Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral ischemia rapidly initiates structural and functional changes in brain vessels, including blood-brain barrier disruption, inflammation, and angiogenesis. Molecular events that accompany these changes were investigated in brain microvessels extracted using laser-capture microdissection (LCM) from Sprague-Dawley rats subjected to a 20 min transient global cerebral ischemia followed by 1, 6, or 24 h reperfusion. Proteins extracted from approximately 300 LCM captured microvessels (20-100 microm) were ICAT-labeled and analyzed by nanoLC-MS. In-house software was used to identify paired ICAT peaks, which were then sequenced by nanoLC-MS/MS. Pattern analyses using k-means clustering method classified 57 differentially expressed proteins in 7 distinct dynamic patterns. Protein function was assigned using Panther Classification system. Early reperfusion (1 h) was characterized by down-regulation of ion pumps, nutrient transporters, and cell structure/motility proteins, and up-regulation of transcription factors, signal transduction molecules and proteins involved in carbohydrate metabolism. The up-regulation of inflammatory cytokines and proteins involved in the extracellular matrix remodeling and anti-oxidative defense was observed in late reperfusion (6-24 h). The up-regulation of IL-1beta and TGF-1beta in ischemic brain vessels was confirmed by ELISA, quantitative PCR, and/or immunohistochemistry. A biphasic postischemic (1 and 24 h) BBB opening for (3)H-sucrose was evident in the same model. Differentially expressed proteins identified in brain vessels during reperfusion are likely involved in orchestrating functional vascular responses to ischemia, including the observed BBB disruption.
 ...
PMID:Characterization of vascular protein expression patterns in cerebral ischemia/reperfusion using laser capture microdissection and ICAT-nanoLC-MS/MS. 1626 Jun 51

Cerebral ischemia (CI) induces dramatic changes in synaptic structure and function that precedes delayed post-ischemic neuronal death. Here, a proteomic analysis was used to identify the effects of focal CI on synaptosomal protein levels. Contralateral and ipsilateral synaptosomes, prepared from adult mice subjected to 60 min middle cerebral artery occlusion, were isolated following 3, 6 and 20 h of reperfusion. Synaptosomal protein samples (n=3) were labeled using the cleavable ICAT system prior to analysis with nanoLC-MS/MS. Each sample was analyzed by LC-MS to identify differential expressions using InDEPT software and differentially expressed peptides were identified by targeted LC-MS/MS. A total of 62 differentially expressed proteins were identified and Gene Ontology classification (cellular component) indicated that the majority of the proteins were located in the mitochondria and other components consistent with synaptic localization. The observed alterations in synaptic protein levels poorly correlated with gene expression, indicating the involvement of post-transcriptional regulatory mechanisms in determining post-ischemic synaptic protein content. Additionally, immunohistochemistry analysis of prosaposin (Psap) and saposin C (SapC) indicates that CI disrupts Psap processing and glycosphingolipid metabolism. These results demonstrate that the synapse is adversely affected by CI and may play a role in mediating post-ischemic neuronal viability.
 ...
PMID:Proteomic analysis of synaptosomal protein expression reveals that cerebral ischemia alters lysosomal Psap processing. 2071 7