Effect of 4-aminopyridine in acute spinal cord injury.
BACKGROUND
The demyelination process has been proven to be an important factor contributing to long-term sensory and motor impairments after spinal cord injury (SCI). The loss of myelin promotes exposure of K+ channels in internodal region of the damaged myelinated axons leading to K+ efflux into the neurons with subsequent blockage of action potentials. The potassium channel blocker 4-aminopyridine (4-AP) has been effective in restoring some sensory and motor impairment in incomplete SCI patients. The effect of this compound given immediately after an acute injury is not known. The objective of this study was to determine if blockage of K+ ions efflux immediately after an acute SCI would improve neuronal conduction in this model of injury.


METHODS
Cortical somatosensory evoked potentials (SSEPs) were recorded before and after a weight-induced compression injury of 120 grams, and were monitored up to 5 hours postinjury. A randomized treatment was initiated with administration of either vehicle or 4-AP. All 4-AP treatments were given as intravenous bolus injections of 1.0, 0.5, and 0.3 mg/kg at 1, 2, and 3 hours after the trauma.


RESULTS
The SSEPs were abolished immediately after the injury in all control and treated animals. Both groups showed spontaneous recovery of the SSEPs at the rate of 44.5% for the 4-AP treated and nontreated groups at the second hour postinjury. This recovery rate remained the same for both groups at the end of the experiments.


CONCLUSIONS
Based on the recovery of the SSEPs, our data indicate that early administration of 4-AP lacks any beneficial effect on axonal function during acute stage of spinal cord injury.
Haghighi
S S
SS
Division of Neurosurgery, University of Missouri-Columbia 65212, USA.
Pugh
S L
SL
Perez-Espejo
M A
MA
Oro
J J
JJ
D015761:4-Aminopyridine / Q000494:pharmacology* / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*
D015761:4-Aminopyridine