Acute changes in cerebral function after elective coronary bypass surgery are a difficult clinical problem. We carried out multicenter study to determine the incidence and predictors of — use resources associated with perioperative adverse neurologic events, including injury.

Delayed neuronal death after transient cerebral ischemia may be mediated, in part, by the induction of apoptosis-regulatory gene products. Caspase-3 is a newly characterized mammalian cysteine protease that promotes cell during brain development, cultures, and other types under many different conditions. To determine whether caspase-3 serves to regulate ischemia, we have (1) cloned cDNA encoding rat caspase-3; (2) examined mRNA protein expression using situ hybridization, Northern Western...

Marijuana and related drugs (cannabinoids) have been proposed as treatments for a widening spectrum of medical disorders. R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (R (+)-WIN 55212-2), synthetic cannabinoid agonist, decreased hippocampal neuronal loss after transient global cerebral ischemia reduced infarct volume permanent focal induced by middle artery occlusion in rats. The less active enantiomer S (−)-WIN...

Bcl-xL is a well characterized death-suppressing molecule of the Bcl-2 family. expressed in embryonic and adult neurons CNS may play critical role preventing neuronal apoptosis that occurs during brain development or results from diverse pathologic stimuli, including cerebral ischemia. In this study, we used novel approach to study potential neuroprotective effect as therapeutic agent murine model focal ischemia/reperfusion. We created fusion protein, designated PTD-HA-Bcl-xL, which contains...

Abstract: During programmed cell death, activation of caspase‐3 leads to proteolysis DNA repair proteins, cytoskeletal and the inhibitor caspase‐activated deoxyribonuclease, culminating in morphologic changes damage defining apoptosis. The participation evolution neuronal death after traumatic brain injury rats was examined. Cleavage pro‐caspase‐3 cytosolic cellular fractions an increase caspase‐3‐like enzyme activity were seen injured versus control. substrates DNA‐dependent protein kinase...

Loss of mitochondrial membrane integrity and release apoptogenic factors are a key step in the signaling cascade leading to neuronal cell death various neurological disorders, including ischemic injury. Emerging evidence has suggested that intramitochondrial protein apoptosis-inducing factor (AIF) translocates nucleus promotes caspase-independent induced by glutamate toxicity, oxidative stress, hypoxia, or ischemia. However, mechanism which AIF is released from mitochondria after injury not...

The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an immediate early gene induced by synaptic activity in brain. COX2 important mediator inflammation, but it not known whether pathogenic To study role ischemic injury brain, expression mRNA and protein effect treatment with a inhibitor on neuronal survival rat model global ischemia were determined. Expression both was increased after CA1 hippocampal neurons before their death. There rats treated COX2-selective SC58125...

Many central nervous system (CNS) diseases display sexual dimorphism. Exposure to circulating sex steroids is felt be a chief contributor this phenomenon; however, CNS of childhood and the elderly also demonstrate gender predominance and/or sexually dimorphic response therapies. Here we show that XY XX neurons cultured separately are differentially susceptible various cytotoxic agents treatments. were more sensitive nitrosative stress excitotoxicity versus neurons. In contrast, etoposide-...

Poly(ADP-ribosylation), primarily via poly(ADP-ribose) polymerase-1 (PARP-1), is a pluripotent cellular process important for maintenance of genomic integrity and RNA transcription in cells. However, during conditions oxidative stress energy depletion, poly(ADP-ribosylation) paradoxically contributes to mitochondrial failure cell death. Although it has been presumed that within the nucleus mediates this pathologic process, PARP-1 other poly(ADP-ribosyltransferases) are also localized...

Stress proteins are induced after a variety of neuronal injuries. The inducible 72-kDa heat shock protein (hsp70) is stress that protects neurons from glutamate toxicity in vitro. Hsp70 has also been proposed to underlie the phenomenon ischemic tolerance whereby brief sublethal intervals global ischemia protect hippocampus subsequent lethal prolonged ischemia. To determine if occurs cortex focal ischemia, rat middle cerebral artery (MCA) was occluded by suture method. Three 10-min transient...

Background and Purpose —Cerebral injury after cardiac surgery is now recognized as a serious costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation new clinical strategies. No such subgroup has been identified; however, undergoing intracardiac are thought to high risk, but comprehensive data regarding specific impact on cost, discharge disposition not available....

The bcl-2 and caspase families are important regulators of programmed cell death in experimental models ischemic, excitotoxic, traumatic brain injury. Bcl-2 family members Bcl-xL suppress death, whereas Bax promotes death. Activated caspase-1 (interleukin-1β converting enzyme) caspase-3 (Yama/Apopain/Cpp32) cleave proteins that maintaining cytoskeletal integrity DNA repair, activate deoxyribonucleases, producing with morphological features apoptosis. To address the question whether these...

