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Matrix metalloproteinase signals following neurotrauma are right on cue

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Abstract

Neurotrauma, a term referencing both traumatic brain and spinal cord injuries, is unique to neurodegeneration in that onset is clearly defined. From the perspective of matrix metalloproteinases (MMPs), there is opportunity to define their temporal participation in injury and recovery beginning at the level of the synapse. Here we examine the diverse roles of MMPs in the context of targeted insults (optic nerve lesion and hippocampal and olfactory bulb deafferentation), and clinically relevant focal models of traumatic brain and spinal cord injuries. Time-specific MMP postinjury signaling is critical to synaptic recovery after focal axonal injuries; members of the MMP family exhibit a signature temporal profile corresponding to axonal degeneration and regrowth, where they direct postinjury reorganization and synaptic stabilization. In both traumatic brain and spinal cord injuries, MMPs mediate early secondary pathogenesis including disruption of the blood–brain barrier, creating an environment that may be hostile to recovery. They are also critical players in wound healing including angiogenesis and the formation of an inhibitory glial scar. Experimental strategies to reduce their activity in the acute phase result in long-term neurological recovery after neurotrauma and have led to the first clinical trial in spinal cord injured pet dogs.

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Acknowledgements

We would like to acknowledge the following grant support for this work: Department of Defense grant DOD SCIRP W81XWH-11-1-79 to LJN-H, and National Institutes of Health Grants NS39278 to LJN-H, NS56247 to LP and NS57758 to TR.

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Authors and Affiliations

  1. Department of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 760, San Francisco, CA, 94143, USA

    Alpa Trivedi

  2. Departments of Psychology, College of Liberal Arts, and Neurology, the Dell Medical School, University of Texas, Austin, TX, 78712, USA

    Linda J. Noble-Haeusslein

  3. Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA

    Jonathan M. Levine

  4. Department of Neuroscience, Skidmore College, Saratoga Springs, NY, 12866, USA

    Alison D. Santucci

  5. Department of Anatomy and Neurobiology, Medical Campus, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Thomas M. Reeves & Linda L. Phillips

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  1. Alpa Trivedi
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Correspondence to Alpa Trivedi.

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Trivedi, A., Noble-Haeusslein, L.J., Levine, J.M. et al. Matrix metalloproteinase signals following neurotrauma are right on cue. Cell. Mol. Life Sci. 76, 3141–3156 (2019). https://doi.org/10.1007/s00018-019-03176-4

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