Targeting vascular ion channels for ischemic stroke

来源 :国际神经病学中山高峰论坛·2012暨中新帕金森病与运动障碍疾病诊疗新进展研讨会 | 被引量 : 0次 | 上传用户:hellogph
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  Stroke is common with a 3.65% prevalence rate in the Singapore population and an expected rising incidence with our ageing population.It is the leading cause of adult disability and 4th most common cause of mortality in Singapore.Ischemic stroke is the predominant stroke subtype affecting elder patients due to the occlusion of cerebral blood vessels.Acute treatment focuses on the vascular recanalization.Transient receptor potential melastatin channel 4 (TRPM4), in together withTRPM5, are the only two non-selective, Ca2+-impermeable cation channels which are activated by elevated cy tosolic Ca2+ levels.TRPM4 is upregulated in vascular endothelium after ischemic stroke which con tributes to the oncotic cell death and edema.Blocking TRPM4 channel could enhance angiogenesis and increase the therapeutic time window for thrombolysis therapy.Voltage-gated calcium channel CaV 1.2 channel is widely expressed in vascular smooth mus cles.Blockers of CaV 1.2 channel are used to treat hypertension and arrhythmia.In stroke, blocking CaV1.2 channels does not improve survival due to side effects such as systemic hypotension.Wei dentified the molecular structural changes of CaV 1.2 channel after hypoxia in cerebral smooth mus cles which may provide novel targets to generate stroke specific blockers.
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