3 - Glial Cells, Inflammation, and CNS Trauma: Modulation of the Inflammatory Environment After Injury Can Lead to Long-Distance Regeneration Beyond the Glial Scar

Abstract

In the years since their discovery, glial cells of the developing and mature central nervous system (CNS) have been extensively studied and recognized as important functional components of the brain and spinal cord, in addition to their role in the structural arrangement of the CNS. Glial cells of the central nervous system (CNS), as first described by Virchow (1846), were originally considered to be simply a mechanical framework to support neurons, as evidenced by their designation as “neuroglia,” which literally translated means “nerve glue” (Weigert, 1895). Injury to the central nervous system (CNS) in adult mammals leads to significant pathology associated with permanent disability. The reactivity of glial cells to injuries in the brain and spinal cord, including the importance of inflammatory influences, has been identified as one component of the failure of the nervous system to regenerate when healing occurs. This chapter will review selected aspects of reactive gliosis at the tissue, cellular, and molecular levels as it relates to oligodendrocyte, astrocyte, and microglial/macrophage responses to trauma and the abortive attempts of neuronal regeneration. The historical perspective and modem approaches detailed in this review will demonstrate that the field of glial cell biology has allowed us to go beyond purely mechanical considerations of the glial scar, and in doing so has provided new insights into the complex reactions and interactions of glial cells following injury that generate the generally nonpermissive nature of lesion sites in the adult CNS. Recent advances in the field have demonstrated that significant regeneration can occur when modifications to the inflammatory sequelae are made to create optimal conditions for axon growth.