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)

The present studies were initiated to investigate whether p53 transactivated target genes are induced in a rat model of focal cerebral ischemia. Therefore, we applied in situ hybridization, immunocytochemistry and western blotting to study the temporal and spatial expression of p53 and its transcriptional targets Bax, p21 and cyclin G1 following permanent middle cerebral artery occlusion in the rat. Cyclin G1 immunoreactivity was constitutively expressed in the nuclei of cells in the choroid plexus and ependymal cell layer and in the cytoplasm of cell bodies and dendrites of pyramidal neurons of the cerebral cortex. Cyclin G1 messenger RNA and protein levels transiently increased to 150% of contralateral levels in neurons of the ipsilateral frontal and parietal cortex and striatum 3 h following middle cerebral artery occlusion. A low level of constitutively expressed p21 messenger RNA and protein was found in nuclei of cells in the choroid plexus, oligodendrocytes and neurons. p21 messenger RNA and protein levels gradually increased to 250% and 140% of contralateral levels in areas bordering the infarct core up to 6 h following middle cerebral artery occlusion. In contrast, p53 and Bax messenger RNA and protein levels, and protein levels of p27, cyclin-dependent kinase 5, p35 and cyclin E decreased in the infarct core and border areas with time after middle cerebral artery occlusion. The selective up-regulation of cyclin G1 and p21 in neurons in the border zone of a focal ischemic infarct indicates their involvement in an adaptive response to ischemic injury. The possible participation of cyclin G1 and p21 in a signal transduction pathway associated with ischemia-induced cellular stress is discussed.
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PMID:Cell cycle-related gene expression in the adult rat brain: selective induction of cyclin G1 and p21WAF1/CIP1 in neurons following focal cerebral ischemia. 957 98

After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in various conditions including ischemia. We demonstrate that loss of endogenous cyclin-dependent kinase (Cdk) inhibitor p16(INK4a) is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral ischemia in vivo. Loss of p27(Kip1), another Cdk inhibitor, precedes cell death in neocortical neurons subjected to oxygen-glucose deprivation in vitro. The loss of Cdk inhibitors is followed by upregulation of cyclin D1, activation of Cdk2, and subsequent cytoskeletal disintegration. Most neurons undergo cell death before entering S-phase, albeit a small number ( approximately 1%) do progress to the S-phase before their death. Treatment with Cdk inhibitors significantly reduces cell death in vitro. These results show that alteration of cell cycle regulatory mechanisms is a prelude to delayed neuronal death in focal cerebral ischemia and that pharmacological interventions aimed at neuroprotection may be usefully directed at cell cycle regulatory mechanisms.
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PMID:Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. 1143 80

Cell cycle inhibition of neural stem and progenitor cells is critical for maintaining the stability of central nervous system in adults, but it may represent a significant hurdle for neural regeneration after injury. We have previously demonstrated that the cyclin-dependent kinase inhibitor (CKI) p21(cip1/waf1) (p21) maintains the quiescence of neural stem-like cells under cerebral ischemia, as similarly shown for the hematopoietic stem cells. Here, we report the distinct role of another CKI member, p27(kip1) (p27) in neural progenitor cells (NPCs) from adult brain (subventricular zone and hippocampal subgranular zone) under both homeostatic and ischemic conditions. The basal level of NPC proliferation in the p27-/- mice was higher than that in p27+/+ mice. Upon ischemia, the overall proliferation of NPCs continued to be higher in p27-/- mice than that in p27+/+ mice. Moreover, the increase of NPC proliferation in p27-/- mice remained until 2 weeks after ischemia, whereas it resumed back to the basal level in p27+/+ mice. As a result, newly generated neuronal cells in the granular layer of p27-/- brain were more abundant compared with p27+/+ controls. These new data demonstrate that p27 functions as a distinct inhibitor for NPC proliferation under homeostatic as well as ischemic conditions.
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PMID:p27Kip1 constrains proliferation of neural progenitor cells in adult brain under homeostatic and ischemic conditions. 1935 20

The purpose of this study was to investigate the mechanisms by which electroacupuncture (EA) enhances hippocampal neural stem cells (NSCs) proliferation in cerebral ischemia-reperfusion (I/R) injured rats. A total of 72 male adult Sprague-Dawley rats were randomly divided into the sham operation control group (SC), the ischemia control group (IC) and the EA group. Middle cerebral artery occlusion (MCAO) was performed to establish the focal cerebral I/R injury model. Proliferation of hippocampal NSCs in cerebral I/R injured rats was determined by the Nestin immunohistochemical staining. Activation of the notch signaling pathway was detected by Western blotting and reverse transcription polymerase chain reaction analysis. The serum level of neurotrophic factors, e.g., the brain-derived neurotrophic factor (BDNF) and the Glial cell line-derived neurotrophic factor (GDNF), was measured using enzyme-linked immunosorbent assay (ELISA). The results showed that EA at Quchi (LI11) and Zusanli (ST36) acupoints significantly alleviated neurological deficits, reduced infarct volumes and promoted the proliferation of hippocampal NSCs in cerebral I/R injured rats. The crucial signaling molecules in the notch signaling pathway were activated and the secretion of BDNF and GDNF was increased upon EA. The protein and mRNA levels of Cyclin D1, Cdk4 and p-Rb were increased, while p21 and p27 transcripts were suppressed by notch signaling. These results suggest that the up-regulatory effect of EA on the notch signaling pathway and neurotrophic factor secretion may result in the promotion of NSCs proliferation and consequently a therapeutic effect on cerebral ischemia.
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PMID:Electroacupuncture enhances hippocampal NSCs proliferation in cerebral ischemia-reperfusion injured rats via activation of notch signaling pathway. 2400 40

The aim of this study was to investigate the effect of electroacupuncture (EA) on cell proliferation and its molecular mechanisms. Sixty rats were randomly divided into 5 groups: sham operation control (SC), ischemia control (IC), EA, EA and DMSO injection (ED), EA and U0126 injection (EU). All the groups, with the exception of SC, underwent middle cerebral artery occlusion (MCAO), and DMSO or U0126 was injected into the rat in the ED or EU group 30 min prior to MCAO. Cell proliferation was evaluated by proliferating cell nuclear antigen (PCNA) immunostaining. The changes of cell cycle proteins (cyclin D1, CDK4, cyclin E, CDK2, p21 and p27) and the ERK1/2 pathway activation were examined by RT-PCR and western blot analysis. The results showed that the positive cell numbers of PCNA immunostaining in the EA and ED groups were more than those in the IC group (P<0.05). The mRNA and protein levels of p21 or p27 were obviously increased, however, the mRNA and protein levels of cyclin D1, CDK4, cyclin E and CDK2 were reduced in the IC and EU groups. The findings suggested that EA activates the ERK1/2 signaling pathway to protect brain injury during cerebral ischemia. However, this positive effect of EA can be blocked by U0126.
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PMID:Electroacupuncture promotes neural cell proliferation in vivo through activation of the ERK1/2 signaling pathway. 2463 71

Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.
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PMID:Long noncoding RNA mediates stroke-induced neurogenesis. 3234 40