Autoradiographic [3H]nimodipine distribution after experimental spinal cord injury in rats.
Because of its potential for augmentation of blood flow and protection of neurons after neurological insult, nimodipine has been investigated as a treatment of spinal cord injury (SCI). The results have been inconsistent, possibly because of poor delivery of nimodipine to the injured spinal cord. The following study was designed to determine the delivery of nimodipine to the injured spinal cord. It was also hoped that information about the temporal and spatial pattern of binding of nimodipine after SCI might further elucidate the relationship between calcium channel activation and injury. Fourteen female Wistar rats were divided into three groups: control (n = 3), 30 min post-SCI (n = 6); and 4 h post-SCI (n = 5). The injury was produced by acute clip compression for 1 min at T1. [3H]Nimodipine was administered 5 min after laminectomy in the control group, and at the above-specified times after injury in the SCI groups. The drug was then allowed to equilibrate for 30 min before the animals were killed. The spatial patterns and concentrations of [3H]nimodipine in various segments of the spinal cord were autoradiographically determined. The highest concentrations of [3H]nimodipine were at the injury site after SCI. Also, the mean [3H]nimodipine concentrations in all sites in each animal were higher in the injury groups than in the control group (p < 0.05). This study indicates that delivery of this agent to the injured cord is possible, and provides evidence of widespread Ca2+ channel activation in the first 4 h after injury.
Ross
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IB
Section of Neurosurgery, University of Manitoba, Winnipeg, Canada. iross@mail.sbgn.mb.ca
Koyanagi
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I
Wallace
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MC
Tator
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CH
D000818:Animals; D001345:Autoradiography; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002121:Calcium Channel Blockers / Q000378:metabolism*; D005260:Female; D006400:Hematocrit; D009553:Nimodipine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D014316:Tritium
D002121:Calcium Channel Blockers; D014316:Tritium; D009553:Nimodipine