CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis.

Cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most common monogenic form of small vessel disease characterized by migraine with aura, leukoaraiosis, strokes, and dementia. CADASIL mutations cause cerebrovascular dysfunction in both animal models and humans. Here, we showed that 2 different human CADASIL mutations (Notch3 R90C or R169C) worsen ischemic stroke outcomes in transgenic mice; this was explained by the higher blood flow threshold to maintain tissue viability compared with that in wild type (WT) mice.

Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents.

Spontaneous spreading depolarizations are frequent after various forms of human brain injury such as ischemic or hemorrhagic stroke and trauma, and worsen the outcome. We have recently shown that supply-demand mismatch transients trigger spreading depolarizations in ischemic stroke. Here, we examined the mechanisms triggering recurrent spreading depolarization events for many days after subarachnoid hemorrhage.

Abnormal synaptic Ca(2+) homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice.

Objective: Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels.

Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations.

Background: 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.

Cortical spreading depression impairs oxygen delivery and metabolism in mice.

Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism.

Enhanced subcortical spreading depression in familial hemiplegic migraine type 1 mutant mice.

Familial hemiplegic migraine type 1, a monogenic migraine variant with aura, is linked to gain-of-function mutations in the CACNA1A gene encoding Ca(V)2.1 channels. The S218L mutation causes severe channel dysfunction, and paroxysmal migraine attacks can be accompanied by seizures, coma, and hemiplegia; patients expressing the R192Q mutation exhibit hemiplegia only.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression.

Migraine with aura is often the first manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome (CADASIL), a disorder caused by NOTCH3 gene mutations expressed predominantly in vascular smooth muscle. Here, we report that cortical spreading depression (CSD), the electrophysiological substrate of migraine aura, is enhanced in mice expressing a vascular Notch 3 CADASIL mutation (R90C) or a Notch 3 knockout mutation. The phenotype was stronger in Notch 3 knockout mice, implicating both loss of function and neomorphic mutations in its pathogenesis.

Anterior-wall aneurysm of the internal carotid artery successfully treated solely by stenting: With special reference to etiology.

In this case, a ruptured anterior wall aneurysm of the internal carotid artery disappeared on angiography immediately after stent placement. We focus on the underlying nature of the lesion and this possible alternative treatment.

Soluble guanylate cyclase alpha1beta1 limits stroke size and attenuates neurological injury.

Background And Purpose: Nitric oxide mediates endothelium-dependent vasodilation, modulates cerebral blood flow, and determines stroke outcome. Nitric oxide signals in part by stimulating soluble guanylate cyclase (sGC) to synthesize cGMP. To study the role of sGC in stroke injury, we compared the outcome of cerebral ischemia and reperfusion in mice deficient in the alpha(1) subunit of sGC (sGCalpha(1)(-/-)) with that in wild-type mice.

Neurocysticercosis: assessing where the infection was acquired from.

Histopathological specimen of a neurocysticercosis patient, who had been living in several endemic countries, was retrospectively analyzed for assessing the origin of the infection. Mitochondrial DNA analysis strongly suggested that the patient became infected with the parasite in Nepal at least 10 years before the onset of the disease.

An oral administration of cilostazol before focal ischemia reduces the infarct volume with delayed cerebral blood flow increase in rats.

We studied the acute brain protection provided by an antiplatelet agent, cilostazol, in rat experimental focal ischemia model. We administered 30 mg/kg of cilostazol or vehicle orally 2 hours before transient middle cerebral artery (MCA) occlusion (MCAO) by the intraluminal thread method. We measured the absolute cerebral blood flow (CBF) 2 hours after cilostazol administration, the regional CBF (rCBF) of MCA territory during MCAO, and neurologic deficits and the infarct volume at 22 hours after reperfusion.

Efficacy of a direct puncture approach for anterior circulation aneurysms using a newly developed guiding catheter - especially for geriatric patients.

Background: Endovascular surgery is being increasingly used as an alternative to craniotomy clipping surgery, especially for aged patients and complicated cases. However, tortuous atherosclerotic arteries sometimes interfere with advancement of catheters so that direct puncture may be necessary. Short guiding catheters for use with this approach have been newly developed, as discussed in this article.

Chronic cerebral venous hypertension model in rats.

Although cerebral venous hypertension is known as an important determinant factor for clinical manifestation and outcome in patients with dural arteriovenous malformation (AVM), the pathophysiology of that condition is not well understood. We have created a chronic rat model by cervical arteriovenous fistularization with jugular vein occlusion and examined effect of cerebral venous hypertension on cerebral blood flow regulation. This model may be suitable for investigating mechanisms of cerebrovascular alteration after venous hypertension.