[Posttraumatic pyogenic and granulomatous encephalitis. An animal experimental contribution on inflammation (author's...

The present studies were performed to elucidate the factors responsible for the relative resistance of the brain to bacterial infections. As a model, group A streptococci were used to produce an experimental brain infection in mice. Attention was focussed on the activity of brain macrophages, the function of which to date is poorly understood. The primary purpose of the experiments was to compare the types of inflammation elicited in the brain by the injection of either killed or living group A streptococci. As a result, two fundamentally different types of encephalitis were observed histologically. A granulomatous inflammation was induced by killed streptococci; when deposited in the brain by intracerebral injection, these were phagocytosed by invading mononuclear macrophages and polymorphonuclear granulocytes during the first day p.i. There was no necrosis of brain tissue excepting the stab wound at the site of injection. The number of granulocytes in the inflammatory infiltrates decreased during the first week p.i. whereas, during the same period, the number of macrophages forming granuloma-like cell accummulations increased. At the beginning of the third week a fading of the granulomatous encephalitis was observed. In contrast, living streptococci produced a pyogenic inflammation of the meninges as well as of the grey and white matter in the region of the stab wound combined with extended tissue necrosis surrounding deposits of bacteria. This pyogenic infection progressed until the end of the first week, forming a brain abscess. A phlegmonous spreading of the pyogenic inflammation predominantly in the white matter and pyocephalus internus was also observed. In contrast to the increase of mononuclear macrophages in the border zone of the abscesses, the granulocytic inflammation decreased. During the second and third weeks p.i. granulation tissue consisting of proliferating connective tissue cells, macrophages and lymphocytes replaced pyogenic necrosis. A secondary purpose was to determine the fate of living and killed streptococci within the pyogenic and granulomatous encephalitis. In these studies immunohistologic, electron microscopic, bacteriologic and serologic methods were employed in addition to the techniques already mentioned. In the majority of the experimental animals streptococci were killed by granulocytes within the first week after injection of the living bacteria. At this time, most of the streptococci were contained within granulocytes and macrophages located to the periphery of the brain abscesses. Corresponding to the granulomatous encephalitis produced by injection of killed streptococci it was possible to detect persistent cell wall material in macrophages by immunohistology. By electronmicroscopy streptococci and their cell walls were found within the phagocytic vacuoles of macrophages. During the course of degradation the group-specific cell wall carbohydrate was enzymatically converted into the group A-variant specific structure...