■脑小血管病是血管性认知障碍和痴呆的常见原因。目前迫切需要预防性治疗血管性认知障碍和痴呆,减少血管功能障碍可能提供治疗途径。这里,我们调查是否长期服用尼莫地平,中枢神经系统选择性二氢吡啶类钙通道阻断剂,保护血管,新陈代谢,脑小血管病动物模型的认知功能,自发性高血压中风易感大鼠。
■在3至6月龄之间,雄性自发性高血压中风易感大鼠随机分配接受安慰剂(n=24)或尼莫地平(n=24)饮食。每天检查动物的任何神经缺陷,在3个月和6个月大时,根据神经血管和神经代谢偶联评估血管功能,和6个月大的脑血管反应性。在6个月大时使用新的物体识别测试评估认知功能。
■六只未经治疗的对照动物因中风而过早终止,包括一个因癫痫发作,但没有接受治疗的动物出现卒中,因此存活率较高(P=0.0088).血管功能随着疾病进展而显著受损,但尼莫地平治疗部分保留了神经血管偶联和神经代谢偶联,由更大(P<0.001)和更迅速的响应(P<0.01)表示,重复刺激习惯较少(P<0.01)。此外,用尼莫地平治疗的动物表现出更大的脑血管反应性,表现为小动脉扩张较大(P=0.015)和血流速度增加(P=0.001)。通过尼莫地平治疗实现的血管和代谢功能的这种保护与治疗动物中更好的认知功能相关(P<0.001)。
■尼莫地平慢性治疗可防止中风,自发性高血压中风易感大鼠的血管和认知障碍。尼莫地平可以为脑小血管病的卒中和认知功能减退提供有效的预防性治疗。
UNASSIGNED: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat.
UNASSIGNED: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age.
UNASSIGNED: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals.
UNASSIGNED: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.