PMID- 28821269 OWN - NLM STAT- MEDLINE DCOM- 20180507 LR - 20220321 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 14 IP - 1 DP - 2017 Aug 18 TI - Age exacerbates microglial activation, oxidative stress, inflammatory and NOX2 gene expression, and delays functional recovery in a middle-aged rodent model of spinal cord injury. PG - 161 LID - 10.1186/s12974-017-0933-3 [doi] LID - 161 AB - BACKGROUND: Spinal cord injury (SCI) among people over age 40 has been steadily increasing since the 1980s and is associated with worsened outcome than injuries in young people. Age-related increases in reactive oxygen species (ROS) are suggested to lead to chronic inflammation. The NADPH oxidase 2 (NOX2) enzyme is expressed by microglia and is a primary source of ROS. This study aimed to determine the effect of age on inflammation, oxidative damage, NOX2 gene expression, and functional performance with and without SCI in young adult (3 months) and middle-aged (12 months) male rats. METHODS: Young adult and middle-aged rats were assessed in two groups-naive and moderate contusion SCI. Functional recovery was determined by weekly assessment with the Basso, Beattie, and Breshnahan general motor score (analyzed two-way ANOVA) and footprint analysis (analyzed by Chi-square analysis). Tissue was analyzed for markers of oxidative damage (8-OHdG, Oxyblot, and 3-NT), microglial-related inflammation (Iba1), NOX2 component (p47(PHOX), p22(PHOX), and gp91(PHOX)), and inflammatory (CD86, CD206, TNFalpha, and NFkappaB) gene expression (all analyzed by unpaired Student's t test). RESULTS: In both naive and injured aged rats, compared to young rats, tissue analysis revealed significant increases in 8-OHdG and Iba1, as well as inflammatory and NOX2 component gene expression. Further, injured aged rats showed greater lesion volume rostral and caudal to the injury epicenter. Finally, injured aged rats showed significantly reduced Basso-Beattie-Bresnahan (BBB) scores and stride length after SCI. CONCLUSIONS: These results show that middle-aged rats demonstrate increased microglial activation, oxidative stress, and inflammatory gene expression, which may be related to elevated NOX2 expression, and contribute to worsened functional outcome following injury. These findings are essential to elucidating the mechanisms of age-related differences in response to SCI and developing age-appropriate therapeutics. FAU - von Leden, Ramona E AU - von Leden RE AUID- ORCID: 0000-0002-2554-6451 AD - Neuroscience Program, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. Ramona.von-leden.ctr@usush.edu. AD - Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Room C2099, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. Ramona.von-leden.ctr@usush.edu. FAU - Khayrullina, Guzal AU - Khayrullina G AD - Neuroscience Program, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. AD - Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Room C2099, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. FAU - Moritz, Kasey E AU - Moritz KE AD - Neuroscience Program, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. FAU - Byrnes, Kimberly R AU - Byrnes KR AD - Neuroscience Program, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. AD - Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Room C2099, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. LA - eng GR - F31 NS090737/NS/NINDS NIH HHS/United States GR - R01 NS073667/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170818 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - EC 1.6.3.- (Cybb protein, rat) RN - EC 1.6.3.- (NADPH Oxidase 2) SB - IM MH - Age Factors MH - Aging/genetics/*metabolism/pathology MH - Animals MH - *Disease Models, Animal MH - Gene Expression MH - Inflammation/metabolism/pathology MH - Male MH - Microglia/*metabolism/pathology MH - Motor Skills/physiology MH - NADPH Oxidase 2/*biosynthesis/genetics MH - Oxidative Stress/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/physiology MH - Rodentia MH - Spinal Cord Injuries/genetics/*metabolism/pathology PMC - PMC5563003 OTO - NOTNLM OT - Aging OT - Inflammation OT - Microglia OT - NOX2 OT - Spinal cord injury COIS- ETHICS APPROVAL: All animal procedures were approved by the Uniformed Services University IACUC and complied fully with the principles set forth in the "Guide for the Care and Use of Laboratory Animals" prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council (DHEW pub. No. (NIH) 85-23, 2985). CONSENT FOR PUBLICATION: Not Applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/08/20 06:00 MHDA- 2018/05/08 06:00 PMCR- 2017/08/18 CRDT- 2017/08/20 06:00 PHST- 2017/03/23 00:00 [received] PHST- 2017/08/04 00:00 [accepted] PHST- 2017/08/20 06:00 [entrez] PHST- 2017/08/20 06:00 [pubmed] PHST- 2018/05/08 06:00 [medline] PHST- 2017/08/18 00:00 [pmc-release] AID - 10.1186/s12974-017-0933-3 [pii] AID - 933 [pii] AID - 10.1186/s12974-017-0933-3 [doi] PST - epublish SO - J Neuroinflammation. 2017 Aug 18;14(1):161. doi: 10.1186/s12974-017-0933-3.