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KMID : 0378019640070010041
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New Medical Journal
1964 Volume.7 No. 1 p.41 ~ p.63
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Experimental histopathologic study in the brain following administration of chlorpromazine alone and chlorpromazine combining with insulin or electroshock.
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Abstract
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A study on the histopathologic findings in various part of the brain comparing with control groups of normal, insulin and electroshock was made in young dogs of the effect of one shot or prolonged administration of chlorpromazine; given doses ranging from 15 mg to 50 mg per kg b.w. by one shot, and 300 mg to 500 mg for 15 to 25 days on long term group. In the control groups, persisted insulin coma hours were ranging from one half to four, and applied daily electroshock ranging from 5 to 15 times.
Histological sections obtained from various part of the brain were stained & impregnated according to routine staining method of Nissl & H-E stains, for fat, microglia, astrocyte & cell processes.
The findings obtained from the study were summerized as follows;
1. Hardly any alterations were found in the group of one shot.
2. In the group of long term administration of chlorpromazine revealed no evidence of alteration ´in axon, neurofibril & myelin sheath, but following a series of diffuse degenerative changes were encountered with nerve cells; e.g. swelling, chromatolysis, vacuol, edematous change, shadow & necrotic area. Moreover, diffuse productive response of glia cells were noted.
3. All the changes were striking diffuse, in nature, over all the area of the brain, but the cerebral cortex seemed to most susceptible area.
4. Presumably, intensity of the alteration attributed to the period of administration rather than given doses of chlorpromazine; e.g. the dog treated with 300 mg for 15-days found to be more pronounced changes than the dog treated with the same doses for 25-days.
5. Comparing the control group of insulin & electroshock, the author couldn´t found any difference of the change, in nature, from chlorpromazine treated group.
6. Thereafter, discussed on the mechanism of occuring alteration due to chlorpromzine, which had to be related closelly to the mechanism of action of chlorpromazine itself.
Chapter II. Study following administration of chlorpromazine combining with insulin or electroshock.
The author made two categories of study subsequently with the result of Chapter I.
2. In the group of long term administration of chlorpromazine revealed no evidence of alteration ´in axon, neurofibril & myelin sheath, but following a series of diffuse degenerative changes were encountered with nerve cells; e.g. swelling, chromatolysis, vacuol, edematous change, shadow & necrotic area. Moreover, diffuse productive response of glia cells were noted.
3. All the changes were striking diffuse, in nature, over all the area of the brain, but the cerebral cortex seemed to most susceptible area.
4. Presumably, intensity of the alteration attributed to the period of administration rather than given doses of chlorpromazine; e.g. the dog treated with 300 mg for 15-days found to be more pronounced changes than the dog treated with the same doses for 25-days.
5. Comparing the control group of insulin & electroshock, the author couldn´t found any difference of the change, in nature, from chlorpromazine treated group.
6. Thereafter, discussed on the mechanism of occuring alteration due to chlorpromzine, which had to be related closelly to the mechanism of action of chlorpromazine itself.
Chapter II. Study following administration of chlorpromazine combining with insulin or electroshock.
The author made two categories of study subsequently with the result of Chapter I.
Ist; The effect of chlorpromazine combining with insulin; given doses of chlorpromazine & setting of coma hours were just the same as one shot group of chlorpromazine & insulin control group in Chapter I.
2nd; The effect of chlorpromazine combining with electroshock; given doses of chlorpromazine & applied shock times were likely the setting of long term shot group of chlorpromazine & electroshock control group in Chapter I.
Materials & all the histopathological procedure were the same with Chapter 1.
The findings obtained from combined study were like follows;
1. Clinical observation revealed that convulsion was apparently more extensive by combined apply in both category.
2. Generally, predisposing brain area of susceptible to the alteration couldn´t found even combined procedure, but cerebral cortex occupied still dominant position likely to the result of Chapter 1.
3. Productive changes of glia cells revealed inverselly paralleled with the intensity of the necresis.
4. In the group of chlorpromazine combined with insulin, noteworthy summation of the change could be seen, therefore it seems reasonable, in conclusion, to assume that chlorpromazine & insulin dealt with some synergistic acts each other.
In this point of view, the author dare to recommend that therapeutic combination of insulin with chlorpromazine must definitely be rejected.
5. On the other hand, in the group of chlorpromazine combined with electroshock, no striking evidence of summated alterations were noted, particulary, standing point of view on necrosis. But, in spite of this result, the author never join with optimistic standing to the therapeutic combination of electroshock with chlorpromazine, too.
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