroid also significantly reduced astrocyte proliferation and microglial activation. Furthermore, allopregnanolone treatment significantly enhanced myelination in mutant mice. Taken together, our results clearly show that allopregnanolone treatment not only reduces cholesterol accumulation and improves autophagic/lysosomal function but also enhances myelination and reduces inflammation. These results provide further support for the potential usefulness of allopregnanolone for treating NPC disease. PMID:19328188

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

2009-05-13

158

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

PubMed

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 4h 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 4h 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

2013-02-01

159

Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats  

Microsoft Academic Search

Growing literature suggests important sex-based differences in outcome following traumatic brain injury (TBI) in animals and humans. Progesterone has emerged as a key hormone involved in many potential neuroprotective pathways after acute brain injury and may be responsible for some of these differences. Many studies have utilized supraphysiologic levels of post-traumatic progesterone to reverse pathologic processes after TBI, but few

Courtney L. Robertson; April Puskar; Gloria E. Hoffman; Anne Z. Murphy; Manda Saraswati; Gary Fiskum

2006-01-01

160

Conjugated deferoxamine reduces blood-brain barrier disruption in experimental optic neuritis.  

PubMed

The purpose of this paper was to investigate the role of deferoxamine (DFO) scavenging of hydroxyl radical (.OH) on disruption of the blood-brain barrier (BBB) and demyelination in experimental optic neuritis. Eighteen strain-13 guinea pigs were sensitized for experimental allergic encephalomyelitis. Nine animals received 100 mg/kg of hydroxyethyl starch-conjugated (HES) DFO by daily intraperitoneal injection commencing the day of antigenic sensitization. Nine paired litter mates received daily IP injections of HES. Serial fat-suppressed magnetic resonance imaging of the optic nerves was obtained with a T2 weighting (T2w) to evaluate demyelination and after intravascular administration of Gd-DTPA to evaluate BBB disruption. The intensity of Gd-DTPA enhancement and T2w signal of the optic nerves was quantitated 3, 7, 10 and 14 days after antigenic sensitization. Animals were then sacrificed and the optic nerves processed for light and transmission electron microscopy with ultracytochemical localization of endogenous hydrogen peroxide (H2O2) and immunogold colocalization of extravasated serum albumin. The area of the optic nerve head, intensity of toluidine blue staining, and the cellular infiltrate were digitized and quantitated. Administration of HES-DFO significantly reduced the intensity of Gd-DTPA enhancement in the optic nerves of HES-DFO-treated animals compared to paired control HES animals (p = 0.0236), with the mean difference between control and treated animals of 19.39. The difference in T2w signal was not significant (p = 0.39), with a mean difference between control and treated animals of -5.51. The intensity of toluidine blue staining of optic nerve specimens was slightly less with HES-DFO compared to untreated animals (mean pair difference 2.48), and the inflammatory infiltrate was reduced with HES-DFO compared to untreated animals (mean pair difference = 61.57); these differences were not statistically significant. In the optic nerve specimens of both groups cerium perhydroxide-derived H2O2 reaction product was evident in a predominantly perivascular and perineural distribution. Immunogold-labeled serum albumin showed extravasation at foci of perivascular inflammation in both the presence and absence of H2O2-derived reaction product. Conjugated DFO reduces disruption of the BBB, as measured by Gd-DTPA enhancement, suggesting the .OH radical generated from perivascular H2O2 may play a role in alterations of vascular permeability in experimental optic neuritis. PMID:7533278

Guy, J; McGorray, S; Qi, X; Fitzsimmons, J; Mancuso, A; Rao, N

1994-01-01

161

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

PubMed

We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca2+ accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 ?M) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca2+ accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat acute ischemic stroke. PMID:24953828

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

2014-10-01

162

Connectivity of Default-Mode Network Is Associated with Cerebral Edema in Hepatic Encephalopathy  

PubMed Central

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p?=?0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis. PMID:22623966

Lin, Wei-Che; Hsu, Tun-Wei; Chen, Chao-Long; Wu, Changwei W.; Lu, Cheng-Hsien; Chen, Hsiu-Ling; Li, Shau-Hsuan; Yeh, Pin-Yang

2012-01-01

163

Protective effect of ginkgolide B on high altitude cerebral edema of rats.  

PubMed

Ginkgolide B (GB) is one of the ginkgolides isolated from leaves of the Ginkgo biloba tree. The aim of this study was to investigate whether GB has a protective effect on high altitude cerebral edema (HACE) of rats. HACE was induced by hypobaric hypoxia exposure for 24 hours in an animal decompression chamber with the chamber pressure of 267 mmHg to simulate an altitude of 8000 m. Before the exposure, three doses (3, 6, and 12 mg·kg(-1)) of GB were given intraperitoneally (ip) daily for 3 days. Effects of GB on brain water content (BWC), activity of superoxide dismutase (SOD), concentration of glutathione (GSH) and malondialdehyde (MDA), expression of active caspase-3 and poly(ADP-ribose) polymerase (PARP) were measured. In GB pretreatment groups (6 and 12 mg·kg(-1), but not 3 mg·kg(-1)), BWC, the concentration of MDA, the expression of active caspase-3 and PARP were reduced significantly, while the activity of SOD and concentration of GSH were significantly increased. In conclusion, these results indicate that GB has a protective effect on cerebral edema caused by high altitude in rats. The protective effect of GB might be attributed to its antioxidant properties and suppression of the caspase-dependent apoptosis pathway. PMID:23537262

Botao, Yu; Ma, Jie; Xiao, Wenjing; Xiang, Qingyu; Fan, Kaihua; Hou, Jun; Wu, Juan; Jing, Weihua

2013-03-01

164

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain[S  

PubMed Central

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID:22058426

Larsen, Scott D.; Wilson, Michael W.; Abe, Akira; Shu, Liming; George, Christopher H.; Kirchhoff, Paul; Showalter, H. D. Hollis; Xiang, Jianming; Keep, Richard F.; Shayman, James A.

2012-01-01

165

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

166

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...

167

Reexpansion pulmonary edema in children  

PubMed Central

OBJECTIVE To present a case of a patient with clinical and radiological features of reexpansion pulmonary edema, a rare and potentially fatal disease. CASE DESCRIPTION An 11-year-old boy presenting fever, clinical signs and radiological features of large pleural effusion initially treated as a parapneumonic process. Due to clinical deterioration he underwent tube thoracostomy, with evacuation of 3,000 mL of fluid; he shortly presented acute respiratory insufficiency and needed mechanical ventilation. He had an atypical evolution (extubated twice with no satisfactory response). Computerized tomography findings matched those of reexpansion edema. He recovered satisfactorily after intensive care, and pleural tuberculosis was diagnosed afterwards. COMMENTS Despite its rareness in the pediatric population (only five case reports gathered), the knowledge of this pathology and its prevention is very important, due to high mortality rates. It is recommended, among other measures, slow evacuation of the pleural effusion, not removing more than 1,500 mL of fluid at once. PMID:24142327

Rodrigues, Antonio Lucas L.; Lopes, Carlos Eduardo; Romaneli, Mariana Tresoldi das N.; Fraga, Andrea de Melo A.; Pereira, Ricardo Mendes; Tresoldi, Antonia Teresinha

2013-01-01

168

Diabetic Macular Edema: Current and Emerging Therapies  

PubMed Central

Diabetic macular edema is a leading cause of vision impairment among people within the working- age population. This review discusses the pathogenesis of diabetic macular edema and the treatment options currently available for the treatment of diabetic macular edema, including for focal/grid photocoagulation, intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor agents. The biologic rationale for novel therapeutic agents, many of which are currently being evaluated in clinical trials, also is reviewed. PMID:22346109

Wenick, Adam S.; Bressler, Neil M.

2012-01-01

169

Absence of TLR4 Reduces Neurovascular Unit and Secondary Inflammatory Process after Traumatic Brain Injury in Mice  

PubMed Central

Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. Toll-like receptors (TLRs) are signaling receptors in the innate immune system, although emerging evidence indicates their role in brain injury. We have therefore investigated the role played by TLR4 signaling pathway in the development of mechanisms of secondary inflammatory process in traumatic brain injury (TBI) differ in mice that lack a functional TLR4 signaling pathway. Methods/Principal Findings Controlled cortical impact injury was performed on TLR4 knockout (KO) mice (C57BL/10ScNJ) and wild-type (WT) mice (C57BL/10ScNJ). TBI outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected at 24 h after TBI. When compared to WT mice, TLR4 KO mice had lower infarct volumes and better outcomes in neurological and behavioral tests (evaluated by EBST and rotarod test). Mice that lacked TLR4 had minor expression of TBI-induced GFAP, Chymase, Tryptase, IL-1?, iNOS, PARP and Nitrotyrosine mediators implicated in brain damage. The translocation of expression of p-JNK, I?B-? and NF-?B pathway were also lower in brains from TLR4 KO mice. When compared to WT mice, resulted in significant augmentation of all the above described parameters. In addition, apoptosis levels in TLR4 KO mice had minor expression of Bax while on the contrary with Bcl-2. Conclusions/Significance Our results clearly demonstrated that absence of TLR4 reduces the development of neuroinflammation, tissues injury events associated with brain trauma and may play a neuroprotective role in TBI in mice. PMID:23555560

Campolo, Michela; Genovese, Tiziana; Esposito, Emanuela; Cuzzocrea, Salvatore

2013-01-01

170

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

171

Mild Hypothermia Reduces Tissue Plasminogen Activator-Related Hemorrhage and Blood Brain Barrier Disruption After Experimental Stroke  

PubMed Central

Therapeutic hypothermia has shown neuroprotective promise, but whether it can be used to improve outcome in stroke has yet to be determined in patients. Recombinant tissue plasminogen activator (rt-PA) is only given to a minority of patients with acute ischemic stroke, and is not without risk, namely significant brain hemorrhage. We explored whether mild hypothermia, in combination with rt-PA, influences the safety of rt-PA. Mice were subjected to middle cerebral artery occlusion (MCAO) using a filament model, followed by 24 hours reperfusion. Two paradigms were studied. In the first paradigm, cooling and rt-PA treatment began at the same time upon reperfusion, whereas in the second paradigm, cooling began soon after ischemia onset, and rt-PA began after re-warming and upon reperfusion. Experimental groups included: tPA treatment at normothermia (37°C), rt-PA treatment at hypothermia (33°C), no rt-PA at normothermia, and no rt-PA treatment at hypothermia. Infarct size, neurological deficit scores, blood brain barrier (BBB) permeability, brain hemorrhage, and expression of endogenous tissue plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor (PAI-1) were assessed. For both paradigms, hypothermia reduced infarct size and neurological deficits compared to normothermia, regardless of whether rt-PA was given. rt-PA treatment increased brain hemorrhage and BBB disruption compared to normothermia, and this was prevented by cooling. However, mortality was higher when rt-PA and cooling were administered at the same time, beginning 1–2 hours post MCAO. Endogenous tPA expression was reduced in hypothermic mice, whereas PAI-1 levels were unchanged by cooling. In the setting of rt-PA treatment, hypothermia reduces brain hemorrhage, and BBB disruption, suggesting that combination therapy with mild hypothermia and rt-PA appears safe. PMID:23781399

Tang, Xian Nan; Liu, Liping; Koike, Maya A.

2013-01-01

172

Brain BDNF levels elevation induced by physical training is reduced after unilateral common carotid artery occlusion in rats.  

PubMed

We investigated the contribution of blood flow elevation in the cerebrovasculature to physical training-induced brain-derived neurotrophic factor (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein levels were measured in the motor cortex 24?h after the last session of a forced treadmill walking (30?minutes a day, 18?m/minute for 7 consecutive days). Unilateral common carotid artery occlusion and modulation of exercise intensity (0 versus -10% inclination of the treadmill) were used as strategies to reduce the (normal) elevation of flow in the cerebrovasculature occurring during exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60?mg/kg before each exercise sessions) and genetic hypertension (spontaneously hypertensive rats) were used as approaches to reduce stimulation of nitric oxide production in response to shear stress elevation. Vascular occlusion totally and partially abolished the effect of physical training on BDNF levels in the hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels were higher after high than low exercise intensity. In addition, both genetic hypertension and L-NAME treatment blunted the effects of physical training on BDNF. From these results, we propose that elevation of brain BDNF levels elicited by physical training involves changes in cerebral hemodynamics. PMID:25052557

Banoujaafar, Hayat; Hoecke, Jacques Van; Mossiat, Claude M; Marie, Christine

2014-10-01

173

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

174

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

175

Brain acetylcholinesterase, malondialdehyde and reduced glutathione as biomarkers of continuous exposure of tench, Tinca tinca, to carbofuran or deltamethrin  

Microsoft Academic Search

In this study, the chronic effect of the insecticides carbofuran and deltamethrin on acetylcholinesterase (AChE) activity and malondialdehyde (MDA) and reduced glutathione (GSH) levels were examined in the brain of tench. Both pesticides were evaluated in two separate experiments, and animals were exposed in a continuous flow-system to three different concentrations of carbofuran (0, 10 and 100?g\\/L) and deltamethrin (0,

D. Hernández-Moreno; F. Soler; M. P. Míguez; M. Pérez-López

2010-01-01

176

Single Administration of Tripeptide ?-MSH(11-13) Attenuates Brain Damage by Reduced Inflammation and Apoptosis after Experimental Traumatic Brain Injury in Mice  

PubMed Central

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

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

2013-01-01

177

Predominant vasogenic edema in a patient with fatal cerebral air embolism.  

PubMed

Cerebral air embolism (CAE) is a rare neurologic complication that can occur in patients undergoing various medical procedures or trauma. CAE can sometimes result in death caused by severe brain edema. In spite of these implications, the pathophysiologic mechanisms and radiologic features of fatal CAE remain to be elucidated. In this case report, a patient with carcinomatous pleuritis lost consciousness and developed quadriplegia and had generalized seizures during intrathoracic lavage. Serial computed tomography (CT) revealed the presence of air in intracranial blood vessels following severe brain edema; these are typically observed on the CT scans of patients with fatal CAE. Diffusion-weighted imaging (DWI) of the brain obtained at 24 hours after the onset of CAE revealed scattered cortical gyriform high signal intensity often observed in CAE cases, whereas the apparent diffusion coefficient and T2-weighted imaging revealed diffuse hyperintensity in the subcortical deep white matter, indicating vasogenic edema. Our case showed predominant vasogenic edema rather than cortical ischemic changes in the subcortical deep white matter area. These findings indicate that diffuse subcortical vasogenic edema could be the main cause of mortality in fatal CAE. PMID:21185741

Tanaka, Ryota; Shimada, Yoshiaki; Shimura, Hideki; Oizumi, Hideki; Hattori, Nobutaka; Tanaka, Shigeki

2012-08-01

178

Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide  

PubMed Central

Background Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in the inflammatory process. The objective of the current study was to examine whether celecoxib, a selective COX-2 inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction and sensorimotor behavioral impairments. Methods Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in rat pups on postnatal Day 5 (P5), and celecoxib (20 mg/kg) or vehicle was administered (i.p.) five minutes after LPS injection. Sensorimotor behavioral tests were carried out 24 h after LPS exposure, and brain injury was examined on P6. Results Our results showed that LPS exposure resulted in impairment in sensorimotor behavioral performance and injury to brain dopaminergic neurons, as indicated by loss of tyrosine hydroxylase (TH) immunoreactivity, as well as decreases in mitochondria activity in the rat brain. LPS exposure also led to increases in the expression of ?-synuclein and dopamine transporter proteins and enhanced [3H]dopamine uptake. Treatment with celecoxib significantly reduced LPS-induced sensorimotor behavioral disturbances and dopaminergic neuronal dysfunction. Celecoxib administration significantly attenuated LPS-induced increases in the numbers of activated microglia and astrocytes and in the concentration of IL-1? in the neonatal rat brain. The protective effect of celecoxib was also associated with an attenuation of LPS-induced COX-2+ cells, which were double labeled with TH + (dopaminergic neuron) or glial fibrillary acidic protein (GFAP) + (astrocyte) cells. Conclusion Systemic LPS administration induced brain inflammatory responses in neonatal rats; these inflammatory responses included induction of COX-2 expression in TH neurons and astrocytes. Application of the COX-2 inhibitor celecoxib after LPS treatment attenuated the inflammatory response and improved LPS-induced impairment, both biochemically and behaviorally. PMID:23561827

2013-01-01

179

[Clinical symptoms and symptomatic management of brain metastases].  

PubMed

Cancer patients frequently develop brain metastases. Symptomatic treatments are important to stabilize these patients before an oncological procedure (usually radiotherapy, sometimes surgery or chemotherapy) can be started. These symptomatic treatments mainly rely on steroids to reduce the peritumoral edema; anti-epileptic drugs for patients who previously had seizures, and low-molecular-weight heparin for patients at risk of thrombo-embolic events. PMID:21540137

Kallel, Ahmed; Bailon, Olivier; Carpentier, Antoine F

2011-04-01

180

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

ERIC Educational Resources Information Center

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

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

2012-01-01

181

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

ERIC Educational Resources Information Center

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

Wade, Shari L.; Carey, Joanne; Wolfe, Christopher R.

