Induction of a neurite-promoting factor in rat brain following injury or deafferentation.
Ablation of the entorhinal/occipital cortex in young adult rats caused a several-fold increase in the neurite-promoting activity in extracts of the tissue surrounding the wound and in areas that had been deafferented by the lesion. The time course of induction closely paralleled reactive axon sprouting in the deafferented hippocampus, with maximal levels of neurite-promoting activity reached between 9 and 15 days post-lesion. Aged animals, in which reactive sprouting is deficient, showed no increase in activity by 12 days after deafferentation of the hippocampus. The neurite-promoting activity of brain extracts was non-diffusible, heat-labile, and sensitive to proteolysis. All of the activity bound to diethylaminoethyl (cellulose) and was eluted at 200 mM NaCl. The apparent molecular weight (by gel filtration) of the activity in extracts of uninjured brain was 9-17 kilodaltons, whereas the extracts of injured brain also had peaks or shoulders at 30, 70 and greater than or equal to 200 kilodaltons. These data suggest that the brain neurite-promoting activity resides in one or more proteins. Both the injury-induced and basal activities were different from laminin, nerve growth factor, and polyornithine-bindable neurite-promoting factors. The injury-induced activity was sensitive to repeated freezing and thawing, but this inactivation was reversed by thiol reagents such as glutathione, thioglycerol, and mercaptoethanol. We report a neurite-promoting factor that is induced following brain injury or denervation, and may also be important for reactive axon sprouting after brain injury. The induction of this factor is abnormal in aged animals, as is the reactive sprouting response. The properties of the injury-induced activity distinguish it from the basal activity (found in uninjured brain) and from other characterized neurite-promoting factors.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003714:Denervation; D007839:Functional Laterality / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000302:isolation & purification; D009416:Nerve Regeneration / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009414:Nerve Growth Factors