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SPARC regulates microgliosis and functional recovery following cortical ischemia.
J Neurosci 2013; 33(10):4468-81JN

Abstract

Secreted protein acidic rich in cysteine (SPARC) is a matricellular protein that modulates the activity of growth factors, cytokines, and extracellular matrix to play multiple roles in tissue development and repair, such as cellular adhesion, migration, and proliferation. Throughout the CNS, SPARC is highly localized in mature ramified microglia, but its role in microglia--in development or during response to disease or injury--is not understood. In the postnatal brain, immature amoeboid myeloid precursors only induce SPARC expression after they cease proliferation and migration, and transform into mature, ramified resting microglia. SPARC null/CX3CR1-GFP reporter mice reveal that SPARC regulates the distribution and branching of mature microglia, with significant differences between cortical gray and white matter in both controls and SPARC nulls. Following ischemic and excitotoxic lesion, reactive, hypertrophic microglia rapidly downregulate and release SPARC at the lesion, concomitant with reactive, hypertrophic perilesion astrocytes upregulating SPARC. After photothrombotic stroke in the forelimb sensorimotor cortex, SPARC nulls demonstrate enhanced microgliosis in and around the lesion site, which accompanies significantly enhanced functional recovery by 32 d after lesion. Microglia from SPARC nulls also intrinsically proliferate at a greater rate in vitro--an enhanced effect that can be rescued by the addition of exogenous SPARC. SPARC is thus a novel regulator of microglial proliferation and structure, and, in addition to regulating glioma progression, may play an important role in differently regulating the gray and white matter microglial responses to CNS lesion--and modulating behavioral recovery--after injury.

Authors+Show Affiliations

Department of Zoology, Life Sciences Institute and Brain Research Centre, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23467362

Citation

Lloyd-Burton, Samantha M., et al. "SPARC Regulates Microgliosis and Functional Recovery Following Cortical Ischemia." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 33, no. 10, 2013, pp. 4468-81.
Lloyd-Burton SM, York EM, Anwar MA, et al. SPARC regulates microgliosis and functional recovery following cortical ischemia. J Neurosci. 2013;33(10):4468-81.
Lloyd-Burton, S. M., York, E. M., Anwar, M. A., Vincent, A. J., & Roskams, A. J. (2013). SPARC regulates microgliosis and functional recovery following cortical ischemia. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33(10), pp. 4468-81. doi:10.1523/JNEUROSCI.3585-12.2013.
Lloyd-Burton SM, et al. SPARC Regulates Microgliosis and Functional Recovery Following Cortical Ischemia. J Neurosci. 2013 Mar 6;33(10):4468-81. PubMed PMID: 23467362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SPARC regulates microgliosis and functional recovery following cortical ischemia. AU - Lloyd-Burton,Samantha M, AU - York,Elisa M, AU - Anwar,Mohammad A, AU - Vincent,Adele J, AU - Roskams,A Jane, PY - 2013/3/8/entrez PY - 2013/3/8/pubmed PY - 2013/4/27/medline SP - 4468 EP - 81 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 33 IS - 10 N2 - Secreted protein acidic rich in cysteine (SPARC) is a matricellular protein that modulates the activity of growth factors, cytokines, and extracellular matrix to play multiple roles in tissue development and repair, such as cellular adhesion, migration, and proliferation. Throughout the CNS, SPARC is highly localized in mature ramified microglia, but its role in microglia--in development or during response to disease or injury--is not understood. In the postnatal brain, immature amoeboid myeloid precursors only induce SPARC expression after they cease proliferation and migration, and transform into mature, ramified resting microglia. SPARC null/CX3CR1-GFP reporter mice reveal that SPARC regulates the distribution and branching of mature microglia, with significant differences between cortical gray and white matter in both controls and SPARC nulls. Following ischemic and excitotoxic lesion, reactive, hypertrophic microglia rapidly downregulate and release SPARC at the lesion, concomitant with reactive, hypertrophic perilesion astrocytes upregulating SPARC. After photothrombotic stroke in the forelimb sensorimotor cortex, SPARC nulls demonstrate enhanced microgliosis in and around the lesion site, which accompanies significantly enhanced functional recovery by 32 d after lesion. Microglia from SPARC nulls also intrinsically proliferate at a greater rate in vitro--an enhanced effect that can be rescued by the addition of exogenous SPARC. SPARC is thus a novel regulator of microglial proliferation and structure, and, in addition to regulating glioma progression, may play an important role in differently regulating the gray and white matter microglial responses to CNS lesion--and modulating behavioral recovery--after injury. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/23467362/SPARC_regulates_microgliosis_and_functional_recovery_following_cortical_ischemia_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=23467362 DB - PRIME DP - Unbound Medicine ER -