Abstract: Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative were used in a rodent model The level stable product derived from peroxidation arachidonyl residues phospholipids, 8‐ epi ‐prostaglandin F 2α , was increased at 6 and 24 h Furthermore, relative amounts fluorescent end products lipid extracts trauma compared with sham‐operated controls. total antioxidant reserves...

Abstract Programmed cell death occurs after ischemic, excitotoxic, and traumatic brain injury (TBI). Recently, a caspase‐independent pathway involving intranuclear translocation of mitochondrial apoptosis‐inducing factor (AIF) has been reported in vitro ; but whether this acute was unknown. To address question adult rats were sacrificed at various times TBI. Western blot analysis on subcellular protein fractions demonstrated localization AIF ipsilateral cortex hippocampus 2–72 h....

Mild to moderate hypothermia (30–33°C) reduces brain injury after brief (<2-h) periods of focal ischemia, but its effectiveness in prolonged temporary ischemia is not fully understood. Thirty-two Sprague–Dawley rats anesthetized with 1.5% isoflurane underwent 3 h middle cerebral artery occlusion under hypothermic (33°C) or normothermic (37°C) conditions followed by 21 reperfusion ( n = 8/group). Laser–Doppler estimates cortical blood flow showed that intraischemic reduced both...

Neuronal death after experimental traumatic brain injury (TBI) has features of both apoptosis and necrosis. Neurons in the peritrauma cortex, hippocampus, dentate gyrus are particularly vulnerable. The apoptosis-suppressor gene bcl-2 is induced ischemia epilepsy-induced may serve to regulate neuronal death. We studied expression mRNA protein TBI rats. To determine whether occurred cells with evidence apoptosis, triple-labeling studies were performed using (1) antibody against bcl-2, (2)...

Abstract: The observation that delayed death of CA1 neurons after global ischemia is inhibited by protein synthesis inhibitors suggests the these an active process requires new gene expression. Delayed in has some characteristics apoptotic death; however, candidate proapoptotic proteins have not been identified ischemia. We studied expression Bax and mRNA, a member bcl‐2 family effector cell death, four‐vessel model rat compared results with antiapoptotic . mRNA are both expressed before...

c-Jun N-terminal kinase (JNK) is an important stress-responsive that activated by various forms of brain insults. In this study, we have examined the role JNK activation in neuronal cell death a murine model focal ischemia and reperfusion; furthermore, investigated mechanism apoptosis signaling, focusing on mitochondrial-signaling pathway. We show here activity was induced 0.5 to 24 h after ischemia. Systemic administration SP600125, small molecule JNK-specific inhibitor, diminished...

Activation of terminal caspases such as caspase-3 plays an important role in the execution neuronal cell death after transient cerebral ischemia. Although precise mechanism by which are activated ischemic neurons remains elusive, recent studies have postulated that mitochondrial death-signaling pathway may participate this process. The bcl-2 family member protein Bax is a potent proapoptotic molecule that, on translocation from cytosol to mitochondria, triggers activation increasing membrane...

The proto-oncogenes bcl-2 and bcl-x-long have been shown to suppress apoptotic cell death in a variety of vitro systems lines, including neurons. An alternatively spliced form bcl-x, bcl-x-short, is promoter death. Whether these genes are induced after ischemia or play any role determining the fate ischemic neurons unknown. To begin address this issue, we studied expression bcl-2, bcl-x mRNA protein global rat. Ischemia was isoflurane-anesthetized rats by four-vessel occlusion method....

Abstract Peroxisome proliferator‐activated receptor gamma (PPAR‐γ) is a nuclear membrane‐associated transcription factor that governs the expression of various inflammatory genes. PPAR‐γ agonists protect peripheral organs from ischemic injury. In present study, we investigated whether agonist rosiglitazone neuroprotective against focal brain C57/B6 mice underwent 1.5‐h middle cerebral artery occlusion, and received either vehicle or treatment 0.75, 1.5, 3, 6 12 mg/kg ( n = 9 per group)....

Autophagy is a homeostatic process for recycling of proteins and organelles, induced by nutrient deprivation regulated oxygen radicals. Whether autophagy after traumatic brain injury (TBI) not established. We show that TBI in mice results increased ultrastructural biochemical evidence autophagy. Specifically, autophagosomal vacuoles secondary lysosomes were frequently observed cell processes axons ipsilateral regions electron microscopy, lipidated microtubule-associated protein light chain...