2006-01-01

182

Immunomodulation by poly-YE reduces organophosphate-induced brain damage  

Microsoft Academic Search

Accidental organophosphate poisoning resulting from environmental or occupational exposure, as well as the deliberate use of nerve agents on the battlefield or by terrorists, remain major threats for multi-casualty events, with no effective therapies yet available. Even transient exposure to organophosphorous compounds may lead to brain damage associated with microglial activation and to long-lasting neurological and psychological deficits. Regulation of

Arseny Finkelstein; Gilad Kunis; Tamara Berkutzki; Ayal Ronen; Amir Krivoy; Eti Yoles; David Last; Yael Mardor; Kerry Van Shura; Emylee McFarland; Benedict A. Capacio; Claire Eisner; Mary Gonzales; Danise Gregorowicz; Arik Eisenkraft; John H. McDonough; Michal Schwartz

183

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

PubMed Central

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

2013-01-01

184

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

Microsoft Academic Search

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

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

2001-01-01

185

Brain imaging: Reduced sensitivity of RARE-derived techniques to susceptibility effects  

SciTech Connect

Our goal was to evaluate the decreased sensitivity of RARE-derived pulse sequences to susceptibility effects. A variety of RARE-derived T2-weighted fast SE echo (FSE) sequences with echo trains from 6 to 16 were compared with conventional SE (CSE) sequences by means of MRI in phantoms (iron oxides), volunteers (n = 10), and patients (n = 13) with old hemorrhagic brain lesions. All experiments were performed on a 1.5 T clinical MR system (Magnetom SP 4000; Siemens AG, Erlangen, Germany) with constant imaging parameters. Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations and brain areas with physiological iron deposition (red nucleus, substantia nigra) were calculated for CSE and FSE pulse sequences. Areas of old brain hemorrhage were analyzed for lesion conspicuity by blinded analysis with CSE as an internal standard. CNR of iron oxide tubes (TE 90 ins, CSE 45.0 {+-} 3.5, FSE 16 echo trains 28.5 {+-} 3. 1; p {le} 0.01) and iron-containing brain areas decreased with increasing echo trains of FSE sequences. A significantly lower number of old hemorrhagic brain lesions was visible in patients scanned with FSE sequences (6 echo trains: n = 28; 16 echo trains: n = 26) than CSE (n = 40). Our results demonstrate that the sensitivity of RARE-derived techniques to susceptibility effects is significantly decreased compared with CSE. CSE sequences or GE sequences should still be preferred in patients with a history of seizures or intracranial hemorrhage. 25 refs., 3 figs., 1 tabs.

Reimer, P.; Allkemper, T.; Schuierer, G.; Peters, P.E. [Westfalian Wilhelms-Univ. Muenster, Muenster (Germany)] [Westfalian Wilhelms-Univ. Muenster, Muenster (Germany)

1996-03-01

186

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

187

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

PubMed Central

Background Hyaluronidase (Hylase Dessau®) is a hyaluronic acid-metabolizing enzyme, which has been shown to loosen the extracellular matrix, thereby improving the diffusion of local anesthetics. Lower eyelid edema is a common post-interventional complication of cosmetic procedures performed in the lid region, such as the injection of hyaluronic acid fillers for tear-trough augmentation. The purpose of this study was to validate the efficacy of hyaluronidase in the management of lower eyelid edema. Methods We performed a retrospective analysis with 20 patients with lower eyelid edema. Most patients (n?=?14) presented with edema following hyaluronic acid injection (tear-trough augmentation), whereas the minority (n?=?6) were treated due to idiopathic edema (malar edema or malar mounds). Patients were treated by local infiltration of approximately 0.2 ml to 0.5 ml of hyaluronidase (Hylase Dessau® 20 IU to 75 IU) per eyelid. Photographs were taken prior to and seven days after infiltration. Results Hyaluronidase was found to reduce effectively and rapidly or resolve eyelid edema after a single injection. No relevant adverse effects were observed. However, it must be noted that a hyaluronidase injection may also dissolve injected hyaluronic acid fillers and may therefore negatively affect tear-trough augmentations. While the effects of a treatment for edema due to tear-trough augmentation were permanent, malar edema and malar mounds reoccurred within two to three weeks. Conclusion The infiltration of hyaluronidase is rapid, safe and currently the only effective option for the management of eyelid edema. No relevant adverse effects were observed. PMID:24886711

2014-01-01

188

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

189

Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma  

Microsoft Academic Search

Traumatic brain injury (TBI) causes both direct and delayed tissue damage. The latter is associated with secondary biochemical changes such as cell cycle activation, which leads to neuronal death, inflammation, and glial scarring. Flavopiridol—a cyclin-dependent kinase (CDK) inhibitor that is neither specific nor selective—is neuroprotective. To examine the role of more specific CDK inhibitors as potential neuroprotective agents, we studied

Genell D Hilton; Bogdan A Stoica; Kimberly R Byrnes; Alan I Faden

2008-01-01

190

Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat brain  

Microsoft Academic Search

Summary.  The brain and cerebrospinal fluid levels of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation\\u000a and antagonist of the glycineB receptor and the ?7 nicotinic acetylcholine receptor, are elevated in persons with schizophrenia. To evaluate whether this\\u000a increase is related to antipsychotic medication, we examined the effects of haloperidol (HAL), clozapine (CLOZ) or raclopride\\u000a (RAC) on

G. Ceresoli-Borroni; A. Rassoulpour; H.-Q. Wu; P. Guidetti; R. Schwarcz

2006-01-01

191

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

Microsoft Academic Search

ObjectiveGender 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.MethodTo test this we compared brain metabolism (using PET and 18FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral

Nora D. Volkow; Dardo Tomasi; Gene-Jack Wang; Joanna S. Fowler; Frank Telang; Rita Z. Goldstein; Nelly Alia-Klein; Christopher Wong; Kenji Hashimoto

2011-01-01

192

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

PubMed Central

We investigated the role of ERK1/2 in the brain on the effects of centrally administered resistin on thermogenesis. Resistin (7 ?g) into anaesthetized rats significantly decreased brown adipose tissue temperature by 1.0 ± 0.4 °C (P < 0.005). This response was significantly attenuated by over 60% when ERK1/2 was inhibited by U0126 (7 ?g) (P < 0.05). Resistin reduced uncoupling protein-1 mRNA expression (0.11 ± 0.01 vs 1.24 ± 0.85 resistin vs control respectively) and the expression of peroxisome proliferator-activated receptor gamma co-activator 1-?, but the effects were not statistically significant. The results suggest that ERK1/2 in the brain contributes to resistin’s effects on thermogenesis. PMID:24044038

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

2013-01-01

193

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

PubMed

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

2013-11-19

194

Local and systemic treatments for acute edema after burn injury: a systematic review of the literature.  

PubMed

Burn injury is a complex trauma that results in local and generalized edema. Edema fluid limits the exchange of vital nutrients in healing the burn wound and will compromise vulnerable tissues. Although the importance of edema control in tissue salvage is recognized, treatments targeted at edema control have not been critically reviewed. Thus, the objective was to assess the evidence for the effectiveness of local and systemic treatments for edema management immediately after burn injury. Searches for randomized controlled trials were conducted of online databases, research and thesis registers, and grey literature repositories. Handsearches included journals, bibliographies, and proceedings. Authors were contacted to clarify and submit extra study details. Eight studies were included. Management of acute major burn resuscitation including colloid increases lung edema (mean difference [MD], 0.04 ml/ml alv vol; 95% confidence interval [CI], 0.03-0.04; P < .00001) and mortality (risk ratio, 3.67; 95% CI, 1.16-11.58; P = .03). Continuous administration of vitamin C in acute burn resuscitation reduces local wound edema (MD, -3.50 ml/g; 95% CI, -4.63 to -2.37; P < .00001) and systemic fluid retention (MD, -8.60 kg; 95% CI, -13.47 to -3.73; P = .0005). Local acute hand burn edema is reduced (MD, -29.00 ml; 95% CI, -53.14 to -4.86; P = .02), and active hand motion increased (MD, 10.00°; 95% CI, 4.58-15.42; P = .0003), using electrical stimulation with usual physiotherapy. Each review outcome was based on a small single-facility study. Thus, future research in intervention for acute burn edema must focus on multicentre trials and validation of outcome measures in the burn population. PMID:21252688

Edgar, Dale Wesley; Fish, Joel S; Gomez, Manuel; Wood, Fiona Melanie

2011-01-01

195

Observation of post-MCAO cortical inflammatory edema in rats by 7.0 Tesla MRI.  

PubMed

This study aimed to investigate inflammatory edema after cerebral ischemia through 7.0T MRI and proton magnetic resonance spectroscopy (MRS). All SD rats were randomly divided into sham operated group and middle cerebral artery occlusion (MCAO)-1 day, -3 day and -7 day groups. MRI scan of the brain was performed on a 7.0 Tesla MRI scanner. The volume of positive signals in the ischemic side was detected by using a T2 weighted spinecho multislice sequence; the changes in the height of water-peak were measured with point resolved spectroscopy (PRESS) sequences; cortical edema was detected by using wet-dry weight method; the degrees of nerve injury were evaluated by Bederson neurological score system; double-labeling immunofluorescence technique was used to explore the molecular mechanisms of post-ischemia cerebral edema. The results showed that high T2WI signals were observed in MCAO-1 day, -3 day and -7 day groups, and the water-peak height and water-peak area of MCAO groups were higher than those of sham operated group (P<0.05). Neurological score results were consistent with the degree of brain edema, and a large number of microglia accumulated in the ischemic cortex. Our results suggested that non-invasive MRI technology with the advantage of high spatial resolution and tissue resolution can comprehensively and dynamically observe inflammatory edema after cerebral ischemia from a three-dimensional space, and contribute to evaluation and treatments in clinic. PMID:24496690

Xiong, Ying; Zhu, Wen-zhen; Zhang, Qiang; Wang, Wei

2014-02-01

196

Reduced brain reward response during cooperation in first-degree relatives of patients with psychosis: an fMRI study.  

PubMed

Background. Psychosis is characterized by a profound lack of trust and disturbed social interactions. Investigating the neural basis of these deficits is difficult because of medication effects but first-degree relatives show qualitatively similar abnormalities to patients with psychosis on various tasks. This study aimed to investigate neural activation in siblings of patients in response to an interactive task. We hypothesized that, compared to controls, siblings would show (i) less basic trust at the beginning of the task and (ii) reduced activation of the brain reward and mentalizing systems. Method. Functional magnetic resonance imaging (fMRI) data were acquired on 50 healthy siblings of patients with psychosis and 33 healthy controls during a multi-round trust game with a cooperative counterpart. An a priori region-of-interest (ROI) analysis of the caudate, temporoparietal junction (TPJ), superior temporal sulcus (STS), insula and medial prefrontal cortex (mPFC) was performed focusing on the investment and repayment phases. An exploratory whole-brain analysis was run to test for group-wise differences outside these ROIs. Results. The siblings' behaviour during the trust game did not differ significantly from that of the controls. At the neural level, siblings showed reduced activation of the right caudate during investments, and the left insula during repayments. In addition, the whole-brain analysis revealed reduced putamen activation in siblings during investments. Conclusions. The findings suggest that siblings show aberrant functioning of regions traditionally involved in reward processing in response to cooperation, which may be associated with the social reward deficits observed in psychosis. PMID:25065732

Gromann, P M; Shergill, S S; de Haan, L; Meewis, D G J; Fett, A-K J; Korver-Nieberg, N; Krabbendam, L

2014-12-01

197

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

198

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

199

Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels  

PubMed Central

Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca2+-activated K+ channel (BKCa) channels, and BKCa channel blockade suppressed the neuroprotection of the extract, suggesting that the BKCa is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BKCa channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BKCa channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BKCa channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia. PMID:21364615

Chi, S; Cai, W; Liu, P; Zhang, Z; Chen, X; Gao, L; Qi, J; Bi, L; Chen, L; Qi, Z

2010-01-01

200

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

PubMed

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

2013-07-12

201

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain.  

PubMed

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID:22058426

Larsen, Scott D; Wilson, Michael W; Abe, Akira; Shu, Liming; George, Christopher H; Kirchhoff, Paul; Showalter, H D Hollis; Xiang, Jianming; Keep, Richard F; Shayman, James A

2012-02-01

202

Novel inhibitors of Anthrax edema factor  

PubMed Central

Several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema factor (EF) of Bacillus anthracis. These disturb cellular metabolism by catalyzing production of excessive amounts of the regulatory molecule cAMP. Here, a structure-based method, where a 3D- pharmacophore that fit the active site of EF was constructed from fragments, was used to identify non-nucleotide inhibitors of EF. A library of small molecule fragments was docked to the EF- active site in existing crystal structures and those with the highest HINT scores were assembled into a 3D-pharmacophore. About 10,000 compounds, from over 2.7 million compounds in the ZINC database, had a similar molecular framework. These were ranked according to their docking scores, using methodology that was shown to achieve maximum accuracy (i.e., how well the docked position matched the experimentally determined site for ATP analogues in crystal structures of the complex). Finally, 19 diverse compounds with the best AutoDock binding/docking scores were assayed in a cell based assay for their ability to reduce cAMP secretion induced by EF. Four of the test compounds, from different structural groups, inhibited in the low micromolar range. One of these has a core structure common to phosphatase inhibitors previously identified by high-throughput assays of a diversity library. Thus, the fragment based pharmacophore identified a small number of diverse compounds for assay, and greatly enhanced the selection process of advanced lead compounds for combinatorial design. PMID:18620864

Chen, Deliang; Misra, Milind; Sower, Laurie; Peterson, Johnny W.; Kellogg, Glen E.; Schein, Catherine H.

2008-01-01

203

The effect of sleep-specific brain activity versus reduced stimulus interference on declarative memory consolidation.  

PubMed

Studies suggest that the consolidation of newly acquired memories and underlying long-term synaptic plasticity might represent a major function of sleep. In a combined repeated-measures and parallel-group sleep laboratory study (active waking versus sleep, passive waking versus sleep), we provide evidence that brief periods of daytime sleep (42.1 ± 8.9 min of non-rapid eye movement sleep) in healthy adolescents (16 years old, all female), compared with equal periods of waking, promote the consolidation of declarative memory (word-pairs) in participants with high power in the electroencephalographic sleep spindle (sigma) frequency range. This observation supports the notion that sleep-specific brain activity when reaching a critical dose, beyond a mere reduction of interference, promotes synaptic plasticity in a hippocampal-neocortical network that underlies the consolidation of declarative memory. PMID:23398120

Piosczyk, Hannah; Holz, Johannes; Feige, Bernd; Spiegelhalder, Kai; Weber, Friederike; Landmann, Nina; Kuhn, Marion; Frase, Lukas; Riemann, Dieter; Voderholzer, Ulrich; Nissen, Christoph

2013-08-01

204

Traumatic Brain Injury May Increase the Risk for Frontotemporal Dementia through Reduced Progranulin  

PubMed Central

Frontotemporal lobar degeneration with TAR-DNA-binding protein inclusions (FTLD-TDP) is the most common pathological subtype of frontotemporal dementia (FTD). Mutations leading to a loss of function in the progranulin gene (PGRN) are the most common known cause of FTLD-TDP. In agreement with the proposed loss of function disease mechanism, several groups have reported decreased plasma levels of PGRN in patients carrying PGRN mutations compared to individuals without PGRN mutations. We propose that traumatic brain injury (TBI), an environmental factor, may also increase the risk of FTD by altering PGRN metabolism. TBI may lead to an increase in the central nervous system levels of microglial elastases, which proteolyze PGRN into proinflammatory products called granulins causing a reduction in PGRN levels. Hence, inhibiting microglial activation may have an important implication for the prevention of FTD in patients with TBI. PMID:20145419

Jawaid, Ali; Rademakers, Rosa; Kass, Joseph S.; Kalkonde, Yogeshwar; Schulz, Paul E.

2010-01-01

205

Gonadectomy reduces the concentrations of putative receptors for arginine vasotocin in the brain of an amphibian.  

PubMed

Putative receptors for arginine vasotocin (AVT) in the brain of the newt (Taricha granulosa) were measured using quantitative autoradiography with tritium-labelled vasopressin. Specific binding sites were observed in the olfactory bulb, medial (hippocampal) pallium, dorsal pallium, amygdala para lateralis and tegmental region of the medulla oblongata. In both male and female newts, concentrations of binding sites in the amygdala, but not in the other four areas, were significantly lower in gonadectomized animals than in sham-operated controls. The equilibrium dissociation constants (KdS) were not altered by gonadectomy. Since long-tem castration abolishes the effect of AVT injection on sexual behaviors, these results support the hypothesis that gonadal steroids maintain sexual behaviors in this amphibian by maintaining AVT receptors in the amygdala. PMID:2054637

Boyd, S K; Moore, F L

1991-02-15

206

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier  

PubMed Central

BACKGROUND Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB). METHODS CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema. RESULTS Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P <.001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 ?m/min, P <.001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 ?m, P <.01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P <.01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05). CONCLUSIONS PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation. PMID:24112683

Pascual, Jose L.; Murcy, Mohammad A.; Li, Shenghui; Gong, Wanfeng; Eisenstadt, Rachel; Kumasaka, Kenichiro; Sims, Carrie; Smith, Douglas H.; Browne, Kevin; Allen, Steve; Baren, Jill

2014-01-01

207

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

PubMed

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

Irwin, Lynn G; Fortune, Dónal G

2014-03-01

208

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

PubMed Central

Background We report our findings in three cases of unilateral macular edema associated with retinal vein occlusion (RVO) that improved after successful treatment of systemic hypertension alone. Methods All three cases had systemic hypertension but no diabetes mellitus or other ocular diseases associated with macular edema. All patients were treated only with medication for systemic hypertension. Optical coherence tomography was performed to determine the foveal thickness before and after treatment. Results Case one was a 72-year-old woman with a central RVO who had macular edema in her left eye and a visual acuity (VA) of 20/50. Her blood pressure (BP) was 169/96 mmHg. One month after the initiation of a calcium blocker to treat her systemic hypertension, her BP was decreased, macular edema was reduced, and her VA improved to 20/20. Case two was a 62-year-old woman with branch RVO. Her VA was 20/40 and her BP was 165/97 mmHg. Six weeks after initiation of medication to treat her systemic hypertension, her RVO-related macular edema had decreased and her VA improved to 20/20. Case three was a 71-year-old man with branch RVO. His VA was 20/50 and his BP was 165/87 mmHg. One month after initiation of treatment for systemic hypertension, his RVO-related macular edema had disappeared and his VA improved to 20/20. All three cases had nonischemic RVO by fluorescein angiography, and they did not develop ischemic changes for at least 1 year. Conclusion The reduction of macular edema following a decrease in the systemic hypertension suggests that the edema was most likely caused by leakage of fluids from the blood vessels. We recommend that the blood pressure should be measured in all patients with macular edema before initiating intravitreal anti-VEGF therapy. PMID:24876761

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

2014-01-01

209

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

210

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

211

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

PubMed

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

Tasker, Robert C; Acerini, Carlo L

2014-06-01

212

Brain injury-induced proteolysis is reduced in a novel calpastatin overexpressing transgenic mouse  

PubMed Central

The calpain family of calcium-dependent proteases has been implicated in a variety of diseases and neurodegenerative pathologies. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components and membrane receptors, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains. Pharmacological and gene knockout strategies have targeted calpains to determine their contribution to neurodegenerative pathology; however, limitations associated with treatment paradigms, drug specificity, and genetic disruptions have produced inconsistent results and complicated interpretation. Specific, targeted calpain inhibition achieved by enhancing endogenous calpastatin levels offers unique advantages in studying pathological calpain activation. We have characterized a novel calpastatin overexpressing transgenic mouse model, demonstrating a substantial increase in calpastatin expression within nervous system and peripheral tissues and associated reduction in protease activity. Experimental activation of calpains via traumatic brain injury resulted in cleavage of ?-spectrin, collapsin response mediator protein-2, and voltage-gated sodium channel, critical proteins for the maintenance of neuronal structure and function. Calpastatin overexpression significantly attenuated calpain-mediated proteolysis of these selected substrates acutely following severe controlled cortical impact injury, but with no effect on acute hippocampal neurodegeneration. Augmenting calpastatin levels may be an effective method for calpain inhibition in TBI and neurodegenerative disorders. PMID:23305291

Schoch, Kathleen M.; von Reyn, Catherine R.; Bian, Jifeng; Telling, Glenn C.; Meaney, David F.; Saatman, Kathryn E.

