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Combined treatment with GSNO and CAPE accelerates functional recovery via additive antioxidant activities in a mouse model of TBI.
Khan, Mushfiquddin; Shunmugavel, Anandakumar; Dhammu, Tajinder S; Khan, Hamza; Singh, Inderjit; Singh, Avtar K.
Afiliação
  • Khan M; Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
  • Shunmugavel A; Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
  • Dhammu TS; Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
  • Khan H; College of Medicine, University of South Carolina, Columbia, South Carolina.
  • Singh I; Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
  • Singh AK; Ralph H. Johnson VA Medical Center, Charleston, South Carolina.
J Neurosci Res ; 96(12): 1900-1913, 2018 12.
Article em En | MEDLINE | ID: mdl-30027580
ABSTRACT
Traumatic brain injury (TBI) is the major cause of physical disability and emotional vulnerability. Treatment of TBI is lacking due to its multimechanistic etiology, including derailed mitochondrial and cellular energy metabolism. Previous studies from our laboratory show that an endogenous nitric oxide (NO) metabolite S-nitrosoglutathione (GSNO) provides neuroprotection and improves neurobehavioral function via anti-inflammatory and anti-neurodegenerative mechanisms. To accelerate the rate and enhance the degree of recovery, we investigated combining GSNO with caffeic acid phenethyl ester (CAPE), a potent antioxidant compound, using a male mouse model of TBI, controlled cortical impact in mice. The combination therapy accelerated improvement of cognitive and depressive-like behavior compared with GSNO or CAPE monotherapy. Separately, both GSNO and CAPE improved mitochondrial integrity/function and decreased oxidative damage; however, the combination therapy had greater effects on Drp1 and MnSOD. Additionally, while CAPE alone activated AMPK, this activation was heightened in combination with GSNO. CAPE treatment of normal animals also significantly increased the expression levels of pAMPK, pACC (activation of AMPK substrate ACC), and pLKB1 (activation of upstream to AMPK kinase LKB1), indicating that CAPE activates AMPK via LKB1. These results show that while GSNO and CAPE provide neuroprotection and improve functional recovery separately, the combination treatment invokes greater recovery by significantly improving mitochondrial functions and activating the AMPK enzyme. Both GSNO and CAPE are in human consumption without any known adverse effects; therefore, a combination therapy-based multimechanistic approach is worthy of investigation in human TBI.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Álcool Feniletílico / Ácidos Cafeicos / S-Nitrosoglutationa / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Álcool Feniletílico / Ácidos Cafeicos / S-Nitrosoglutationa / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2018 Tipo de documento: Article