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)

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) and trkB both have a role in plasticity following brain insults and exercise increases BDNF and trkB mRNA levels in the normal brain. We attempted to determine whether treadmill exercise improves motor function following experimental cerebral ischemia, and whether motor outcome is associated with BDNF and trkB expression. We subjected adult male Sprague-Dawley rats to a permanent ischemia, followed by either 12 days of treadmill exercise or non-exercise. In the exercise group, improvements in the motor behavior index were found and BDNF and trkB proteins in contralateral hemisphere were increased. This study suggests that after permanent brain ischemia, exercise improves motor performance and elevates BDNF and trkB proteins in the contralateral hemisphere.
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PMID:Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain. 1605 99

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.
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PMID:I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. 1622 56

Erythropoietin (EPO) is a hormone that is neuroprotective in models of neurodegenerative diseases. This study examined whether EPO can protect against neuronal death in the CA1 region of the rat hippocampus following global cerebral ischemia. Recombinant human EPO was infused into the intracerebral ventricle either before or after the induction of ischemia produced by using the four-vessel-occlusion model in rat. Hippocampal CA1 neuron damage was ameliorated by infusion of 50 U EPO. Administration of EPO was neuroprotective if given 20 hr before or 20 min after ischemia, but not 1 hr following ischemia. Coinjection of the phosphoinositide 3 kinase inhibitor LY294002 with EPO inhibited the protective effects of EPO. Treatment with EPO induced phosphorylation of both AKT and its substrate, glycogen synthase kinase-3beta, in the CA1 region. EPO also enhanced the CA1 level of brain-derived neurotrophic factor. Finally, we determined that ERK activation played minor roles in EPO-mediated neuroprotection. These studies demonstrate that a single injection of EPO ICV up to 20 min after global ischemia is an effective neuroprotective agent and suggest that EPO is a viable candidate for treating global ischemic brain injury.
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PMID:Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms. 1651 66

This study is to investigate the effects of huperzine A on memory deficits, neuronal damage and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice, as well as the potential downstream signaling pathway. Bilateral common carotid occlusion (BCCAo) combined with systemic hypotension induced severe memory deficits in a water maze task and neuronal degeneration in cerebral cortex and hippocampus in mice. Oral administration of huperzine A (0.2 mg/kg, once per day, started 2 days before surgery and lasted for 7 days after surgery) markedly attenuated the memory deficits and neuronal damage. Meanwhile, huperzine A significantly increased the mRNA and protein levels of NGF, BDNF and TGF-beta(1), and potentiated phosphorylation of MAPK/ERK 1/2 in both cerebral cortex and hippocampus compared with transient cerebral ischemia and reperfusion group. This study provides evidence for the protective effects of huperzine A against transient cerebral ischemia and reperfusion in mice, and suggests potentially important roles that neurotrophic factors might play in these effects. It also indicates that the MAPK/ERK pathway might be involved in the in vivo neurotrophic effects of huperzine A against transient cerebral ischemia and reperfusion.
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PMID:Effects of huperzine A on memory deficits and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice. 1668 66

1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus after ischemia. 2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min. 3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after ischemia. 4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient cerebral ischemia.
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PMID:Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in the gerbil hippocampus: pharmacological approach. 1681 May 63

We studied the effect of hypertension on brain damage and brain-derived neurotrophic factor (BDNF) expression in the hippocampal formation and cerebral cortex after permanent occlusion of bilateral common carotid arteries (CCA). Two groups of rats were used, including normotensive Wistar-Kyoto (WKY) rat and spontaneous hypertensive rat (SHR). Each group contained sham operation, 1 week and 4 weeks after bilateral CCA occlusion (n=5-10 in each time point). The blood pressure showed a significant elevation in WKY rats from 1 h after operation to 4 weeks before sacrifice (P<0.05), but was not changed in SHR (P>0.05). However, rectal temperature showed no significant change after operation in WKY rat and SHR (P>0.05) and showed no significant difference at any time point between WKY rat and SHR (P>0.05). Hematoxylin and eosin staining showed SHR had a significantly larger necrotic volume than WKY rats (n=10 in each group, 6044+/-6895 microm(3) vs. 144+/-174 microm(3), P<0.05) at 4 weeks after ischemia. In SHR, BDNF immunoreactivity and mRNA decreased significantly from 1 week to 4 weeks in both the hippocampal CA1 and cortical areas (P<0.01) but decreased transiently in dentate gyrus. However, in WKY rats, BDNF immunoreactivity and mRNA decreased transiently at 1 week (P<0.05) and recovered at 4 weeks after cerebral ischemia. Our study demonstrates that after bilateral CCA occlusion, preexisting hypertension may aggravate the brain injury and downregulate the expression of BDNF immunoreactivity and mRNA in the ischemia-vulnerable hippocampal CA1 and cortical areas but not in ischemia-resistant dentate gyrus.
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PMID:Hypertension downregulates the expression of brain-derived neurotrophic factor in the ischemia-vulnerable hippocampal CA1 and cortical areas after carotid artery occlusion. 1696 81

