Autoradiographic Studies on Histogenesis of Brain Macrophages in the Mouse

Abstract

Adult mice of the dd strain were repeatedly injected with tritiated thymidine to label (a high percentage of circulating monocytes. Subsequently, five of them received stab wounds in the cerebral cortex made with a heated needle and were sacrificed by perfusion fixation from 6 to 74 hours after the time of injury. Labeled and unlabeled cells appearing in the neighborhood of the wound were examined by light and electron microscopic autoradiography, and their relationship to blood monocytes and perivascular cells was studied. The following results were obtained. Monocytes extravasate in and around the area of damaged tissue and are transformed into brain macrophages. Brain macrophages do not originate from cells other than blood monocytes. Monocytes undergo a marked morphological transformation as they migrate out from the blood vessels. There is an increment of cytoplasm and they assume an amoeboid form. Some of them develop numerous phagosomes and change into typical full-blown macrophages. In the walls of small blood vessels near the lesion, some macrophages or their precursor monocytes are located in the pericytic position, although they can be distinguished from proper pericytes by the presence of label in their nuclei. They are also morphologically distinct from the pericytes; their cytoplasmic matrix is much more electron dense and frequently there are small spaces between their cell surfaces and the surrounding basement membrane. Pericytes are not transformed into macrophages and are vulnerable to brain injury. They are proper constituents of the blood vessel wall and do not belong to the macrophage system.