Experimental spinal cord injury: effect of a calcium channel antagonist (nicardipine).
Variable benefits from the use of a number of calcium channel blockers in experimental spinal cord injury have been reported. To our knowledge, these agents have not been previously tested in a contusion model of cord injury in which neurological outcome is one of the critical outcome parameters. We carried out preliminary behavioral toxicity testing to identify a range of low, moderate, and high dosage levels of the calcium channel blocker, nicardipine; these dosage levels were to be used subsequently in formal testing. After laminectomy at T8 under general anesthesia in rats, a 10-g weight was dropped from a height of 5 cm onto the spinal cord. The animals were randomly assigned to four groups: control or one of three nicardipine treatment groups: (a) low dose (1 mg/kg, followed by a continuous 23-hour infusion of 0.5 mg/kg/hour), (b) moderate dose (10 mg/kg, followed by 5 mg/kg/hour for 23 hours, and (c) high dose (20 mg/kg, followed by 23-hour infusion of 10 mg/kg/hour). Functional recovery was tested over the course of 4 weeks with the Tarlov scale, the inclined plane, and a sensory-motor battery of tests (combined behavioral score). After sacrifice at 4 weeks, morphometric analysis of residual gray and white matter was performed at the epicenter of the spinal cord injury. Statistical analysis of the behavioral data failed to reveal any differences among the control or nicardipine treatment groups. The morphometric analysis similarly failed to show differences between the control and any treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)
Black
P
P
Department of Neurosurgery, Hahnemann University School of Medicine, Philadelphia, Pennsylvania.
Markowitz
R S
RS
Finkelstein
S D
SD
McMonagle-Strucko
K
K
Gillespie
J A
JA
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005260:Female; D006614:Hindlimb / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D009529:Nicardipine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D002121:Calcium Channel Blockers; D009529:Nicardipine