期刊
NEUROCHEMISTRY INTERNATIONAL
卷 63, 期 6, 页码 583-593出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2013.09.012
关键词
Traumatic brain injury; NADPH oxidase; Apocynin; Object recognition task; Oxidative stress
资金
- Conselho Nacional de Desenvolvimento Cientifico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES) (Brazil)
- CNPq [301552/2007-0]
- CNPq/FAPERGS [11/2082-4]
Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies have indicated that overproduction of free radicals, especially superoxide (O-2(-)) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a common underlying mechanism of pathophysiology of TBI, little information is available regarding the role of apocynin, an NADPH oxidase inhibitor, in neurological consequences of TBI. Therefore, the present study evaluated the therapeutic potential of apocynin for treatment of inflammatory and oxidative damage, in addition to determining its action on neuromotor and memory impairments caused by moderate fluid percussion injury in mice (mLFPI). Statistical analysis revealed that apocynin (5 mg/kg), when injected subcutaneously (s.c.) 30 min and 24 h after injury, had no effect on neuromotor deficit and brain edema, however it provided protection against mLFPI-induced object recognition memory impairment 7 days after neuronal injury. The same treatment protected against mLFPI-induced IL-1 beta, TNF-alpha, nitric oxide metabolite content (NOx) 3 and 24 h after neuronal injury. Moreover, apocynin treatment reduced oxidative damage (protein carbonyl, lipoperoxidation) and was effective against mLFPI-induced Na+,K+-ATPase activity inhibition. The present results were accompanied by effective reduction in lesion volume when analyzed 7 days after neuronal injury. These data suggest that superoxide (O-2(-)) derived from NADPH oxidase can contribute significantly to cognitive impairment, and that the post injury treatment with specific NADPH oxidase inhibitors, such as apocynin, may provide a new therapeutic approach to the control of neurological disabilities induced by TBI. (C) 2013 Published by Elsevier Ltd.
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