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KMID : 0378019620050070099
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New Medical Journal
1962 Volume.5 No. 7 p.99 ~ p.117
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Experimental Studies on the Influence of the Ovary upon Allergic Changes of the Spinal Cord
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Abstract
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Since Arthus(1903) published his studies of allegric tissue changes, edema of subcutaneous tissue, hyperemia of blood vessels, cellular infiltration and local necrosis etc., which had been induced by repeated subcutaneous injection of horse serum into domestic rabbits, many interesting experimental studies about the influences of various organs and tissues on allergic changes have been performed and reported. Those had drown significant attention pathologically as well as clinically. It has been already well established that endocrine organs do not infrequently influence allergic response directly and indirectly. Thus prof. Yun and Pistochi reported that thyroidectomy and thymectomy suppressed anaphylactic shock. prof. Yun also reported orchiectomy had produced similar result. Wyman and Mikami reported enhancement of anaphylactic shock following adrenalectomy, but injection of interenin, a substance of adrenal gland, suppressed anaphylactic shock. Molonut recognized enhancement of anaphylactic shock following hypophysectomy. Also Alan, Wood and Yamamoto noted that injection of ACTH and cortisone suppressed anaphylactic shock. Kimura described that excision of parathyroid suppressed anaphylactic shock.
After Sakai reported that sex hormones were directly related with hypersensitivity and antibody formation, Prof. Yun recognized enhancement of anaphylactic shock in bilateral oophorectomized animals. Lee stated that corpus luteum hormone had suppressive effect on anaphylactic shock, and Nemoto verified it experimentally. Yamata reported that ovarian hormone suppressed anaphylaxis in both male and female. Since 1945 Zondeck proposed hormonal allergic theory, theory has been discussed by many, ovarian pain syndromes which Heckel mentioned in 1951 have many similarities to premenstrual disturbances.
Their basic mechanisms may be closely related with alleigy.
Some effects of which might be influenced on allergic changes of the spinal cord by the ovary, were studied and reported in this paper.
Experimental Material and Method
Material: Adult female domestic rabbits, about 2kg. body weight, were used as experimental animals. Fresh healthy horse serum, produced at the National Institute of Prevention of Contagious Diseases, was used as antigen. Estradiol benzoate in sesame oil 20,000 i.u. per cc., produced at U.S. Pacific States Laboratory, was used as estrogen.
Method : Animals were divided in to the following four groups.
1. normal group(control group).
2. oophorectomized group.
3. the group of oophorectomy followed by estrogen injection.
4. the group of estrogen injection in normal rabbits.
They were further subdivided into pretreatment, non-sensitized and sensitized groups.
Pretreatment group : In this group, normal horse serum, 1.0 cc. per kg. of body weight, was injected subcutaneously into the abdomen once daily for 4 days.
Non-sensitized group : This group was not sensitized. A single injection of normal horse serum, O.lcc. per kg. of body weight was done in spinal cord.
Sensitized group : In this group, reinjection in spinal cord was done, with normal horse serum, O.lcc. per kg. of body weight in 15th dey after completion of sensitization.
Estrogen, 500 i.u. per kg. of body weight was injected in the gluteal muscle twice a week.
The animals were sacrificed by air embolization via vein at the end of 3, 6, 12, 24, 48, 72 hours and 1, 2 weeks after the final injection. These spinal cord of injection area were removed, which were examined grossly and were studied histologically with Hematoxylin-Eosin, Van Gieson, Silver impregnation and Weigert´s Stain methods.
Results
Pretreatment group: These were generally no significant changes in macroscopical and microscopical examination in the following four groups; 1. normal group, 2, oophorectomized group, 3. the group of oophorectomy followed by estrogen injection, 4. the group of estrogen injection in normal rabbits. There were no special changes in all except edema on 12-72 hours and 1 week´s specimens after oophorectomy followed by estrogen injection.
