Pronounced hypoperfusion during spreading depression in mouse cortex

Pronounced hypoperfusion during spreading depression in mouse cortex
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DOI:
10.1097/01.wcb.0000137057.92786.f3
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发表时间:
2004-10-01
影响因子:
6.3
通讯作者:
Moskowitz, MA
Moskowitz, MA
中科院分区:
医学1区
文献类型:
--
作者:
Ayata, C;Shin, HK;Moskowitz, MA

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我们研究了独特的脑血流(CBF)的反应,皮质扩散性抑制小鼠使用一种新的二维CBF成像技术,激光散斑血流仪。皮层扩散性抑制引起大鼠和小鼠皮层的三相CBF反应。在大鼠中,轻度初始灌注不足(约为基线的75%),随后出现一过性充血,约为基线的220%。在小鼠中,初始灌注不足明显(基线的40-50%),预期的充血期几乎没有达到基线。低灌注的持续时间与DC移位的持续时间显著相关。作为一个可能的解释,明显的低灌注,小鼠脑血管表现出增强的阻力放松乙酰胆碱(3 μ M)后K+诱导的预收缩(20,40,和80 mM),但扩张正常响应乙酰胆碱预收缩后与U46619,合成血栓烷A2类似物。相比之下,K+预收缩后,大鼠血管很容易因乙酰胆碱而扩张。L-NA可消除小鼠低灌注后CBF的短暂正常化,但7-NI不能。总之,小鼠脑血流对皮层扩散性抑制的反应与大鼠相反,在小鼠脑血流中,最初的低灌注是明显的,充血期明显减少。种属间CBF反应的差异可能部分是由小鼠脑血管对升高的细胞外K+的敏感性增加引起的。
We studied unique cerebral blood flow (CBF) responses to cortical spreading depression in mice using a novel two-dimensional CBF imaging technique, laser speckle flowmetry. Cortical spreading depression caused a triphasic CBF response in both rat and mouse cortex. In rats, mild initial hypoperfusion (approximately 75% of baseline) was followed by a transient hyperemia reaching approximately 220% of baseline. In mice, the initial hypoperfusion was pronounced (40-50% of baseline), and the anticipated hyperemic phase barely reached baseline. The duration of hypoperfusion significantly correlated with the duration of the DC shift. As a possible explanation for the pronounced hypoperfusion, mouse cerebral vessels showed enhanced resistance to relaxation by acetylcholine (3 muM) after K+-induced preconstriction (20, 40, and 80 mM) but dilated normally in response to acetylcholine after preconstriction with U46619, a synthetic thromboxane A2 analog. By contrast, rat vessels dilated readily to acetylcholine after preconstriction by K+. The transient normalization of CBF after hypoperfusion in the mouse was abolished by L-NA but not 7-NI. In summary, the CBF response to cortical spreading depression in mice contrasts with the rat in that the initial hypoperfusion is pronounced, and the hyperemic phase is markedly diminished. The differences in CBF response between species may be in part caused by an increased sensitivity of mouse cerebral vessels to elevated extracellular K+.