2013-01-01

213

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

214

Low Intensity Millimeter Waves Reduce the Brain Bioelectrical Activity Reactions, Arising from the Mobile Phone EMF  

Microsoft Academic Search

The protection action of millimeter wave electromagnetic irradiation is demonstrated for the case of mobile telephone communication. Antenna-coupled Gunn diode or FET oscillator were used as a source of the irradiation. Double blind testing was performed with 54 volunteers. A microminiature EHF generator, inserted to the handset, can reduce the negative effects of the mobile telephone electromagnetic field.

V. E. Lyubchenko; O. V. Betski; N. N. Lebedeva; V. D. Kotov; E. O. Yunevich

215

Radiation-induced edema after Gamma Knife treatment for meningiomas.  

PubMed

A retrospective study was performed to analyze some parameters in a consecutive series of 35 Gamma Knife treatments in 34 patients with benign meningiomas. The minimum dose to the tumors was never less than 12 Gy. The follow-up period was from 1 to 3 years. A semiquantitative method of tumor volume assessment was used to measure the tumor response to treatment. The presence and clinical significance of postradiation edema were noted. Even in this short follow-up period, 11 of the 35 tumors were reduced in volume. No tumors increased in size. Edema developed preferentially in nonbasal tumors, especially those around the midline and sagittal sinus. In all but one case where radiation-induced edema was observed was the margin tumor dose 18 Gy or more. It is suggested that doses of 18 Gy or more should probably be avoided in the Gamma Knife treatment of meningiomas and that the greatest care should be taken in selecting non-skull base tumors for this form of treatment. PMID:9032853

Ganz, J C; Schröttner, O; Pendl, G

1996-01-01

216

The historical discovery of macular edema.  

PubMed

The occurrence of macular edema, or of intraretinal fluid in general, was largely unknown prior to the invention of the ophthalmoscope. One of the first reports on 'Retinitis in Glycosuria', a disease complex, which today would partly be described as diabetic maculopathy, was published in 1856 by Jaeger. His observations were confirmed less than twenty years later by Nettleship in London, and in 1875 Appolinaire Bouchardat from Paris described fluid and lipid accumulation in the macula which led--in his words--to a glucose induced amblyopia. The first pathophysiological hypotheses of fluid accumulation in the posterior pole were then put forward in 1882 by Tartuferi, who thought the edema represented swelling of photoreceptor sheaths. In 1896, the Frenchman Nuel coined the term 'oedème maculaire' which he had observed in a retinitis pigmentosa patient. However, it was not until the end of the first World War, that the Swiss ophthalmologist Alfred Vogt observed macular edema in a variety of other ocular conditions such as iridocyclitiOFF macular edema to a macular hole. A quarter of a century later Bangerter coined the German term 'Zystoides Makulaödem', and in 1950, Hruby was the first to draw attention to the development of macular edema after cataract extraction. Three years later this was followed by Irvine's classical paper on cystoid macular edema after intra- and extracapsular cataract extraction which had been complicated by incarceration of the vitreous in the anterior segment with consecutive tugging on the macula. A decade later, the phenomenon of cystic fluid accumulation in the macula after cataract extraction was further characterised by Gass and Norton using fluorescein angiography. The ensuing years saw the emergence of new concepts regarding the blood-retinal barrier and the paramount role of its dysfunction in the development of macular edema. PMID:10896334

Wolfensberger, T J

1999-01-01

217

Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury  

PubMed Central

Background The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Methods Pregnant ewes (n?=?18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n?=?6), or were ventilated using an injurious high VT strategy (LPSINJ; n?=?5) or a protective ventilation strategy (LPSPROT; n?=?7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. Results LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Conclusions Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis. PMID:25379714

Barton, Samantha K.; Moss, Timothy J. M.; Hooper, Stuart B.; Crossley, Kelly J.; Gill, Andrew W.; Kluckow, Martin; Zahra, Valerie; Wong, Flora Y.; Pichler, Gerhard; Galinsky, Robert; Miller, Suzanne L.

2014-01-01

218

The burn edema process: current concepts.  

PubMed

Massive tissue edema after thermal injury is a well-recognized entity. Although this process is responsible for the patient's large fluid needs during resuscitation and also for local problems, such as a compartment syndrome, there have been no effective treatment modalities introduced into clinical care to control the degree of edema. A review of what is now known about the edema process is presented here, including attempted prevention and treatment modalities. The pathogenesis involves changes in most of the physical forces controlling fluid flux across the capillary and also how fluid accumulates in the interstitium. Increased capillary permeability to protein is but one of these changes. The presence of an initial profound negative interstitial pressure "sucking" fluid into the tissues and a marked increase in interstitial space compliance are equally important components. A host of mediators, especially oxidants, have been reported to cause these physical changes, and some mediator inhibitors appear to be of benefit, especially antioxidants. However, few clinical trials, aimed at decreasing edema, have been performed. With these new insights into the edema process, future prevention and treatment modalities can be developed. PMID:15879742

Demling, Robert H

2005-01-01

219

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

220

Insufficient Intake of l-Histidine Reduces Brain Histamine and Causes Anxiety-Like Behaviors in Male Mice.  

PubMed

l-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. l-histidine is also important as a precursor of histamine. Brain histamine is synthesized from l-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary l-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g l-histidine/kg diet) or the low l-histidine diet (LHD) (1.28 g l-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice. PMID:25056690

Yoshikawa, Takeo; Nakamura, Tadaho; Shibakusa, Tetsuro; Sugita, Mayu; Naganuma, Fumito; Iida, Tomomitsu; Miura, Yamato; Mohsen, Attayeb; Harada, Ryuichi; Yanai, Kazuhiko

2014-10-01

221

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.  

PubMed

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia. PMID:19529857

Zarubina, I V; Shabanov, P D

2009-03-01

222

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

223

Diabetic papillopathy with macular edema treated with intravitreal ranibizumab  

PubMed Central

We report a case of diabetic papillopathy that demonstrated a resolution of optic disk swelling and rapid visual recovery when intravitreal ranibizumab was administered. A 51-year-old male presented with acute painless visual loss in his right eye. His vision was 20/320 in the right eye and 20/50 in the left eye. Fundus examination of the right eye showed nonproliferative diabetic retinopathy with macular edema and a swollen optic disk. Fluorescein angiography showed dye leakage from the right optic disk. Optical coherent tomography revealed a significant increase in retinal nerve fiber-layer thickness. Magnetic resonance imaging of the brain was normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks following injection, there was marked regression of the disk swelling and improvement of macular edema, with vision improving to 20/100. Three months following injection, there was complete resolution of the optic disk swelling. No further treatment was required. PMID:24348012

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

2013-01-01

224

Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in A?PP/PS1 transgenic mouse brain.  

PubMed

Metal dyshomeostasis in the brain helps promote amyloid-? (A?) deposition in Alzheimer's disease (AD). Therefore, targeting the interactions between metal and A? is a potential therapeutic approach for AD. The metal chelator, clioquinol (CQ), is thought to reduce A? deposits in the AD transgenic mouse brain, and attenuate the clinical symptoms of AD patients. However, whether oral administration of CQ reduces zinc accumulation in A? plaques and inhibits the amyloidogenic pathway have not been properly established in AD transgenic mice. By means of autometallographic analysis, we show for the first time that both the number and size of the zinc-containing plaques were significantly reduced in the brain of amyloid-? protein precursor (A?PP)/presenilin 1 (PS1) double transgenic mice treated with CQ (30 mg/kg/day) orally for 2 months. This was accompanied by a reduction in A? burden in the CQ-treated mouse brain. Furthermore, CQ treatment markedly reduced the expression levels of A?PP protein, the ?-site of A?PP cleaving enzyme 1 (BACE1), PS1, and the secreted ?-secretase-derived fragments of A?PP (sA?PP?). The present data indicate that CQ is able to reduce zinc accumulation in the neuritic plaques and inhibit amyloidogenic A?PP processing in the A?PP/PS1 mouse brain. PMID:22269164

Wang, Tao; Wang, Chun-Yan; Shan, Zhong-Yan; Teng, Wei-Ping; Wang, Zhan-You

2012-01-01

225

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

226

Establishment and evaluation of an experimental animal model of high altitude cerebral edema.  

PubMed

The aim of our study was to develop a model of high altitude cerebral edema (HACE) using an acute, hypobaric hypoxia environment combined with exhaustive exercise. Forty healthy male Sprague-Dawley rats were randomly divided into a plains control group (PC group) and a plateau altitude hypoxia group (AH group). After 2 days of treadmill adaptation under normoxic conditions, the AH group was housed in hypobaric conditions (simulating 4000 m above sea level) for 2 days while performing exhaustive exercise. The simulated altitude was then increased to 8000 m for 3 days of simple hypobaric hypoxia exposure. Compared with the PC group, the AH group showed significantly greater (P<0.01) water content and Evans blue staining in their brain tissue. Furthermore, the hippocampal formation was seriously damaged, and the number of pyramidal cells decreased. In addition, the brain structure was altered into a loose state with notable edema, which was demonstrated by the leakage of lanthanum nitrate particles from brain microvessels into the surrounding tissue through widened tight junctions. Some neurons and glial cell organelles were swollen and some nerve fibers were demyelinated as well. We have shown that acute hypobaric hypoxia exposure with exhaustive exercise increases the permeability of the blood-brain barrier and leads to cerebral edema, making this a valid animal model of HACE. PMID:23680461

Guo, Ping; Luo, Han; Fan, Yong; Luo, Yongjun; Zhou, Qiquan

2013-06-28

227

Disruption of ion homeostasis in the neurogliovascular unit underlies the pathogenesis of ischemic cerebral edema.  

PubMed

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; Walcott, Brian P; Gerzanich, Volodymyr; Simard, J Marc

2014-02-01

228

Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.  

PubMed

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. PMID:25080597

Biddinger, Jessica E; Fox, Edward A

2014-07-30

229

Inhibition of Src phosphorylation reduces damage to the blood-brain barrier following transient focal cerebral ischemia in rats.  

PubMed

The disruption of the blood-brain barrier (BBB) caused by cerebral ischemia determines the extent of injury and patient prognosis. Inhibitors of Src can markedly minimize the infarct size and preserve neurological function. The Src protein tyrosine kinase (PTK) inhibitor, PP2, protects the rat brain against ischemic injury, possibly through the reduction of vascular endothelial growth factor A (VEGFA) expression and the upregulation of claudin-5 expression, which preserves the integrity of the BBB. In this study, the expression levels of phosphorylated (p)-Src, VEGFA and claudin-5 were determined to investigate the changes occurring in the levels of these proteins and to determine the benefits of PP2 treatment following cerebral ischemia/reperfusion (I/R). Our study included a sham-operated group, an I/R group, a vehicle-treated group (V) and a PP2-treated group (PP2). We found that the rats in the PP2 group exhibited greater preservation of neurological function and reduced VEGFA and p-Src protein expression compared with the rats in the I/R and V groups. Moreover, the mRNA and protein levels of claudin-5 were markedly higher in the PP2 group than in the I/R group or the V group after 3 days of reperfusion. Immunofluorescence staining revealed that the co-localized immunostaining of fibrinogen and claudin-5 was reduced in the PP2 group, which suggests that the exudation of fibrinogen in this group was less than that in the I/R and V groups. Furthermore, the reduced co-localization of immunostaining of glial fibrillary acidic protein (GFAP) and claudin-5 indicated that the rats in the PP2 group had only a slight disruption of the BBB. These findings suggested that PP2 treatment attenuated the disruption of the BBB following ischemia and minimized the neurological deficit; these effects were associated with a decreased VEGFA expression and an increased claudin-5 expression. Members of the Src PTK family may be critical targets for the protection of the BBB following cerebral ischemia. PMID:25269821

Bai, Yongsheng; Xu, Guanghui; Xu, Mengxue; Li, Qi; Qin, Xinyue

2014-12-01

230

Inhibition of Src phosphorylation reduces damage to the blood-brain barrier following transient focal cerebral ischemia in rats  

PubMed Central

The disruption of the blood-brain barrier (BBB) caused by cerebral ischemia determines the extent of injury and patient prognosis. Inhibitors of Src can markedly minimize the infarct size and preserve neurological function. The Src protein tyrosine kinase (PTK) inhibitor, PP2, protects the rat brain against ischemic injury, possibly through the reduction of vascular endothelial growth factor A (VEGFA) expression and the upregulation of claudin-5 expression, which preserves the integrity of the BBB. In this study, the expression levels of phosphorylated (p)-Src, VEGFA and claudin-5 were determined to investigate the changes occurring in the levels of these proteins and to determine the benefits of PP2 treatment following cerebral ischemia/reperfusion (I/R). Our study included a sham-operated group, an I/R group, a vehicle-treated group (V) and a PP2-treated group (PP2). We found that the rats in the PP2 group exhibited greater preservation of neurological function and reduced VEGFA and p-Src protein expression compared with the rats in the I/R and V groups. Moreover, the mRNA and protein levels of claudin-5 were markedly higher in the PP2 group than in the I/R group or the V group after 3 days of reperfusion. Immunofluorescence staining revealed that the co-localized immunostaining of fibrinogen and claudin-5 was reduced in the PP2 group, which suggests that the exudation of fibrinogen in this group was less than that in the I/R and V groups. Furthermore, the reduced co-localization of immunostaining of glial fibrillary acidic protein (GFAP) and claudin-5 indicated that the rats in the PP2 group had only a slight disruption of the BBB. These findings suggested that PP2 treatment attenuated the disruption of the BBB following ischemia and minimized the neurological deficit; these effects were associated with a decreased VEGFA expression and an increased claudin-5 expression. Members of the Src PTK family may be critical targets for the protection of the BBB following cerebral ischemia. PMID:25269821

BAI, YONGSHENG; XU, GUANGHUI; XU, MENGXUE; LI, QI; QIN, XINYUE

2014-01-01

231

Arsenic reduces the antipyretic activity of paracetamol in rats: modulation of brain COX-2 activity and CB? receptor expression.  

PubMed

We examined whether subacute arsenic exposure can reduce paracetamol-mediated antipyretic activity by affecting COX pathway and cannabinoid CB1 receptor regulation. Rats were preexposed to elemental arsenic (4 ppm) as sodium arsenite through drinking water for 28 days. Next day pyrexia was induced with lipopolysaccharide and paracetamol's (200 mg/kg, oral) antipyretic activity was assessed. The activities of COX-1 and COX-2, the levels of PGE?, TNF-? and IL-1? and expression of CB? receptors were assessed in brain. Arsenic inhibited paracetamol-mediated antipyretic activity. COX-1 activity was not affected by any treatments. Paracetamol decreased COX-2 activity, levels of PGE?, TNF-? and IL-1? and caused up-regulation of CB1 receptors. Arsenic caused opposite effects on these parameters. In the arsenic-preexposed rats, paracetamol-mediated effects were attenuated, while CB? receptor up-regulation was reversed to down-regulation. Results suggest that elevated COX-2 activity and reduced CB? expression could be involved in the arsenic-mediated attenuation of the antipyretic activity of paracetamol. PMID:24448467

Vijayakaran, Karunakaran; Kannan, Kandasamy; Kesavan, Manickam; Suresh, Subramaniyam; Sankar, Palanisamy; Tandan, Surendra Kumar; Sarkar, Souvendra Nath

2014-01-01

232

Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain.  

PubMed

The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1? and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation. PMID:24373829

Ahmad, Aliya; Ramasamy, Kalavathy; Jaafar, Siti Murnirah; Majeed, Abu Bakar Abdul; Mani, Vasudevan

2014-03-01

233

Current status in diabetic macular edema treatments  

PubMed Central

Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients. PMID:24147200

Romero-Aroca, Pedro

2013-01-01

234

Interstitial lung edema triggered by marathon running.  

