NOX2 inhibition with apocynin worsens stroke outcome in aged rats.
This study utilized middle cerebral artery occlusion (MCAO) with tissue plasminogen activator (tPA) to assess inhibition of the NOX2 isoform of NADPH oxidase on brain injury and functional recovery in aged rats. Effects of NOX2 on the degree of brain injury and functional recovery following MCAO and tPA reperfusion was assessed in young adult and aged rats. Rats received apocynin (NOX2 inhibitor; 5 mg/kg) or saline 30 min prior to MCAO. At 24 h following MCAO, blood-brain barrier permeability (BBB), stroke infarct volume, edema formation, and oxidative damage were measured. Apocynin treatment in aged rats increased mortality rate and failed to improve functional outcome, total infarct volume, edema formation, and BBB permeability. Aged rats displayed increased BBB permeability to sucrose in the contralateral hemisphere following MCAO and diminished antioxidant capacity in the brain as compared to young adult rats. We conclude that inhibition of NOX2 in the aged rat exacerbates stroke injury and diminishes functional outcome. These results suggest age is an important factor in stroke damage and more rigorous examination of apocynin as a therapeutic agent for treatment of stroke must be done.
Kelly
Kimberly A
KA
Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, PO Box 9530, Morgantown, WV 26506, USA.
Li
Xinlan
X
Tan
Zhenjun
Z
VanGilder
Reyna L
RL
Rosen
Charles L
CL
Huber
Jason D
JD
D000098:Acetophenones / Q000494:pharmacology*; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D020521:Stroke / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013395:Sucrose / Q000378:metabolism; D010959:Tissue Plasminogen Activator; D016896:Treatment Outcome
D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D013395:Sucrose; C056165:acetovanillone; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010959:Tissue Plasminogen Activator