PMID- 18077567 OWN - NLM STAT- MEDLINE DCOM- 20080421 LR - 20071213 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 1122 DP - 2007 Dec TI - A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury. PG - 95-111 AB - 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. FAU - Sharma, Hari Shanker AU - Sharma HS AD - Department of Surgical Sciences, University Hospital, Uppsala University, SE-75421 Uppsala, Sweden. sharma@surgsci.uu.se LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) SB - IM MH - Animals MH - Behavior, Animal MH - Blood-Brain Barrier/drug effects/physiopathology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Drug Therapy, Combination MH - Hindlimb/drug effects/physiopathology MH - Male MH - Motor Activity/drug effects MH - Nerve Growth Factors/*therapeutic use MH - Neuroprotective Agents/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/*drug effects/physiology MH - Spinal Cord Injuries/*drug therapy/pathology/physiopathology MH - Time Factors EDAT- 2007/12/14 09:00 MHDA- 2008/04/22 09:00 CRDT- 2007/12/14 09:00 PHST- 2007/12/14 09:00 [pubmed] PHST- 2008/04/22 09:00 [medline] PHST- 2007/12/14 09:00 [entrez] AID - 1122/1/95 [pii] AID - 10.1196/annals.1403.007 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2007 Dec;1122:95-111. doi: 10.1196/annals.1403.007.