title: Central neuron-glial and glial-glial interactions following axon injury.
abstract: Axon injury rapidly activates microglial and astroglial cells close to the axotomized neurons. Following motor axon injury, astrocytes upregulate within hour(s) the gap junction protein connexin-43, and within one day glial fibrillary acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate towards the axotomized neuron perikarya. Analogous responses occur in central termination territories of peripherally injured sensory ganglion cells. The activated microglia express a number of inflammatory and immune mediators. When neuron degeneration occurs, microglia act as phagocytes. This is uncommon after peripheral nerve injury in the adult mammal, however, and the functional implications of the glial cell responses in this situation are unclear. When central axons are injured, the glial cell responses around the affected neuron perikarya appears to be minimal or absent, unless neuron degeneration occurs. Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration. Although microglia develop into phagocytes, they eliminate the disintegrating myelin very slowly, presumably because they fail to release molecules which facilitate phagocytosis. During later stages of Wallerian degeneration, oligodendrocytes express clusterin, a glycoprotein implicated in several conditions of cell degeneration. A hypothetical scheme for glial cell activation following axon injury is discussed, implying the injured neurons initially interact with adjacent astrocytes. Subsequently, neighbouring resting microglia are activated. These glial reactions are amplified by paracrine and autocrine mechanisms, in which cytokines appear to be important mediators. The specific functional properties of the activated glial cells will determine their influence on neuronal survival, axon regeneration, and synaptic plasticity. The control of the induction and progression of these responses are therefore likely to be critical for the outcome of, for example, neurotrauma, brain ischemia and chronic neurodegenerative diseases.
authors.affiliation: Department of Neuroscience, Biomedical Center, Uppsala, Sweden. Hakan.Aldskogius@anatomi.uu.se
authors.forename: H
authors.initials: H
authors.lastname: Aldskogius
authors.forename: E N
authors.initials: EN
authors.lastname: Kozlova
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D002450:Cell Communication / Q000502:physiology*; D002490:Central Nervous System / Q000473:pathology*; D006801:Humans; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*