Combined treatment with neurotrophin-3 and LSD facilitates behavioral recovery from double-hemisection spinal injury in neonatal rats.
We explored functional recovery in two spinal cord injury models following a novel combination treatment (NT-3 + LSD). One group of rats received a staggered double hemisection (DH) at postnatal day 2 (P2) of the left hemicord at T11 and the right hemicord at T12. Another group received complete transection (CT) at T11 on P2. A third group was sham operated. Each of these groups was also treated with the drug combination. Drugs were administered intrathecally above the lesion during surgery, and again s.c. at P4, P6, P8, and P10. Intracellular recording in an in vitro spinal cord preparation at P10-P12 in DH rats revealed weak polysynaptic connections to lumbar motoneurons through the injury region, but only in those receiving NT-3 + LSD; NT-3 or LSD alone had no effect. In behavioral experiments, the frequency of rearing in an open field and hindlimb kicks during swimming was assessed every 3-4 days from P9 to P58. Both CT and DH injury severely impaired rearing and hindlimb kicking during swimming. DH rats treated with NT-3 + LSD showed significantly more kicks during swimming than untreated DH or CT rats and treated CT rats beginning as early as P9 and lasting through the duration of testing. Rearing behavior was also improved by treatment but beginning only in the 3rd postnatal week, the time at which it normally develops. Rearing frequency reached sham control levels by P40. Our results suggest this combination treatment may be a promising new strategy for facilitating recovery from moderate spinal cord injury.
Arvanian
Victor L
VL
Department of Neurobiology & Behavior, Stony Brook University, Stony Brook, New York 11794-5230, USA.
Manuzon
Honeyleen
H
Davenport
Michael
M
Bushell
Georgia
G
Mendell
Lorne M
LM
Robinson
John K
JK
D000818:Animals; D000831:Animals, Newborn; D003714:Denervation; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007278:Injections, Spinal; D008159:Lumbar Vertebrae; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D020933:Neurotrophin 3 / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D004338:Drug Combinations; D020933:Neurotrophin 3; D017366:Serotonin Receptor Agonists; D008238:Lysergic Acid Diethylamide