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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of intracellular calcium homeostasis has been regarded an important factor underlying neuron cell death after cerebral ischemic insult. In the brain, a major mechanism for regulation of intracellular calcium is through the signal transduction pathway involving hydrolysis of poly-phosphoinositides and release of the second messenger, inositol 1,4,5-trisphosphate (IP3). IP3 mobilizes calcium by interacting with an intracellular receptor. Upon its release after agonist stimulation, this second messenger is catabolized by a 3-kinase and a 5-phosphatase. In this study, in situ hybridization was carried out to examine the mRNA expression of IP3, receptor (IP3R) and IP3 3-kinase (IP3K) in rat brain cortex after transient focal cerebral ischemia induced by temporary occlusion of the middle cerebral artery (MCA) and the common carotid arteries (CCAs). Results indicate a large decrease (52%) in IP3R mRNA levels in the ischemic cortex as compared to that in the contralateral side at 4 h after a 45 min ischemic insult. By 16 h, practically no IP3R mRNA could be detected in the ischemic cortex. On the other hand, IP3K mRNA levels remained unaltered until 16 h after reperfusion, during which time, expression in the infarct core decreased but that surrounding the core area increased instead. Hybridization of adjacent brain sections with probes for neuron specific enolase (NSE) and beta-actin indicated also a time-dependent decrease in mRNA levels after ischemia, but these changes were less dramatic as compared to IP3R. At 16 and 24 h after reperfusion, there was an increase in beta-actin mRNA in cortical areas outside the MCA cortex, suggesting of reactive gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ hybridization of mRNA expression for IP3 receptor and IP3-3-kinase in rat brain after transient focal cerebral ischemia. 750 Aug 36

We investigated the expression of cyclin D1 and its kinase, cdk4, after induction of focal cerebral ischemia in the rat. Brain from rats (n = 6) subjected to 2 hours of transient middle cerebral artery occlusion and 46 hours of reperfusion, and control sham-operated (n = 3) and normal (n = 2) rats were processed for dual label immunohistochemical study for cellular identification of the expression of these cell cycle proteins. Antibodies raised against microtubule-associated protein 2 and neuronal specific enolase for neurons, glial fibrillary acidic protein for astrocytes, myelin basic protein for oligodendrocytes and lectin histochemical study with the B4-isolectin for microglia were used for cell type identification. Double staining for DNA fragmentation detection (TUNEL) and expression of cyclin D1 and cdk4 also was performed. Cyclin D1 and cdk4 were selectively expressed in morphologically intact or altered neurons and oligodendrocytes localized to the ischemic tissue. Apoptotic cells were not immunoreactive to cyclin D1 and cdk4 at 46 hours after 2 hours of middle cerebral artery occlusion. The selective expression of cell cycle proteins observed in nonapoptotic ischemic postmitotic neurons and oligodendrocytes suggests a role for these proteins in cell survival after transient focal cerebral ischemia.
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PMID:Immunoreactivity of cyclin D1/cdk4 in neurons and oligodendrocytes after focal cerebral ischemia in rat. 929 May 82

Global cerebral ischemia induced to Mongolian gerbils by ligation of common carotid arteries (CCAs) is known to result in injury to the hippocampal CA1 region. In this study, we examined whether neuronal injury can be depicted by measuring levels of mRNA encoding inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), neuron specific enolase (NSE) and beta-actin and whether these measurements can be use to assess ischemic tolerance. Gerbils were subjected either to cerebral ischemia induced by ligation of both CCAs for 5 min, or to an ischemic tolerance paradigm in which a 2 min ischemic preconditioning was performed 24 hr prior to the 5 min ischemia. At 48 hr after the 5 min ischemic insult, significant decreases in mRNA levels for IP3R1 (26%), NSE (38%) and beta-actin (50%) could be observed in the hippocampal CA1 region. Although levels of mRNA in the preconditioning group were decreased as compared to the sham control, the levels were significantly higher than those in the ischemic group. These results indicate the feasibility of using mRNA measurement as a parameter to assess cerebral ischemic damage. In addition, based on the differences in the decline in mRNA levels between the ischemia group and the preconditioned ischemia group, it can be concluded that this ischemic tolerance paradigm could offer partial protection (around 45%) against the injury due to the 5 min cerebral ischemic insult.
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PMID:Effects of ischemic tolerance on mRNA levels of IP3R1, beta-actin, and neuron-specific enolase in hippocampal CA1 area of the gerbil brain. 956 89

