Postnatal cell proliferation in the rat cerebrum: immunohistochemical study with bromodeoxyuridine (BrdU)

The postnatal cell proliferation in the rat cerebrum was studied immunohistochemically using a monoclonal antibody to bromodeoxyuridine (BrdU). Since BrdU, a halogenated analogue of thymidine, is incorporated into nuclear DNA during duplication, S-phase cells can be detected by demonstrating intranuclear BrdU. 200 mg/kg of BrdU was administered to normal Wistar rats intraperitoneally on the day of birth or intravenously 1, 2, 3, 5, 8 or 24 weeks after birth. Thirty minutes later, the brain was fixed by perfusion with ethanol, and the paraffin-embedded sections were processed for the avidin biotin peroxidase-complex method. BrdU-positive nuclei were counted among 500 to 10,000 cells in several regions of the brain to obtain the BrdU-labeling index (the number of BrdU-positive cells per 100 cells scored, LI, %). The present study demonstrated that (1) proliferating cells in the gray matter (cerebral cortex and caudate-putamen) are only few at birth (LI = 0.54-0.78%), which further decrease during the following few weeks, and disappear by adulthood, (2) in the white matter (corpus callosum), cell proliferation is relatively active within 1 week after birth (LI = 5.6-6.3%), but becomes inactive thereafter, (3) the proliferative activity of the cells in the subependymal layer of the lateral ventricle is very high at birth (LI = 15.5%), which somewhat decreases during the following few weeks, but still remains high in adulthood (LI = 7.5%). This kind of continued cell proliferation in the brain after birth seems important in the postnatal development of the normal cerebral structure, and in several pathologic processes such as tissue repair and the development of brain neoplasm.