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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of mRNA for c-fos, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), TrkB, and TrkC were studied using in situ hybridization in the rat brain at different reperfusion times after unilateral middle cerebral artery occlusion (MCAO). Short-term (15 min) MCAO, which does not cause neuronal death, induced elevated BDNF mRNA expression confined to ipsilateral frontal and cingulate cortices outside the ischemic area. With a longer duration of MCAO (2 h), which leads to cortical infarction, the increase was more marked and elevated BDNF mRNA levels were also detected bilaterally in dentate granule cells and CA1 and CA3 pyramidal neurons. Maximum expression was found after 2 h of reperfusion. At 24 h BDNF mRNA expression had returned to control values. In the ischemic core of the parietal cortex only scattered neurons were expressing high levels of BDNF mRNA after 15 min and 2 h of MCAO. Analysis of different BDNF transcripts showed that MCAO induced a marked increase of exon III mRNA but only small increases of exon I and II mRNAs in cortex and hippocampus. In contrast to BDNF mRNA, elevated expression of c-fos mRNA was observed in the entire ipsilateral cerebral cortex, including the ischemic core, after both 15 min and 2 h of MCAO. Two hours of MCAO also induced transient, bilateral increases of NGF and TrkB mRNA levels and a decrease of NT-3 mRNA expression, confined to dentate granule cells. The upregulation of BDNF mRNA expression in cortical neurons after MCAO is probably triggered by glutamate through a spreading depression-like mechanism. The lack of response of the BDNF gene in the ischemic core may be due to suppression of signal transduction or transcription factor synthesis caused by the ischemia. The observed pattern of gene expression after MCAO agrees well with a neuroprotective role of BDNF in cortical neurons. However, elevated levels of NGF and BDNF protein could also increase synaptic efficacy in the postischemic phase, which may promote epileptogenesis.
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PMID:Regulation of brain-derived neurotrophic factor gene expression after transient middle cerebral artery occlusion with and without brain damage. 758 36

The neuroprotective effect of nerve growth factor (NGF) on the pyramidal cells in the vulnerable CA1-CA2 sectors of the hippocampus was investigated in a rat model of transient forebrain ischemia. A genetically modified fibroblast line that secretes high levels of NGF was implanted 7 days before induction of ischemia between the hippocampal CA1-CA2 subfields in the right hemisphere. Rats were then subjected to 10 min of cerebral ischemia in a four vessel occlusion model. Morphological changes in the CA1 and CA2 subfields were evaluated 7 days after ischemia. Animals in the NGF-protected group had significantly higher numbers of normal appearing neurons in the right CA1 and CA2 regions, compared with their non-implanted left hemispheres, to non-implanted animals or to animals implanted with non-modified cells. The data confirmed that NGF can protect CA1-CA2 hippocampal neurons from ischemic damage by implantation of genetically engineered cells producing NGF.
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PMID:Genetically modified fibroblasts producing NGF protect hippocampal neurons after ischemia in the rat. 760 24

We examined the effect of interleukin-6 (human recombinant) on glutamate-induced neuronal death of cultured 20-day fetal rat hippocampal neurons. After 7 days in culture, the hippocampal neurons were markedly degenerated by the addition of L-glutamate and also N-methyl-D-aspartate. The neuronal death was prevented by the addition of MK801, a potent N-methyl-D-aspartate antagonist. Interleukin-6 at the concentration of 50 ng/ml has a significant preventive effect on the glutamate-induced neuronal death. Basic fibroblast growth factor at the concentration of 100 ng/ml gave also significant protective effect on hippocampal neurons, but nerve growth factor was ineffective in preventing the toxicity. It has been postulated that glutamate plays an important role in the pathogenesis of neuronal death such as ischemia and the various neurological diseases. Interleukin-6 might have somewhat physiological or pathological role in these events.
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PMID:Interleukin-6 protects cultured rat hippocampal neurons against glutamate-induced cell death. 791 97

In an attempt to search for neuronal models to investigate the molecular pharmacology of central nervous system ischemia, we have focused on PC12 pheochromocytoma cultures which are now popular in neuroscience research. These chromaffinergic transformed cells, originary from the adrenal medulla, synthesize and release catecholamines and, upon treatment with nerve growth factor (NGF), differentiate to a sympathetic phenotype expressing neurites and excitability. To measure eicosanoid production, undifferentiated or NGF-treated PC12 cultures have been exposed for 1 h to a mixture of N2/CO2 (95:5%), resulting in hypoxia (5 +/- 1% O2), followed by 1 h reoxygenation (21% O2) using a special ischemic device. Hypoxia, up to 2 h, was not followed by significant cytotoxicity or significant production of prostaglandin PGE2. However, upon reoxygenation, a specific release of PGE2 (2-3 fold over control) was measured. A similar PGE2-enhanced release could be induced by 'chemical hypoxia' using 2-deoxyglucose and oligomycin to reduce cellular adenosine triphosphate (ATP). Anoxia (0.1-1% O2, 1 h) achieved by a reduction of culture incubation volume and the reduction in ATP level have been found as critical parameters leading to PC12 cells cytotoxicity. These results emphasize the simplicity and applicability of the tissue culture ischemic device proposed to investigate hypoxia and ischemia at a cellular level.
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PMID:A tissue culture ischemic device to study eicosanoid release by pheochromocytoma PC12 cultures. 810 1

