Effects of chronic, post-injury Cyclosporin A administration on motor and sensorimotor function following severe, experimental traumatic brain injury.
OBJECTIVE
Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI.


METHODS
Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test.


RESULTS
Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration.


CONCLUSIONS
These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI.
Riess
P
P
Department of Neurosurgery, School of Medicine, University of Pennsylvania, 3320 Smith Walk, Philadelphia PA 19104, USA.
Bareyre
F M
FM
Saatman
K E
KE
Cheney
J A
JA
Lifshitz
J
J
Raghupathi
R
R
Grady
M S
MS
Neugebauer
E
E
McIntosh
T K
TK
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality; D003071:Cognition; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine