BRAIN-DERIVED NEUROTROPHIC FACTOR AND INSULIN-LIKE GROWTH-FACTOR-I ATTENUATE UP-REGULATION OF NITRIC-OXIDE SYNTHASE AND CELL INJURY FOLLOWING TRAUMA TO THE SPINAL-CORD - AN IMMUNOHISTOCHEMICAL STUDY IN THE RAT

The possibility that brain derived neurotrophic factor (BDNF) and insu lin like growth factor-1 (IGF) induced neuroprotection is influenced b y mechanisms involving nitric oxide was examined in a rat model of foc al spinal cord injury. BDNF or IGF-I (0.1 mu g/10 mu l in phosphate bu ffer saline) was applied topically 30 min before injury on the exposed spinal cord followed by repeated doses of growth factors immediately before and 30 min after injury. Thereafter application of BDNF or IGF was carried out at every 1 h interval until sacrifice. Five hours afte r injury, the tissue pieces from the T9 segment were processed for nNO S immunostaining, edema and cell injury. Untreated injured rats showed a profound upregulation of nNOS which was most pronounced in the nerv e cells of the ipsilateral side. A marked increase in the blood-spinal cord barrier (BSCB) permeability to I-125-albumin, water content and cell injury in these perifocal segments was also found. Pretreatment w ith BDNF and IGF significantly reduced the upregulation of nNOS in the spinal cord. This effect of the growth factors was most pronounced in the contralateral side. Rats treated with these neurotrophic factors showed much less signs of BSCB damage, edema and cell injury. These re sults suggest that BDNF and IGF pretreatment is neuroprotective in spi nal cord injury and that these neurotrophic factors have the capacity to down regulate nNOS expression following trauma to the spinal cord. Our data provide new experimental evidences which suggest that BDNF an d IGF may exert their potential neuroprotective effects probably via r egulation of NOS activity.