An aberrant elevation in intraneuronal calcium levels resulting from energy failure and excitatory amino acid receptor activation is believed to play a major role in the neuronal damage and death that occur in stroke. We have found that several growth factors can protect cultured rat hippocampal and septal neurons and human cortical neurons from excitotoxic damage caused by glucose deprivation or hypoxia. Using the calcium indicator dye fura 2 and whole-cell patch-clamp recording, we found that glucose deprivation initially results in calcium current inhibition and a reduction in intraneuronal free calcium levels without morphological signs of cell damage. After 12 to 16 hours of glucose deprivation, a large elevation in intraneuronal calcium levels occurred that involved N-methyl-D-aspartate receptor activation and mediated the cell damage and death. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each prevented, in a dose-dependent manner, glucose deprivation-induced loss of calcium homeostasis and neuronal damage. The growth factors were effective to varying degrees when added up to 12 hours after the onset of glucose deprivation. NGF, bFGF, and IGFs also protected neurons against damage caused by exposure to a hypoxic environment. By stabilizing intraneuronal calcium levels within a window of concentrations conducive to neuronal survival, growth factors can protect neurons against the damaging effects of ischemia-like insults. Because ATP levels are expected to be reduced under ischemia-like conditions, we determined whether the growth factors would protect neurons against a more selective reduction in ATP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factors protect neurons against excitotoxic/ischemic damage by stabilizing calcium homeostasis. 824 11

Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain-derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions.
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PMID:Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia. 835 Sep 88

We have established an in vitro model of ischemia incorporating the combination of anoxia with glucose deprivation, which is toxic to PC12 cells. In this model, nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) improve PC12 cell survival. K252a, a specific inhibitor of NGF-induced trk p140 autophosphorylation, did not alter the neuroprotection provided by EGF or bFGF, yet it completely abolished the protection provided by NGF. Activation of protein kinase A (PKA) with dibutyryl-cAMP also protected during ischemia, although it was not additive with the effect provided by growth factors. Furthermore, growth factors protected a PKA-deficient mutant as effectively as the parental cell line; thus, activation of PKA is protective against ischemia but is not necessary for the action of peptide growth factors. Neither the stimulation of protein kinase C (PKC) with acute phorbol ester treatment nor the downregulation of PKC with chronic high-dose phorbol ester treatment resulted in an altered response to growth factors in either the PC12 wild type or PKA-deficient mutant. Thus, protection by peptide growth factors depends on neither PKA nor PKC. Furthermore, downregulation of PKC alone was protective, indicating that PKC may contribute to toxicity. Interestingly, treatment with the kinase inhibitor H-7 was neuroprotective and may have enhanced the neuroprotective effect of NGF. In contrast, staurosporine, a broadly acting kinase inhibitor, inhibited the neuroprotective effect of NGF, but not of EGF or FGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis. 841 Jan 84

Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxidation of protein and lipids. Exposure of cultured rat hippocampal neurons to iron (FeSO4) caused a dose-dependent reduction in neuronal survival, which was potentiated by ascorbate. Damage to neurons was associated with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration caused by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity was associated with an elevation of [Ca2+]i and was attenuated by NMDA receptor antagonists. Since recent findings demonstrated neuroprotective effects of growth factors in cell culture and in vivo models of ischemia, we examined the effects of growth factors on iron-induced damage. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the data suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention or attenuation of oxidative damage.
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PMID:Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron-induced degeneration. 847 96

We studied the temporal profile of nerve growth factor-like immunoreactivity (NGF-LI) in the rat brains following 30 min of middle cerebral artery occlusion. The rats were decapitated at 4 h, 1, 3, 7, and 14 days of recirculation. Brain sections at the level of striatum were immunostained against NGF as well as a stress protein, HSP70. Also, double immunostaining of NGF and glial fibrillary acidic protein was performed. In the sham-control rats, NGF-LI was normally present in the cortical and striatal neurons. However, at 4 h of recirculation, there was a significant decrease of NGF-LI in the ischemic cortex and striatum. From 1 day, NGF-LI was absent completely in the ischemic striatum. However, in the ischemic cortex, NGF-LI decreased to the lowest level at 1 day, but it recovered gradually from 3 days and increased significantly to above sham-control level at 7 days. At 14 days of recirculation, NGF-LI returned to a near sham-control level. In the non-ischemic cortex, NGF-LI increased gradually from 4 h with a peak at 7 days, and returned to the sham-control level at 14 days of recirculation. A HSP70 was induced in the ischemic cortex at 1 and 3 days, when there was a significant reduction of NGF-LI. The number of reactive astrocytes increased gradually and NGF-LI in the reactive astrocytes became gradually intense after ischemia. The present finding showing that NGF-LI can be recovered in the stressed cortical neurons suggests a possible involvement of NGF in the process of neuronal survival after focal cerebral ischemia. The expression of NGF in reactive astrocytes indicates that astrocyte may also play a role in supporting neuronal survival after ischemia.
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PMID:Temporal profile of nerve growth factor-like immunoreactivity after transient focal cerebral ischemia in rats. 872 92

We have identified 4'-(4-methylphenyl)-2,2':6',2-terpyridine: trihydrochloride (SS701), which belongs to a family of a small unique neuroprotective agents. SS701 accelerated the production of nerve growth factor (NGF) in cultured astroglial cells, dose- and time-dependently. In in vivo studies, SS701, when administered 30 min after induced cerebral ischemia, neuroprotective effects on delayed neuronal death in Mongolian gerbils were evident. The neuroprotective effects of SS701 against ischemia-induced delayed neuronal death are attributed to stimulation of the production of NGF.
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PMID:Neuroprotective effect of 4'-(4-methylphenyl)-2,2':6',2-terpyridine trihydrochloride, a novel inducer of nerve growth factor. 895 Mar 17


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