电刺激小脑顶核对血管性痴呆大鼠认知能力的影响(英文)

Effect of electrical stimulation of fastigial nucleus on cognitive ability in rats with vascular dementia

背景:近年来血管性痴呆的治疗虽有许多进展,但多数药物效果并不能令人满意。慢性前脑灌注不足是血管性痴呆的主要原因,自发现刺激小脑顶核可使大脑血流量增加后,一些作者相继在大鼠脑梗死模型上使用顶核电刺激(fastigialnucleusstimulation,FNS)治疗并取得疗效。目的:研究电刺激小脑顶核对血管性痴呆(vasculardementia,VD)大鼠的治疗作用与机制。设计:完全随机设计,对照实验研究。地点和材料:第三军医大学中心实验室,材料为雄性Wistar老龄大鼠44只(>12月龄),体质量300～400g。干预:随机分为假手术对照组、缺血2个月组、缺血4个月组;每组12～14只大鼠。持久性双侧颈总动脉结扎制备大鼠慢性前脑灌注不足模型。假手术对照组动物仅行颈前切开,不结扎颈总动脉。各组动物随机均分为FNS和非FNS两种处理。前者将电极插入双侧小脑顶核(以前囟为原点,坐标为:P11.8,L0.5,H5.7,单位:mm),并以电流强度50μA,频率50Hz的直角方波脉冲连续刺激30min,后者只插入电极,不予电刺激。主要观察指标:用电脑控制穿梭箱系统检测大鼠的认知能力,记录灯光刺激大鼠即完成穿梭动作的主动回避反应和经电刺激才能完成穿梭动作的被动回避反应。结果:大鼠学习能力检测的被动回避反应,非FNS缺血2个月成功率为15.3%,缺血4个月成功率为8.7%;

BACKGROUND:During recent years, many achievements have been made in medicinal treatment of vascular dementia, but the effects of most drugs were not satisfactory.Main cause of vascular dementia was chronic forebrain hypoperfusion.Since stimulation of cerebellar fastigial nucleus was found to increase the blood flow,many investigators conducted electrical stimulation of the cerebellar fastigial nucleus(FN) to infarct rat model and ideal outcomes were obtained. OBJECTIVE:To investigate the effect and mechanisms of fastigial nucleus stimulation(FNS) on the treatment of vascular dementia (VD) in rats. DESIGN:A completely randomized and controlled study. SETTING and MATERIALS:The experiment was done in the Central Laboratory of Third Military Medical University.Forty four male Wistar rats with age over 12 months, weighing 300 to 400g, were involved. INTERVENTIONS:The Wistar rats were randomly divided into 3 groups: Sham stimulation control group,2 month ischemia group and 4 month ischemia group,12 to 14 rats in each group.The animal model of chronic hypoperfusion of cerebral blood flow was established by permanent bilateral common carotid artery occlusion.Rats as control were treated in the same way but without artery ligation.Each group was randomly sub divided as FNS and non FNS.In FNS group the electrode was implanted into the bilateral cerebellar fastigial nucleus(bregma as the origin,coordinates:P 11.8,L 0.5,H 5.7,unit:mm) and rectangular impulse at intensity of current 50μA and frequency 50 Hz was given for 30 minutes.In non FNS group the electrode was implanted but no FNS was given. MAIN OUTCOME MEASURES:The cognitive function of rats was measured with a computerized shuttle training case before and after FNS.The rats shuttling after light stimulus were considered active avoidance response(AAR),and those shuttling only after electric stimulus were passive avoidance response(PAR). RESULTS:PAR of learning ability test:success rates were 15.3%and 8.7%in 2 month ischemia and 4 month ischemia non FNS group respectively;those were 32.6%and 38.3%in 2 month ischemia and 4 month ischemia FNS group respectively.AAR of learning ability test:success rate was 34.8%in 2 month ischemia non FNS group,those were 60.1%and 62.4%in 2 month ischemia and 4 month ischemia FNS group respectively.The learning and memory abilities of rats were obviously reduced 2 months after chronic cerebral hypoperfusion and became worse 4 months after that,but they were distinctly improved after FNS treatment,especially the learning ability. CONCLUSION:FNS can greatly improve the cognitive impairment of aging rats with VD.