An L-type calcium channel blocker, nimodipine influences trauma induced spinal cord conduction and axonal injury in the rat.
The influence of the potent L-type Ca[2+] channel antagonist Nimodipine on spinal cord evoked potentials (SCEP) and axonal injury following trauma to the spinal cord was examined in a rat model. Spinal cord injury (SCI) was produced by an incision into the right dorsal horn of the T10-11 segments under urethane anaesthesia (1.5 g/kg, i.p.). SCEPs were recorded by epidural electrodes placed over the T9 (rostral) and T12 (caudal) segments after stimulation of the right tibial and sural nerves. SCI induced a pronounced decrease of the SCEP negative amplitude in the rostral (T9) recordings immediately after trauma. Axonal injury seen as degradation of myelin basic protein (MBP) immunostaining and myelin vesiculation at the ultrastructural level was most pronounced at 5 h. Continuous administration of Nimodipine (2 microg/kg/min, i.v.) from 30 min prior to injury until sacrifice markedly attenuated the changes in SCEP amplitude and latency. Axonal damage, loss of MBP, and myelin vesiculation were much less evident in the nimodipine treated traumatised rats. These observations suggest that Ca[2+] channels play an important role in the trauma induced alterations in SCEP and axonal injury, and indicate a therapeutic value of Ca[2+] blockers in SCI.
Winkler
T
T
Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden.
Sharma
H S
HS
Stålberg
E
E
Badgaiyan
R D
RD
Gordh
T
T
Westman
J
J
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020833:Diffuse Axonal Injury / Q000209:etiology* / Q000473:pathology; D004487:Edema / Q000517:prevention & control; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000517:prevention & control; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009553:Nimodipine