PubMed

The purpose of this study was to determine whether marathon running causes lung edema, and if so, to determine its effects on runners. Posterior/anterior (PA) radiographs were taken one day before the marathon and at 19, 55, and 98min post-marathon in 26 runners. The pre and post exercise radiographs of each runner were collated, and then read simultaneously. Two physicians interpreted the images independently in a blinded fashion. The PA radiographs were viewed together at each time-point and findings suggestive for interstitial lung edema were rated as 'mild,' 'moderate,' or 'severe' based on four different radiological criteria. Forty-six percent of the runners presented radiographic findings suggestive of mild to severe interstitial lung edema. Radiographic findings persisted until 98-min post-marathon, with at least moderate degree increases found more frequently in women (55%) than men (6%) (p<0.01). In conclusion, about half of the runners developed interstitial lung edema of varying degrees post-exercise with the incidence being higher in women compared to men. PMID:24369923

Zavorsky, Gerald S; Milne, Eric N C; Lavorini, Federico; Rienzi, Joseph P; Lavin, Kaleen M; Straub, Allison M; Pistolesi, Massimo

2014-01-01

235

Strength training reduces circulating interleukin-6 but not brain-derived neurotrophic factor in community-dwelling elderly individuals.  

PubMed

Ageing is associated with a chronic low-grade inflammatory profile (CLIP). Physical exercise could circumvent the deleterious effects of CLIP by influencing circulating inflammatory mediators and neurotrophic growth factors. This study aimed at assessing whether 12 weeks of progressive strength training (PST) influences circulating brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and IL-10 in elderly individuals. Forty community-dwelling persons aged 62-72 years participated. Twenty participants were assigned to 12-week PST (70-80 % of maximal strength, three times per week). Matched control individuals (n?=?20) maintained daily activity levels. Serum was collected for BDNF, IL-6 and IL-10 assay from all participants before and after 12 weeks (for PST subjects 24-48 h after the last training). In PST, muscle strength was significantly improved (+49 % for leg extension, p?=?0.039), and basal IL-6 levels significantly reduced (p?=?0.001), which remained unchanged in control (p?=?0.117). No significant change in BDNF was observed in PST subjects (p?=?0.147) or control (p?=?0.563). IL-10 was below the detection limit in most subjects. Gender and health status did not influence the results. Our results show that after 12-week PST, muscle performance improved significantly, and basal levels of IL-6 were significantly decreased in older subjects. However, serum BDNF was not altered. The lack of an observable change in BDNF might be due to a short-lived BDNF response, occurring acutely following exercise, which might have been washed out when sampling. Furthermore, blood levels of BDNF may not reflect parallel increases that occur locally in the brain and muscle. These hypotheses need confirmation by further studies. PMID:25128203

Forti, Louis Nuvagah; Njemini, Rose; Beyer, Ingo; Eelbode, Elke; Meeusen, Romain; Mets, Tony; Bautmans, Ivan

2014-10-01

236

[Effects of pikamilon on the brain water-electrolyte balance and in models of responses to the noise and vibration exposure, and their combination with motion sickness].  

PubMed

Electric impedance measurements on awake rabbits with electrodes implanted into cortex, thalamus, and hypothalamus showed that modeling of the noise and general (wide-band) vibration, as well as their combination with sea-sickness action, leads to disturbances in the aqueous-electrolyte balance in brain. This is manifested by extracellular and (less pronounced) intracellular edema development. Picamilon administration (10 mg/kg, i.v.) completely prevented development of the vibration-induced intracellular edema and markedly reduced the development of damage in all other cases studied. PMID:11109535

Sapegin, I D

2000-01-01

237

Rosuvastatin reduces microglia in the brain of wild type and ApoE knockout mice on a high cholesterol diet; implications for prevention of stroke and AD.  

PubMed

We have previously shown that a high cholesterol (HC) diet results in increases in microglia load and levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the brains of wild type (WT) and apolipoprotein E knockout (ApoE-/-) mice. In the present investigation, we analyzed whether treatment with rosuvastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, would prevent the increases in inflammatory microglia and IL-6 levels in the brain and plasma of WT and ApoE-/- mice. We report that a HC diet resulted in an increased microglia load in the brains of WT and ApoE-/- mice, in support of our previous study. Treatment with rosuvastatin significantly decreased the microglia load in the brains of WT and ApoE-/- mice on a HC diet. Rosuvastatin treatment resulted in lowered plasma IL-6 levels in WT mice on a HC diet. However, in the present study the number of IL-6 positive cells in the brain was not significantly affected by a HC diet. A recent clinical study has shown that rosuvastatin reduces risk of ischemic stroke in patients with high plasma levels of the inflammatory marker C-reactive protein by 50%. The results from our study show that rosuvastatin reduces inflammatory cells in the brain. This finding is essential for furthering the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and stroke. PMID:20946880

Famer, D; Wahlund, L-O; Crisby, M

2010-11-12

238

Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces A? level and microglia activation in the brains of 3xTg-AD mice.  

PubMed

Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced A?40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD. PMID:24918340

Chen, Yanxing; Zhao, Yang; Dai, Chun-Ling; Liang, Zhihou; Run, Xiaoqin; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

2014-11-01

239

Postobstructive pulmonary edema induced by endotracheal tube occlusion  

Microsoft Academic Search

Pulmonary edema is a well-described complication of upper airway obstruction, most commonly caused in adults by postanesthetic laryngospasm. The mechanism initiating the formation of postobstructive pulmonary edema is believed to be the markedly negative intrapleural pressure generated by a forceful inspiratory effort against an obstructed extrathoracic airway. We herein describe a young, male patient who developed pulmonary edema postoperatively, upon

P. V. Dicpinigaitis; D. C. Mehta

1995-01-01

240

Reduced numbers of cortical GABA-immunoreactive neurons in the chronic D-galactose treatment model of brain aging.  

PubMed

Chronic administration of d-galactose (d-gal) is widely used to mimic the process of brain aging; however, the neural mechanisms are still poorly understood. In this study, we investigated the effect of long-term d-gal treatment on the number of GABA-immunoreactive neurons in rat cerebral cortex and the behavioral correlates. After eight weeks of daily subcutaneous injection of d-gal (100mg/ml/kg), rats showed reduced exploratory activity and lower ambulation in the open field compared to controls. There was no significant reduction in total neurons in the cortex, but there was a marked decrease in the number of GABA-immunoreactive neurons in all cortical layers of d-gal-treated rats. The ratio of GABA-immunoreactive neurons to total neurons was significantly lower in all cortical layers of d-gal-treated rats, with greatest reductions in output layers III (39.9% reduction), V (46.3%), and VI (48.4%). Our study provides the first evidence that chronic d-gal treatment may decrease cortical GABAergic neurotransmission, especially in cerebral output layers. The reduction in GABA-immunoreactive cell number likely disrupts the intracortical excitatory/inhibitory balance and may contribute to the behavioral deficits observed in this aging model. PMID:23806602

Gu, Xiaosu; Zhou, Yong; Hu, Xiaowei; Gu, Qin; Wu, Xiaomei; Cao, Maohong; Ke, Kaifu; Liu, Chunfeng

2013-08-01

241

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, Remy; Madey, Steven M.; Bottlang, Michael

2013-01-01

242

Towards reducing impact-induced brain injury: lessons from a computational study of army and football helmet pads.  

PubMed

We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterise the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the head injury criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry and material stiffness. We find that (1) the football pad materials do not outperform the currently used military pad material in militarily relevant impact scenarios; (2) optimal material properties for a pad depend on impact energy and (3) thicker pads perform better at all velocities. Although we considered only the isolated response of pad materials, not entire helmet systems, our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be reduced. PMID:23244512

Moss, William C; King, Michael J; Blackman, Eric G

2014-01-01

243

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

244

Acute pulmonary edema after intramyometrial prostodin.  

PubMed

A 25 year old, 68 kg, primigravida, was taken up for emergency caesarean section for meconium stained liquor and fetal distress. She was a known case of pre eclampsia and her blood pressure was controlled on tab methyl dopa. she was administered general anaesthesia. after delivery of baby she went into postpartum hemorrhage which was controlled with intramyometrial prostodin. but immediately after its administration she went into acute pulmonary edema. PMID:21772700

Baduni, Neha; Sanwal, Manoj K; Jain, Aruna

2011-04-01

245

Acute pulmonary edema after intramyometrial prostodin  

PubMed Central

A 25 year old, 68 kg, primigravida, was taken up for emergency caesarean section for meconium stained liquor and fetal distress. She was a known case of pre eclampsia and her blood pressure was controlled on tab methyl dopa. she was administered general anaesthesia. after delivery of baby she went into postpartum hemorrhage which was controlled with intramyometrial prostodin. but immediately after its administration she went into acute pulmonary edema. PMID:21772700

Baduni, Neha; Sanwal, Manoj K; Jain, Aruna

2011-01-01

246

Combination Therapy for Diabetic Macular Edema  

PubMed Central

Diabetic macular edema is a main reason for visual loss in diabetic patients. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenetic process of DME gave reason for intravitreal treatment with corticosteroids. The introduction of anti-VEGF drugs brought a revolutionary change in the treatment of DME. This paper will review the important clinical trials with an emphasis on combination therapies. PMID:22523648

Zur, Dinah; Loewenstein, Anat

2012-01-01

247

Oxygen-deficient metabolism and corneal edema  

Microsoft Academic Search

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

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

2011-01-01

248

Downregulation of an astrocyte-derived inflammatory protein, S100B, reduces vascular inflammatory responses in brains persistently infected with Borna disease virus.  

PubMed

Borna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca(2+)-binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM-1), as well as the infiltration of encephalitogenic T cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S100B in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection. PMID:17376896

Ohtaki, Naohiro; Kamitani, Wataru; Watanabe, Yohei; Hayashi, Yohei; Yanai, Hideyuki; Ikuta, Kazuyoshi; Tomonaga, Keizo

2007-06-01

249

Downregulation of an Astrocyte-Derived Inflammatory Protein, S100B, Reduces Vascular Inflammatory Responses in Brains Persistently Infected with Borna Disease Virus?  

PubMed Central

Borna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca2+-binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM-1), as well as the infiltration of encephalitogenic T cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S100B in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection. PMID:17376896

Ohtaki, Naohiro; Kamitani, Wataru; Watanabe, Yohei; Hayashi, Yohei; Yanai, Hideyuki; Ikuta, Kazuyoshi; Tomonaga, Keizo

2007-01-01

250

Pulmonary edema after aneurysm surgery is modified by mannitol.  

PubMed Central

Abdominal aortic aneurysmectomy (AAA) results in thromboxane (Tx)A2 generation, a rise in mean pulmonary artery pressure (MPAP), leukopenia, and noncardiogenic pulmonary edema. This study tests whether mannitol, a hydroxyl radical scavenger, modifies these events. Patients received mannitol 0.2 g/kg (n = 14) or saline (n = 12) intravenously before infrarenal aortic clamping. With saline, 30 minutes after clamping, plasma TxB2 levels rose from 124 to 290 pg/mL (p less than 0.01), and MPAP rose from 19 to 27 mmHg (p less than 0.01). Aortic clamp release led to further increases in plasma TxB2 to 378 pg/mL (p less than 0.01) and MPAP to 34 mmHg (p less than 0.01). The white blood count (WBC) fell from 9800 to 4400/mm3 (p less than 0.01). Four to eight hours after surgery, physiologic shunting (Q[sc]S[xsc]/Q[sc]T[xsc]) rose from 9% to 20% (p less than 0.01) and peak inspiratory pressure (PIP) increased from 22 to 32 cmH2O (p less than 0.01). Chest radiography demonstrated pulmonary edema while the pulmonary wedge pressure was 12 mmHg, excluding left ventricular failure. By 24 hours pulmonary edema resolved and the PIP and PaO2 returned to baseline. Mannitol treatment relative to saline, during and after aortic clamping reduced plasma TxB2 levels to 155 and 198 pg/mL, respectively (p less than 0.01); MPAP to 21 and 26 mmHg (p less than 0.01); minimized the decline in WBC to 5850/mm3 (p less than 0.01), and the postoperative rise in Q[sc]S[xsc]/Q[sc]T[xsc] to 12%, and PIP to 28 cmH2O (both p less than 0.01). Chest radiography showed no pulmonary edema. Finally in vitro studies documented that mannitol 1 to 10(-4)M, but not dextrose, in a dose-dependent manner inhibited Tx synthesis by ADP-activated platelets. These data indicate that mannitol maintains pulmonary function after AAA by limiting ischemia-induced thromboxane synthesis. PMID:2511812

Paterson, I S; Klausner, J M; Goldman, G; Pugatch, R; Feingold, H; Allen, P; Mannick, J A; Valeri, C R; Shepro, D; Hechtman, H B

1989-01-01

251

Transcranial Doppler sonography and intracranial pressure monitoring in children and juveniles with acute brain injuries or hydrocephalus  

Microsoft Academic Search

Transcranial Doppler sonography is a noninvasive method of obtaining information about changes in cerebral hemodynamics and intracranial pressure. After severe head injuries the development of brain swelling and brain edema can be assessed and the efficacy of treatment monitored. Development of severe brain edema accompanied by a rapid increase in intracranial pressure can be recognized by a decrease in blood

P. Sanker; K. E. Richard; H. C. Weigl; N. Klug; K. van Leyen

1991-01-01

252

Prognosis for Severe Traumatic Brain Injury Patients Treated with Bilateral Decompressive Craniectomy  

Microsoft Academic Search

\\u000a \\u000a Purpose  Decompressive craniectomy for traumatic brain injury patients has been shown to reduce intracranial hypertension, while it\\u000a often results in increased brain edema and\\/or contralateral space-occupied hematoma. The purpose of this study was to determine\\u000a the prognosis of bilateral decompressive craniectomy in severe head injury patients with the development of either bilateral\\u000a or contralateral lesions after ipsilateral decompressive craniectomy.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twelve patients

Hiroshi Yatsushige; Yoshio Takasato; Hiroyuki Masaoka; Takanori Hayakawa; Naoki Otani; Yoshikazu Yoshino; Kyoko Sumiyoshi; Takashi Sugawara; Hiroki Miyawaki; Chikashi Aoyagi; Satoru Takeuchi; Go Suzuki

253

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

254

Improved perioperative neurological monitoring of coronary artery bypass graft patients reduces the incidence of postoperative delirium: the Haga Brain Care Strategy  

PubMed Central

OBJECTIVES Postoperative delirium is a major cause of morbidity and mortality after cardiovascular surgery. Risk factors for postoperative delirium include poor cerebral haemodynamics and perioperative cerebral desaturations. Our aim was to reduce the postoperative delirium rate by using a new prevention strategy called the Haga Brain Care Strategy. This study evaluates the efficacy of the implementation of the Haga Brain Care Strategy to reduce the postoperative delirium rate after elective coronary artery bypass graft (CABG) procedures. The primary endpoint was the postoperative delirium rate, and the secondary endpoint was the length of stay in the intensive care unit. METHODS The Haga Brain Care Strategy consisted of the conventional screening protocol for delirium with the addition of preoperative transcranial Doppler examinations, perioperative cerebral oximetry, modified Rankin score, delirium risk score and (if indicated) duplex examination of the carotid arteries. In case of poor preoperative haemodynamics, the cerebral blood flow was optionally optimized by angioplasty or the patient was operated on under mild hypothermic conditions. Perioperative cerebral desaturations >20% outside the normal range resulted in intervention to restore cerebral oxygenation. Cerebral oximetry was discontinued when patients regained consciousness. Patients undergoing elective CABG procedures in 2010 were compared with patients scheduled for coronary bypass graft procedures in 2009 who had not been exposed to additional Haga Brain Care Strategy assessment. RESULTS A total of 233 and 409 patients were included in 2009 and 2010, respectively. The number of patients subjected in 2010 to transcranial Doppler examinations, cerebral oximetry or both (Haga Brain Care Strategy) were 262 (64.1%), 201 (49.1%) and 139 (34.0%), respectively. The overall rate of postoperative delirium decreased from 31 (13.3%) in 2009 to 30 (7.3%) in 2010 (P = 0.019). A binary logistic regression model showed that the Haga Brain Care Strategy was an independent predictor of a reduced risk of developing a postoperative delirium (odd ratio = 0.37, P = 0.021). CONCLUSIONS With the implementation of the Haga Brain Care Strategy in 2010, a reduction of the incidence of postoperative delirium in patients undergoing elective CABG procedures was observed. In addition, the length of stay in the intensive care unit showed an overall tendency to decline. The limited number of observations and the current study design do not allow a full evaluation of the Haga Brain Care Strategy but the data support the idea that a sophisticated preoperative assessment of cerebral haemodynamics and perioperative monitoring of cerebral oximetry reduce the incidence of the postoperative delirium in CABG surgery. PMID:22778141

Palmbergen, Wijnand A.C.; van Sonderen, Agnes; Keyhan-Falsafi, Ali M.; Keunen, Ruud W.M.; Wolterbeek, Ron

2012-01-01

255

Structure-based redesign of an edema toxin inhibitor  

PubMed Central

Edema Factor toxin (EF) of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3?,5?-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-Oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 ?g/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin-(ET) catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria. PMID:22154558

Chen, Deliang; Ma, Lili; Kanalas, John J.; Gao, Jian; Pawlik, Jennifer; Jimenez, Maria Estrella; Walter, Mary A.; Peterson, Johnny W.; Gilbertson, Scott R.; Schein, Catherine H.

2011-01-01

256

Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats  

PubMed Central

Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability of Rhodiola crenulata extract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1?) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications of Rhodiola crenulata for antihigh altitude illness. PMID:23710233

Li, Min-Hui; Shi, Li-Shian; Ho, Cheng-Wen

2013-01-01

257

A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor  

Microsoft Academic Search

We have conducted studies to determine the potential of dietary factors to affect the capacity of the brain to compensate for insult. Rats were fed with a high-fat sucrose (HFS) diet, a popularly consumed diet in industrialized western societies, for 4 weeks before a mild fluid percussion injury (FPI) or sham surgery was performed. FPI impaired spatial learning capacity in

A. WU; R. MOLTENI; Z. YING; F. GOMEZ-PINILLA

2003-01-01

258

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

259

Reduced brain corticotropin-releasing factor receptor activation is required for adequate maternal care and maternal aggression in lactating rats.  

