Experimental studies on the influence of the ovary upon allergic changes of the spinal cord
[영문]Since Arthus(1903) published his studies of allergic tissue changes, with 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. It has been already well established that endocrine organs frequently influence allergic response directly and indirectly.
After Sakai(1932) reported that sex hormones were directly related with hypersensitivity and antibody formation, Prof. Yun (1932) recognized enhancement of anaphylactic shock in bilateral oophorectomized animals.
It is the purpose of this study to see the influence of ovary on the allergic changes of the spinal cord in rabbits.
Material and Method
Material: Adult female domestic rabbits. about 2 kg 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 co., produced at U.S Pacific States Laboratories, was used.
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, 0.1cc. per kg. of body weight was made in the spinal curd.
Sensitized group: In this group, reinjection in the spinal cord was made with normal horse serum 0.1cc. per kg. of body weight in 15th day 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 at the end of 3, 6, 12, 24, 48, 72 hours and 1, 2 weeks after the final injection. These spinal cords of injection area were removed, which were examined grossly and were studied histologically with
Hematoxylin-Eosin, Van Gieson, Silver impregnation, stain methods.
Pretreatment group: There were generally no significant changes in macroscopical and microscopical examination in the fellowing 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 in 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 in 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 leucocytic infiltration and necrosis, were noted microscopically on leptomeninges and the spinal cord, especially in 6 hours' specimens after injection on the posterior half where injection were made.
Such changes were no longer present in 72 hours' specimens in the oophorectomized group: 1 week's specimens of oophorectomized group fellowed 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 the changes, hyperemia, hemorrhages and edema were the main features, but polymorphonuclear leucocytic 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 least 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 in 3∼72 hours or 1 week's specimens after retreatment.
Microscopically, cloudy swelling, hyperemia and hemorrhages were present already in 3 hours' specimens after retreatment. These changes did net 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 leucocytic infiltration were prominent, in proportion to these degenerative changes, especially intramedullary and periarterial region in 3∼12 hours' specimens after reinjection. however eosinophilic leucocytic infiltration in 6∼ 12 hours' specimens. They were gradually replaced by small round cells after 12∼24 hours.
Similar changes were observed prominently in normal group in 12 hours' specimens after reinjection. 6 hours' specimens in oophorectomized group, in 24 hours' specimens in the group of oophorectomy followed by estrogen injection and in 6 hours' specimens in the group of estrogen injection in normal rabbits. These were generally most prominent in 12∼48 hours' specimens; which were lasting for 1∼2 weeks. The various changes above described were most prominent in the oophorectomized group, while they were slightest in those with estrogen injection group in normal rabbits.
Hyperemia. hemorrhages and edema can be induced in 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-sen-sitized group. Parts 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 leucocytic infiltration were characteristically observed in sensitized group only.
Such fibrinoid or necrotizing arteritis were 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 least 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 withdrawal of estrogen.
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 fur 3 months in
normal rabbits, was discussed.
2. The cardinal allergic changes of the spinal cord were hyperemia, hemorrhages, edema and inflammatory reaction, particularly necrotizing arteritis in pin and medullary, portion of the spinal cord.
3. Allergic changes of the spinal cord were enhanced by oophorectomy and were suppressed by estrogen injection.