TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Stanniocalcin 1 is important for poststroke functionality, but dispensable for ischemic tolerance.

Stanniocalcin 1 (STC1), originally described as an antihypercalcemic hormone in fish, is highly expressed in differentiated mammalian neurons. Mild hypoxic treatment and focal cerebral ischemia induce upregulation of STC1 in the brain. These findings prompted us to investigate whether STC1 contributes to neuroprotection after ischemia and whether STC1 is required for development of ischemic tolerance. We induced 60 minutes of temporary middle cerebral artery occlusion in wild type (WT) and STC1-deficient mice (STC1(-/-)) with or without prior hypoxic preconditioning (HPC, 8% oxygen for 6 hours followed by reoxygenation for 24 hours). Infarct sizes, neurological scores, and Stc1, Stc2, and Il-6 mRNA brain levels were measured 24 hours after ischemia. Additionally, we examined blood-brain barrier (BBB) integrity (Evans Blue fluorescence) under normal conditions and 0 and 24 hours after hypoxia. STC1(-/-) and WT mice developed brain infarcts of similar size. In both strains, HPC triggered ischemic tolerance with similar reduction in infarct size. However, STC1(-/-) mice had worse neurological scores in both scenarios. HPC induced upregulation of STC1 and STC2 in WT mice and of STC2 in STC1(-/-) mice. Ischemic STC1(-/-) mice showed significantly lower Il-6 mRNA expression than ischemic WT mice. Evans Blue fluorescence levels showed no difference in between WT and STC1(-/-) mice under evaluated conditions, thus BBB integrity is preserved despite STC1 deficiency. STC1 was not crucial for the development of ischemic tolerance triggered by HPC or for preserving BBB integrity but may be involved in functional recovery after stroke.