PubMed

The brain corticotropin-releasing factor (CRF) system triggers a variety of neuroendocrine and behavioural responses to stress. Whether maternal behaviour and emotionality in lactation are modulated by CRF has rarely been investigated. In the present study, we measured CRF mRNA expression within the parvocellular part of the paraventricular nucleus in virgin and lactating Wistar rats bred for high (HAB) and low (LAB) anxiety-related behaviour or non-selected for anxiety (NAB). Further, we intracerebroventricularly infused synthetic CRF or the CRF receptor (CRF-R) antagonist D-Phe to manipulate CRF-R1/2 non-specifically in lactating HAB, LAB, and NAB dams, and monitored maternal care, maternal motivation, maternal aggression, and anxiety. The CRF mRNA expression in the parvocellular part of the paraventricular nucleus was higher in HAB vs. LAB rats independent of reproductive status. The lactation-specific decrease of CRF mRNA was confirmed in LAB and NAB dams but was absent in HAB dams. Intracerebroventricular CRF decreased maternal care under basal conditions in the home cage in all breeding lines and reduced attack behaviour in HAB and LAB dams during maternal defence. In contrast, D-Phe rescued maternal care after exposure to maternal defence in the home cage without influencing maternal aggression. Furthermore, D-Phe decreased and CRF tended to increase anxiety in HAB/NAB and LAB dams, respectively, suggesting an anxiogenic effect of CRF in lactating females. In conclusion, low CRF-R activation during lactation is an essential prerequisite for the adequate occurrence of maternal behaviour. PMID:23742269

Klampfl, Stefanie M; Neumann, Inga D; Bosch, Oliver J

2013-09-01

260

Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.  

PubMed

Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of ?-7 nicotinic acetylcholine receptor (?-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, ?-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (?-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68(+) , M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN(+) TUNEL(+) ), fewer CD68(+) and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that ?-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the ?-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture. PMID:25040630

Han, Zhenying; Li, Li; Wang, Liang; Degos, Vincent; Maze, Mervyn; Su, Hua

2014-11-01

261

An update on the role of brain glutamine synthesis and its relation to cell-specific energy metabolism in the hyperammonemic brain: Further studies using NMR spectroscopy  

Microsoft Academic Search

Ammonia is a neurotoxin that is implicated in the pathogenesis of hepatic encephalopathy due to acute and chronic liver failure. However, its relation to neurological damage and brain edema is poorly understood. During the last decades, it has been the prevailing hypothesis that an osmotic disturbance induced by the astrocytic accumulation of glutamine leads to brain edema. However, various findings

Claudia Zwingmann; Roger Butterworth

2005-01-01

262

Cardiac MRI of Edema in Acute Myocardial Infarction using Cine Balanced SSFP: A Translational Study  

PubMed Central

Objective To investigate the capabilities of balanced steady-state-free-precession (bSSFP) MRI as a novel cine imaging approach for characterizing myocardial edema in animals and patients following reperfused myocardial infarction. Background Current MRI methods require two separate scans for assessment of myocardial edema and cardiac function. Methods Mini-pigs (n=13) with experimentally induced reperfused myocardial infarction and patients with reperfused STEMI (n=26) underwent MR scans on days 2–4 post reperfusion. Cine bSSFP, T2-STIR, and late-gadolinium enhancement (LGE) were performed at 1.5T. Cine bSSFP and T2-STIR images were acquired with body coil to mitigate surface coil bias. Signal, contrast and the area of edema were compared. Additional patients (n=10) were analyzed for the effect of microvascular obstruction on bSSFP. A receiver-operator-characteristic analysis was performed to assess the accuracy of edema detection. Results An area of hyperintense bSSFP signal consistent with edema was observed in the infarction zone (contrast-to-noise ratio (CNR) 37±13) in all animals and correlated well with the area of LGE (R=0.83, p<0.01). In all patients, T2-STIR and bSSFP images showed regional hyperintensity in the infarction zone. Normalized CNR were not different between T2-STIR and bSSFP. On a slice-basis, the volumes of hyperintensity on T2-STIR and bSSFP images correlated well (R=0.86, p<0.001), and their means were not different. When compared with T2-STIR, bSSFP was positive for edema in 25/26 patients (sensitivity of 96%) and was negative in all controls (specificity 100%). All patients with MVO showed a significant reduction of signal in the subendocardial infarction zone, compared to infarcted epicardial tissue without MVO (p<0.05). Conclusion Myocardial edema from STEMI can be detected using cine bSSFP imaging with image contrast similar to T2-STIR. This new imaging approach allows for evaluating cardiac function and edema simultaneously, thereby reducing patient scan time and increasing efficiency. Further work is necessary to optimize edema contrast in bSSFP images. PMID:22172783

Kumar, Andreas; Beohar, Nirat; Arumana, Jain Mangalathu; Larose, Eric; Li, Debiao; Friedrich, Matthias G; Dharmakumar, Rohan

2012-01-01

263

Bradykinin in blood and cerebrospinal fluid after acute cerebral lesions: correlations with cerebral edema and intracranial pressure.  

PubMed

Bradykinin (BK) was shown to stimulate the production of physiologically active metabolites, blood-brain barrier disruption, and brain edema. The aim of this prospective study was to measure BK concentrations in blood and cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke and to correlate BK levels with the extent of cerebral edema and intracranial pressure (ICP). Blood and CSF samples of 29 patients suffering from acute cerebral lesions (TBI, 7; SAH,: 10; ICH, 8; ischemic stroke, 4) were collected for up to 8 days after insult. Seven patients with lumbar drainage were used as controls. Edema (5-point scale), ICP, and the GCS (Glasgow Coma Score) at the time of sample withdrawal were correlated with BK concentrations. Though all plasma-BK samples were not significantly elevated, CSF-BK levels of all patients were significantly elevated in overall (n=73) and early (?72?h) measurements (n=55; 4.3±6.9 and 5.6±8.9 fmol/mL), compared to 1.2±0.7 fmol/mL of controls (p=0.05 and 0.006). Within 72?h after ictus, patients suffering from TBI (p=0.01), ICH (p=0.001), and ischemic stroke (p=0.02) showed significant increases. CSF-BK concentrations correlated with extent of edema formation (r=0.53; p<0.001) and with ICP (r=0.49; p<0.001). Our results demonstrate that acute cerebral lesions are associated with increased CSF-BK levels. Especially after TBI, subarachnoid and intracerebral hemorrhage CSF-BK levels correlate with extent of edema evolution and ICP. BK-blocking agents may turn out to be effective remedies in brain injuries. PMID:23638655

Kunz, Mathias; Nussberger, Juerg; Holtmannspötter, Markus; Bitterling, Harro; Plesnila, Nikolaus; Zausinger, Stefan

2013-10-01

264

Investigation of whole-brain white matter identifies altered water mobility in the pathogenesis of high-altitude headache.  

PubMed

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10?hours in normoxia (21% O2) and hypoxia (12% O2) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2?hours and globally reduced throughout cerebral white matter by 10?hours in hypoxia. However, no changes in T2 relaxation time (T2) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T2 both supra and subtentorially after 2 and 10?hours, with headache score after 10?hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache. PMID:23736642

Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H

2013-08-01

265

Investigation of whole-brain white matter identifies altered water mobility in the pathogenesis of high-altitude headache  

PubMed Central

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10?hours in normoxia (21% O2) and hypoxia (12% O2) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2?hours and globally reduced throughout cerebral white matter by 10?hours in hypoxia. However, no changes in T2 relaxation time (T2) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T2 both supra and subtentorially after 2 and 10?hours, with headache score after 10?hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache. PMID:23736642

Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H

2013-01-01

266

Treatment of macular edema due to retinal vein occlusions  

PubMed Central

Retinal vein occlusion (RVO) is a prevalent retinal vascular disease, second only to diabetic retinopathy. Previously there was no treatment for central retinal vein occlusion (CRVO) and patients were simply observed for the development of severe complications, generally resulting in poor visual outcomes. The only treatment for branch vein occlusion (BRVO) was grid laser photocoagulation, which reduces edema very slowly and provides benefit in some, but not all patients. Within the past year, clinical trials have demonstrated the effects of three new pharmacologic treatments, ranibizumab, triamcinolone acetonide, and dexamethasone implants. The benefit/risk ratio is best for intraocular injections of ranibizumab, making this first-line therapy for most patients with CRVO or BRVO, while intraocular steroids are likely to play adjunctive roles. Standard care for patients with RVO has changed and will continue to evolve as results with other new agents are revealed. PMID:21629578

Channa, Roomasa; Smith, Michael; Campochiaro, Peter A

2011-01-01

267

Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies  

PubMed Central

Background Structural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done. Methods In global and regional meta-analyses of 9 voxel-based morphometry (VBM) studies, with a total of 228 eating disorder participants (currently ill with anorexia nervosa), and 240 age-matched healthy controls, we compare brain volumes using global and regional analyses. Results Anorexia nervosa (AN) patients have global reductions in gray (effect size?=??0.66) and white matter (effect size?=??0.74) and increased cerebrospinal fluid (effect size?=?0.98) and have regional decreases in left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate, and no significant increases. No significant difference in hemispheric lateralization was found. Conclusions Global and regional meta-analyses suggest that excessive restrained eating as found in those with anorexia nervosa coincides with structural brain changes analogous to clinical symptoms. PMID:23570420

2013-01-01

268

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

269

Intravitreal bevacizumab for macular edema from idiopathic juxtafoveal retinal telangiectasis.  

PubMed

To assess the potential visual benefit of intravitreal bevacizumab in a patient with idiopathic juxtafoveal retinal telangiectasis refractory to focal laser treatment, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1 week, visual acuity improved from 20/50 to 20/25 and optical coherence tomography demonstrated complete resolution of macular edema. There was no adverse effect. The macular edema recurred after 3 months, requiring a repeat injection of bevacizumab with subsequent resolution of macular edema. An intravitreal injection of bevacizumab may provide potential short-term visual benefit in patients with macular edema from idiopathic juxtafoveal retinal telangiectasis. PMID:17396701

Moon, Suk J; Berger, Adam S; Tolentino, Michael J; Misch, David M

2007-01-01

270

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

271

Corticosteroid withdrawal precipitates perilesional edema around calcified Taenia solium cysts.  

PubMed

Calcified Taenia solium granulomas are the focus of repeated episodes of perilesional edema and seizures in 50% of persons with calcifications, history of seizures, and a positive serology for cysticercosis. The pathophysiology is unclear but recent studies suggest the edema is caused by inflammation. We report two new cases and four other published cases where cessation of corticosteroids appeared to result in recurrence or new appearance of perilesional edema around calcifications. This suggests that perilesional edema is an immune-mediated phenomenon. PMID:24002482

Mejia, Rojelio; Nash, Theodore E

2013-11-01

272

The Episodic Engram Transformed: Time Reduces Retrieval-Related Brain Activity but Correlates It with Memory Accuracy  

ERIC Educational Resources Information Center

We took snapshots of human brain activity with fMRI during retrieval of realistic episodic memory over several months. Three groups of participants were scanned during a memory test either hours, weeks, or months after viewing a documentary movie. High recognition accuracy after hours decreased after weeks and remained at similar levels after…

Furman, Orit; Mendelsohn, Avi; Dudai, Yadin

2012-01-01

273

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...

274

Genetic deletion of Rheb1 in the brain reduces food intake and causes hypoglycemia with altered peripheral metabolism.  

PubMed

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

275

Anti-Amyloid-? Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer's Disease Mouse Model.  

PubMed

Accumulation of amyloid-? protein (A?) in the brain is thought to be a causal event in Alzheimer's disease (AD). Immunotherapy targeting A? holds great promise for reducing A? in the brain. Here, we evaluated the efficacy and safety of anti-A? single-chain antibody (scFv59) delivery via recombinant adeno-associated virus (rAAV) on reducing A? deposits in an AD mouse model (TgA?PPswe/PS1dE9). First, delivery of scFv59 to the brain was optimized by injecting rAAV serotypes 1, 2, and 5 into the right lateral ventricle. Symmetrical high expression of scFv59 was found throughout the hippocampus and partly in the neocortex in both hemispheres via rAAV1 or rAAV5, while scFv59 expression via rAAV2 was mostly limited to one hemisphere. rAAV1, however, induced apoptosis and microglial activation but rAAV5 did not. Therefore, rAAV5 was selected for therapeutic scFv59 delivery in TgA?PPswe/PS1dE9 mice. rAAV5 was similarly injected into the ventricle of 10-month-old TgA?PPswe/PS1dE9 mice and 5 months later its efficacy and safety were evaluated. Immunoreactive A? deposits reduced in the hippocampus. A?42 levels in cerebrospinal fluid (CSF) tended to increase and the A?40 : 42 ratio decreased in CSF, suggesting that A?42 was relocated from the parenchyma to CSF. Hemorrhages associated with a focal increase in blood vessel amyloid were found in the brain. While immunotherapy has great potential for clearing cerebral A?, caution for cerebrovascular effects should be exercised when rAAV-mediated anti-A? immunotherapy is applied. PMID:21709371

Kou, Jinghong; Kim, HongDuck; Pattanayak, Abhinandan; Song, Min; Lim, Jeong-Eun; Taguchi, Hiroaki; Paul, Sudhir; Cirrito, John R; Ponnazhagan, Selvarangan; Fukuchi, Ken-ichiro

2011-01-01

276

Blood-brain barrier: interface between internal medicine and the brain.  

PubMed

The blood-brain barrier separates brain interstitial space from blood and is formed by brain capillary endothelial cells that are fused together by epithelial-like tight junctions. Study of the blood-brain barrier traditionally has been a relatively arcane field, even for neurobiologists. However, advances over the last 10 years in understanding the transport physiology and cell biology of the brain capillary endothelial cell now provide insights into the pathogenesis of such problems as brain glucopenia, hepatic encephalopathy, therapeutic efficacy of alpha-methyldopa, brain edema in diabetic ketoacidosis, Alzheimer's disease, brain tumors, and lupus cerebritis. PMID:2872846

Pardridge, W M; Oldendorf, W H; Cancilla, P; Frank, H J

1986-07-01

277

Deficiency of complement receptors CR2/CR1 in Cr2-/- mice reduces the extent of secondary brain damage after closed head injury  

PubMed Central

Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2 -/- mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2 -/- mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2 -/- mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2 -/- genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2 -/- mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2 -/- had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury. PMID:24885042

2014-01-01

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

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

280

ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain  

Microsoft Academic Search

BACKGROUND: ZnT3 is a membrane Zn2+ transporter that is responsible for concentrating Zn2+ into neuronal presynaptic vesicles. Zn2+ homeostasis in the brain is relevant to Alzheimer's disease (AD) because Zn2+ released during neurotransmission may bind to A? peptides, accelerating the assembly of A? into oligomers which have been shown to impair synaptic function. RESULTS: We quantified ZnT3 mRNA levels in

Nancy Beyer; David TR Coulson; Shirley Heggarty; Rivka Ravid; G Brent Irvine; Jan Hellemans; Janet A Johnston

2009-01-01

281

The administration of food supplemented with cocoa powder during nutritional recovery reduces damage caused by oxidative stress in rat brain  

Microsoft Academic Search

Malnutrition contributes to the development of oxidative damage in the central nervous system. The selective administration\\u000a of nutrients tends to show positive results in individuals who have suffered from malnutrition. To determine the effect of\\u000a the administration of cocoa powder on the peroxidation of lipids and glutathione level during the nutritional recovery in\\u000a brain, rats of 21 days old were subjected

Gerardo Barragán Mejía; David Calderón Guzmán; Hugo Juárez Olguín; Nancy Hernández Martínez; Edna García Cruz; Aline Morales Ramírez; Norma Labra Ruiz; Gabriela Esquivel Jiménez; Norma Osnaya Brizuela; Raquel García Álvarez; Esperanza Ontiveros Mendoza

282

A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats.  

PubMed

Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated at 2?h after TBI with either the anti-CD11d antibody or an isotype-matched control antibody 1B7, and both short (24- to 72-h) and long (4-week) recovery periods were examined. The anti-CD11d integrin treatment reduced neutrophil and macrophage levels in the injured brain, with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The reduced neuroinflammation seen in anti-CD11d-treated rats correlated with improved performance on a number of behavioral tests. At 24?h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti-CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI. PMID:22676851

Bao, Feng; Shultz, Sandy R; Hepburn, Jeff D; Omana, Vanessa; Weaver, Lynne C; Cain, Donald P; Brown, Arthur

2012-09-20

283

Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet.  

