Hall E D, Smith S L
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Brain Res. 1991 Jul 12;553(2):243-8. doi: 10.1016/0006-8993(91)90832-g.
Cortical spreading depression (SD) has been implicated in the pathophysiology of classical migraine headache and cerebral ischemia. A reduction in cerebral blood flow (CBF), mimicking that seen during the aura and headache phase of migraine, is typically observed following SD in the rat. This phenomenon may also play a role in potentiating ischemic brain damage. In the present study, brief cortical exposure to 1 M KCl produced a marked suppression of EEG amplitude which persisted 20 min in the rat. Upon normalization of the EEG, cortical blood flow declined 20-30% and remained low for at least 2 h. Treatment with a 1 mg/kg i.v. dose of the 21-aminosteroid antioxidant tirilazad mesylate (U-74006F), 2 min following KCl application, completely blocked the hypoperfusion while leaving the magnitude and duration of the EEG suppression and mean arterial pressure unchanged. Tirilazad mesylate is a potent inhibitor of oxygen radical-mediated lipid peroxidation both in vitro and in vivo. Thus, based on present results, an oxygen radical hypothesis is proposed to account for the SD-induced cerebral hypoperfusion.
皮层扩散性抑制（SD）与典型偏头痛性头痛及脑缺血的病理生理学有关。在大鼠中，SD后通常会观察到脑血流量（CBF）减少，类似于偏头痛先兆和头痛期所见。这种现象也可能在加重缺血性脑损伤中起作用。在本研究中，大鼠短暂皮层暴露于1M氯化钾会导致脑电图幅度显著抑制，持续20分钟。脑电图恢复正常后，皮层血流量下降20 - 30%，并至少持续低水平2小时。在应用氯化钾2分钟后，静脉注射1mg/kg剂量的21 - 氨基类固醇抗氧化剂甲磺酰替拉扎德（U - 74006F）进行治疗，可完全阻断灌注不足，而脑电图抑制的幅度和持续时间以及平均动脉压保持不变。甲磺酰替拉扎德在体外和体内都是氧自由基介导的脂质过氧化的有效抑制剂。因此，基于目前的结果，提出了氧自由基假说以解释SD诱导的脑灌注不足。
