The time course of the microglial cell reaction in central nervous system primary sensory projection territories has been examined following peripheral nerve injury in the adult rat using qualitative and quantitative analysis of immunoreactivity with the monoclonal antibody OX-42, which recognises the complement receptor CR3. The regions examined included the gracile nucleus, the column of Clarke and the spinal cord dorsal horn (superficial and deep laminae separately) after unilateral sciatic nerve transection, and the spinal trigeminal nucleus following unilateral infraorbital nerve transection. In all territories examined a qualitative increase in OX-42 immunoreactivity was observed 24 h postlesion. Further, quantitative analysis revealed an exponential development of the OX-42 immunoreactivity, with a peak at one week postlesion, thereafter showing a slow exponential decline. Our results show that the signal (or signals) that induces the microglial cell response in primary sensory projection territories is rapid in comparison to previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration). These findings are compatible with the hypothesis that activated microglia play a pathogenetic role in the development of transganglionic degeneration.
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.
The time course of the astroglial cell reaction in the nucleus gracilis and the spinal cord dorsal horn was examined following sciatic nerve transection in the adult rat with qualitative and quantitative analysis of glial fibrillary acidic protein immunoreactivity and in situ hybridization for its mRNA. In addition, the potential effect of exogenous nerve growth factor (NGF) was examined on the astroglial and microglial cells in the spinal cord dorsal horn at certain time points following sciatic nerve transection. An increase in glial fibrillary acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day after lesioning, with a peak at about 1 week and 2 days after lesioning, respectively, followed by a decline. However, NGF application during 1, 2 and 4 weeks following nerve transection did not result in any significantly reduced astroglial or microglial activity. Our results show that the astroglial cell response in the nucleus gracilis and the spinal cord dorsal horn is rapid in comparison with previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration), that the astroglial cell reaction develops concomitantly with the microglial cell reaction previously described and that the "signal" from the axotomized neurons which induces these reactions can not be prevented by exogenous NGF applied to the peripheral nerve.
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