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- W2883407856 abstract "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." @default.
- W2883407856 created "2018-08-03" @default.
- W2883407856 creator A5005658722 @default.
- W2883407856 creator A5020986701 @default.
- W2883407856 creator A5022548683 @default.
- W2883407856 creator A5032747758 @default.
- W2883407856 creator A5044613830 @default.
- W2883407856 creator A5057247883 @default.
- W2883407856 date "2018-07-19" @default.
- W2883407856 modified "2023-10-13" @default.
- W2883407856 title "Combined treatment with GSNO and CAPE accelerates functional recovery via additive antioxidant activities in a mouse model of TBI" @default.
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