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)

Damage-induced neuronal endopeptidase (DINE) is a unique nerve-injury associated molecule, which was recently identified in a peripheral nerve injury model. The aim of this study was to determine the expression profiles and distribution of DINE in adult rats after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced late-onset and prolonged expression of DINE mRNA in the peri-infarct cortex and specific nuclei of thalamus. Double labeling using immunohistochemistry and in situ hybridization revealed that DINE mRNA was exclusively expressed in cells that were positive to a neuronal marker NeuN. Previously established knowledge on neuroanatomical fiber connection suggests that DINE mRNA was expressed in areas projecting their axons to or through the core region of the infarction. This unique expression profile was similar to that of activating transcription factor-3 (ATF-3), which is a marker of nerve-injured neuron. More than 98% of ATF-3 immunoreactive neurons simultaneously expressed DINE mRNA, suggesting that DINE expression is observed in injured neurons of CNS as well as PNS. Since DINE expression promotes antioxidant activity, our results suggest that DINE may act as a neuroprotective molecule in neurons under ischemic insult.
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PMID:Expression of damage-induced neuronal endopeptidase (DINE) mRNA in peri-infarct cortical and thalamic neurons following middle cerebral artery occlusion. 1552 49

In this study, we examined whether ischemia-induced amyloidogenesis could be modulated by environmental "experience," and whether this modulation is associated with improved cognitive functioning. Rats were subjected to either global ischemia or sham surgery and then were randomly assigned to either enriched environment housing (EE) or socially paired housing (controls). After 14 days of differential environmental housing, the rats were tested in the water maze. Our results show decreased C-terminal fragments of the beta-amyloid precursor protein (betaAPP) and decreased amyloid beta (Abeta) load in the ischemic EE rats compared to the ischemic control animals. In addition, Abeta oligomerization was significantly decreased in the ischemic EE animals compared to the ischemic control rats. Further, significantly increased levels of neprilysin, but not insulin-degrading enzyme, amyloid-degrading enzymes, were seen in the ischemic EE rats compared to the ischemic control animals. Behavioral analyses showed that ischemic EE rats performed significantly better on the memory task compared to the ischemic control group. These results suggest that use of multi-sensory environmental enrichment following cerebral ischemia may reduce the accumulation of Abeta peptide in the more pathologic oligomeric form, and consequently may enhance functional recovery.
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PMID:Environmental experience modulates ischemia-induced amyloidogenesis and enhances functional recovery. 2773 69

We have previously demonstrated aggregation of amyloid precursor protein (APP) and beta-amyloid (Abeta) to dense plaque-like deposits in the thalamus of rats subjected to transient middle cerebral artery occlusion (MCAO). Here, we investigated the underlying molecular effects of MCAO on APP processing and expression profiles of Abeta degrading enzymes in the cortex adjacent to the infarct (penumbra) and ipsilateral thalamus 2, 7 and 30 days after ischemic insult. Enhanced beta-amyloidogenic processing of APP and altered insulin degrading enzyme and neprilysin expression were observed in the thalamus, but not the penumbral cortex, 7 and 30 days after MCAO coinciding with increased calcium levels and beta-secretase (BACE) activity. Consecutively, increased BACE activity associated with depletion of BACE trafficking protein GGA3, suggesting a post-translational stabilization of BACE. These results demonstrate that focal cerebral ischemia leads to complex pathogenic events in the thalamus long after the initial insult.
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PMID:Focal cerebral ischemia in rats alters APP processing and expression of Abeta peptide degrading enzymes in the thalamus. 1942 2

Cerebral ischemia, traumatic brain injury, intracerebral hemorrhage and other brain insults trigger neurogenesis in the subventricular zone and hippocampal subgranular zone, and newly formed blood vessels promote the migration of these new neuronal cells to damaged brain regions. The molecular steps involved in brain injury-induced angiogenesis and neurogenesis are unclear. Here we used a rat model of collagenase-induced intracerebral hemorrhage (ICH) to examine whether matrix metalloproteinase-9 (MMP-9), a zinc endopeptidase that regulates growth factor levels during recovery from brain injury, is involved in neurogenesis and angiogenesis following ICH. Induction of ICH led to significant increases in the levels of MMP-9, vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), as well as in the numbers of 5-bromo-2-deoxyuridine (BrdU)- and doublecortin (DCX)-positive cells, in the ipsilateral brain. Intracerebroventricular injection of MMP-9 siRNA reduced these ICH-induced increases. These findings suggest that MMP-9 may promote angiogenesis and neurogenesis during recovery from ICH.
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PMID:Activation of cerebral recovery by matrix metalloproteinase-9 after intracerebral hemorrhage. 2320 Dec 58

Dementias including Alzheimer's disease (AD) are multifactorial disorders that involve several different etiopathogenic mechanisms. Cerebral ischemia has been suspected in the altered regulation of protein kinases and phosphatases that leads to hyperphosphorylation of tau and further neurofibrillary pathology, a key hallmark of AD and related neurodegenerative diseases. However, the deregulation of these enzymes and their relationship with ischemia and AD remain unclear. Previously, we reported a mechanism by which the lysosomal enzyme asparagine endopeptidase (AEP) is associated with brain acidosis and AD. In this study, we subjected mice to middle cerebral artery occlusion and found that compared with wild type mice, the ischemia-induced brain injury and motor deficit in AEP-knockout mice are reduced, probably because ischemia activates AEP. AEP cleaves inhibitor 2 of protein phosphatase 2A (I2PP2A), which translocates from the neuronal nucleus to the cytoplasm and produces hyperphosphorylation of tau through inhibition of PP2A. These findings suggest a possible mechanism of tau pathology associated with ischemia.
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PMID:Mechanism of Tau Hyperphosphorylation Involving Lysosomal Enzyme Asparagine Endopeptidase in a Mouse Model of Brain Ischemia. 2968 17

Recanalization therapy by intravenous thrombolysis or endovascular therapy is critical for the treatment of cerebral infarction. However, the recanalization treatment will also exacerbate acute brain injury and even severely threatens human life due to the reperfusion injury. So far, the underlying mechanisms for cerebral ischaemia-reperfusion injury are poorly understood and effective therapeutic interventions are yet to be discovered. Therefore, in the research, we subjected SK-N-BE(2) cells to oxygen-glucose deprivation/reperfusion (OGDR) insult and performed a pooled genome-wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) knockout screen to discover new potential therapeutic targets for cerebral ischaemia-reperfusion injury. We used Metascape to identify candidate genes which might involve in OGDR resistance. We found that the genes contributed to OGDR resistance were primarily involved in neutrophil degranulation, mitochondrial translation, and regulation of cysteine-type endopeptidase activity involved in apoptotic process and response to oxidative stress. We then knocked down some of the identified candidate genes individually. We demonstrated that MRPL19, MRPL32, MRPL52 and MRPL51 inhibition increased cell viability and attenuated OGDR-induced apoptosis. We also demonstrated that OGDR down-regulated the expression of MRPL19 and MRPL51 protein. Taken together, our data suggest that genome-scale screening with Cas9 is a reliable tool to analyse the cellular systems that respond to OGDR injury. MRPL19 and MRPL51 contribute to OGDR resistance and are supposed to be promising targets for the treatment of cerebral ischaemia-reperfusion damage.
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PMID:CRISPR/Cas9-mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen-glucose deprivation/reperfusion resistance. 3261 81