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)

Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time.
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PMID:Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia. 2324 26

The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically used for the treatment of stroke. The active fraction of XXMD (AF-XXMD) exhibits pharmacological effects that are similar to those of XXMD. In this study, 21 primary compounds of AF-XXMD with potential anti-ischemic-stroke activities were selected as effective candidates to perform comparisons of their pharmacokinetic differences between control and cerebral ischemic rats and to characterize their pharmacokinetic behaviors in cerebral ischemic rats. After oral administration of AF-XXMD to control and cerebral ischemic rats, plasma and brain were harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry. Reverse molecular docking results indicate that 21 AF-XXMD-derived compounds exert potential neuroprotection, anti- inflammation, and vascular dilation effects via interaction with multiple targets in stroke-related pathways. The blood-brain permeability, cerebral exposure and brain region distribution of these compounds were found to change in cerebral ischemic models. Flavonoids were identified as the predominant form in plasma, whereas chromones were found to be the major form in the brain, and alkaloids possessed moderate blood-brain permeability. Collectively, the cerebral pharmacokinetic behaviors of chromones, flavonoids and alkaloids were found to change under pathological conditions. The efficacy of AF-XXMD against cerebral ischemia is relevant to the synergistic effects of these compounds in targeting different receptors and pathways. Chromones exhibit relatively high brain permeability, and their activity and mechanism warrant further investigation.
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PMID:Pharmacokinetics of 21 active components in focal cerebral ischemic rats after oral administration of the active fraction of Xiao-Xu-Ming decoction. 2685 60