Background and Purpose-The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of ␣-tocotrienol (TCT), but not ␣-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase. Methods-The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT. Results-Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site. Conclusion-The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate-and stroke-induced neurodegeneration. (Stroke. 2005;36:e144-e152.)

Background and Purpose:We describe a new rat model of temporary focal ischemia that produces neocortical ischemia without the need for prolonged anesthesia.Methods: Temporary focal cerebral ischemia was initiated during halothane anesthesia, maintained for varying periods without anesthesia, and reversed by clip removal requiring brief anesthesia. Tandem carotid and middle cerebral artery occlusion for 1-4 hours and permanent occlusion were used to determine the duration and extent of ischemia necessary to produce predictable volumes of neocortical infarction in Wistar and spontaneously hypertensive rats.Results :

Cerebral vasoregulation is impaired with minor stroke, and cerebral blood flow depends on blood pressure. Decline of blood flow velocities during orthostatic stress may pose a risk of silent hypoperfusion.

The peripheral neuropathy seen with necrotizing angiopathy is said to begin classically as a mononeuritis multiplex, usually associated with polyarteritis nodosa, rheumatoid arthritis, or systemic lupus erythematosus. Our experience, however, suggests that a large number of these patients do not have a well-defined collagen vascular disease or the typical clinical pattern. In 350 consecutive nerve biopsies (sural or superficial radial), 16 patients showed a necrotizing angiopathy in the epineurial blood vessels. Six of these 16 patients had a distal symmetrical sensorimotor polyneuropathy. The remaining 10 had a mononeuritis multiplex, although in 8 overlapping nerve involvement somewhat obscured the picture of mononeuritis. In 12 patients, no specific underlying collagen vascular disease could be diagnosed by accepted criteria despite extensive clinical, radiological, and serological evaluations. The peripheral neuropathy was the only objective evidence of vasculitis in 7 of these 12 patients. Our findings suggest that patients with a peripheral neuropathy secondary to necrotizing angiopathy often do not have a definable collagen vascular disease. In fact, peripheral neuropathy may be the sole manifestation of vasculitis. Furthermore, the neuropathy was found to be a distal symmetrical sensorimotor neuropathy in a higher proportion of cases than has been documented previously.

Objectives This work aimed to refine a large animal in minimally invasive reversible middle cerebral artery (MCA) occlusion (MCAO) model to account for leptomeningeal collateral formation. Materials and Methods An angiographically based methodology allowed for transient MCA and carotid terminus occlusion in 12 mongrel dogs and assessment of pial collateral recruitment. Outcome measures included 1- and 24-hour magnetic resonance imaging-based infarct volume calculation, a behavioral scale and histopathologic sections. Results MCAO succeeded in 8 of 12 dogs (67% efficiency). One-hour postreperfusion infarct volume predicted 24-hour postreperfusion infarct volume (r2 = 0.997, P < 0.0001). Pial collateral recruitment varied with time and reproducibly assessed predicted infarct volume on 1-hour postre-perfusion mean diffusivity maps (P < 0.0001; r2 = 0.946) and 24-hour fluid-attenuated inversion recovery FLAIR magnetic resonance imaging (P < 0.0033; r2 = 0.961). The canine stroke scale score correlated with infarct volumes and pial collateral score. Conclusion This canine MCAO model produces defined cerebral infarct lesions whose volumes correlate with leptomeningeal collateral formation and canine behavior.

No abstract

Thunderclap headache is an acute high intensity headache similar to that seen in the setting of ruptured saccular aneurysm. We report four patients without subarachnoid hemorrhage who presented with thunderclap headache. Three patients had transient neurologic signs or symptoms. Cerebral angiography revealed diffuse segmental intracerebral arterial vasoconstriction which was reversible in the one patient in whom angiography was repeated. The headaches resolved spontaneously in all cases and after 1 week did not recur. These cases highlight the specific clinical and angiographic features and the self-limited course of patients with thunderclap headache and suggest that thunderclap headache may represent a unique headache category. On the basis of these cases and others reported in the literature, we propose diagnostic criteria for thunderclap headache.

Background and Purpose:We examined the cytoprotective effect of the lipid peroxidation inhibitor tirilazad mesylate (U74006F) in rodent models of neocortical infarction induced by transient and permanent focal cerebral ischemia.Methods: Wistar rats (experiment 1) and spontaneously hypertensive rats (experiment 2) were subjected to 2 hours of transient middle cerebral artery occlusion followed by 22 hours of reperfusion and pretreated with 10 mg/kg i.p. tirilazad, vehicle, or saline. Repeat doses were given at 4 and 10 hours after reperfusion. Spontaneously hypertensive rats were also subjected to permanent middle cerebral artery occlusion and either pretreated with tirilazad, vehicle, or saline intraperitoneally (experiment 3) or treated with either tirilazad or vehicle intravenously after ischemia (experiment 4). Cortical infarct volumes were measured 24 hours after the onset of either transient or permanent ischemia, and changes in core regional cerebral blood flow were monitored with laser Doppler flowmetry.Results: Tirilazad reduced infarct volume after transient ischemia by 40% in Wistar rats (p=0.08) (experiment 1) and 23% in spontaneously hypertensive rats (/?<0.05) (experiment 2) but did not reduce infarction after permanent ischemia whether it was given intraperitoneally (experiment 3) or intravenously (experiment 4). Ischemic core blood flows were not affected during ischemia, nor were they affected during reperfusion after transient ischemia.Conclusions: Tirilazad reduces cortical infarction in transient but not permanent ischemia, an effect not related to improvement in regional cerebral blood flow. Tirilazad might prove to be useful as an adjuvant therapy after successful thrombolysis in acute stroke patients. (Stroke 1992^3:894-899) KEY WORDS • cerebral blood flow • free radicals • lipid peroxidation • reperfusion • rats