Steroids Modulate Astroglia Plasticity after Brain Injury

Gonadal steroids and neurosteroids not only modulate physiological astroglial plasticity, but also affect astroglial responses in pathological conditions (22,35). The effect of steroids on astroglia has been studied in rats after a penetrating injury of the cerebral cortex and hippocampus. Such a lesion results in the proliferation and hypoertrophy of astrocytes in the proximity of the wound. Castration of rats of both sexes increases the proliferation of astrocytes after injury. In contrast, administration of high physiological levels of estradiol or PROG to ovariectomized females, or the administration of T to castrated males, decreases the proliferation and hypertrophy of astrocytes in the injured brain. This effect was observed either after systemic administration of the hormones or after their intracerebroventricular administration. Intracerebroventricular administration of neurosteroids, such as PREG and dehydroepiandrosterone, also decreased astroglial proliferation (22,22a).

The participation of astrocytes in the wounding response is considered to be in part detrimental and in part beneficial for the restoration of functional neuronal circuits after the lesion. Astrocytes located near the site of injury help to restore the structural integrity of the neural parenchyma, are a source of peptides and trophic factors that promote neuronal survival and neuritic growth, and secrete basal lamina components involved in regenerating axonal guidance. On the other hand, the reactive astrocytes form a physical barrier between the wound and the nerve parenchyma that impedes axonal growth. The modulation of reactive gliosis and astrocyte proliferation by gonadal steroids and neurosteroids is of important practical interest because there is limited knowledge regarding substances that reduce astrocyte reaction to injury.

The mechanisms involved in the effect of steroids on astroglia proliferation after brain injury are yet unknown. Recent studies on hippocampal cultured slices (36) have revealed that the response of astroglia to neurosteroids and gonadal hormones is affected by the extracellular concentration of K+. Because extracellular K+ levels rise in the brain parenchyma after injury, this may be one of the reasons why androgens affect astroglia proliferation after injury, but do not affect astroglia proliferation during normal development of the hypothalamic arcuate nucleus (37).

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