PubMed

Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18 °C, subjected to 60 min of DHCA, re-warmed and recovered for 8-9 h. At the end of experiment, the brains were perfused, fixed and cut into 10 µm transverse sections. Apoptotic cells were visualized by in situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm(2). The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46 ± 0.37 to 3.67 ± 1.57 (p = 0.002); in the CA1, from 0.11 ± 0.19 to 5.16 ± 1.57 (p = 0.001), and in the CA3, from 0.28 ± 0.25 to 2.98 ± 1.82 (p = 0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51 and 37 %, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA. PMID:25082120

Pastuszko, Peter; Schears, Gregory J; Greeley, William J; Kubin, Joanna; Wilson, David F; Pastuszko, Anna

2014-11-01

284

Excellent Tolerance to Cilnidipine in Hypertensives with Amlodipine - Induced Edema  

PubMed Central

Background: Ankle edema is a common adverse effect of amlodipine, an L-type calcium channel blocker (CCB). Cilnidipine is a newer L/N-type CCB, approved for treatment of essential hypertension. Aim: This study was designed to determine whether cilnidipine can produce resolution of amlodipine-induced edema while maintaining adequate control of hypertension. Materials and Methods: A prospective study was performed on 27 patients with essential hypertension with amlodipine-induced edema. Concomitant nephropathy, cardiac failure, hepatic cirrhosis, or other causes of edema, and secondary hypertension were excluded by appropriate tests. Amlodipine therapy was substituted in all the cases with an efficacy-equivalent dose of cilnidipine. Clinical assessment of ankle edema and measurement of bilateral ankle circumference, body weight, blood pressure, and pulse rate were performed at onset of the study and after 4 weeks of cilnidipine therapy. Results: At completion of the study, edema had resolved in all the patients. There was a significant decrease in bilateral ankle circumference and body weight (P < 0.001). There was no significant change in mean arterial blood pressure and pulse rate. Conclusions: Therapy with cilnidipine resulted in complete resolution of amlodipine-induced edema in all the cases without significant worsening of hypertension or tachycardia. Cilnidipine is an acceptable alternative antihypertensive for patients with amlodipine-induced edema. PMID:23378956

Shetty, Ranjan; Vivek, G; Naha, Kushal; Tumkur, Anil; Raj, Abhinav; Bairy, K L

2013-01-01

285

Parietal Occipital Edema in Hypertensive Encephalopathy: A Pathogenic Mechanism  

Microsoft Academic Search

Eight patients with hypertensive encephalopathy from diverse etiologies developed cerebral edema in the vertebrobasilar distribution which resolved after blood pressure was lowered. Parietal occipital edema is a recognized feature of hypertensive encephalopathy. The explanation for this regional pathological variation in hypertensive encephalopathy remains undefined. Some evidence suggests that sympathetic innervation of the anterior cerebral vasculature may be protective, and conversely,

Raj D. Sheth; Jack E. Riggs; John B. Bodenstenier; Alvoro R. Gutierrez; Leena M. Ketonen; Orlando A. Ortiz

1996-01-01

286

Automatic classification of diabetic macular edema in digital fundus images  

Microsoft Academic Search

Diabetic macular edema is a common complication of diabetic retinopathy due to the presence of exudates in proximity with the fovea. In this paper, an automated method to classify diabetic macular edema is presented. The fovea is localized and the regions of macula are marked based on the Early Treatment Diabetic Retinopathy Studies (ETDRS) grading scale. Extraction method using marker-controlled

S. T. Lim; W. M. D. W. Zaki; A. Hussain; S. L. Lim; S. Kusalavan

2011-01-01

287

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

288

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

289

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; Pourie, G; Helle, D; Gueant, J-L; Bossenmeyer-Pourie, C; Daval, J-L

2013-01-01

290

Validating Imaging Biomarkers of Cerebral Edema in Patients with Severe Ischemic Stroke  

PubMed Central

Background and Purpose There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether MRI-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Methods Serial MRI studies from patients in the EPITHET trial with initial diffusion weighted imaging (DWI) lesion volume >82 cm3 were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and day 3 to 5. We assessed inter-rater agreement, volume change between scans and the association of volume change with early neurological deterioration (END: NIHSS score worsening ?4 points), 90-day modified Rankin Scale (mRS) score 0–4 and mortality. Results Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm3 and 234 cm3, respectively. Mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2±8.3% (p<.0001), and mean percent ventricle volume decrease was 45.6±16.9% (p<0.001). Percent hemisphere growth predicted END (area under the curve [AUC]=0.92, p=0.0005) and 90-day mRS 0–4 (AUC 0.80, p=0.02). Conclusions In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation. PMID:22325573

Yoo, Albert J.; Sheth, Kevin N.; Kimberly, W. Taylor; Chaudhry, Zeshan A.; Elm, Jordan J.; Jacobson, Sven; Davis, Stephen M.; Donnan, Geoffrey A.; Albers, Gregory W.; Stern, Barney J.; Gonzalez, R. Gilberto

2012-01-01

291

Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin  

Microsoft Academic Search

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal hind-paw skin by antidromic

Jih-Pyang Wang; Shue-Ling Raung; Ling-Chu Chang; Sheng-Chu Kuo

1995-01-01

292

Effect of Vascular Normalization by Antiangiogenic Therapy on Interstitial Hypertension, Peritumor Edema, and Lymphatic Metastasis: Insights from a Mathematical Model  

PubMed Central

Preclinical and clinical evidence shows that antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel “normalization.” The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with antiangiogenic therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that antiangiogenic therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases. This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies. PMID:17363594

Jain, Rakesh K.; Tong, Ricky T.; Munn, Lance L.

2009-01-01

293

Pharmacologic aspects of a phlebotropic drug in CVI-associated edema.  

PubMed

Several phlebotropic drugs, or edema-protecting drugs, are available, the most important of which are found in the gamma-benzopyrone family (flavonoids). gamma-Benzopyrones can be plant extracts, semisynthetic preparations, or synthetic preparations. This family is divided into two different groups: flavones and flavonols, and flavanes (flavanones). The flavone group contains various types of molecule and includes diosmin. Here we discuss the pharmacologic aspects in edema associated with chronic venous insufficiency (CVI) of one of the reference phlebotropic drugs, micronized purified flavonoid fraction (MPFF), a semisynthetic preparation from the diosmin group, which represents the latest improvement in flavonoid formulation. Before we detail the pharmacologic aspects, a brief summary of the pathophysiology of edema in CVI is necessary. Several factors are implicated: the veins, which create the conditions favorable to edema; the microcirculation, which is the site of fluid transfer into the interstitial tissue; and the lymphatics, which have a limited possibility to reduce edema. Major discoveries are currently being made in CVI and the microcirculation. Results of studies show that MPFF decreases capillary permeability and increases capillary resistance, which could partly be explained by inhibition of leukocyte activation, migration, and adhesion. This inhibition is linked to a significant decrease in plasma levels of endothelial adhesion molecules (VCAM-1 and ICAM-1) after MPFF treatment. Thus, the CVI-induced damage to the microcirculation is counteracted by MPFF. The lymphatic system is also improved by MPFF treatment. The lymphagogue activity of MPFF has been demonstrated in experimental animal models and confirmed by microlymphographic measurement in patients suffering from severe CVI. The pharmacologic activity of MPFF in lymphedema was observed in a study using an animal model of acute lymphedema and in a study in patients with upper limb lymphedema secondary to breast cancer treatment. All these findings point to the importance of acting on each factor involved in the formation and maintenance of edema. This pharmacologic activity is indeed reflected by the clinical efficacy on edema observed during treatment with MPFF. PMID:10667639

Ramelet, A A

2000-01-01

294

Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke  

NASA Astrophysics Data System (ADS)

The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is then shown to correlate to mitochondrial swelling, as observed with electron microscopy. The system is finally used to study mitochondrial and cellular swelling. Evidence of the susceptibility of certain hippocampal regions, CA1 and the dentate gyrus, to exhibit mitochondrial swelling as the result of oxygen and glucose deprivation is presented. In addition, for the first time, the time course of mitochondrial swelling is seen. Finally, experiments with scatter imaging and measurement of nitric oxide with carbon fiber electrodes demonstrate a clear link between nitric oxide and cellular swelling. A potential mechanism of the action of nitric oxide is evaluated. Nitric oxide appears to act to cause cellular swelling without the release of glutamate. The use of targeted nitric oxide inhibitors may be useful for the reduction of edema.

Johnson, Lee James

2001-08-01

295

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

296

Aging reduces the GABA-dependent /sup 36/Cl/sup -/ flux in rat brain membrane vesicles  

SciTech Connect

The function of the chloride channel associated to GABA/sub A/ receptor complex was analyzed in the brain of aged rats by measuring the chloride flux across the neuronal membrane and its modulation by drugs acting at the level of the GABA receptor complex and /sup 35/S-TBPS binding. The basal /sup 36/Cl/sup -/ uptake by brain membrane vesicles of aged rats was higher than that observed in those of adult rats. The higher /sup 36/Cl/sup -/ uptake found in cortical membrane vesicles of senescent rats was not sensitive to the action of bicuculline indicating that it was not the consequence of a tonic GABAergic modulation. Moreover, the stimulation of /sup 36/Cl/sup -/ uptake induced by GABA was markedly lower in membrane vesicles of aged rats than that observed in those of adult rats. Accordingly, the stimulation of /sup 36/Cl/sup -/ efflux elicited by GABA and pentobarbital was higher in membrane vesicles of adult rats with respect to that of old rats. Finally a significant decrease of /sup 35/S-TBPS binding was observed in membrane preparation from the cerebral cortex, cerebellum and hippocampus of aged-rats.

Concas, A.; Pepitoni, S.; Atsoggiu, T.; Toffano, G.; Biggio, G.

1988-01-01

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

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

299

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

300

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

301

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

302

Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson's disease by reducing oxidative stress.  

PubMed

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson's disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group. PMID:25392203

Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

2014-12-01

303

A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain  

PubMed Central

Dynorphin peptides and the kappa opioid receptor play important roles in the rewarding properties of cocaine, heroin and alcohol. We tested polymorphisms of the prodynorphin gene (PDYN) for association with cocaine dependence and cocaine/alcohol codependence. We genotyped six SNPs, located in the promoter region, exon 4 coding and 3? untranslated region (UTR), in 106 Caucasians and 204 African Americans who were cocaine dependent, cocaine/alcohol codependent or controls. In Caucasians, we found point-wise significant associations of 3?UTR SNPs (rs910080, rs910079, and rs2235749) with cocaine dependence and cocaine/alcohol codependence. These SNPs are in high linkage disequilibrium, comprising a haplotype block. The haplotype CCT was significantly experiment-wise associated with cocaine dependence and with combined cocaine dependence and cocaine/alcohol codependence (FDR, q=0.04 and 0.03, respectively). We investigated allele-specific gene expression of PDYN, using SNP rs910079 as a reporter, in postmortem human brains from eight heterozygous subjects, using SNaPshot assay. There was significantly lower expression for C allele (rs910079), with ratios ranging from 0.48 to 0.78, indicating lower expression of the CCT haplotype of PDYN in both the caudate and nucleus accumbens. Analysis of total PDYN expression in 43 postmortem brains also showed significantly lower levels of preprodynorphin mRNA in subjects having the risk CCT haplotype. This study provides evidence that a 3?UTR PDYN haplotype, implicated in vulnerability to develop cocaine addiction and/or cocaine/alcohol codependence, is related to lower mRNA expression of the PDYN gene in human dorsal and ventral striatum. PMID:18923396

Yuferov, Vadim; Ji, Fei; Nielsen, David A.; Levran, Orna; Ho, Ann; Morgello, Susan; Shi, Ruijin; Ott, Jurg; Kreek, Mary Jeanne

2009-01-01

304

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

PubMed Central

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

305

Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats.  

PubMed

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

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

2013-01-01

306

Safety and Efficacy of Mild Compression (18-25 mm Hg) Therapy in Patients with Diabetes and Lower Extremity Edema  

PubMed Central

Background Patients with diabetes often present with lower extremity (LE) edema; however, because of concomitant peripheral arterial disease, compression therapy is generally avoided by providers in fear of compromising arterial circulation. This pilot study sought to assess whether diabetic socks with mild compression (18–25 mm Hg) can reduce LE edema in patients with diabetes without negatively impacting vascularity. Methods Eighteen subjects (9 males, 9 females) aged 61 ± 11 years with diabetes, LE edema, and a mean ankle–brachial index (ABI) of 1.10 ± 0.21 successfully completed this uncontrolled study. At baseline, subjects were fitted and instructed to wear the socks during all waking hours. Follow-up visits occurred weekly for four consecutive weeks. Edema was quantified through midfoot, ankle, and calf circumferences and cutaneous fluid measurements. Vascular status was tracked via ABI. Results Repeated measures analysis of variance and least significant difference post hoc analyses were used for data analyses. Calf circumferences showed a statistically significant (p < .05) decrease of 1.3 ± 0.28 cm after just one week and remained significantly smaller than baseline throughout the study. Foot circumferences were significantly reduced at week 2 (?0.98 ± 0.35 cm) and remained significantly below baseline for the remainder of the study. The ankle also demonstrated a trend of circumference reduction but was not statistically significant. Cutaneous edema significantly reduced by week 3 (?3.1 ± 1.3 U) and remained so at week 4. Ankle–brachial index significantly increased (0.14 ± 0.049) at week 2 but was not significantly higher at weeks 3 or 4. No adverse events occurred during the study. Conclusions Mild compression therapy (18–25 mm Hg) decreased swelling in diabetes patients with LE edema without compromising vascularity. PMID:22768895

Wu, Stephanie C; Crews, Ryan T; Najafi, Bijan; Slone-Rivera, Nancy; Minder, Jessica L; Andersen, Charles A

2012-01-01

307

Suppressive effect of 2-phenyl-4-quinolone (YT 1) on hind-paw edema and cutaneous vascular plasma extravasation in mice  

Microsoft Academic Search

Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48\\/80-induced mouse ear edema was suppressed

Jih-Pyang Wang; Mei-Feng Hsu; Shue-Ling Raung; Sheng-Chu Kuo

1994-01-01

308

Reduced expression of endogenous secretory receptor for advanced glycation endproducts in hippocampal neurons of Alzheimer's disease brains.  

PubMed

The receptor for advanced glycation endproducts (RAGE) is a cell-surface multiligand receptor, which interacts with amyloid beta (Abeta), a key protein in Alzheimer's disease (AD). RAGE-Abeta interaction is thought to be associated with pathological progression in AD. A splice variant of RAGE, endogenous secretory RAGE (esRAGE) can act as a decoy receptor for RAGE ligands that would prevent the progression of some pathologic conditions. In this study, the expression of esRAGE in the hippocampal tissues from AD brains compared with control (non-AD) was examined by immunohistochemistry and Western blot analysis. Semiquantitative immunohistochemical analysis of hippocampal tissues using esRAGE-specific antibody revealed significantly decreased immunoreactivities in pyramidal cells in CA1 and CA3 regions of AD compared with non-AD. On the other hand, immunoreactivities of astrocytes for esRAGE significantly increased in those regions. Dentate granule cells and astrocytes showed essentially invariant immunoreactivities between AD and non-AD. Changes in esRAGE immunoreactivity in CA3 neurons and astrocytes were observed from the early pathological stages. Moreover, the esRAGE-immunoreactive bands of AD samples were weaker than those of non-AD samples in Western blot analysis. The results indicate that low expression of esRAGE in the hippocampus would be associated with the development of AD. PMID:18431028

Nozaki, Ichiro; Watanabe, Takuo; Kawaguchi, Makoto; Akatsu, Hiroyasu; Tsuneyama, Koichi; Yamamoto, Yasuhiko; Ohe, Kazuyo; Yonekura, Hideto; Yamada, Masahito; Yamamoto, Hiroshi

2007-12-01

309

Patterns of diabetic macular edema with optical coherence tomography  

Microsoft Academic Search

PURPOSE: We report cross-sectional images of diabetic macular edema and correlation between tomographic features and visual acuity with best correction by means of optical coherence tomography.METHOD: In a prospective study, optical coherence tomography was performed in 59 eyes of 42 patients with diabetic macular edema and in 10 eyes of 10 normal control subjects.RESULTS: Optical coherence tomography showed three patterns

Tomohiro Otani; Shoji Kishi; Yasuhiro Maruyama

1999-01-01

310

Appraising Pulmonary Edema Using Supine Chest Roentgenograms in Ventilated Patients  

Microsoft Academic Search

The role of portable, anteroposterior, supine chest X-rays (CXRs) in distinguishing hydrostatic pulmo- nary edema (HPE) from permeability pulmonary edema (PPE) in mechanically ventilated patients is controversial. We prospectively obtained and evaluated such CXRs in 33 supine, mechanically venti- lated intensive-care-unit patients with pulmonary artery catheters. Three chest radiologists indepen- dently reviewed CXRs without clinical information and recorded the cardiothoracic

JASON W. W. THOMASON; E. WESLEY ELY; CAROLINE CHILES; GILBERT FERRETTI; RITA I. FREIMANIS; EDWARD F. HAPONIK

1998-01-01

311

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

312

Raised Leg Exercises for Leg Edema in the Elderly  

Microsoft Academic Search

Leg edema is a common problem in the elderly and requires further evaluation and management. Method: From October 1990 to July 1992, 245 patients presented to the Cleveland Clinic Florida with leg edema. All patients were counseled about the benefits of twenty-minute, three-times-a-day raised-leg exercises. Fifty seven (57) of the 245 patients were not compliant with this regimen (nonexercise group).

Jerry O. Ciocon; Daisy Galindo-Ciocon; Diana J. Galindo

1995-01-01

313

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

314

Proton beam therapy reduces the incidence of acute haematological and gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors.  

