AXONAL REGENERATION AND LIMITED FUNCTIONAL RECOVERY FOLLOWING HIPPOCAMPAL DEAFFERENTATION

Although central neurons do not naturally recover following injury, da maged adult septal neurons can regenerate when nerve growth factor (NG F) is provided along with a suitable cellular substrate. This study in vestigates the outgrowth of axotomized septal neurons grafted with pri mary fibroblasts genetically modified to produce NGF. Confocal microsc ope images of double staining for neuritic markers (neurofilament or l ow-affinity NGF receptor) and the astrocytic marker glial fibrillary a cidic protein (GFAP) demonstrated that regenerating neurites crossed d ense buildups of astrocytic processes at the edges of NGF-producing gr afts and were in apposition with astrocytic processes within NGF-produ cing grafts. Immunoreactivity for acetylcholinesterase and low-(p75) a nd high-affinity (TrkA) NGF receptors was dense in NGF-producing graft s but absent in control grafts. NGF-grafted rats exhibited significant ly increased hippocampal density of p75-immunoreactive fibers and sign ificantly decreased ectopic hippocampal sympathetic ingrowth as compar ed to control-grafted rats. Rats with unilateral fimbria-fornix lesion s and NGF-producing grafts exhibited ameliorated performance on a simp le memory task. These findings demonstrate that implantation of NGF-pr oducing grafts to the lesion cavity allows axotomized septal cholinerg ic neurons to reinnervate the hippocampus, and that rats receiving the se grafts show a partial recovery of function. (C) 1995 Wiley-Liss, In c.