Influences of Activated Microglia/Brain Macrophages on Spinal Cord Injury and Regeneration
Damage to the central nervous system (CNS) systematically elicits the activation of both astrocytes and microglia, often termed reactive gliosis. This article is focused on the principal features that characterize cellular events associated with the activation of microglia after spinal cord injury (SCI) that govern the regenerative success or failure of injured neurons. In addition to discussing the role of microglia as immunocompetent cells of the CNS, it addresses the influences of activated microglia/brain macrophages on astrogliosis. The controversial issue of whether reactive microgliosis is a beneficial or harmful process with respect to neuroprotection is addressed, and a resolution of this dilemma is offered by suggesting different interpretations of the term “activated microglia” depending on its usage during experimentation in vivo or in vitro. Importantly, it provides a critical discussion regarding the distinction and relation between microglia-derived brain macrophages and infiltrating peripheral macrophages, and their conflicting roles in creating a pro-regenerative environment. To this end, evidence is reviewed that suggests that microglia-derived brain macrophages are capable of overriding many of the inhibitory obstacles to regeneration following SCI through their production of growth factors and cytokines, as well as their deposition or modulation of the extacellular matrix in the injured environment.
KeywordsSpinal Cord Injury Nerve Growth Factor Schwann Cell Microglial Cell Injured Spinal Cord
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- Batchelor PE, Liberatore GT, Wong JY, Porritt MJ, Frerichs F, Donnan GA, Howells DW (1999). Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 19:1708–1716.PubMedGoogle Scholar
- Blakemore WF (1983). Remyelination of demyelinated spinal cord axons by Schwann cells. In: Spinal Cord Reconstruction (Kao CC, Bunge RP, Reier PJ, eds.), pp 281–291. New York: Raven Press.Google Scholar
- Giulian D, Li J, Li X, George J, Rutecki PA (1994). The impact of microglia-derived cytokines upon gliosis in the CNS. Dey Neurosci 16:128–136.Google Scholar
- Harvey AR, Fan Y, Connor AM, Grounds MD, Beilharz MW (1993). The migration and intermixing of donor and host glia on nitrocellulose polymers implanted into cortical lesion cavities in adult mice and rats. Int J Dey Neurosci 11:569–581.Google Scholar
- Kiefer R, Streit WJ, Toyka KV, Kreutzberg GW, Hartung HP (1995). Transforming growth factor-beta 1: a lesion-associated cytokine of the nervous system. Int J Dey Neurosci 13:331–339.Google Scholar
- Mallat M, Houlgatte R, Brachet P, Prochiantz A (1989). Lipopolysaccharide-stimulated rat brain macrophages release NGF in vitro. Dey Biol 133:309–311.Google Scholar
- Martinou JC, Le Van Thai A, Valette A, Weber MJ (1990). Transforming growth factor beta 1 is a potent survival factor for rat embryo motoneurons in culture. Brain Res Dey Brain Res 52:175–181.Google Scholar
- Rabchevsky AG, Streit WJ (1998). Role of microglia in postinjury repair and regeneration of the CNS. MRDD Res Rev 4:187–192.Google Scholar
- Reier PJ, Stensaas LJ, Guth L (1983). The astrocytic scar as an impediment to regeneration in the central nervous system. In: Spinal Cord Reconstruction (Kao CC, Bunge RP, Reier PJ, eds.), pp 163–195. New York: Raven Press.Google Scholar
- Río Hortega Pd (1932). Microglia. In: Cytology and cellular pathology of the nervous system (Penfield W, ed.), pp 481–534. New York: P.B. Hoeber.Google Scholar
- Streit WJ, Kincaid-Colton CA (1995). The brain’s immune system. Sci Am 273:38–43.Google Scholar