Evidence for activation of astrocytes via reactive microglial cells following hypoglossal nerve transection

Abstract

Following peripheral nerve injury, resident microglial cells proliferate and astrocytes undergo hypertrophy, as evidenced, e.g., by an increase in the levels of glial fibrillary acidic protein (GFAP). In a previous study we have shown that infusion of cytosine arabinoside (ARA-C) into the rat brain blocks the axotomy-induced proliferation of microglial cells. This experimental approach has been used in the present study in order to explore the issue of whether the reactive microglial cells are mediators of the increased GFAP expression in the hypoglossal nucleus of the rat following axotomy. Quantitative analysis of sections processed for immunocytochemistry or in situ hybridization demonstrated a marked increase in GFAP-like immunoreactivity and GFAP-mRNA, respectively, in the ipsilateral hypoglossal nucleus 4 and 7 days after axotomy in control experiments. These increases failed to occur in axotomized animals treated with ARA-C. Therefore, our data are compatible with the hypothesis that activation of astrocytes following axotomy as measured by increased expression of GFAP and its mRNA is induced secondarily to the microglial response.

BQ788, an endothelin ETB receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain

“…The increase in the number of microglia/macrophages is a primary event to induce activation of astrocytes. It has been shown that reduction of in the number of microglia/macrophages leads to attenuation of astrocytic activation (Giulian et al, 1989;Svensson et al, 1993). In the present study, the stub wound increased the number of microglia/macrophages, which was revealed by a staining of GSA-I B 4 (Marty et al, 1991), though which effect was not affected by BQ788 and FR139317 (Table 2).…”

Phenotypic diversity and kinetics of proliferating microglia and astrocytes following cortical stab wounds

“…Since microglia are activated and replicate earlier than astrocytes, cytokines released by activated microglia may contribute to the hypertrophy and hyperplasia of neighboring astrocytes. This suggestion is strongly supported by the finding that inhibition of microglial proliferation following hypoglossal axotomy also prevents increases in GFAF' immunostaining and GFAP mRNA (Svensson, et al, 1993).…”

A Critical Role of Toll-like Receptor 2 in Nerve Injury-induced Spinal Cord Glial Cell Activation and Pain Hypersensitivity

“…Cell Activation-It is well known that peripheral nerve injury induces glial cell activation in the spinal cord (35)(36)(37). The activation of microglia and astrocytes in the nerve-damaged mice was tested by immunostaining with anti-CD11b and anti-GFAP antibodies, respectively.…”