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Pretreatment with Lovastatin Improves Depression-Like Behavior After Traumatic Brain Injury Through Activation of the AMPK Pathway.
Chen, Yu-Ting; Nyam, Tee-Tau Eric; Tsai, Li-Chen; Chang, Chih-Hua; Su, Chun-Lin; Ho, Chung-Han; Chio, Chung-Ching; Gean, Po-Wu; Kuo, Jinn-Rung.
Afiliação
  • Chen YT; Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan.
  • Nyam TE; Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan.
  • Tsai LC; Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
  • Chang CH; Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
  • Su CL; Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
  • Ho CH; Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
  • Chio CC; Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan.
  • Gean PW; Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
  • Kuo JR; Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of Post-Baccalaureate Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: kuojinnrung@gmail.com.
World Neurosurg ; 180: e350-e363, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37757945
BACKGROUND: The beneficial effect of pretreatment with statins on traumatic brain injury (TBI)-induced depression and anxiety and its mechanism of action remain unclear. In this study, we combined epidemiological and experimental animal data to clarify this issue. METHODS: We used the Taiwan National Health Insurance database to identify patients who were diagnosed with TBI from 2000 to 2013 and compared patients with and without statin treatment matched by age, sex, and underlying comorbidities in a 1:1 ratio. The risk of developing depression and/or anxiety was compared between patients with and without a statin using Cox proportional hazards regression. We also used a rat model to assess the effect of lovastatin pretreatment on neurobehavioral and neuropathological changes following TBI. RESULTS: The risk of developing depression was lower in the 41,803 patients in the statin cohort than nonstatin cohort (adjusted hazard ratio, 0.91 [95% confidence interval, 0.83-0.99]). In animal models, the lovastatin group had significantly reduced infarct volume, decreased immobility time and latency to eat, a reduced number of Fluoro- Jade-positive cells and levels of glial fibrillary acidic protein and tumor necrosis factor-alpha, and increased adenosine monophosphate -activated protein kinase (AMPK) and its upstream kinase liver kinase B1 in the hippocampal dentate gyrus. These effects were blocked in AMPK inhibitor-pretreated TBI rats. CONCLUSIONS: Our epidemiological data showed that a decreased risk of depression was associated with statin pretreatment, which was supported by an animal study. The underlying mechanism for this appears to involve AMPK activation in the statin pretreatment-induced alleviation of TBI.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores de Hidroximetilglutaril-CoA Redutases / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores de Hidroximetilglutaril-CoA Redutases / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article