Focal lesions in the rat central nervous system induced by endothelin-1.
ABSTRACT Axon injury following cerebral ischemia has received little scientific attention compared to the abundance of information dealing with the pathophysiology of grey matter ischemia. There are differences in the initial response of grey and white matter to ischemia in vitro. In this study we investigate whether the vasoactive peptide, endothelin-1, can generate a focal ischemic lesion in the white matter and compare the findings with endothelin-1-induced lesions in the grey matter. Using a minimally invasive technique to microinject endothelin-1 into selected brain regions, we observed an acute reduction in local MRI perfusion in the injected hemisphere after 1 hour. Twenty-four hours after microinjection of 10 pmoles of endothelin-1, we observed a loss of neurons in the grey matter. At 72 hours, neutrophils were absent and a macrophage/microglia response and astrocyte gliosis were detected. No breakdown in the blood-brain barrier was detected. After injection of 10 pmoles endothelin-1 into the cortical white matter, we observed prolific amyloid precursor protein-positive immunostaining (indicative of axonal disruption) and an increase in tau-1 immunostaining in oligodendrocytes at 6 hours. Similar to the grey matter lesions, no neutrophils were present, a macrophage/microglia response did not occur until 72 hours and there was no disruption in the blood-brain barrier. Focal injections of endothelin-1 into specific areas of the rat CNS represent a model to investigate therapeutic approaches to white matter ischemia.
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ABSTRACT: Stroke has been identified as the second leading cause of death worldwide. Stroke is a focal neurologic deficit caused by a change in cerebral circulation. The use of animal models in recent years has improved our understanding of the physiopathology of this disease. Rats and mice are the most commonly used stroke models, but the demand for larger models, such as rabbits and even nonhuman primates, is increasing so as to better understand the disease and its treatment. Although the basic mechanisms of stroke are nearly identical among mammals, we here discuss the differences between the human encephalon and various animals. In addition, we compare common surgical techniques used to induce animal models of stroke. A more complete anatomic knowledge of the cerebral vessels of various model species is needed to develop more reliable models for objective results that improve knowledge of the pathology of stroke in both human and veterinary medicine.Comparative medicine 01/2011; 61(4):305-13. · 1.05 Impact Factor
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ABSTRACT: White matter damage is a clinically important part of stroke. However, compared to the mechanisms of neuronal injury in gray matter, white matter pathophysiology remains relatively understudied and poorly understood. This mini-review aims at summarizing current knowledge on experimental systems for analyzing the role of white matter injury relevant to stroke. In vitro platforms comprise primary cultures of both mature oligodendrocytes (OLGs) as well as oligodendrocyte precursor cells (OPCs). Tissue platforms involve preparations of optic nerve systems. Whole-animal platforms comprise in vivo models of cerebral ischemia that attempt to target white matter brain areas. While there is no single perfect model system, the collection of these experimental approaches have recently allowed a better understanding of the molecular and cellular pathways underlying OLG/OPC damage and demyelination. A systematic utilization of these cell, tissue and whole-animal platforms may eventually lead us to discover new targets for treating white matter injury in stroke and other CNS disorders.Experimental and Translational Stroke Medicine 01/2009; 1:6.