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KMID : 0350519960490020757
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Journal of Catholic Medical College
1996 Volume.49 No. 2 p.757 ~ p.777
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Effects of Chlorpromazine and Nimodipine on Nerve Regeneration in Rats with Sciatic Nerve Transection Injury
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Abstract
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Chlorpromazine (CPZ) has been hypothesized to enhance the functional recovery of the transected peripheral nerve injury through the arrest of wallerian degeneration but no objective evidences to confirm this hypothesis has been established yet.
Use
of
nimodipine (NDP) in a ischemic lesion of CAS has resulted in better functional outcome and decreased mortality but its effect on peripheral nerve injury has yet to be probed.
The aims of this study were to evaluate the effects of CPZ and NDP on nerve regeneration in rats with peripheral nerve transection injury by electrophysiologic and histologic methods, and to determine whether early functional recovery by CPZ was
resulted from its capability of the arrest of wallerian degeneration.
One hundred and sixty Wistar adult female rats were subjected to scissors transection of the right sciatic nerve under intramuscular ketamine HC1 (Ketalar, Yuhan, Korea) anesthesia and were randomized into four groups, one control and three
experimental
groups: 1mM CPZ (Sepamin, Sam Sung, Korea) and 20 mg/100㎖ NDP (Nimotop, Bayer Korea Ltd., Korea) solutions were instilled for 10 mmutes to the cut nerve ends immediately after injury in the first and second experimental group, respectively and
combination of the two solutions was applied to the third (CPZ+NDP). The control group received no treatment at. All animals underwent epineurial repair. Latency, amplitude and area of compound muscle action potential (CMAP) from right
gastrosoleus
muscles were measured and quantitative histology was performed to measure total area (TA) of axon, total number f axons 0.5-3.0㎛ in diameter (TN<3.0㎛) and thickness of myelin sheath (TMS) of myelinated nerve fibers per 13,000㎛*, using Image
Analysis
System (VIDAS 2.0, Kontron, Germany). In a preliminary study , normal CMAP values were measured from another forty animals and six of them were sacrificed to obtain normal histology.
@ES The results were as follows:
@EN 1. In normal group, latency of CMAP was 0.93±0.12 msec (mean±S.D.), amplitude, 49.25±10.04mV and area, 32.61±7.72 msec * mV. In histological examination, TA was 4192.94±5999.84㎛*, TN<3.0㎛ was 18.50±3.54 and TMS was 2.07±0.53㎛. The
distribution of myelinated fibers according to the diameter shwed bimodal appearance with the first park at 3.0-4.0㎛ and the second one at 7.0-8.0㎛.
2. On 2nd day following injury, all experimental groups showed markedly delayed latency and decreased amplitude and area. When compared to the control, CPZ group showed significantly larger amplitude and area (P<0.05). CPZ±NDP group also showed
larger
area and shorter latency (P<0.05), but no remarkable changes were noted in NDP group.
3. No CMAPs were obtained in all groups at 1st and 2nd week and the histological examination revealed that wallerian degeneration was most prominent at 2nd week. CMAPs reappeared at 4th week and all three treated groups showed significantly
larger
amplitude and area (P<0.01) than those of control at 12th week following injury.
4. After 8 weeks of injury, the distribution of myelinated fibers showed unimodal appearances with the peak less than 3.0㎛ in diameter in all four experimental groups. At 8th week, TA, TN<3.0㎛ and TMS of all three treated groups were
significantly
larger than those of control (P<0.01). CPZ and CPZ+NDP groups still showed significant increase in them at 12th week (P<0.05).
5. After 8 weeks following injury, latency showed negative correlation with TMS, whereas amplitude did positive correlation with TN<3.0㎛ in all four experimental groups.
These results of present study suggest that CPZ and NDP have promoting effects on nerve regeneration in peripheral nerve transection injury and that the effect of CPZ be resulted from its capability of alleviating the degree of wallerian
degeneration.
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