PMID- 22201549 OWN - NLM STAT- MEDLINE DCOM- 20120419 LR - 20211021 IS - 1090-2430 (Electronic) IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 234 IP - 1 DP - 2012 Mar TI - Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice. PG - 50-61 LID - 10.1016/j.expneurol.2011.12.016 [doi] AB - Aging alters the ability of the brain to respond to injury. One of the major differences between the adult and aged brain is that comparable injuries lead to greater blood brain barrier disruption in the aged brain. The goals of these studies were to quantify the effects of age on BBB permeability using high field strength MRI T1 mapping and to determine whether activation of matrix metalloproteases, their inhibitors, or expression of blood brain barrier structural proteins, occludin, zonnula occludins-1 (ZO-1) and claudin-5 were altered following injury to the aged C57/BL6 mouse brain. T1 mapping studies revealed greater blood brain barrier permeability in the aged (21-24 months old) brain than in the adult (4-6 months old) following controlled cortical impact. The increased blood brain barrier permeability in the pericontusional region was confirmed with IgG immunohistochemistry. MMP-9 activity was increased following controlled cortical impact in the aged brain, and this was accompanied by increased MMP-9 gene expression. MMP-2 activity was higher in the uninjured aged brain than in the adult brain. Occludin and ZO-1 mRNA levels were unchanged following injury in either age group, but claudin-5 mRNA levels were lower in the aged than the adult brain following injury. These results demonstrate quantitative increases in blood brain barrier permeability in the aged brain following injury that are accompanied by increased MMP-9 activation and decreased blood brain barrier repair responses. CI - Copyright A(c) 2011. Published by Elsevier Inc. FAU - Lee, Phil AU - Lee P AD - Hoglund Brain Imaging Center, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. FAU - Kim, Jieun AU - Kim J FAU - Williams, Rachel AU - Williams R FAU - Sandhir, Rajat AU - Sandhir R FAU - Gregory, Eugene AU - Gregory E FAU - Brooks, William M AU - Brooks WM FAU - Berman, Nancy E J AU - Berman NE LA - eng GR - P20 RR016475/RR/NCRR NIH HHS/United States GR - P30 AG035982/AG/NIA NIH HHS/United States GR - P30 HD02528/HD/NICHD NIH HHS/United States GR - R01 AG031140/AG/NIA NIH HHS/United States GR - R01AG31140/AG/NIA NIH HHS/United States GR - P30 HD002528/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20111219 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Membrane Proteins) RN - 0 (Occludin) RN - 0 (Ocln protein, mouse) RN - 0 (Phosphoproteins) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Tjp1 protein, mouse) RN - 0 (Zonula Occludens-1 Protein) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - K2I13DR72L (Gadolinium DTPA) SB - IM MH - *Aging MH - Animals MH - Blood-Brain Barrier/*physiopathology MH - Brain Injuries/*enzymology/*pathology MH - Brain Mapping MH - Cerebral Cortex/*pathology MH - Disease Models, Animal MH - Gadolinium DTPA MH - Gene Expression Regulation/physiology MH - Magnetic Resonance Imaging MH - Male MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Membrane Proteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Occludin MH - Permeability MH - Phosphoproteins/metabolism MH - Time Factors MH - Tissue Inhibitor of Metalloproteinases/metabolism MH - Trauma Severity Indices MH - Zonula Occludens-1 Protein PMC - PMC4042317 MID - NIHMS584356 EDAT- 2011/12/29 06:00 MHDA- 2012/04/20 06:00 PMCR- 2014/06/03 CRDT- 2011/12/29 06:00 PHST- 2011/10/10 00:00 [received] PHST- 2011/12/05 00:00 [revised] PHST- 2011/12/09 00:00 [accepted] PHST- 2011/12/29 06:00 [entrez] PHST- 2011/12/29 06:00 [pubmed] PHST- 2012/04/20 06:00 [medline] PHST- 2014/06/03 00:00 [pmc-release] AID - S0014-4886(11)00468-7 [pii] AID - 10.1016/j.expneurol.2011.12.016 [doi] PST - ppublish SO - Exp Neurol. 2012 Mar;234(1):50-61. doi: 10.1016/j.expneurol.2011.12.016. Epub 2011 Dec 19.