PubMed

Abstract Background. The benefits of proton beam craniospinal irradiation (PrBCSI) in children have been extensively reported in dosimetric studies. However, there is limited clinical evidence supporting the use of PrBCSI. We compared the acute toxicity of PrBCSI relative to that of conventional photon beam CSI (PhBCSI) in children with brain tumours. Material and methods. We prospectively evaluated the haematological and gastrointestinal toxicities in 30 patients who underwent PrBCSI between April 2008 and December 2012. As a reference group, we retrospectively evaluated the medical records of 13 patients who underwent PhBCSI between April 2003 and April 2012. The median follow-up time from starting CSI was 22 months (range 2-118 months). The mean irradiation dose was 32.1 Gy (range 23.4-39.6 Gy) and 29.4 CGE (cobalt grey equivalents; range 19.8-39.6), in the PrBCSI and PhBCSI groups, respectively (p = 0.236). Results. There was no craniospinal fluid space relapse after curative therapy in either group of patients. Thrombocytopenia was less severe in the PrBCSI group than in the PhBCSI group (p = 0.012). The recovery rates of leukocyte and platelet counts measured one month after treatment were significantly greater in the PrBCSI group than in the PhBCSI group (p = 0.003 and p = 0.010, respectively). Diarrhoea was reported by 23% of patients in the PhBCSI group versus none in the PrBCSI group (p = 0.023). Conclusions. The incidence rates of thrombocytopenia and diarrhoea were lower in the PrBCSI group than in the PhBCSI group. One month after completing treatment, the recovery from leukopenia and thrombocytopenia was better in patients treated with PrBCSI than in those treated with PhBCSI. PMID:24913151

Song, Sanghyuk; Park, Hyeon Jin; Yoon, Jong Hyung; Kim, Dae Woong; Park, Jeonghoon; Shin, Dongho; Shin, Sang Hoon; Kang, Hyoung Jin; Kim, Seung-Ki; Phi, Ji Hoon; Kim, Joo-Young

2014-09-01

315

Beta Amyloid in Alzheimer’s Disease: Increased Deposition in Brain Is Reflected in Reduced Concentration in Cerebrospinal Fluid  

PubMed Central

Background A decreased concentration of beta amyloid (1–42) (A?42) has consistently been found in the cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD) and is considered a diagnostic biomarker. However, it is not clear to which extent CSF A?42 levels are reflective of cerebral pathology in AD. The aim of the study was to determine the association between cerebral amyloid plaque load, as measured by means of the positron emission tomography (PET) tracer carbon-11-labeled Pittsburgh Compound B ([11C]PiB) and CSF A?42 in AD. Methods A group of 30 patients with probable AD, as defined by established clinical criteria and by an AD-typical pattern of tracer uptake in fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) PET, were included. In all patients, [11C]PiB PET and CSF analysis were performed. The association between amyloid load and CSF A?42 levels was examined in three different ways: by linear regression analysis using an overall [11C]PiB value for the entire cerebrum, by correlation analyses using [11C]PiB measurements in anatomically defined regions of interest, and by voxel-based regression analyses. Results All patients showed a positive [11C]PiB scan demonstrating amyloid deposition. Linear regression analysis revealed a significant inverse correlation between the overall [11C]PiB uptake and CSF A?42 levels. Voxel-based regression and regional correlation analyses did not attain statistical significance after correction for multiple comparisons. Numerically, correlation coefficients were higher in brain regions adjacent to CSF spaces. Conclusions The study demonstrates a moderate linear negative association between cerebral amyloid plaque load and CSF A?42 levels in AD patients in vivo and suggests possible regional differences of the association. PMID:19268916

Grimmer, Timo; Riemenschneider, Matthias; Förstl, Hans; Henriksen, Gjermund; Klunk, William E.; Mathis, Chester A.; Shiga, Tohru; Wester, Hans-Jürgen; Kurz, Alexander; Drzezga, Alexander

2009-01-01

316

S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke  

Microsoft Academic Search

Preservation of endothelial functions with low-dose nitric oxide (NO) and inhibition of excessive production of NO from inducible NO synthase (iNOS) is a potential therapeutic approach for acute stroke. Based on this hypothesis, an NO modulator, S-nitrosoglutathione (GSNO) was used, which provided neuroprotection in a rat model of focal cerebral ischemia. Administration of GSNO after the onset of ischemia reduced

Mushfiquddin Khan; Bipanjeet Sekhon; Shailendra Giri; Manu Jatana; Anne G Gilg; Kamesh Ayasolla; Chinnasamy Elango; Avtar K Singh; Inderjit Singh

2005-01-01

317

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

318

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.  

PubMed

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. PMID:24338618

Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

2014-06-01

319

The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions  

PubMed Central

Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25–0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1–12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence. PMID:16942635

Pak, Arlene C.; Ashby, Charles R.; Heidbreder, Christian A.; Pilla, Maria; Gilbert, Jeremy; Xi, Zheng-Xiong; Gardner, Eliot L.

2013-01-01

320

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

321

The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats.  

PubMed

This report compares the effects of progesterone and its metabolite, allopregnanolone, on the early injury cascade (apoptosis) and long-term functional deficits after TBI. Progesterone (16 mg/kg) or allopregnanolone (4, 8, or 16 mg/kg) were injected at 1 h, 6 h, and then for 5 consecutive days after bilateral contusions of the frontal cortex in adult male rats. Within one day after injury, progesterone and allopregnanolone reduced both the expression of pro-apoptotic proteins caspase-3 and Bax, and apoptotic DNA fragmentation. Progesterone and allopregnanolone also reduced the size of glial fibrillary acid protein (GFAP)-positive astrocytes at the lesion site 24 h after injury. Compared to sham-operated controls at 19 days after injury, injured rats given either progesterone or any of three doses of allopregnanolone had equivalent numbers of ChAT-positive cells in the nucleus basalis magnocellularis. At 19 days post-injury, rats given progesterone or allopregnanolone (8 mg/kg) showed improved performance in a spatial learning task compared to injured rats given only the vehicle. These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone and allopregnanolone and help to explain why better cognitive performance is observed after injury when animals are given either neurosteroid. PMID:15665606

Djebaili, Myriam; Guo, Qingmin; Pettus, Edward H; Hoffman, Stuart W; Stein, Donald G

2005-01-01

322

Isotropic submillimeter fMRI in the human brain at 7 T: combining reduced field-of-view imaging and partially parallel acquisitions.  

PubMed

Echo-planar imaging is the most widely used imaging sequence for functional magnetic resonance imaging (fMRI) due to its fast acquisition. However, it is prone to local distortions, image blurring, and signal voids. As these effects scale with echo train length and field strength, it is essential for high-resolution echo-planar imaging at ultrahigh field to address these problems. Partially parallel acquisition methods can be used to improve the image quality of echo-planar imaging. However, partially parallel acquisition can be affected by aliasing artifacts and noise enhancement. Another way to shorten the echo train length is to reduce the field-of-view (FOV) while maintaining the same spatial resolution. However, to achieve significant acceleration, the resulting FOV becomes very small. Another problem occurs when FOV selection is incomplete such that there is remaining signal aliased from the region outside the reduced FOV. In this article, a novel approach, a combination of reduced FOV imaging with partially parallel acquisition, is presented. This approach can address the problems described above of each individual method, enabling high-quality single-shot echo-planar imaging acquisition, with submillimeter isotropic resolution and good signal-to-noise ratio, for fMRI at ultrahigh field strength. This is demonstrated in fMRI of human brain at 7T with an isotropic resolution of 650 ?m. PMID:22231859

Heidemann, Robin M; Ivanov, Dimo; Trampel, Robert; Fasano, Fabrizio; Meyer, Heiko; Pfeuffer, Josef; Turner, Robert

2012-11-01

323

Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats.  

PubMed

Angiotensin-converting enzyme inhibitors have been demonstrated to protect spontaneously hypertensive rats from cerebral ischemia. The present study investigated the protective effect of enalapril and moexipril in models of permanent focal cerebral ischemia in normotensive mice and rats. To elucidate the mechanism of neuroprotection the influence of these angiotensin-converting enzyme inhibitors on glutamate-, staurosporine- or Fe2+/3+-induced generation of reactive oxygen species and neuronal cell death in primary cultures from chick embryo telencephalons was studied. Treatment with moexipril or enalapril dose-dependently reduced the percentage of damaged neurons, as well as mitochondrial reactive oxygen species generation induced by glutamate, staurosporine or Fe2+/3+. Furthermore, moexipril and enalapril attenuated staurosporine-induced neuronal apoptosis as determined by nuclear staining with Hoechst 33258. In mice, 1 h pretreatment with enalapril (0.03 mg/kg) or moexipril (0.3 mg/kg) significantly reduced brain damage after focal ischemia as compared to control animals. Additionally, moexipril (0.01 mg/kg) was able to reduce the infarct volume in the rat model after focal cerebral ischemia. The results of the present study indicate that the angiotensin-converting enzyme inhibitors enalapril and moexipril promote neuronal survival due to radical scavenging properties. PMID:10408248

Ravati, A; Junker, V; Kouklei, M; Ahlemeyer, B; Culmsee, C; Krieglstein, J

1999-05-28

324

Long term exendin-4 treatment reduces food intake and body weight and alters expression of brain homeostatic and reward markers.  

PubMed

Repeated administration of the long-acting glucagon-like peptide 1 receptor agonist exendin-4 (EX-4) has been shown to reduce food intake and body weight and do so without a rebound increase in food intake after treatment termination. The current study examines the neural mechanisms underlying these actions. After 6 weeks of maintenance on a standard chow or a high-fat (HF) diet, male Sprague Dawley rats were treated with EX-4 (3.2 ?g/kg, i.p., twice a day) or vehicle for 9 consecutive days. Food intake and body weight (BW) were monitored daily. Expression of the genes for the hypothalamic arcuate nucleus (ARC) peptides proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti gene-related protein was determined. Expression of the dopamine precursor tyrosine hydroxylase (TH) gene in the ventral tegmental area and genes for dopamine receptors 1 (D1R) and dopamine receptor 2 in the nucleus accumbens were also determined. Pair-fed groups were included to control for the effects of reduced food intake and BW. Treatment with EX-4 significantly decreased food intake and BW over the 9-day period in both the standard chow and HF groups. HF feeding decreased POMC without changing NPY/agouti gene-related protein gene expression in the ARC. Treatment with EX-4 increased POMC and decreased NPY expression independent of the reduction of food intake and BW. Mesolimbic TH and D1R gene expression were decreased significantly in chronic HF diet-fed rats, and these changes were reversed in both EX-4 and pair-fed conditions. These results suggest a role for increased POMC and decreased NPY expression in the ARC in the effects of EX-4 on food intake and BW. Our findings also suggest that EX-4 induced the recovery of mesolimbic TH and D1R expression in HF diet-fed rats may be secondary to HF intake reduction and/or weight loss. PMID:24949661

Yang, Yan; Moghadam, Alexander A; Cordner, Zachary A; Liang, Nu-Chu; Moran, Timothy H

2014-09-01

325

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

PubMed Central

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. PMID:23800689

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

2013-01-01

326

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

327

[Negative pressure pulmonary edema. Post-obstructive lung edema after use of a laryngeal mask].  

PubMed

A 31-year-old male patient was scheduled for surgical treatment of a distal radius fracture under general anaesthesia using a laryngeal mask airway and spontaneous ventilation. The intraoperative course was uneventful. During recovery, the patient strongly bit the laryngeal mask, producing a complete obstruction of the artificial airway in combination with very forceful inspiratory efforts until the mask was removed. In the recovery room the patient developed dyspnea and desaturation. A portable chest radiograph demonstrated bilateral alveolar infiltration suggesting pulmonary edema. The patient was transferred to the intensive care unit where drug therapy (furosemide and hydrocortisone) and treatment with the continuous flow continuous positive airway pressure (CF-CPAP) system led to complete recovery within 24 h. PMID:16132936

Sickmann, K; Seider, R; Dahm, M; Nold, H

2005-12-01

328

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.

Ahmed, Iftekhar

2014-01-01

329

Subtenon Vs Intravitreal Triamcinolone injection in Diabetic Macular Edema, A prospective study in Chinese population  

PubMed Central

Objective: Purpose of this study was to validate that Subtenon (SB) Triamcinolone (TA) injection is an alternative to Intravitreal (IV) Triamcinolone (TA) injection for the treatment of diabetic macular edema (DME). Methods: Forty eyes were selected having DME due to type 1 or type 2 diabetes. All the patients were treated with photocoagulation. IVTA was administered in one eye and SBTA in following eye of same patient. Improvement in visual acuity, macular edema and intraocular pressure was assessed before treatment and on 2nd, 4th, 8th and 12th week after treatment. Results: After administration of IVTA, MVA was reduced from baseline value (0.805 ± 0.069Log/MAR) to (0.577 ± 0.091 Log/MAR, p<.001) at the end of treatment. Similar results were observed after SBTA administration. MVA was reduced from (0.814 ± 0.082Log/MAR) to (0.49 ± 0.080 Log/MAR, p<.001) at 12th week. After IVTA injection Central macular thickness was significantly reduced to (246.8 ± 25 µm, p<0.001) from (390.5 ± 17 µm). There were no significant (p=0.51) difference in both eyes receiving different routes of same treatment. After SBTA injection CMT was significantly reduced to lower values (241.5 ± 27 µm, p<0.001) from (394.4 ± 21 µm). Intraocular pressure after IVTA administration was high (2.32 ± 0.72 mm/Hg, p=0.04) as compared to baseline (1.82 ± 0.94 mm/Hg). Similar pattern was also seen after SBTA administration but to significant extent. Elevation of IoP was observed in both eyes. Conclusion: Subtenon Triamcinolone injection is an alternative to Intravitreal Triamcinolone Injection for Diabetic Macular Edema. PMID:25097510

Luo, Dawei; Zhu, Bijun; Zheng, Zhi; Zhou, Haidong; Sun, Xiaodong; Xu, Xun

2014-01-01

330

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

331

Laparoscopy to Evaluate Scrotal Edema During Peritoneal Dialysis  

PubMed Central

Background: Acute scrotal edema is an infrequent complication in patients who undergo continuous ambulatory peritoneal dialysis (CAPD), occurring in 2% to 4% of patients. Inguinal hernia is usually the cause, but the diagnosis is sometimes confusing. Imaging modalities such as computed tomographic peritoneography are helpful but can be equivocal. We have used diagnostic laparoscopy in conjunction with open unilateral or bilateral hernia repair for diagnosis and treatment of peritoneal dialysis (PD) patients with acute scrotal edema. Technique and Cases: Three patients with acute scrotal edema while receiving CAPD over the span of 7 years had inconclusive results at clinical examination and on diagnostic imaging. All patients underwent diagnostic laparoscopy that revealed indirect inguinal hernia, which was concomitantly repaired using an open-mesh technique. Results: Diagnostic laparoscopy revealed the etiology of the scrotal edema 100% of the time, with no complications, and allowed concomitant repair of the hernia. One patient had postoperative catheter outflow obstruction, which was deemed to be unrelated to the hernia repair. Conclusion: Diagnostic laparoscopy is helpful in confirming the source of acute scrotal edema in CAPD patients and can be performed in conjunction with an open-mesh repair with minimal added time or risk. PMID:24018081

Jorge, Juaquito M.

2013-01-01

332

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

333

Management of venous edema: insights from an international task force.  

PubMed

An International Task Force made up of a panel of 16 experts has reviewed and objectively evaluated all aspects of chronic venous disease of the leg (CVDL). All available publications on CVDL from 1983 to 1997 were identified through computerized search in Medline and by a manual search. Next, three different screenings were performed in order to select only relevant papers providing a level of scientific evidence that was considered moderate to strong. Final conclusions and further therapeutic recommendations were made based on these publications. Medication, compression, local therapy, sclerotherapy, and surgery are the accepted available therapeutic options for CVDL. For edema, the following recommendations can be made: edema is an early sign of CVDL, but before starting any treatment, nonvenous causes of edema should be excluded. Medication and compression are the therapeutic options for edema that are accepted by the Task Force. Evaluation of their efficacy is based on objective measures of edema. Several well-conducted, placebo-controlled trials have shown efficacy of drugs such as micronized purified flavonoid fraction, rutosides, calcium dobesilate, and coumarin rutin. Graduated compression stockings have been shown to be effective; compression needs to be exerted at least at 35 mm Hg. Bandages, if properly applied, both fixed and stretched, can produce favorable results. Sclerotherapy or surgery is not indicated unless there is saphenofemoral or saphenopopliteal reflux. In the absence of such reflux or following deep venous thrombosis, there is no evidence to support sclerotherapy or surgery. PMID:10667638

Clement, D L

2000-01-01

334

Regression of diabetic macular edema after subcutaneous exenatide.  

PubMed

The aim of this study is to report a case of complete regression of diabetic macular edema after subcutaneous injection of exenatide in a patient with type 2 diabetes mellitus. This study is an interventional case report. Blood investigations, complete ophthalmic examinations and optical coherence tomography were performed. A 55-year-old female affected by poorly controlled type 2 diabetes mellitus presented with visual impairment due to macular edema in the right eye. The left eye showed mild edema without visual loss. Best-corrected visual acuity (BCVA) was 20/80 and 20/20, respectively. The patient was encouraged to improve metabolic control, and the antidiabetic therapy was modified combining exenatide 10 ?g subcutaneously twice daily to her regimen of oral metformin. The patient did not receive any ocular treatment. A complete tomographic resolution of macular edema was observed after 1 month and BCVA improved to 20/63. These findings were confirmed for the entire 6-month follow-up duration. No ocular or non-ocular adverse events were recorded. This is the first reported case of complete regression of macular edema in a diabetic patient after subcutaneous injection of exenatide. PMID:23925692

Sarao, Valentina; Veritti, Daniele; Lanzetta, Paolo

2014-06-01

335

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

336

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

337

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.

Watanabe, Toru

2014-01-01

338

MRI Evidence: Acute Mountain Sickness Is Not Associated with Cerebral Edema Formation during Simulated High Altitude  

PubMed Central

Acute mountain sickness (AMS) is a common condition among non-acclimatized individuals ascending to high altitude. However, the underlying mechanisms causing the symptoms of AMS are still unknown. It has been suggested that AMS is a mild form of high-altitude cerebral edema both sharing a common pathophysiological mechanism. We hypothesized that brain swelling and consequently AMS development is more pronounced when subjects exercise in hypoxia compared to resting conditions. Twenty males were studied before and after an eight hour passive (PHE) and active (plus exercise) hypoxic exposure (AHE) (FiO2?=?11.0%, PiO2?80 mmHg). Cerebral edema formation was investigated with a 1.5 Tesla magnetic resonance scanner and analyzed by voxel based morphometry (VBM), AMS was assessed using the Lake Louise Score. During PHE and AHE AMS was diagnosed in 50% and 70% of participants, respectively (p>0.05). While PHE slightly increased gray and white matter volume and the apparent diffusion coefficient, these changes were clearly more pronounced during AHE but were unrelated to AMS. In conclusion, our findings indicate that rest and especially exercise in normobaric hypoxia are associated with accumulation of water in the extracellular space, however independent of AMS development. Thus, it is suggested that AMS and HACE do not share a common pathophysiological mechanism. PMID:23226263

Mairer, Klemens; Gobel, Markus; Defrancesco, Michaela; Wille, Maria; Messner, Hubert; Loizides, Alexander; Schocke, Michael; Burtscher, Martin

2012-01-01

339

Real-time monitoring of changes in brain extracellular sodium and potassium concentrations and intracranial pressure after selective vasopressin-1a receptor inhibition following focal traumatic brain injury in rats.  

