A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury.
Previously, we have shown that topical application of brain-derived neurotrophic factor (BDNF) or insulin-like growth factor 1 (IGF-1) given within 5 to 30 min after a focal trauma to the rat spinal cord attenuates spinal cord injury (SCI)-induced breakdown of the blood-spinal cord barrier (BSCB), edema formation, motor dysfunction, and cell injury. This investigation was undertaken to find out whether a combination of select neurotrophins (BDNF, glial cell line-derived neurotrophic factor [GDNF], neurotrophin 3 [NT-3], or nerve growth factor [NGF]) will further enhance the neuroprotective efficacy of growth factors in SCI. The neurotrophins (0.1-1 microg/10 microL in phosphate-buffered saline) were applied 30, 60, or 90 min after injury topically over the traumatized spinal cord either alone or in combination. The SCI was performed by making a unilateral incision into the right dorsal horn of the T10-T11 segment under Equithesin anesthesia. The rats were allowed to survive 5 h after trauma. Topical application of BDNF, GDNF, or NGF 30 min after SCI in high concentration (0.5 microg and 1 microg) significantly improved the motor functions and reduced the BSCB breakdown, edema formation, and cell injury seen at 5 h. These beneficial effects of neurotropins were absent when administered separately either 60 or 90 min after SCI. However, a combination of BDNF and GDNF (but not with NT-3 or NGF) given either 60 or 90 min after SCI significantly reduced the motor dysfunction and spinal cord pathology at 5 h. These novel observations suggest that a select group of neurotrophins in combination have potential therapeutic value for the treatment of SCI in clinical situations.
Sharma
Hari Shanker
HS
Department of Surgical Sciences, University Hospital, Uppsala University, SE-75421 Uppsala, Sweden. sharma@surgsci.uu.se
D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents