BDNF PREVENTS AND REVERSES ADULT-RAT MOTOR-NEURON DEGENERATION AND INDUCES AXONAL OUTGROWTH

To assess the therapeutic potential of brain-derived neurotrophic fact or (BDNF) in clinics, we extensively investigated the effects of BDNF on adult motor neurons in a rat spinal root avulsion model. Intratheca l administration of BDNF immediately after the spinal root avulsion gr eatly protected against the motor neuron cell death. BDNF also showed a protective effect on the atrophy of soma and on the reduction of tra nsmitter-related enzymes such as choline acetyl transferase and acetyl choline esterase. Very interestingly, BDNF induced axonal outgrowth of severely damaged motor neurons at the avulsion site. The BDNF adminis tration following 2-week treatment with phosphate-buffered saline afte r avulsion prevented further augmentation of cell death and reversed c holinergic transmitter-related enzyme deficiency. BDNF was demonstrate d to possess a wide variety of biological effects on survival, soma si ze, cholinergic enzymes, and axonal outgrowth of adult motor neurons. These results provide a rationale for BDNF treatment in motor neuron d iseases such as spinal cord injury and amyotrophic lateral sclerosis. (C) 1997 Academic Press.