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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The amnesia induced by various stress stimuli through hypoxia and cerebral ischemia was evaluated by the shortening of the response latency in a step-through task in mice. 2. The hypoxia-induced amnesia was reduced by cromakalim, a K+ channel opener (KCO), given 10 min before or immediately after the hypoxic treatment. 3. Similarly, the ischemia-induced amnesia was also reduced by cromakalim given 30 min before the occlusion. 4. In ischemic-induced amnesic mice, pyknotic cells, indicating the condensation of chromatin, were observed histochemically at the dentate gyrus granule cells in hippocampal regions 96 hr after ischemic treatment. In addition, cromakalim inhibited the induction of pyknotic cells. 5. These results suggest that KCOs might produce prophylactically neuroprotective effects against hypoxia- and cerebral ischemia-induced amnesia.
Cell Mol Neurobiol 1998 Aug
PMID:Antiamnesic action of cromakalim, a potassium channel opener, in mice treated with hypoxia- and cerebral ischemia-type stress stimuli. 961 98

Ciliary neurotrophic factor (CNTF) is a member of cytokines, with trophic effects on ciliary, motor sympathetic, sensory, retinal and hippocampal neurons. In the present study, we examined the temporal and spatial expression profiles of CNTF and CNTF receptor alpha (CNTFR alpha) mRNAs in a focal cerebral ischemia model induced by transient occlusion of the right middle cerebral artery and both common carotid arteries. Northern blot analysis showed a slow and sustained increase in the 1.2 kb transcript of CNTF mRNA in the ischemic cortex of rats subjected to a transient 60 min ischemic insult. A delayed decrease in the 2.1 kb transcript of CNTFR alpha mRNA in the ischemic cortex was observed in rats subjected to 60 min ischemia followed by 72 h of reperfusion. In situ hybridization studies revealed constitutive expression of CNTFR alpha mRNA in the majority of neurons in the brain. Following 4 h of reperfusion, increased expression of CNTFR alpha mRNA was observed in the ipsilateral dentate gyrus, which is opposite to the down-regulation noted in the ischemic cortex. Within the infarct area CNTFR alpha mRNA had a marked increase in cortical layer II but a decrease in cortical layer V following 1 day of reperfusion. No signal of CNTFR alpha mRNA was detected within the infarct region following 3 days of reperfusion. Following 1 week of reperfusion, although no marked changes was observed in the level of CNTFR alpha mRNA in the area immediately surrounding the necrosis region where the reactive astrocytes were noted, a striking increase in the CNTF mRNA signal was noted. In summary, differential regulation of CNTF and CNTFR alpha mRNAs was noted in the ischemic cortex. Regional differences in CNTF receptor expression were noted between the ischemic cortex and ipsilateral dentate gyrus as well as between cortical layer II and V within the infarct region. CNTF mRNA, but not CNTFR alpha mRNA, had a marked increase in the area immediately adjacent to the necrosis. The mechanisms and patho-physiological significance for these differential regulation remain to be studied.
Brain Res Mol Brain Res 1998 Mar 30
PMID:Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha) expression following focal cerebral ischemia. 964 62

The objective of this paper is to review the published information available on the effect of hypoxia on fetal cerebral integrity, and to attempt to define limits of fetal tolerance to asphyxia Data were obtained in experimental animals following imposed hypoxia or asphyxia. Studies were carried out in the fetus by physiologic, biochemical, histologic, and behavioral techniques. Human data were collected from newborns at birth and during subsequent development. It has been established that acute asphyxia of the fetus in utero may result in a spectrum of effects on the fetus, including death, or survival with permanent neurologic damage, or apparent complete recovery. The severity of damage depends on the degree and duration of asphyxia and a number of sensitizing factors, including prior metabolic and cardiovascular status of the fetus, differential sensitivity of the heart and brain to asphyxia, gestational age, plasticity, intermittency of asphyxial insults, and the pattern of intermittency. The fetus has a number of compensatory mechanisms that allow it to survive periods of oxygen limitation without permanent damage to the brain. The fetus can increase cerebral blood flow to increase oxygen delivery to the brain, and can decrease its metabolism by electrophysiological and behavioral state changes. Cerebral ischemia and reduced metabolism to < 50% of control is probably necessary for permanent brain damage to occur. In human pregnancy, factors consistent with intrapartum asphyxia lasting until delivery as a cause of fetal neurologic damage include absent fetal heart rate variability, umbilical cord arterial pH < 6.8, base access < -20 mEql-1, severe and prolonged newborn depression with Apgar score of < or = 3 at 10 min, seizure activity in the first day of life, and damage to the noncerebral organs and regions. However, these factors are neither independently nor collectively predictive of asphyxial brain damage. It is concluded that permanent neurologic damage or death can occur in the fetus due to single or repetitive episodes of hypoxia or asphyxia, but it is not yet possible to predict the occurrence or extent of such damage in an individual fetus.
Comp Biochem Physiol A Mol Integr Physiol 1998 Mar
PMID:Effects of fetal asphyxia on brain cell structure and function: limits of tolerance. 968 10

