The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells. 1. Introduction Myelin represents a nonpermissive substrate for neuronal adhesion, sprouting, and neurite growth [1, 2], and several myelin-associated inhibitor proteins have been identified including the myelin-associated glycoprotein (MAG) [3, 4], oligodendrocyte myelin glycoprotein (OMgp) [5, 6] and Nogo-A [7–9]. Since then, numerous studies have been dedicated to understand the mechanisms underlying the action of these inhibitory molecules [10–12]. Previous studies in our laboratory and others have used immunological demyelination to address myelin-associated inhibition and provide a permissive environment for axonal regeneration. Immunological demyelination involves the intraspinal injection of antibodies to galactocerebroside (GalC), the major sphingolipid in myelin, plus complement proteins, and results in a well-defined region of complete demyelination that spares oligodendrocytes. This treatment paradigm has been shown to promote axonal regeneration following spinal cord injury in embryonic chicks [13], hatchling chicks [14],
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