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Nrf2→ER stress inhibition→synaptogenesis and neuroprotection
Atorvastatin exerts neuroprotective effects post-TBI by inhibiting ER stress, activating Nrf2 antioxidant pathways, and promoting synaptogenesis and angiogenesis; 3 papers with a 50% support ratio including both animal models and clinical GCS/GOS outcome data provide solid evidence. This is an active translational research area.
“Conclusions: This study demonstrated that Atorvastatin could reduce the rate of inflammatory factors in TBI patients.”
— The Effect of Low-Dose Atorvastatin on Inflammatory Factors in Patients with Traumatic Brain Injury: A Randomized Clinical Trial (2020)DOI“Our present study evaluated the neuroprotection effects of atorvastatin by inhibiting TBI-induced ER stress, as well as the potential role of the Nrf2/HO-1 pathway in experimental TBI.”
— Atorvastatin prevents endoplasmic reticulum stress-mediated apoptosis via the Nrf2/HO-1 signaling pathway in TBI mice. (2023)DOI“This study aimed to evaluate the effect of atorvastatin administration on the Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), and Disability Rating Scale (DRS) in patients with TBI.”
— Evaluation of the Effect of Atorvastatin Administration on the Outcomes of Patients with Traumatic Brain Injury: A Double-blinded Randomized Clinical Trial. (2021)DOI“Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear.”
— Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats. (2023)DOI“This study suggests either simvastatin 40 mg, atorvastatin 20 mg, or rosuvastatin 20 mg for 10 days as the optimal therapeutic forms and doses to be applied in the management of TBI.”
— The neuroprotective effect of statin in traumatic brain injury: A systematic review. (2023)DOI