A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury
2007 (English)In: Neuroprotective agents: Eighth international neuroprotection society meeting / [ed] Slikker W; Andrew RJ; Trembly B, 2007, Vol. 1122, 95-111 p.Conference paper (Refereed)
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.
Place, publisher, year, edition, pages
2007. Vol. 1122, 95-111 p.
, Annals of the New York academy of sciences, ISSN 0077-8923 ; 1122
Animals, Behavior, Animal, Blood-Brain Barrier/drug effects/physiopathology, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Therapy, Combination, Hindlimb/drug effects/physiopathology, Male, Motor Activity/drug effects, Nerve Growth Factors/*therapeutic use, Neuroprotective Agents/*therapeutic use, Rats, Rats, Sprague-Dawley, Recovery of Function/*drug effects/physiology, Spinal Cord Injuries/*drug therapy/pathology/physiopathology, Time Factors
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-17159DOI: 10.1196/annals.1403.007ISI: 000252267100007PubMedID: 18077567OAI: oai:DiVA.org:uu-17159DiVA: diva2:44930
8th International Conference on Neuroprotective Agents Mackinac Isl, MI, SEP 18-20, 2006