Effects of Brain derived neurotrophic factor (BDNF) and assessment using MRI on experimentally spinal cord Injury

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We evaluated the effect of brain-derived neurotrophic factor (BDNF) on apoptosis after spinal cord injury. A rat spinal cord injury model was produced by static load, and continuous intrathecal BDNF or vehicle infusion was carried out either immediately or 3 days after the injury. Apoptotic cells were examined by nuclear staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). After injury, typical apoptotic cells were observed. Double staining with TUNEL and specific cell markers revealed that soon after the injury the apoptotic cells at the injury site were neurons and microglia. One week after the injury, apoptotic oligodendrocytes but not apoptotic astrocytes were observed in the white matter rostral and caudal to the injury site, whereas few apoptotic cells were found in the gray matter. The immediate BDNF treatment significantly reduced the number of TUNEL-positive cells in the adjacent rostral site 1 and 2 weeks after the injury, and in the adjacent caudal site 3 days and 1 week after the injury, even though there was no significant difference between BDNF-treated and control rats at the injury site itself. In addition, similar anti-apoptotic effects were observed in these regions 1 week after injury in rats that received BDNF treatment from the third day after injury. These findings suggest that BDNF suppresses delayed apoptosis of oligodendrocytes after spinal cord injury, for which even injections started late are effective. BDNF administration may therefore be useful for the clinical treatment of spinal cord injury through the suppression of secondary events.