Tumor necrosis factor alpha (TNFalpha) is a pleiotrophic cytokine with diverse proinflammatory actions. Focal cerebral ischemia induces rapid and dramatic increases in TNFalpha levels within and surrounding the focus of damaged brain both in striatum and cortex. The actions of TNFalpha during cerebral ischemia may be related to the cell types which deliver and/or accept TNFalpha signals. However, the cellular sources of TNFalpha following cerebral ischemia have not been fully elucidated. The present study was designed to determine the cellular localization of TNFalpha following permanent middle cerebral artery occlusion (MCAO) in mice. As judged by immunohistochemistry, TNFalpha expression in the ischemic hemisphere was increased at 3 h following MCAO, peaked at 6 to 12 h, and decreased at 24 h. Double immunostaining for TNFalpha and neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP) showed that TNFalpha positive neurons were observed in both the ischemic core and perifocal region, while TNFalpha positive astrocytes were observed in the outer cortical layer, the corpus callosum, the molecular layer of the hippocampus, and periventricular areas. The presence of TNFalpha immunoreactivity in neurons and nerve fibers following MCAO suggests that TNFalpha expressed in ischemic neurons might be delivered via axonal transport, while TNFalpha immunoreactivity in astrocyte end-feet and ependymal cells following MCAO suggests that TNFalpha may be involved in blood-brain barrier disruption and the initiation of inflammation in the brain.
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PMID:Cellular localization of tumor necrosis factor alpha following focal cerebral ischemia in mice. 972 36

Nerve tissue protein S-100 and neurone-specific enolase levels in serum were studied in 10 patients before, during and for 2 days after elective carotid endarterectomy performed under general anaesthesia and using a Javid Shunt. In six patients, simultaneous cerebrospinal fluid samples were also obtained. Serum nerve tissue protein S-100 was normal throughout the operation, but in one patient with severe hypertension, levels increased to 1.38 microg. l-1 at 1 h postoperatively. Two patients showed an increase in cerebrospinal fluid nerve tissue protein S-100 during clamping: these patients also had neurological deficits at 6 months. Serum neurone-specific enolase increased from 5.8 to 9.3 microg.l-1 during shunting while cerebrospinal fluid neurone-specific enolase did not change. Uncomplicated carotid endarterectomy does not produce cerebral damage as measured by serum nerve tissue protein S-100; cerebrospinal fluid nerve tissue protein S-100 may be more sensitive for minor cerebral damage. Neurone-specific enolase appeared to be nonspecific. The lack of correlation between the neuroproteins may need to be explained before relying on these simple assays as diagnostic indicators of cerebral ischaemia.
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PMID:Nerve tissue protein S-100 and neurone-specific enolase concentrations in cerebrospinal fluid and blood during carotid endarterectomy. 1094 90

Focal cerebral ischemia elicits an inflammatory response characterized by the infiltration and accumulation of leukocytes, as well as the secretion of inflammatory mediators (Clark et al., Brain Res. Bull., 35 (1994) 387-392; Garcia et al., Am. J. Pathol., 144 (1994) 188-199; Wang et al., J. Neurochem. 71 (1998) 1194-1204). Leukocytes eliminate microbial invaders and necrotizing tissue debris, and can also turn against surrounding healthy tissue and exacerbate tissue injury (Furie and Randolph, Am. J. Pathol., 146 (1995) 1287-1301; Kochanek and Hallenbeck, Stroke 23 (1992) 1367-1379). Inflammatory mediators are considered to play an important role in attracting and stimulating leukocytes (Weiss, N. Engl. J. Med., 320 (1989) 365-376). Monocyte chemoattractant protein-1 (MCP-1) functions as an inflammatory mediator, whose source and role in focal cerebral ischemia is worth studying. MCP-1, a potent chemoattractant factor, may play an important role in ischemia-induced inflammatory response. The aim of the present study is to determine the time course and cell type of MCP-1 protein expression after permanent focal ischemia in mice. ELISA and immunohistochemical staining were used to detect the expression of MCP-1 protein after 0 h, 2 h, 4 h, 12 h, 1 day, 2 days, 3 days, 5 days and 7 days of middle cerebral artery occlusion (n=3-5 in each group). Double-labeled fluorescent staining was used to examine the cellular localization of MCP-1. The results demonstrated that MCP-1 expression was mainly observed in the ischemic core after 12 h of middle cerebral artery occlusion, then gradually increased and extended to the ischemic perifocal area. MCP-1 expression peaked at 2 days and 3 days, and gradually decreased after 5 days of MCAO. Double-labeled immunostaining for MCP-1 and neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP) showed that MCP-1 positive neurons were observed as early as 12 h of ischemia, while MCP-1 positive astrocytes were observed after 2 days of ischemia. These results support the functional role of MCP-1 in ischemic brain injury and reveal a distinct temporal and spatial expression of MCP-1 in cells believed to be neurons and astrocytes.
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PMID:Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. 1138 10

