Affiliations: Department of Neurosugery, School of Medicine,
University of Pennsylvania, Philadelphia PA 19104, USA | Veterans Administration Medical Center Philadelphia,
PA 19104, USA | Biochemical and Experimental Division, Second
Department of Surgery, University of Cologne, Cologne, 51109, Germany
Note: [] Corresponding author: Tracy K. Mcintosh (Ph.D), Department of
Neurosurgery, University of Pennsylvania School of Medicine, 105 Hayden Hall,
3320 Smith Walk, Philadelphia, PA 19104-6316, USA. Tel.: +1 215 573 3156; Fax
+1 215 573 3808; E-mail: mcintosh@seas.upenn
Abstract: Purpose: 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. Conclusion:
These data suggest that daily post-injury treatment with CsA improves certain
aspects of motor and sensorimotor function following experimental TBI.
