|
KMID : 0350519930460041517
|
|
Journal of Catholic Medical College
1993 Volume.46 No. 4 p.1517 ~ p.1529
|
|
|
Effects of 21-Aminosteroid U-74389F on Experimental Spinal Cord Injury in Rats
|
|
|
|
|
Abstract
|
|
|
Numerous experimental studies of spinal cord injury have reported that a variable degree of immediate mechanical damage occurs in spinal blood vessels and axons in proportion to the magnitude of the injury force, and that a considerable amount of
posttraumatic tissue degeneration occurs due to secondary pathophysiological process. These studies suggest that oxygen free radical-induced lipid peroxidation plays a key role in the progressive secondary neuronal degeneration following blunt
injury. A
primary action of methylprednisolone sodium succinate(MP) is to inhibit lipid peroxidation and to preserve the structural and functional integrity of biological membranes. But treatment of human CNS injuries with MP has been complicated by its
biphasic
dose-response characteristics and its glucocorticoid receptor-mediated activity. Recently, a novel series of 21-aminosteroid have been developed that lack glucocorticoid or mineralocorticoid activity and are extremely potent inhibitors of lipid
peroxidation.
This study was conducted to determine the effects of 21-aminosteroid U-74389F) in comparison with the effects of MP on motor evoked potentials(MEP), recovery of motor function, and pathological changes in rats which were injured at the high
thoracic
cord.
Fifty Sprague-Dawley rats were divided into five groups : one control group(distilled water-treated group) and four treatment groups(MP 10 mg/kg-treated group, MP 30 mg/kg-treated group, U-74389F 10 mg/kg-treated group, and U-74389F 30
mg/kg-treated
group). There were 10 rats in each group. The animals were underwent a craniectomy in the right frontal area for electrical stimulation on the motor cortex and laminectomies in the high thoracic area for cord injury and in the low thoracic area
for
recording MEP. The spinal cord was inflicted by weight-drop method, and there was a complete paraplegia in all rats within 30 minutes after injury. Distilled water 1 ml, MP 10 mg/kg and 30 mg/kg or U-74389F 10 mg/kg were given intravenously at 30
minutes after injury and two hours after first administration.
Recording of MEP and evaluation of motor function were observed at preinjury and 1, 2, and 4 weeks after injury. After 4 weeks of postinjury observation, the animals were examined histologically.
@ES The results were as follows :
@EN 1. The amplitude and latency of postinjury MPE improved significantly in treatment groups compared with those in control group(P<0.05), especially in U-74389F-treated groups(P<0.01).
2. Compared with control group, there was asignificant recovery of motor function in treatment groups(P<0.01). U-74389F-treated groups showed more marked recovery than MP-treated groups(P<0.05).
3. There was a loss of gray matter and white matter, central cavitation, and vacuolization of white matter in control group. Bur these findings were observed mildly in treatment groups.
4. There was no significant difference in the effects of tratment between U-74389F 10 mg/kg-treated group and U-74389F 30 ml/kg-treated group.
These results suggest that U-74389F is more potent and effective in the functional recovery on acute spinal cord injury than MP.
|
|
|
KEYWORD
|
|
|
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|