Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Circulation. 2012 Jan 17;125(2):335-45. doi: 10.1161/CIRCULATIONAHA.111.045096. Epub 2011 Dec 5.
Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms.
Here, we show that FHM type 1 (FHM1) mutations in Ca(V)2.1 voltage-gated Ca(2+) channels render the brain more vulnerable to ischemic stroke. Compared with wild-type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist.
We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk.
偏头痛是中风的独立危险因素。这种关联的机制尚不清楚。家族性偏瘫性偏头痛（FHM）是偏头痛的一种亚型，也会增加中风风险，它是常见偏头痛表型的有用模型，因为它具有共享的先兆和头痛特征、触发因素以及潜在的谷氨酸能机制。
在这里，我们表明，Ca(V)2.1 电压门控钙 (Ca2+) 通道中的 FHM1 突变使大脑更容易受到缺血性中风的影响。与野生型小鼠相比，2 种 FHM1 突变鼠种更早地发生缺氧去极化，并且更频繁地发生与弥散加权磁共振成像上梗死核心快速扩张和激光散斑流量计上更大的灌注不足相关的peri-infarct 去极化。在突变体中，为组织存活所需的脑血流更高，导致轻度缺血性梗死。结果，突变体在中风后发生更大的梗死和更严重的神经功能障碍，而谷氨酸受体拮抗剂选择性地减轻了这种影响。
我们提出，类似于扩散性抑制的缺血去极化易感性使偏头痛患者在轻度缺血事件中更容易发生梗死，从而增加中风风险。
