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Gelatinases (matrix metalloproteinase [MMP]2, MMP9) and their substrate osteopontin (OPN) are candidate mediators of synaptogenesis after central nervous system (CNS) insult, including olfactory axon damage. Here, we examined the time course of MMP9, OPN, and OPN receptor CD44 response to diffuse OB injury. FVBV\/NJ mice received mild midline fluid percussion insult (mFPI), after which MMP9 activity and both OPN and CD44 protein expression were measured. Diffuse mFPI induced time-dependent increase in OB MMP9 activity and elevated the cell signaling 48-kD OPN fragment. This response was bimodal at 1 and 7 days post-injury. MMP9 activity was also correlated with 7-day reduction in a second 32-kD OPN peptide. CD44 increase peaked at 3 days, delayed relative to MMP9\/OPN response. MMP9 and OPN immunohistochemistry suggested that deafferented tufted and mitral neurons were the principal sites for these molecular interactions. Analysis of injured MMP9 knockout (KO) mice showed that 48-kD OPN production was dependent on OB MMP9 activity, but with no KO effect on CD44 induction. Olfactory marker protein (OMP), used to identify injured olfactory axons, revealed persistent axon damage in the absence of MMP9. MMP9 KO ultrastructure at 21 days post-injury indicated that persistent OMP reduction was paired with delayed removal of degenerated axons. These results provide evidence that diffuse, concussive brain trauma induces a post-injury interaction between MMP9, OPN, and CD44, which mediates synaptic plasticity and reinnervation within the OB.<\/jats:p>","DOI":"10.1089\/neu.2018.5994","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T07:20:57Z","timestamp":1542352857000},"page":"1615-1631","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Matrix Metalloproteinase 9 and Osteopontin Interact to Support Synaptogenesis in the Olfactory Bulb after Mild Traumatic Brain Injury"],"prefix":"10.1177","volume":"36","author":[{"given":"Melissa A.","family":"Powell","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, Virgina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raiford T.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, Virgina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, Virgina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, Virgina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda L.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, Virgina."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1989.6.99"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1037\/h0076401"},{"key":"e_1_3_3_4_2","first-page":"106","article-title":"Mild fluid percussion injury induces diffuse axonal damage and reactive synaptic plasticity in the mouse olfactory bulb","volume":"317","author":"Powell M.A.","year":"2017","unstructured":"Powell M.A., , Black R.T., , Smith T.L., , Reeves T.M., , and Phillips L.L. 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