Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After occlusion of the right common carotid artery in the gerbil, we monitored the progression of ischemic damage and postischemic damage and the repair process in the brain immunohistochemically by using tubulin, creatine kinase BB-isoenzyme (CK-BB), and neuron-specific enolase as the neuronal markers and astroprotein, glial fibrillary acidic protein, and CK-BB as the astrocytic markers. The earliest ischemic lesion was detected in the hippocampus and the cerebral cortex after ischemia for 5 minutes as loss of the reaction in the neuropil, nerve cell bodies, and dendrites. The reaction disappeared more promptly in the dendrites than in the nerve cell bodies. The reaction for tubulin was the most sensitive for detection of the neuronal ischemic damage. After an ischemic period of 30 minutes and subsequent reestablishment of cerebral circulation, the immunohistochemical lesions affecting the neuronal structure expanded during the first 3 hours and then slowly afterward for up to 12 hours. Reactive astrocytes were already identified 24 hours after reperfusion. The current investigation demonstrated that early ischemic damage can be clearly visualized by use of the immunohistochemical technique soon after the onset of cerebral ischemia but that considerable heterogeneity exists not only in different anatomic regions but also within the neuronal structure. This technique has potential for further investigation of cerebral ischemia or other pathophysiologic conditions when used in combination with other morphologic, physiologic, or biochemical techniques.
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PMID:Early detection of cerebral ischemic damage and repair process in the gerbil by use of an immunohistochemical technique. 243 12

Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins. S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7 1/2 hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1 1/2 days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.
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PMID:S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. 280 27

The mechanisms underlying the response of the brain to ischemia are not fully understood. Biochemical and morphological changes following neocortical infarction can be investigated in rats using a model of focal cerebral ischemia induced by unilateral occlusion of the middle cerebral artery (MCA). Evaluation of ischemic damage often employs conventional histologic stains. Immunocytochemistry can be used as a valuable tool in this model to define changes in specific proteins of interest. In this study, an antiserum raised against insulin-like growth factor II (IGF-II) receptor was used to evaluate changes of IGF-II receptor immunoreactivity in the cerebral cortex of rats 4 and 7 days following permanent MCA occlusion. IGF-II receptor immunoreactivity was found to be associated with neocortical pyramidal neurons within the core of the ischemic infarct itself. The staining intensity was markedly elevated above that observed in nonischemic neurons. Immunopositive neurons exhibited a punctate staining pattern. These neurons appeared to correspond to argentophilic neurons, as defined by modified Bielschowsky silver staining. Evaluation of other neuronal markers revealed the absence of immunoreactivity for neuron-specific enolase and for tyrosine hydroxylase within the ischemic area. These observations show an increase in a specific growth factor receptor within neurons in the ischemic core of a focal infarct several days following permanent focal infarction, a time when neurons are presumed to be dead. The significance and the potential role of IGF-II receptor in lesion-induced plasticity are discussed.
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PMID:Increase in insulin-like growth factor II receptor within ischemic neurons following focal cerebral infarction. 759 34

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF and other physiological parameters were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 29%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 27%, 37%, and 52%, respectively. Nicardipine also reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.
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PMID:Attenuation of brain injury and reduction of neuron-specific enolase by nicardipine in systemic circulation following focal ischemia and reperfusion in a rat model. 934 82

Heme oxygenase-1 (HO-1, HSP32) is an early gene that is responsive to an array of pathological conditions including, but not limited to, hypoxia and cerebral ischemia. HO-1 cleaves the heme molecule and produces carbon monoxide (CO) and biliverdin (an antioxidant) and is essential for iron homeostasis. The purpose of this study was to investigate, using transgenic (Tg) mice, whether overexpression of HO-1 in the brain augments or attenuates cellular injury caused by ischemic stroke. Homozygous HO-1 Tg mice that overexpress HO-1 under the control of the neuron-specific enolase promoter (characterized previously) were used. Under halothane anesthesia and normothermic conditions, wild-type nontransgenic (nTg; n = 22) and HO-1 Tg (n = 24) mice were subjected to middle cerebral artery occlusion (MCAo). Six hours after induction of ischemia, Tg and nTg mice developed infarcts that were 39 +/- 6 and 63 +/- 9 mm3, respectively (p < 0.01). No significant difference between the two strains was observed in the values of brain edema (11.3 +/- 4% in Tg vs. 14.6 +/- 5% in nTg; p < 0.1). At 24 h after MCAo, Tg mice exhibited significant neuroprotection as determined by the stroke volumes (41 +/- 2 mm3 in Tg vs. 74 +/- 5 mm3 in nTg; p < 0.01) and values of ischemic cerebral edema (21 +/- 6% in Tg vs. 35 +/- 11% in nTg; p < 0.01). Data suggest that neuroprotection in Tg mice was, at least in part, related to the following findings: (a) constitutively up-regulated cyclic GMP and bcl-2 levels in neurons; (b) inhibition of nuclear localization of p53 protein; and (c) antioxidant action of HO-1, as detected by postischemic neuronal expression of ferritin, and decreases in iron staining and tissue lipid peroxidation. We suggest that pharmacological stimulation of HO-1 activity may constitute a novel therapeutic approach in the amelioration of ischemic injury during the acute period of stroke.
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PMID:Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. 1003 92

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.
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PMID:Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion. 1082 28

