Effect of flunarizine and methylprednisolone on functional recovery after experimental spinal injury.
The effect of flunarizine and methylprednisolone on the recovery of somatosensory evoked potentials (SEPs) was evaluated in an experimental model of spinal cord impact injury in anesthetized cats. In addition, the effect of flunarizine on posttraumatic spinal cord blood flow (SCBF) (using the hydrogen clearance technique) and interstitial calcium and potassium activity (ion-selective electrodes) was investigated. After the injury (600 g.cm), SEPs disappeared, followed by a spontaneous recovery to 17% of the preinjury amplitude at the end of the 4 h observation period. Flunarizine treatment (0.1 mg/kg IV, given 5 and 120 min after injury) resulted in a significantly improved recovery of SEPs, reaching 52% of the preinjury amplitude. Methylprednisolone treatment (30 mg/kg IV, given 5 min after injury) resulted in a 30% recovery level, significantly better than in untreated animals but significantly inferior to flunarizine treatment. Combination of both treatments resulted in a 62% recovery level, significantly better than after methylprednisolone treatment alone. Flunarizine treatment had no significant effect on the postinjury evolution of SCBF and interstitial potassium activity; it did, however, significantly accelerate the recovery of interstitial calcium activity, which sharply decreased immediately after injury. It is concluded that intravenous administration of the calcium entry blocker flunarizine improves the functional recovery of the spinal cord in the acute phase after experimental spinal impact injury. The observed improvement is not achieved by an effect on local blood flow but is possibly related to an inhibitory effect of the drug on cellular calcium entry.
De Ley
G
G
Laboratorium voor Normale en Pathologische Fysiologie, Universiteit Gent, Belgium.
Leybaert
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D005260:Female; D005444:Flunarizine / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D005444:Flunarizine; D011188:Potassium; D002118:Calcium; D008775:Methylprednisolone