Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury

Abstract

Astrocytes are a target for gonadal steroids in the normal brain. The putative modulation by gonadal hormones of the astrocytic reaction to brain injury was assessed in this study. Male and female adult Wistar albino rats were gonadectomized and, one month later, their brains were lesioned by a longitudinal incision crossing the parietal cerebral cortex, the CA1 field of the dorsal hippocampus and the dentate gyrus. Males were injected either with testosterone (20 μg/rat) or vehicle immediately after surgery. Females were injected either with 17β estradiol (250 μg/rat), progesterone (500 μg/rat) or vehicle. Hormonal injections were repeated 24 and 48 h after brain injury. All animals received injections of 5′-bromodeoxyuridine (BrdU) to label proliferating cells. Histological sections from the brain of animals killed 72 h after surgery were used for the double immunohistochemical localization of BrdU and glial fibrillary acidic protein (GFAP). The number of GFAP-immunoreactive astrocytes and the number of double labelled astrocytes (GFAP+BrdU) were recorded as a function of the distance to the lesion site in the parietal cerebral cortex, the CA1 field of the hippocampus and the dentate gyrus. Testosterone, estradiol and progesterone treatments resulted in a significant decrease in the number of GFAP-immunolabelled reactive astrocytes in the vicinity of the wound. The number of double labelled cells and the labelling index (proportion of GFAP-immunoreactive astrocytes labelled with BrdU) varied according to the cerebral area, the distance to the wound and the sex of the animals, and were significantly decreased by gonadal steroids in all the areas examined. These results ndicate that gonadal hormones may decrease gliosis and astrocyte proliferation after a penetrating brain injury.