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Neuronal transplants used to repair ischemic lesions in the rat central nervous system : histological, immunohistochemical and electrophysiological characterization of development and function

University of British Columbia

Cerebral ischemia can be caused by many diverse conditions such as cardiac arrest and severe hypotension and is often the cause of secondary brain damage following head injury or infantile birth trauma. The inadequate cerebral blood flow can result in the permanent loss of essential brain circuitries and neurological deficits. Since methods are not currently available for the prevention of neuronal loss following cerebral ischemia, experiments were undertaken to investigate whether transplanted neurons had the potential to afford some measure of repair. In the present study a model was developed whereby the hippocampal CA1 region of the rat brain could be lesioned by transient forebrain ischemia and subsequently repopulated with suspensions of fetal hippocampal tissue. Histological, immunohistochemical and electrophysiological techniques were used to examine the functional capabilities of the transplanted neurons by assessing their ability to survive when transplanted into the degenerating brain region, to develop intrinsic properties characteristic of the cells they had replaced and, to integrate into the host tissue by reestablishing some of the normal synaptic circuitries. The ability of the transplanted neurons to remain viable when placed into a degenerating environment was confirmed by the histological demonstration of ³H-thymidine labelled neurons in the lesioned region and the demonstration that the transplanted neurons were electrically active. Histological and immunohistochemical techniques showed that the transplanted neurons developed cytological features that were indistinguishable from their normal counterparts, showed a remarkable degree of organization, and expressed some of the same neuron specific proteins; specifically calbindin-D[sub 28K] and parvalbumin. Acetylcholinesterase histochemistry and retrograde axonal transport of Fluoro-Gold demonstrated that some afferent and efferent fibre projections could be reinstated. Electrophysiological recordings confirmed the functional integration of the transplanted neurons in the host tissue. Intracellular and extracellular recordings showed that the restored neural connections formed functional synaptic contacts and that the transplanted neurons developed biophysical properties that were similar to the cells they had replaced. The data from the present study have demonstrated that transplanted neurons can develop many of the anatomical and electrophysiological properties that are characteristic of the adult cells they have replaced and consequently, have the potential to mediate normal functional capabilities.

Text

2010-10-18

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http://hdl.handle.net/2429/29247

Neuroscience

University of British Columbia

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