■据报道,局灶性缺血性脑的功能激活可通过增加侧支血流来改善预后。然而,功能激活也会增加代谢需求,从而可能使结果恶化。的确,临床前和临床报告相互矛盾.这里,我们使用远端大脑中动脉闭塞在麻醉小鼠中测试了急性缺血性卒中期间功能激活的影响.
■使用在神经元中表达通道视紫红质2的转基因小鼠,我们使用生理水平的经颅光遗传刺激中度缺血皮质(即,半影),在1小时的大脑中动脉远端微血管夹期间,使用实时全场激光散斑灌注成像进行识别。使用诱发场电位证实了神经元激活,48小时后在组织切片中测量梗死体积。
■半影的光遗传学刺激与对侧同位区刺激和假刺激组的梗死面积大2倍以上相关(n=10、7和9;11.0±5.6对5.1±4.3对4.1±3.7mm3;P=0.008,单向方差分析)。在不表达通道视紫红质-2的野生型小鼠中相同的刺激没有效果。光遗传学刺激与半影灌注的少量增加有关,但不能解释梗死扩大。
■我们的数据表明,急性局灶性动脉闭塞期间神经元活动增加可能是有害的,可能是由于代谢需求增加,并可能对超急性卒中患者的临床管理产生影响。
UNASSIGNED: Functional activation of the focal ischemic brain has been reported to improve outcomes by augmenting collateral blood flow. However, functional activation also increases metabolic demand and might thereby worsen outcomes. Indeed, preclinical and clinical reports have been conflicting. Here, we tested the effect of functional activation during acute ischemic stroke using distal middle cerebral artery occlusion in anesthetized mice.
UNASSIGNED: Using transgenic mice expressing channelrhodopsin-2 in neurons, we delivered functional activation using physiological levels of transcranial optogenetic stimulation of the moderately ischemic cortex (ie, penumbra), identified using real-time full-field laser speckle perfusion imaging during a 1-hour distal microvascular clip of the middle cerebral artery. Neuronal activation was confirmed using evoked field potentials, and infarct volumes were measured in tissue slices 48 hours later.
UNASSIGNED: Optogenetic stimulation of the penumbra was associated with more than 2-fold larger infarcts than stimulation of the contralateral homotopic region and the sham stimulation group (n=10, 7, and 9; 11.0±5.6 versus 5.1±4.3 versus 4.1±3.7 mm3; P=0.008, 1-way ANOVA). Identical stimulation in wild-type mice that do not express channelrhodopsin-2 did not have an effect. Optogenetic stimulation was associated with a small increase in penumbral perfusion that did not explain enlarged infarcts.
UNASSIGNED: Our data suggest that increased neuronal activity during acute focal arterial occlusions can be detrimental, presumably due to increased metabolic demand, and may have implications for the clinical management of hyperacute stroke patients.