Non-sensitized group : Edema, subpial hyperemia and petechiae were noted grossly on 6-48 hours´ specimens after normal horse serum injection in spinal cords upon the following four groups ; 1. normal group, 2, oophorectomized group, 3. the group of oophorectomy followed by estrogen injection. 4. the group of estrogen injection in normal rabbits.
Cloudy swelling, hyperemia, hemorrhages, perivascular inflammatory changes with polymorphonuclear leucocyte infiltration and necrosis, were noted microscopically on leptomeninges and the spinal cord, especially in 6 hours´ specimens after injection on the posterior half at where injection were made.
Such changes were no longer present on 72 hours´ specimens in the oophorectomized group ; 1 week´s specimens of oophorectomized group followed by estrogen injection ; 48 hours´ specimens of estrogen injection group in normal rabbits. Those various changes above described were more prominent in 12-24 hours´ specimens. Among these changes, hyperemia, hemorrhages and edema were main features, but polymorphonuclear leucocyte infiltration and perivascular inflammatory changes were mild. Severe vasculitis as necrotizing vasculitis was observed only in the estrogen injected group. However the oophorectomized group showed the slightest changes.
Sensitized group : The following four groups ; 1. normal group, 2, oophorectomized group, 3, group with oophorectomy followed by estrogen injection, 4. group with estrogen injection in normal rabbits, showed edema, subpial hyperemia and petechiae grossly on 3-72 hours or 1 week´s specimens after retreatment.
Microscopically, cloudy swelling, hyperemia and hemorrhages were present already on 3 hours´ specimens after retreatment. These changes did not return completely to the normal state. There were some trace changes which resemble "encephalomalacia" in those groups except for normal rabbits and the group with estrogen injection after oophorectomy. Inflammatory changes, polymorphonuclear leucocyte infiltration were prominent, in proportion to these degenerative changes, especially intramedullary and periarterial region on 3-12 hours´ specimens after reinjection, however eosinophilic leucocyte infiltration on 6-12 hours´ specimens. They were gradually replaced by small round cells after 12-24 hours.
Similar changes were observed prominently in normal group on 12 hours´ specimens after reinjection, 6 hours´ specimens in oophorectomized group, on 24 hours´ specimens in the group of oophorectomy followed. by estrogen injection and on 6 hours´ specimens in the group of estrogen injection in normal rabbits. These were generally most prominent on 12-48 hours´ specimens; which were lasting for 1-2 weeks. The various charges above described were most prominent in the oophorectomized group, while they were slightest in those with estrogen injection group in normal rabbits.
Discussion
Hyperemia, hemorrhages and edema can be induced on spinal cord by normal horse serum injection only. These changes can be noted only in the posterior half of the spinal cord even in the non-sensitized group. Part of such changes, at least, were thought as local trauma. On the contrary, pial, medullary and blood vessel wall inflammatory changes, especially fibrinoid or necrotizing arteritis and prominent eosinophilic leucocyte infiltration are characteristically observed in sensitized group only.
Such fibrinoid or necrotizing arteritis to be considered as the primary features of allergic reaction, while others should be considered as the secondary or traumatic changes. Such allergic reaction of the spinal cord is most prominent in the oophorectomized group, while it is slightest in the group of estrogen injection in normal rabbits. So that we may consider that ovarian hormone, particularly estrogen has suppressive action in allergic changes, and the allergic changes are enhanced by withdraw of estrogen.
Conclusion
1. Allergic reaction of spinal cord, induced by injection of healthy horse serum into normal rabbits, group of bilateral oophorectomy, bilateral oophorectomy followed by estrogen injection for 3 months and estrogen injection for 3 months in normal rabbits, were discussed.
2. The cardinal allergic changes of the spinal cord were hyperemia, hemorrhages, edema and inflammatory reaction, particularly necrotizing arteritis on pia and medullary.
3. Allergic changes of the spinal cord were enhanced by oophorectomy were suppressed by estrogen injection.
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