The expression of the gene encoding the C/EBP-homologous protein (CHOP), which is also known as growth arrest and DNA-damage-inducible gene 153 (gadd153), has been shown to be specifically activated under conditions that disturb the functioning of the endoplasmic reticulum (ER). To investigate a possible role of ER dysfunction in the pathological process of ischemic cell damage, we studied ischemia-induced changes in gadd153 expression using quantitative PCR. Transient cerebral ischemia was produced in rats by four-vessel occlusion. In the hippocampus, ischemia induced a pronounced increase in gadd153 mRNA levels, peaking at 8 h of recovery (6.4-fold increase, p<0.01), whereas changes in the cortex were less marked (non-significant increase). To elucidate the possible mechanism underlying this activation process, gadd153 mRNA levels were also evaluated in primary neuronal cell cultures under two different conditions, both leading to a depletion of ER calcium pools in the presence or absence of an increase in cytoplasmic calcium activity. The first procedure, exposure to thapsigargin, an irreversible inhibitor of ER Ca2+-ATPase, caused a marked increase in gadd153 mRNA levels both in cortical and hippocampal neurons, peaking at 12-18 h after treatment. The second procedure, immersion of cells in calcium free medium supplemented with EGTA, caused only a transient increase in gadd153 mRNA levels, peaking at 6 h of recovery, indicating that a depletion of ER calcium stores in the absence of an increase in cytoplasmic calcium activity is sufficient to activate neuronal gadd153 expression. The results imply that transient cerebral ischemia disturbs the functioning of the ER and that these pathological changes are more pronounced in the hippocampus compared to the cortex.
Brain Res Mol Brain Res 1998 Sep 18
PMID:Activation of gadd153 expression through transient cerebral ischemia: evidence that ischemia causes endoplasmic reticulum dysfunction. 974 29

Several growth factors have been implicated in the pathogenesis of Alzheimer's disease (AD). We considered whether the vascular endothelial growth factor (VEGF) is involved in the vascular pathology associated with most cases of AD. We observed enhanced VEGF immunoreactivity in clusters of reactive astrocytes in the neocortex of subjects with AD compared to elderly controls. VEGF reactivity was also noted in walls of many large intraparenchymal vessels and diffuse perivascular deposits. In addition, we established that astrocytic and perivascular VEGF reactivity was enhanced in cerebral cortex of rats subjected to cerebral ischemia and to chronic hypoxia; experimental conditions known to be associated with astrogliosis and angiogenesis. We suggest the increased VEGF reactivity, also observed in infarcted human brain tissue, implicates compensatory mechanisms to counter insufficient vascularity or reduced perfusion (oligemia) apparent in AD.
Brain Res Mol Brain Res 1998 Nov 12
PMID:Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. 979 65

The Zac1 gene encodes a zinc finger protein that regulates both apoptosis and cell cycle arrest in vitro. Furthermore, Zac1 protein seems to trans-activate the gene encoding the type I receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Northern blot analysis revealed high levels of Zac1 mRNA in the rodent brain. In the present study, we demonstrate by in situ hybridization histochemistry a progressive increase in Zac1 transcripts in the mouse brain from day 1 to day 3 following transient focal cerebral ischemia. Moreover, we observed an up-regulation of PACAP type I receptor mRNA expression showing a similar temporospatial distribution. Late induction of cell death promoting Zac1 in the post-ischemic brain may be attributed to delayed or secondary cell death. Co-induction of the type I receptor for neurotrophic PACAP however, points to a role in restorative processes.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Delayed up-regulation of Zac1 and PACAP type I receptor after transient focal cerebral ischemia in mice. 979 21

Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.
J Mol Cell Cardiol 1998 Oct
PMID:Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats. 982 20

The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.
Brain Res Mol Brain Res 1998 Dec 10
PMID:The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. 983 92

1. Free radical-dependent lipid peroxidation processes have long been thought to contribute to brain damage following stroke or cerebral ischemia/reperfusion. 2. The preponderance of evidence for this belief has been derived indirectly, through diminution of tissue injury indices (e.g., brain infarct volume) facilitated by application of free radical scavenger substances. 3. Direct, unequivocal evidence for lipid peroxidation in terms of classical assays (detection of conjugated diene absorbance or thiobarbituric acid-reactive substances) is considerably less common, and its validity can be questioned. 4. Correlations of treatment-induced diminishment of brain injury indices with reductions in lipid peroxidation level are rarer still. 5. Reasons underlying the disparity between the belief that lipid peroxidation contributes to ischemic brain injury and direct evidence for this contribution (at least acutely) are proposed, along with evidence that new methods are being developed which should provide the basis for obtaining a definitive answer.
Cell Mol Neurobiol 1998 Dec
PMID:Usual and unusual methods for detection of lipid peroxides as indicators of tissue injury in cerebral ischemia: what is appropriate and useful? 987 67

1. Nitric oxide radicals (NO) play an important role in the pathophysiology of focal cerebral ischemia. 2. Vascular NO can reduce ischemic brain injury by increasing CBF, whereas neuronal NO may mediate neurotoxicity following brain ischemia, mainly by its reaction with superoxide to generate peroxynitrite. 3. These findings could contribute to a strategy for the treatment of cerebral ischemia.
Cell Mol Neurobiol 1998 Dec
PMID:Role of superoxide dismutase in ischemic brain injury: a study using SOD-1 transgenic mice. 987 69


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