PubMed

Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na(+) and K(+) concentrations ([Na(+)]e; [K(+)]e). Ion-selective Na(+) and K(+) electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na(+)]e, [K(+)]e, and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na(+)]e to 80.1 ± 15 and 87.9 ± 7.9 mM and increase in [K(+)]e to 20.9 ± 3.8 and 13.4 ± 3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p<0.001 vs. baseline; ns between groups). Importantly, [Na(+)]e in CCI-SR49059-ISE was reduced 5-20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na(+)]e recovery. In contrast, [K(+)]e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na(+)]e recovery and reduced ICP. By augmenting the [Na(+)]e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI. PMID:24635833

Filippidis, Aristotelis S; Liang, Xiuyin; Wang, Weili; Parveen, Shanaaz; Baumgarten, Clive M; Marmarou, Christina R

2014-07-15

340

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

341

Flash pulmonary edema in an orthotopic heart transplant recipient.  

PubMed

Flash pulmonary edema (FPE) is a severe renovascular disease that leads to acute recurring pulmonary edema and acute systemic hypertension. Though rarely reported in the literature, its incidence is probably underestimated secondary to misdiagnosis, especially in patients with normal left ventricular function. We report the case of an orthotopic heart transplant recipient who presented with FPE despite having normal left ventricular function and no signs or symptoms of transplant rejection. Discovery of severe bilateral atherosclerotic renal artery stenosis in this patient led to emergency hepatorenal bypass surgery and a favorable postoperative course. PMID:21118836

Kindo, Michel; Gerelli, Sébastien; Billaud, Philippe; Mazzucotelli, Jean-Philippe

2011-02-01

342

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.

343

Is helmet CPAP first line pre-hospital treatment of presumed severe acute pulmonary edema?  

Microsoft Academic Search

Purpose  Non-invasive continuous positive airway pressure (CPAP) is effective in reducing intubation rate and mortality of patient\\u000a with acute cardiogenic pulmonary edema (ACPE). We report our experience on pre-hospital application of CPAP by helmet as an\\u000a adjunct to medical therapy or as a stand alone procedure in patient with presumed ACPE.\\u000a \\u000a \\u000a \\u000a Methods  In pre-hospital treatment of 62 patients with presumed ACPE, CPAP

Giuseppe Foti; Fabio Sangalli; Lorenzo Berra; Stefano Sironi; Marco Cazzaniga; Gian Piera Rossi; Giacomo Bellani; Antonio Pesenti

2009-01-01

344

NEW INSIGHTS INTO BRAIN SWELLING AFTER STROKE  

E-print Network

NEW INSIGHTS INTO BRAIN SWELLING AFTER STROKE W Taylor Kimberly MD PhD 6 May 2013 #12;OBJECTIVES · Background: introduction to stroke · Mechanism: types of cerebral edema · Specific target: preclinical data-Pilot imaging and plasma biomarkers · Next steps: GAMES-RP #12;BACKGROUND · 800,000 strokes occur each year · 4

Sabatini, David M.

345

Dopamine inhibits pulmonary edema through the VEGF-VEGFR2 axis in a murine model of acute lung injury  

PubMed Central

The neurotransmitter dopamine and its dopamine receptor D2 (D2DR) agonists are known to inhibit vascular permeability factor/vascular endothelial growth factor (VEGF)-mediated angiogenesis and vascular permeability. Lung injury is a clinical syndrome associated with increased microvascular permeability. However, the effects of dopamine on pulmonary edema, a phenomenon critical to the pathophysiology of both acute and chronic lung injuries, have yet to be established. Therefore, we sought to determine the potential therapeutic effects of dopamine in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compared with sham-treated controls, pretreatment with dopamine (50 mg/kg body wt) ameliorated LPS-mediated edema formation and lowered myeloperoxidase activity, a measure of neutrophil infiltration. Moreover, dopamine significantly increased survival rates of LPS-treated mice, from 0–75%. Mechanistically, we found that dopamine acts through the VEGF-VEGFR2 axis to reduce pulmonary edema, as dopamine pretreatment in LPS-treated mice resulted in decreased serum VEGF, VEGFR2 phosphorylation, and endothelial nitric oxide synthase phosphorylation. We used D2DR knockout mice to confirm that dopamine acts through D2DR to block vascular permeability in our lung injury model. As expected, a D2DR agonist failed to reduce pulmonary edema in D2DR?/? mice. Taken together, our results suggest that dopamine acts through D2DR to inhibit pulmonary edema-associated vascular permeability, which is mediated through VEGF-VEGFR2 signaling and conveys protective effects in an ALI model. PMID:22003095

Vohra, Pawan K.; Hoeppner, Luke H.; Sagar, Gunisha; Dutta, Shamit K.; Misra, Sanjay; Hubmayr, Rolf D.

2012-01-01

346

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

347

A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model  

Microsoft Academic Search

Cerebral edema, a major complication of tumors in the brain, is the result of an alteration in the blood-brain barrier (B-BB). The vascular ultrastructural changes that underlie edema formation have been described in a variety of tumors. Interendothelial junction abnormalities, fenestrations, and large numbers of tubulo-vesicular profiles in the tumor vascular endothelium have been presumed to represent permeability routes that

P. A. Stewart; K. Hayakawa; E. Hayakawa; C. L. Farrell; R. F. Del Maestro

1985-01-01

348

Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia.  

PubMed

By using two structurally unrelated hydrogen sulfide (H2 S) donors 5-(4-methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H2 S protected blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H2 S donors at 3 h after reperfusion. Infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression were examined at 48 h after MCAO. We also investigated if ADT protected BBB integrity by suppressing post-ischemic inflammation-induced Matrix Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). ADT increased blood H2 S concentrations, decreased infarction, and improved neurological deficits. Particularly, ADT reduced EB extravasation, brain edema and preserved expression of tight junction proteins in the ischemic brain. NaHS also increased blood H2 S levels and reduced EB extravasation following MCAO. Moreover, ADT inhibited expression of pro-inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1? while enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-?B) in the ischemic brain. In conclusion, H2 S donors protected BBB integrity following experimental stroke possibly by acting through NF-?B inhibition to suppress neuroinflammation induction of MMP9 and NOX4-derived free radicals. To determine H2 S effects on blood-brain barrier (BBB) disruption following stroke, we used two structurally unrelated H2 S donors ADT and NaHS. Both ADT and NaHS remarkably protected BBB integrity following experimental stroke. The slow-releasing donor ADT also reduced post-ischemic inflammation-induced expression and activity of MMP9 and NOX4 in the ischemic brain possibly by inhibiting NF-?B activation. PMID:24673410

Wang, Yali; Jia, Jia; Ao, Guizhen; Hu, Lifang; Liu, Hui; Xiao, Yunqi; Du, Huaping; Alkayed, Nabil J; Liu, Chun-Feng; Cheng, Jian

2014-06-01

349

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

PubMed

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

350

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

351

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

352

Atypical Wernicke's syndrome sans encephalopathy with acute bilateral vision loss due to post-chiasmatic optic tract edema  

PubMed Central

A middle aged male presented with acute bilateral vision loss, 4 weeks after undergoing gastric bypass surgery for gastric carcinoma. He had normal sensorium, fundoscopy, normal pupillary reaction to light, but had mild opthalmoparesis and nystagmus with ataxia. Magnetic resonance imaging of the brain revealed post-chiasmatic optic tract edema along with other classical features of Wernicke's syndrome. Thiamine supplementation leads to complete resolution of clinical as well as imaging findings. In appropriate clinical settings, a high index of suspicion and early treatment are essential for managing Wernicke's syndrome even in patients with atypical clinical and imaging presentation. PMID:24753673

Desai, Soaham Dilip; Shah, Diva Sidharth

2014-01-01

353

Extracorporeal Membrane Oxygenation for Acute Life-Threatening Neurogenic Pulmonary Edema following Rupture of an Intracranial Aneurysm  

PubMed Central

Neurogenic pulmonary edema (NPE) leading to cardiopulmonary dysfunction is a potentially life-threatening complication in patients with central nervous system lesions. This case report describes a 28-yr woman with life-threatening fulminant NPE, which was refractory to conventional respiratory treatment, following the rupture of an aneurysm. She was treated successfully with extracorporeal membrane oxygenation (ECMO), although ECMO therapy is generally contraindicated in neurological injuries such as brain trauma and diseases that are likely to require surgical intervention. The success of this treatment suggests that ECMO therapy should not be withheld from patients with life-threatening fulminant NPE after subarachnoid hemorrhage. PMID:23772167

Hwang, Gyo Jun; Sheen, Seung Hun; Kim, Hyoung Soo; Lee, Hee Sung; Lee, Tae Hun; Gim, Gi Ho; Hwang, Sung Mi

2013-01-01

354

[Edema as a measure for severity of chronic venous insufficiency and efficacy of its treatment].  

PubMed

The author characterizes the edema as an important quantitative objective measure of severity for chronic venous diseases in both early and advanced stages. The problems of edema assessment methods and the importance of its management in clinical practice are discussed. The results of studies on the use of micronized purified flavonoid fraction (MPFF, Detralex) for edema syndrome coping are presented. PMID:19791434

Sapelkin, S V

2008-01-01

355

Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Implication of VEGF as a Critical Stimulator  

Microsoft Academic Search

Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO

Peter A Campochiaro; Gulnar Hafiz; Syed Mahmood Shah; Quan Dong Nguyen; Howard Ying; Diana V Do; Edward Quinlan; Ingrid Zimmer-Galler; Julia A Haller; Sharon D Solomon; Jennifer U Sung; Yasmin Hadi; Kashif A Janjua; Nida Jawed; David F Choy; Joseph R Arron

2008-01-01

356

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases.  

PubMed

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation. PMID:20549052

Brasil, Oswaldo Ferreira Moura; Brasil, Maria Vitoria Moura; Ventura, Marcelo Palis; Maia, Hugo Soares

2010-01-01

357

A rare complication of generalized edema in juvenile dermatomyositis: a report of one case  

Microsoft Academic Search

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by inflammation of the muscle, connective tissue, skin, gastrointestinal tract and small nerves. Periorbital and facial edema may also be associated. Although localized edema is a common feature of juvenile dermatomyositis, generalized edema has been reported rarely. In this article, we report a 14-year-old boy with juvenile dermatomyositis presenting with generalized

Hamza Karabiber; Mehmet Aslan; Alpay Alkan; Cengiz Yakinci

2004-01-01

358

From symptoms to leg edema: efficacy of Daflon 500 mg.  

PubMed

This article reviews the mechanisms by which micronized purified flavonoid fraction (MPFF; Daflon 500 mg) acts on symptoms as well as on edema in patients with chronic venous disease, in the light of new advances in the understanding of the pathophysiology of this chronic condition. Deterioration of venous wall tone followed by valve dysfunction leading eventually to varicose veins are the key pathophysiologic features that produce venous hypertension. Both mechanical and biological factors are responsible for the deterioration of the venous wall in large veins. These are decreased shear stress and hypoxia of the media and of the endothelium, which act as triggering factors for biochemical reactions leading to inflammation. There is a body of evidence that inflammation in chronic venous insufficiency (CVI) plays a role right from the early stages of venous dysfunction and venous valve restructuring. The whole process of venous wall stretching and dilation is painful and may present as leg heaviness, a sensation of swelling, and paresthesia. Daflon 500 mg relieves symptoms, edema, and red blood cell aggregation, which cause paresthesia and restless legs. At the level of the microcirculation, dysfunction of microvessels is observed, characterized by an increase in capillary permeability followed by skin changes. The earliest manifestation of microcirculatory disorder is edema. At this level, Daflon 500 mg acts favorably on microcirculatory complications by normalizing the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and inhibits leukocyte activation, trapping, and migration. Its efficacy in decreasing CVI edema and ankle swelling has been proven in rigorous studies that are reviewed in this paper. Daflon 500 mg, a well-established oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin, may be prescribed from the very beginning of the disease for the relief of pain and edema, and in any CVI patient presenting with symptoms as well. Daflon 500 mg is thus the first-line treatment for edema and symptoms of CVI at any stage of the disease. At advanced disease stages, Daflon 500 mg may be used in conjunction with sclerotherapy, surgery, and/or compression therapy or as an alternative treatment when other treatments are not indicated or not feasible. PMID:12934755

Nicolaides, Andrew N

2003-01-01

359

Contributions of Edema Factor and Protective Antigen to the Induction of Protective Immunity by Bacillus anthracis Edema Toxin as an Intranasal Adjuvant  

PubMed Central

We have shown that intranasal coapplication of Bacillus anthracis protective Ag (PA) together with a B. anthracis edema factor (EF) mutant having reduced adenylate cyclase activity (i.e., EF-S414N) enhances anti-PAAb responses, but also acts as a mucosal adjuvant for coadministered unrelated Ags. To elucidate the role of edema toxin (EdTx) components in its adjuvanticity, we examined how a PA mutant lacking the ability to bind EF (PA-U7) or another mutant that allows the cellular uptake of EF, but fails to efficiently mediate its translocation into the cytosol (PA-dFF), would affect EdTx-induced adaptive immunity. Native EdTx promotes costimulatory molecule expression by macrophages and B lymphocytes, and a broad spectrum of cytokine responses by cervical lymph node cells in vitro. These effects were reduced or abrogated when cells were treated with EF plus PA-dFF, or PA-U7 instead of PA. We also intranasally immunized groups of mice with a recombinant fusion protein of Yersinia pestis F1 and LcrVAgs (F1-V) together with EdTx variants consisting of wild-type or mutants PA and EF. Analysis of serum and mucosal Ab responses against F1-V or EdTx components (i.e., PA and EF) revealed no adjuvant activity in mice that received PA-U7 instead of PA. In contrast, coimmunization with PA-dFF enhanced serum Ab responses. Finally, immunization with native PA and an EF mutant lacking adenylate cyclase activity (EF-K346R) failed to enhance Ab responses. In summary, a fully functional PA and a minimum of adenylate cyclase activity are needed for EdTx to act as a mucosal adjuvant. PMID:20952678

Duverger, Alexandra; Carre, Jeanne-Marie; Jee, Junbae; Leppla, Stephen H.; Cormet-Boyaka, Estelle; Tang, Wei-Jen; Tome, Daniel; Boyaka, Prosper N.

2013-01-01

360

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

PubMed Central

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

2010-01-01

361

Oral Leucine Supplementation Is Sensed by the Brain but neither Reduces Food Intake nor Induces an Anorectic Pattern of Gene Expression in the Hypothalamus  

PubMed Central

Leucine activates the intracellular mammalian target of the rapamycin (mTOR) pathway, and hypothalamic mTOR signaling regulates food intake. Although central infusion of leucine reduces food intake, it is still uncertain whether oral leucine supplementation is able to affect the hypothalamic circuits that control energy balance. We observed increased phosphorylation of p70s6k in the mouse hypothalamus after an acute oral gavage of leucine. We then assessed whether acute oral gavage of leucine induces the activation of neurons in several hypothalamic nuclei and in the brainstem. Leucine did not induce the expression of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive neurons in the area postrema. In addition, oral gavage of leucine acutely increased the 24 h food intake of mice. Nonetheless, chronic leucine supplementation in the drinking water did not change the food intake and the weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat diet. We assessed the hypothalamic gene expression and observed that leucine supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK) that metabolize branched-chain amino acids. Despite these effects, leucine supplementation did not induce an anorectic pattern of gene expression in the hypothalamus. In conclusion, our data show that the brain is able to sense oral leucine intake. However, the food intake is not modified by chronic oral leucine supplementation. These results question the possible efficacy of leucine supplementation as an appetite suppressant to treat obesity. PMID:24349566

Zampieri, Thais T.; Pedroso, Joao A. B.; Furigo, Isadora C.; Tirapegui, Julio; Donato, Jose

2013-01-01

362

Reduced levels of brain-derived neurotrophic factor contribute to synaptic imbalance during the critical period of respiratory development in rats.  

PubMed

Previously, our electrophysiological studies revealed a transient imbalance between suppressed excitation and enhanced inhibition in hypoglossal motoneurons of rats on postnatal days (P) 12-13, a critical period when abrupt neurochemical, metabolic, ventilatory and physiological changes occur in the respiratory system. The mechanism underlying the imbalance is poorly understood. We hypothesised that the imbalance was contributed by a reduced expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition. We also hypothesised that exogenous BDNF would partially reverse this synaptic imbalance. Immunohistochemistry/single-neuron optical densitometry, real-time quantitative PCR (RT-qPCR) and whole-cell patch-clamp recordings were done on hypoglossal motoneurons in brainstem slices of rats during the first three postnatal weeks. Our results indicated that: (1) the levels of BDNF and its high-affinity tyrosine receptor kinase B (TrkB) receptor mRNAs and proteins were relatively high during the first 1-1.5 postnatal weeks, but dropped precipitously at P12-13 before rising again afterwards; (2) exogenous BDNF significantly increased the normally lowered frequency of spontaneous excitatory postsynaptic currents but decreased the normally heightened amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period; (3) exogenous BDNF also decreased the normally heightened frequency of miniature IPSCs at P12-13; and (4) the effect of exogenous BDNF was partially blocked by K252a, a TrkB receptor antagonist. Thus, our results are consistent with our hypothesis that BDNF and TrkB play an important role in the synaptic imbalance during the critical period. This may have significant implications for the mechanism underlying sudden infant death syndrome. PMID:24666389

Gao, Xiu-Ping; Liu, Qiuli; Nair, Bindu; Wong-Riley, Margaret T T

2014-07-01