Selected combination of neurotrophins potentiate neuroprotection and functional recovery following spinal cord injury in the rat.
The possibility that a combination of neurotrophins induces long-lasting neuroprotection of the cord following spinal cord injury (SCI) was examined in a rat model. The SCI was performed by making a unilateral incision into the right dorsal horn of the T10-11 segments and the animals were allowed to survive 5 h after trauma. Different combination of neurotrophins, i.e., BDNF in combination with GDNF, NT-3, or NGF was applied topically over the traumatized spinal cord and motor dysfunction, blood-spinal cord barrier (BSCB) breakdown, edema formation, and cell injury were examined. Topical application of BDNF in combination with GDNF and NGF 30 min (but not 60 or 90 min) at high concentrations (0.5 microg each) after SCI significantly improved motor function and reduced BSCB breakdown, edema formation, and cell injury at 5 h. However, concurrent application of BDNF, IGF-1, and GDNF (but not with NT-3 or NGF) even 60 or 90 min after trauma induced a significant reduction in motor dysfunction and spinal cord pathology. These observations suggest that a combination of neurotrophins may have added therapeutic value in the treatment of SCI, not reported earlier.
Sharma
Hari Shanker
HS
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala, Sweden. Sharma@surgsci.uu.se
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods*; D004487:Edema / Q000188:drug therapy / Q000209:etiology; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; 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*
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents