CONTRIBUTION OF PERIPHERAL MACROPHAGES AND MICROGLIA TO THE CELLULAR REACTION AFTER MECHANICAL OR NEUROTOXIN-INDUCED LESIONS OF THE RAT-BRAIN

Lesions of the central nervous system result in invasion of peripheral phagocytes and/or in situ activation and proliferation of microglia, depending on the direct or indirect nature of the injury. Neurotoxins which are widely used to induce neurodegeneration have been reported t o elicit a pure microglial reaction when administered intraventricular ly. However, the mechanical lesion at the injection site, although rem ote from the lesioned area, could give access to blood-derived cells. Therefore, this study compares the phagocytic reaction occurring after a traumatic lesion of the brain causing a breakdown of the blood-brai n barrier (BBB), or after degeneration of the inferior olivary neurons induced by intraperitoneal administration of 3-acetylpyridine, a proc ess that respects the integrity of the BBB as suggested by the results of intravascular injection of Evans blue. The identification of the m acrophages at the lesion site used specific binding of the B-4 isolect in from Griffonia simplicifolia, preloading of the peripheral monocyte s/macrophages with trypan blue, and characteristic morphological featu res. In traumatically lesioned rats, the lectin-labeled macrophages we re mainly large rounded peripheral cells recruited 1-3 days postlesion , whereas in chemically lesioned rats, the cellular reaction appeared 24-36 h postinjection and peaked between 3 and 12 days before undergoi ng a slow decline. Lectin binding and morphological characteristics in dicated that these small cells were reactive microglia. These results confirm that a brain injury leaving the BBB intact involves essentiall y the recruitment and/or the proliferation of microglia. (C) 1994 Acad emic Press, Inc.