EFFECTS OF ACTIVATING THE CHOLINERGIC VASODILATIVE SYSTEM ORIGINATING IN THE BASAL FOREBRAIN ON BLOOD FLOW AND DELAYED NEURONAL DEATH FOLLOWING TRANSIENT ISCHEMIA

最近发现，大脑皮质血流量(CBF)的增加不依赖于代谢性血管扩张，而是通过激活起源于Meynert基底核(NBM)和基底前脑隔区复合体并投射到皮质和海马区的胆碱能神经元来实现的。在本研究中，我们旨在阐明刺激大脑中动脉或隔区复合体后脑血流量的增加是否可以改善大鼠短暂性脑缺血后皮质或海马神经元的迟发性死亡。采用激光多普勒血流仪测量大鼠大脑皮质和海马区的脑血流量，并在组织学上测量大脑皮质或海马区因单侧颈总动脉间歇(每隔5 S)阻断60min而造成的迟发性神经元死亡。在对海马区的研究中，先前进行了双侧椎动脉的永久性结扎。刺激NBM引起的皮质CBF增加阻止了闭塞所致的皮质CBF的减少，并且先前观察到的皮层神经元的迟发性死亡在闭塞后几乎观察到。刺激内侧隔区引起的海马区CBF增加，可阻止闭塞所致的海马区CBF的下降，而先前观察到的海马区CA1区神经元的迟发性死亡几乎看不到。本研究结果提示，基底前脑起源的血管扩张激活可通过阻止皮质和海马区血流量的减少来保护缺血区皮质和海马神经元的迟发性死亡。

An increase in cortical cerebral blood flow (CBF), independent of metabolic vasodilation, via the activation of cholinergic neurons originating in the nucleus basalis of Meynert (NBM) and septal complex in the basal forebrain and projecting to the cortex and hippocampus was recently demonstrated. In the present study, we aimed to clarify whether the increase in CBF following stimulation of the NBM or septal complex can improve delayed death of the cortical or hippocampal neurons following transient ischemia in rats.Cortical and hippocampal CBF was measured using a laser Doppler flowmeter, and delayed neuronal death of the cerebral cortex or hippocampus produced by intermittent (every 5 s) occlusions of the unilateral common carotid artery for 60 min was measured histologically in the cortical hemisphere. In the case of study on hippocampus, permanent ligation of bilateral vertebral arteries was previously performed.The increase in cortical CBF induced by NBM stimulation prevented the occlusion-induced decrease in cortical CBF, and the delayed death of the cortical neurons previously observed after the occlusions was scarcely observable. The increase in hippocampal CBF induced by stimulating the medial septum prevented the occlusion-induced decrease in hippocampal CBF, and the delayed death of the hippocampal CA1 neurons previously observed after the occlusions was scarcely observable.The present results suggest that basal forebrain-originating vasodilative activation can protect ischemia-induced delayed death of cortical and hippocampal neurons by preventing a blood flow decrease in cortex and hippocampus.