Continuous generation of new neurons has been demonstrated in the adult mammalian brain, and this process was shown to be stimulated by various pathologic conditions, including cerebral ischemia. Because brain oxygen deprivation is particularly frequent in neonates and represents the primary event of asphyxia, we analyzed long-term consequences of transient hypoxia in the newborn rat. Within 24 h after birth, animals were exposed to 100% N(2) for 20 min at 36 degrees C, and temporal changes in the vulnerable CA1 hippocampus were monitored. Cell density measurements revealed delayed cell death in the pyramidal cell layer reflecting apoptosis, as shown by characteristic nuclear morphology and expression levels of Bcl-2, Bax, and caspase-3. Neuronal loss was confirmed by reduced density of neuron-specific enolase (NSE)-labeled cells, and peaked by 1 wk post insult, to reach 27% of total cells. A gradual recovery then occurred, and no significant difference in cell density could be detected between controls and hypoxic rats at postnatal d 21. Repeated injections of bromodeoxyuridine (50 mg/kg) showed that newly divided cells expressing neuronal markers increased by 225% in the germinative subventricular zone, and they tended to migrate along the posterior periventricle toward the hippocampus. Therefore, transient hypoxia in the newborn rat triggered apoptosis in the CA1 hippocampus followed by increased neurogenesis and apparent anatomical recovery, suggesting that the developing brain may have a high capacity for self-repair.
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PMID:Neonatal hypoxia triggers transient apoptosis followed by neurogenesis in the rat CA1 hippocampus. 1473 63

Neurological complications contribute significantly to morbidity and mortality of patients after orthotopic liver transplantation (OLT). One possible cause of postoperative neurological complications is cerebral ischemia during the surgical procedure. In this study, we investigated the relationship between intraoperative changes in regional cerebral oxygen saturation (rSo(2)) and postoperative values of neuron-specific enolase (NSE) and S-100, which are specific variables that indicate cerebral disturbances due to hypoxia/ischemia. The rSo(2) was monitored continuously by near-infrared spectroscopy in 16 patients undergoing OLT. In addition, NSE and S-100 were determined in arterial blood before surgery and 24 h after reperfusion of the donor liver. Interestingly, clamping of the recipient's liver led to a significant decline in rSo(2) in eight patients, whereas the others tolerated clamping without major changes in rSo(2). The decrease in rSo(2) after clamping correlated significantly with postoperative increases in NSE (r(2) = 0.57) and S-100 (r(2) = 0.52). However, there were no significant differences between patients with and without rSo(2) decline concerning hemodynamic variables. There were no significant correlations between DeltarSo(2) and cardiac output (r(2) = 0.20), NSE and cardiac output (r(2) = 0.37), or S-100 and cardiac output (r(2) = 0.24). Monitoring of rSo(2) may be a useful noninvasive tool to estimate disturbances in rSo(2) during OLT.
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PMID:Regional cerebral oxygen saturation is a sensitive marker of cerebral hypoperfusion during orthotopic liver transplantation. 1527 2

The transcription factor NF-kappaB is a key regulator of inflammation and cell survival. NF-kappaB is activated by cerebral ischemia in neurons and glia, but its function is controversial. To inhibit NF-kappaB selectively in neurons and glial cells, we have generated transgenic mice that express the IkappaBalpha superrepressor (IkappaBalpha mutated at serine-32 and serine-36, IkappaBalpha-SR) under transcriptional control of the neuron-specific enolase (NSE) and the glial fibrillary acidic protein (GFAP) promoter, respectively. In primary cortical neurons of NSE-IkappaBalpha-SR mice, NF-kappaB activity was partially inhibited. To assess NF-kappaB activity in vivo after permanent middle cerebral artery occlusion (MCAO), we measured the expression of NF-kappaB target genes by real-time polymerase chain reaction (PCR). The induction of c-myc and transforming growth factor-beta2 by cerebral ischemia was inhibited by neuronal expression of IkappaBalpha-SR, whereas induction of GFAP by MCAO was reduced by astrocytic expression of IkappaBalpha-SR. Neuronal, but not astrocytic, expression of the NF-kappaB inhibitor reduced both infarct size and cell death 48 hours after permanent MCAO. In summary, the data show that NF-kappaB is activated in neurons and astrocytes during cerebral ischemia and that NF-kappaB activation in neurons contributes to the ischemic damage.
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PMID:Neuronal activation of NF-kappaB contributes to cell death in cerebral ischemia. 1567 10

Buflomedil hydrochloride (CAS 55837-25-7) is a vasoactive drug with a variety of pharmacodynamic properties. Although a number of studies have been carried out to verify the beneficial effect of buflomedil in ischemic peripheral conditions, few data are reported to justify the efficacious employment of buflomedil in the treatment of cerebrovascular diseases. The aim of the present study was to better investigate the neuroprotective effect of buflomedil in normal pentobarbital-anaesthetized rats subjected to transient bilateral common artery occlusion (BCO) for 20 min. Buflomedil hydrochloride (10 mg/kg) was administered by slow intravenous infusion (90 min), starting 1 h after the onset of ischemia. The rats were sacrificed 48 h after carotid clamping. BCO caused dramatic death of hippocampal CA1 pyramidal neurons, and a significant increase in circulating levels of neuron-specific enolase (NSE) and lactate. Treatment with buflomedil attenuated ischemia-induced histological loss and damage of CA1 pyramidal cells. Furthermore, in ischemic rats, the drug restored blood lactate concentrations and serum NSE concentrations to near normal levels. These data clearly demonstrate that buflomedil is able to protect brain neurons against damage following moderate global cerebral ischemia. One could speculate that this protective effect could be related to the capability of buflomedil to improve cerebral blood flow and energy metabolism, or to a smooth muscle relaxant effect on cerebral blood vessels.
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PMID:Protective effect of buflomedil in a rat model of moderate cerebral ischemia. 1614 10


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