Histopathology of Cerebral Ischemia and Stroke

Introduction

The incidence of focal ischemia or stroke has been increasing over the last two decades with over 16 million new cases of stroke reported worldwide in 2010. Focal ischemic brain injury leads to local neurological deficits and a progression of histopathological changes depending on ischemic severity, location, and duration. In regions of developing infarction, acute neuronal alterations can progress through a series of phases including microvacuolation, and ischemic and homogenizing cell change . In other areas adjacent or remote to the evolving focal infarct, a slower progressive neuronal damage termed selective neuronal necrosis, which may have distinct histopathological mechanisms, is also commonly seen in human ischemic tissues. In addition to neuronal changes, alterations in astrocytes, oligodendrocytes, vascular structures, and microglia/macrophage inflammatory responses are important components of the histopathological changes. Because approximately a quarter of all strokes occur in white matter, injured axons and myelin sheaths are commonly observed in pathological specimens . Together, these previously described yet complicated pathological responses contribute to the behavioral consequences of the stroke and are important targets for stroke therapies. This review will focus on the histopathological changes that characterize the cellular responses to cerebral infarction and selective neuronal necrosis. For this discussion, events at the tissue and cellular levels resulting from profound alterations in local cerebral blood flow and cerebral metabolism will be emphasized.

Cerebral Infarction

Focal brain ischemia lasting more than 30–60 min in the majority of cases produces a cerebral infarct. Brain infracts may be a consequence of either embolic or thrombotic processes. Two common sources of embolization to the brain are the heart and internal carotid artery. A thrombotic arterial brain infarct may result from severe atherosclerosis of an artery leading to vascular occlusion and a severe drop in local cerebral blood flow. Common neuropathological characteristics of ischemic infarction, or pannecrosis, include a well-demarcated area of cellular necrosis including neurons, glia, and endothelial cells. This pathology is usually associated with a defined vascular territory of a major cerebral artery or a single vessel. In a fully developed infarct, the gray matter neuron cytoplasm stains intensely with acidophilic dyes (eosinophilic or red neurons) or fails to stain giving the appearance of ghost neurons. In contrast to cytoplasmic changes, the cell nucleus appears dense and pyknotic. The surrounding neuropil adopts a spongy appearance, whereas other cells types such as astrocytes, oligodendrocytes, and endothelial cells may show evidence of early swelling and pale staining due to edema formation. Acute therapeutic interventions including thrombolytic agents or mechanical removal of thrombotic clots are used to restore blood flow and salvage ischemic tissues.

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