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NeuroScience Associates

Stroke

Overview

Animal models for stroke attempt to induce a cerebral ischemia to mimic the effects of a stroke in humans which tends to be more difficult to replicate in smaller rodents than in larger animals. Neurohistology for stroke research primarily focuses on methods to quantify the ischemic region and characterize the margin of surviving tissue.

Animal Models:

Stroke Endpoint: Blood Brain Barrier (BBB) Breakdown

Stroke Endpoint: Ischemic Area

Protective effects of interventions after stroke are ideally based on clinical neurologic outcomes and subsequent neurohistology. In small animal stroke models, difficulties with long survival times and neurologic evaluation prompt many investigators to perform acute studies and determine protection by histologic evaluations immediately after inducing an infarction. Many stains have been used to identify infarct areas, but it is not clear if these areas include or could delineate the penumbra, i.e., the potentially salvageable tissue at the margin of the infarct. The triphenyltetrazolium chloride (TTC) method, for instance, is known to give variable infarct volumes depending on how long after the infarct the tissue is harvested. A fortuitous observation led to a staining method that delineates the penumbra and highlights the infarcted volume in sharp contrast. Normal tissue is dense black, infarcted areas fail to stain and gradations of gray identify the penumbra zone. Section images are digitized and, based on optical density, the volumes of the infarct, penumbra and normal brain are calculated. Adjacent sections stained with other methods including H&E, thionine and GFAP IHC display less definition of affected areas.

Appearance of stroke in popular animal models with decreasing severity

Stroke Endpoint: Image Analysis of Ischemic

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