{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:52:06Z","timestamp":1788385926476,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,6,20]],"date-time":"2003-06-20T00:00:00Z","timestamp":1056067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The neuropathogenesis of HIV\u20101\u2010associated dementia (HAD) revolves around the secretion of toxic molecules from infected and immune\u2010competent mononuclear phagocytes. Astrocyte activation occurs in parallel but limited insights are available for its role in neurotoxicity and cognitive dysfunction. One means in which astrocytes may affect disease is through their production of tissue inhibitors of metalloproteinases (TIMPs). TIMPs are regulators of matrix metalloproteinases, enzymes that affect blood\u2010brain barrier integrity through altering the extracellular matrix. We hypothesized that in response to injury and inflammation in HAD, astrocytes regulate the production of TIMP\u20101, the inducible type of TIMP that is important in inflammation. To address astrocyte\u2010mediated TIMP\u20101 regulation in HAD, we evaluated the responses of primary human to IL\u20101\u03b2 and HIV\u20101. TIMP\u20101 levels in plasma, CSF, and brain tissue of control, HIV\u20101 infected patients without cognitive impairment, and HAD patients were also studied. Our data show that an upregulation of TIMP\u20101 results from astrocytes acutely activated with IL\u20101\u03b2. In contrast, CSF and brain tissue samples from HAD patients showed reduced TIMP\u20101 levels compared to seronegative controls. MMP\u20102 levels in brains showed the opposite. Consistent with this, prolonged activation of astrocytes led to a reduction in TIMP\u20101 and MMP\u20102, but a sustained elevation in MMP\u20101. Our data suggest that in diseased brain tissue, the ability of astrocytes to counteract the destructive effects of MMP through expression of TIMP\u20101 is diminished by chronic activation. Our studies reveal new opportunities for repair\u2010based therapeutic strategies in HAD. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10266","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T19:30:37Z","timestamp":1062531037000},"page":"47-56","source":"Crossref","is-referenced-by-count":81,"title":["Regulation of tissue inhibitor of metalloproteinase\u20101 by astrocytes: Links to HIV\u20101 dementia"],"prefix":"10.1002","volume":"44","author":[{"given":"Radhika","family":"Suryadevara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spring","family":"Holter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Borgmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisa","family":"Persidsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Labenz\u2010Zink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Persidsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard 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