COMBINED FETAL NEURAL TRANSPLANTATION AND NERVE GROWTH-FACTOR INFUSION - EFFECTS ON NEUROLOGICAL OUTCOME FOLLOWING FLUID-PERCUSSION BRAIN INJURY IN THE RAT

This study was designed to evaluate the histological and behavioral im pact of fetal neural transplantation with and without neurotrophin inf usion in rats subjected to traumatic brain injury using a clinically r elevant model of lateral fluid-percussion brain injury. Adult male Spr ague-Dawley rats received lateral fluid-percussion brain injury of mod erate severity (2.1-2.3 aim). Twenty-four hours after injury, minced f etal cortical grafts (E16) were stereotactically transplanted into the site of injury cavity formation (in 32 rats). Ten control animals rec eived injections of saline. A third group of 29 animals that received transplants also underwent placement of a miniosmotic pump (immediatel y after transplantation) to continuously infuse nerve growth factor (N GF) directly into the region of graft placement for the duration of th e experiment. A fourth group of eight animals underwent transplantatio n of fetal cortical cells that had been dissociated and placed in susp ension. Animals were evaluated at 72 hours, 1 week, and 2 weeks after injury for cognitive function (using the Morris water maze), posttraum atic motor dysfunction, and transplant survival and morphology (using Nissl and modified Palmgren's silver staining techniques). Robust surv ival of whole-tissue transplants was seen in 65.6% of animals and was not increased in animals receiving NGF infusion. Animals receiving tra nsplants of cell suspension had no surviving grafts. Brain-injured ani mals receiving transplants showed significant cognitive improvements c ompared with controls at the 2-week evaluation. Significantly improved memory scores were seen at all evaluation times in animals receiving both NGF and transplants compared with injured controls and compared w ith animals receiving transplants alone at the 72-hour and 1-week eval uations. Neurological motor function scores were significantly improve d in animals receiving transplants alone and those receiving transplan ts with NGF infusion. Histological evaluation demonstrated differentia tion of grafted cells, decreased glial scarring around transplants whe n compared with control animals, and the presence of neuronal fibers b ridging the interface between graft and host. This study demonstrates that fetal cortical cells transplanted into the injured cortex of the adult rat can improve both posttraumatic cognitive and motor function and interact with the injured host brain.