Development of neocortical transplants in the cerebellum of adult rats

Jane Brasko, Purdue University

Abstract

The aim of this investigation was to study the time course and pattern of neural transplant development, along with the sequence of afferent ingrowth to the transplants from the host parenchyma. Seventeen day embryonic neocortical tissue was transplanted into the right cerebellar hemisphere of adult host rats. After survival times of 1 day to 6 months, the host brains were processed for various histological stains to permit visualization of the developmental events. The results of this study demonstrate that the technique of neural transplantation causes damage to the transplant and the host parenchyma, initiating histopathological changes that accompany the phenomena of transplant development and integration. C-V and H&E preparations indicated that these changes began within 24 hours after surgery within the neural transplants, which thereafter exhibited phases of (a) regression, as those transplant cells traumatized by the surgical manipulation became necrotic and died, (b) recovery, as the necrosis and blood were cleared and the viable portions of the transplant became attached to the host parenchyma, (c) resumed volumetric growth, attributable to the proliferation of surviving neuroepithelial cells and the differentiation and dispersion of neuroblasts, which promoted the integration of the transplant with the cerebellum. Within the host, evidence of damage to cerebellar neurons, glia, and axons from the surgical procedure was observed in regions surrounding the transplant in Fink-Heimer preparations beginning on day 1. In addition, terminal degeneration within the deep cerebellar nuclei, noted on day 5, provided further evidence of trauma to the intrinsic cerebellar circuitry as a result of the surgical manipulation. A third locus of axonal degeneration, in folia not immediately apposed to the transplant, was noted between days 9 and 30. The persistence of degeneration within the host suggested the influence of a secondary source of trauma, one introduced by the volumetric growth of the transplants. This process served to compress host fibers, sever them from their perikarya, and/or gradually deprive them of their normal sites of termination. Yet, it also stimulated some host axons into a new growth phase, demonstrated by growth cones found near interface regions. This "plastic" response on the part of the host, though weak, culminated in the development of afferent ingrowth to the transplants, observed initially on day 15 and persisting after 6 months.

Degree

Ph.D.

Advisors

Vanable, Purdue University.

Subject Area

Neurology|Surgery

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