To compare the individual effects of baicalin and jasminoidin with the combined effect of them on cerebral ischemia-reperfusion injury, and test whether the combined administration of baicalin and jasminoidin can improve the therapeutic effect. Male Sprague-Dawley rats underwent focal cerebral ischemia for 1.5 h and reperfusion for 24 h. Just before reperfusion, tested drugs (baicalin, jasminoidin, a drug combination consisting of baicalin and jasminoidin, or nimodipine) were intravenously treated. Diffusion weighted imaging (DWI) of magnetic resonance imaging (MRI), behavior examination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, histological examination, and real-time PCR for BDNF and caspase-3 were performed. All of the drug treatments could significantly ameliorate the results of TTC and histological examination, and the baicalin/jasminoidin combination did so most prominently. This combination could also significantly ameliorate DWI of MRI and behavior examination results, and promote the expression of BDNF and inhibit the expression of caspase-3. On the whole, both baicalin and jasminoidin have a preventive effect against ischemic stroke, although their effects are not very strong. However, the combination of baicalin and jasminoidin can significantly improve their effectiveness. This may be related to its better regulation on the BDNF and caspase-3.
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PMID:A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury. 1706 75

Recently, mesenchymal stem cells (MSCs) have been one of the target cells of gene engineering. To construct the lentiviral (LV) vectors carrying the brain-derived neurotrophic factor (Bdnf) gene, the rat mesenchymal stem cells (rMSCs) were infected and finally the Bdnf gene-modified rMSCs was obtained. The CDS region of the rat Bdnf gene was obtained with reverse transcriptase-polymerase chain reaction (RT-PCR), and the transfer plasmid (PNL-BDNF-IRES2-EGFP) of the LV vector was constructed. The three plasmids of LV vector: PNL-BDNF-IRES2-EGFP, HELPER, and VSVG were cotransfected to 293T cells to produce the LV vectors, which enabled the coexpression of the Bdnf gene and the enhanced green fluorescent protein (Egfp) gene. rMSCs were separated from the bone marrow of 2-month-old F344 rats, cultured in vitro, and identified. rMSCs were infected by the LV vectors that were produced already and were identified with fluorescent microscope, RT-PCR, immunocytochemical staining, and western blot. The result of sequencing showed that the sequence of the cloned Bdnf gene was consistent with that reported in the GenBank. The PNL-BDNF-IRES2-EGFP plasmid that was identified showed the correct sequence. After the 3 plasmids of LV vectors were cotransfected to the 293T cells, considerable green fluorescence in 293T cells was observed under the fluorescent microscope; the supernatant was collected and concentrated using ultracentrifugation, and the titer of the replication-defective LV vector particles measured was found to be 6.7 x 10(7) TU/mL. After the constructed LV vectors infected the rMSCs, the results obtained using RT-PCR, immunocytochemical staining, and western blot showed that the expression of BDNF in the Bdnf-rMSCs group (experimental group, EG) was significantly higher than that in the PNL-IRES2-EGFP-rMSCs group (mock group, MG) and the rMSCs group (control group, CG) at both mRNA and protein levels. LV vectors carrying the Bdnf gene were constructed successfully. The Bdnf gene-modified rMSCs could express BDNF to a higher degree. This greatly facilitates the next step in the study, such as the long period of therapeutic observation of cerebral ischemia with Bdnf gene-modified rMSCs.
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PMID:[Construction of rat bdnf gene lentiviral vector and its expression in mesenchymal stem cells]. 1746 Aug 94

This study investigates the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), on neurodegeneration, gliosis and changes in the neurotrophic protein brain-derived neurotrophic factor (BDNF) and in pro-inflammatory cytokines, following kainic acid (KA)-induced excitotoxic damage in the rat. Male Sprague-Dawley rats were treated with alpha-MSH (intraperitoneally, i.p.) at 20 min, and 24 and 48 h following administration of 10 mg/kg KA (i.p.). The animals were sacrificed at 30 min, 4 h, 24 h and 72 h after KA-administration and the levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were analysed in samples of hippocampus and hypothalamus. Levels of BDNF were analysed in the hippocampus. Stereological quantification showed a markedly reduced number of viable neurons in the CA1 pyramidal cell layer upon KA-administration as compared to animals injected with vehicle (p < 0.05, 79,587 +/- 25,554 vs. 145,254 +/- 27,871). The number of viable neurons upon administration of alpha-MSH was significantly higher than upon KA alone (p < 0.05, 119,776 +/- 33,158, KA+alpha-MSH vs. 79,587 +/- 27,554, KA + Saline). Astrocyte activation due to the KA-induced excitotoxicity was reduced, and the KA-induced increase in IL-1beta levels was delayed by the treatment with alpha-MSH. In conclusion, the degree of reduction in cell viability in the hippocampus CA1 pyramidal cell layer upon KA-induced excitotoxicity was similar to that seen previously upon global cerebral ischaemia. Furthermore, the administration of alpha-MSH resulted in a similar increase in cell viability, supporting the hypothesis that administration of alpha-MSH has rescuing effects on neurons subjected to excitotoxic insults.
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PMID:Alpha-MSH rescues neurons from excitotoxic cell death. 1795 33

Although stem cells are likely to improve neurological deficits seen after cerebral ischemia, the effects of neural progenitor cells (NPCs) on cerebral ischemia-induced learning dysfunction remain to be clarified. We tested whether the delayed injection of exogenous NPCs could prevent learning dysfunction after cerebral ischemia. Cerebral ischemia was produced by the injection of microspheres into the right hemisphere of each rat. Injection of NPCs obtained from green fluorescent protein transgenic rats into the hippocampus on Day 7 after the induction of cerebral ischemia improved the modified neurological severity score and reduced the prolongation of the escape latency seen in the water maze task. A few of the injected NPCs were positive for mature neuronal markers. In addition, the injected NPCs expressed BDNF on Day 28 after cerebral ischemia. Thus, the exogenous NPCs delivered by injection could act as a source of neurotrophic factors and prevent cerebral ischemia-induced learning dysfunction.
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PMID:Delayed injection of neural progenitor cells improved spatial learning dysfunction after cerebral ischemia. 1822 75


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