Bridging grafts and transient nerve growth factor infusions promote long-term central nervous system neuronal rescue and partial functional recovery.
Grafts of favorable axonal growth substrates were combined with transient nerve growth factor (NGF) infusions to promote morphological and functional recovery in the adult rat brain after lesions of the septohippocampal projection. Long-term septal cholinergic neuronal rescue and partial hippocampal reinnervation were achieved, resulting in partial functional recovery on a simple task assessing habituation but not on a more complex task assessing spatial reference memory. Control animals that received transient NGF infusions without axonal-growth-promoting grafts lacked behavioral recovery but also showed long-term septal neuronal rescue. These findings indicate that (i) partial recovery from central nervous system injury can be induced by both preventing host neuronal loss and promoting host axonal regrowth and (ii) long-term neuronal loss can be prevented with transient NGF infusions.
Tuszynski
M H
MH
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0608, USA.
Gage
F H
FH
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D016380:Brain Tissue Transplantation / Q000473:pathology / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D007263:Infusions, Parenteral; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
D009414:Nerve Growth Factors; D000110:Acetylcholinesterase