During implantable cardioverter-defibrillator (ICD) implantation, ventricular defibrillation testing (DFT) is considered a standard procedure. This procedure often requires multiple ventricular fibrillation (VF) inductions. These repeated short episodes of circulatory arrest with global cerebral ischemia may cause neurological damage. In the present study, patients undergoing initial ICD implantation and limited induction of VF for defibrillation safety margin testing were evaluated for pre- and postoperative cognitive and neurologic functions. In addition, the serum neuron specific enolase (NSE) level, which is a biochemical marker of cerebral injury, was evaluated. The study was performed on 16 patients undergoing initial elective transvenous insertion of an ICD. A neurologic examination and cognitive assessment tests were performed 24 to 48 hours before and after ICD. NSE was determined before (NSE 1) and at the end of the surgery (NSE 2), as well as 2 hours (NSE 3), 24 hours (NSE 4), and 48 hours (NSE 5) after implantation. A total of 29 internal shocks (average, 1.8 +/- 0.4) with energy ranging from 14 to 41 J (mean, 20 +/- 5; median, 20 J ) were delivered in the ICD group patients. In one patient, 3 external (50, 200 and 360 J) shocks were required for fast VT induced during ICD lead positioning. The mean duration of VF was 10 +/- 4 seconds and the mean cumulative time in VF was 16 +/- 5 seconds. The mean recovery time between VFs was 5.3 +/- 0.6 minutes. NSE levels were not different from the baseline at any time point in the patients of the group that completed the 48-hour observation period (P > 0.05). The patients did not report any new neurological symptoms after ICD implantation, and repeat examination after the procedure showed no abnormal findings other than those detected in the previous one. There were no statistically significant differences between the preoperative and postoperative scores obtained in the cognitive assessment. Single or two VF inductions and the brief arrest of cerebral circulation during ICD implantation are not associated with permanent neurological injury. However, further studies are needed to confirm this finding.
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PMID:Defibrillation testing and early neurologic outcome. 1897 67

Previous studies have shown that Qing Kai Ling, a traditional Chinese medicine, was able to effectively prevent the inflammation from cerebral ischemia (Chen et al., 2002). The cholalic acid and hyodeoxycholalic acid (cholalic acid mixture) was major active components in Qing Kai Ling. To study the effects of cholalic acid mixture on the damage cascade of cerebral ischemia, rat model of focal cerebral ischemia was established by permanent occlusion of left middle cerebral artery. We found that the administration of cholalic acid mixture could reduce the ischemic infarct size after 24 h of ischemia, and cholalic acid mixture could be detected in cerebrospinal fluid after 2h of administration. We also found that the concentrations of tumor necrosis factor-alpha and interlukin-1beta in rat brain were significantly lower when compared to the untreated animals after 12 h and 24 h of ischemia. The concentrations of von Willebrand factor and neuron specific enolase in the plasma were remarkably decreased in cholalic acid mixture treated animals than in the untreated ones after 12h of ischemia. Our results suggested that cholalic acid mixture is able to decrease the expression of inflammation factors including tumor necrosis factor-alpha and interlukin-1beta after focal cerebral ischemia.
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PMID:The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFalpha and IL-1beta after cerebral ischemia in rats. 1918 78

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation.
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PMID:Circulating biochemical markers of brain damage in infants complicated by ischemia reperfusion injury. 1935 73

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia.
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PMID:Biochemical markers of perinatal brain damage. 2003 28


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