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Remodeling of the mechanically injured cerebral cortex of kittens was studied in the presence of a neural xenograft taken from mouse fetuses. Solid neural tissue from the neopallium of a 14-day-old fetus was transferred into a cavity prepared in visual cortical area 18 of 33-day-old kittens. Injections of bromodeoxyuridine (BrdU) were used to monitor postoperative cell proliferation. Two months after transplantation, the presence of graft tissue in the recipient brain was assessed by Thy-1 immunohistochemistry. Antibodies specific for neurons, astrocytes, and oligodendrocytes and hematoxylin staining for endothelial cells were used for the characterization of proliferating (BrdU+) cells. The following were the major observations: 1) Of ten transplanted kittens, four had the cavity completely filled with neural tissue that resembled the intact cerebral cortex in its cytoarchitecture, whereas, in four other kittens, the cavity was partially closed. In two kittens, the cavity remained or became larger, which was also the case with all four sham-operated (lesioned, without graft) animals. 2) A substantial part of the remodeled tissue was of host origin. Only a few donor cells survived and dispersed widely in the host parenchyme. 3) In the remodeled region of transplanted animals, the densities of nerve, glial, and endothelial cells were similar to those in intact animals. 4) Cell proliferation increased after transplantation but only within a limited time, because, 2 months after the operation, the number of mitotic cells in the grafted cerebral cortex did not differ from that in intact controls. Our data suggest that the xenograft evokes repair processes in the kitten visual cortex that lead to structural recovery from a mechanical insult. The regeneration seems to rely on a complex interplay of many different mechanisms, including attenuation of necrosis, cell proliferation, and immigration of host cells into the wounded area. J. Comp. Neurol. 395:91–111, 1998. © 1998 Wiley-Liss, Inc.