NEUROTROPHIC FACTORS IN CENTRAL-NERVOUS-SYSTEM TRAUMA

Although regeneration of injured neurons does not occur after trauma i n the central nervous system (CNS), there is often significant recover y of functional capacity with time. Little is currently known about th e molecular basis for such recovery, but the increased trophic activit y in injured CNS tissue and the known properties of neurotrophic facto rs in neuronal growth and maintenance suggest that these polypeptides are probably involved in recovery of function. Members of the neurotro phin family, including nerve growth factor (NGF), brain-derived neurot rophic factors (BDNF), and neurotrophin 3 (NT-3), are capable of suppo rting survival of injured CNS neurons both in vitro and in vivo. They also stimulate neurite outgrowth, needed for reorganization of the inj ured CNS, and the expression of key enzymes for neurotransmitter synth esis that may need to be upregulated to compensate for reduced innerva tion. The effects of the neurotrophins are mediated through specific h igh affinity trk receptors (trk A, B, C) as well as a common low affin ity receptor designated p75(NGFR). Another class of neurotrophic polyp eptides also provides candidate recovery-promoting molecules, the hepa rin-binding growth factors' acidic and basic fibroblast growth factor (aFGF, bFGF). FGFs not only sustain survival of injured neurons but al so stimulate revascularization and certain glial responses to injury. Both the neurotrophins and the FGFs, as well as their respective recep tors, have been shown to be upregulated after experimental CNS injury. Further, administration of neurotrophins or FGF has been shown to red uce the effects of experimental injury induced by axotomy, excitotoxin s, and certain other neurotoxins. The cellular basis for the potential therapeutic use of neurotrophic molecules is discussed as well as new strategies to increase neurotrophic activity after CNS trauma based o n the recently obtained information on pharmacological and molecular c ontrol of the expression of these genes.