This is a resubmitted application to determine the role, if any, of microglia in neuronal protection and assistance in regeneration following injury. It has three specific aims.
The first aim i s to measure the cytokines produced by microglia during the regeneration of the facial nerve neurons following axotomy and during rubrospinal nucleus neuronal degeneration following lateral funiculotomy. By RT-PCR synthesis of a number of cytokines and growth factors will be assayed and the time course of their synthesis defined. The second specific aim is to determine if CGRP synthesized by injured neurons activates microglial cells and causes their proliferation, cytokine synthesis or neurotrophin production. This will be done by both histochemical and RT-PCR techniques. In the third aim he will compare and hopefully identify genes differentially expressed by microglial cells in vitro and ex vivo. He will compare unstimulated, LPS activated and CGRP-stimulated microglial cells in vitro. With microglial cells freshly isolated from the facial nucleus following different stimuli, he will compare resting microglia, phagocytic microglia and reactive/activated microglial cells. He will subsequently clone and/or identify by partial sequences the genes differentially expressed.
| Streit, W J; Hurley, S D; McGraw, T S et al. (2000) Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration. J Neurosci Res 61:20-Oct |
| Hurley, S D; Walter, S A; Semple-Rowland, S L et al. (1999) Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system. Glia 25:304-9 |
| Streit, W J; Semple-Rowland, S L; Hurley, S D et al. (1998) Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp Neurol 152:74-87 |
