Effect of Flunarizine and Methylprednisolone on Functional Recovery After Experimental Spinal Injury*

Abstract

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.

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone

“…This regimen was reported as the optimal dose in cats compared with 15 and 60 mg/kg [70]. The bolus dose of 30 mg/kg plus follow-up administration was also used in experimental SCI of rats [71-73]. In a dose–response study using a ventral compression injury model, the best results were yielded when MPSS was administered in the rats with a bolus dose of 30 mg/kg at 30 min post-SCI followed by a second injection of 15 mg/kg (a total of 45 mg/kg) or with a 60 mg/kg bolus at 30 min post-SCI [74].…”

Methylprednisolone Causes Minimal Improvement after Spinal Cord Injury in Rats, Contrasting with Benefits of an Anti-Integrin Treatment

“…However, the effects of MP have been assessed mostly on motor function (Braughler et al, 1987;Holtz et al, 1990;Means et al, 1981;Rabchevsky et al, 2002), and effects on other important consequences of SCI such as neuropathic pain or autonomic dysfunction have not been emphasized. Some investigators propose to use MP as one of a combination of treatments, as an initial neuroprotective therapy coupled with pro-regenerative or other treatments (Baffour et al, 1995;De Ley et al, 1993;Nash et al, 2002;Takami et al, 2002).…”

Effects of Methylprednisolone on the Neural Conduction of the Motor Evoked Potentials in Spinal Cord Injured Rats

“…Two studies (24, 25) have reported significant recovery of the somatosensory evoked potentials (SSEPs) by MP, while others have shown no improvement (7-9). Koyanagi and Tator (9) observed that MP did not improve the SSEP, reflecting mainly the dorsal column pathways.…”