Targeting Mitochondrial and Brain Injury Markers in Acquired Brain Injuries: A Randomized, Double-Blind, Placebo-Controlled Study with Melatonin

Abstract

Purpose: Oxidative stress-induced mitochondrial damage is the main event in acquired braininjuries (ABI). This study aimed to evaluate the effects of melatonin, a mitochondria-targetedantioxidant, on mitochondrial and brain injury markers, and the clinical outcomes of patientswith ABI.Methods: In this randomized controlled trial, intensive care unit (ICU) or neurology patientswith ABI (n=60) received melatonin (21 mg/day) or placebo tablets, within the first 72 hoursof injury onset for five days. As a primary endpoint, serum levels of malondialdehyde (MDA),S100B and C-reactive protein (CRP) were compared at baseline, and after five days’ intervention.Secondary endpoints included assessment of Glasgow Coma Scale (GCS) and sequential organfailure assessment (SOFA) (at the end of day 5), Rancho Los Amigos Revised Scale (RLAS-R) andmodified Rankin Scale (mRS) (at the end of month 3), the duration of mechanical ventilation,the lengths of ICU and hospital stays, and in-hospital and three-month mortality.Results: There were no significant effects of melatonin on the primary and secondary outcomes.However, the subgroup analysis showed a significant reduction in S100B in patients with nontraumaticbrain injuries, receiving melatonin versus placebo (P: 0.016).Conclusion: This study showed that melatonin supplementation in the early phase of braininjury had no significant effects on the injury markers and clinical outcomes of patients withABI. However, it reduced the level of S100B in the non-traumatic subgroup. Further larger-scalestudies are needed to determine the effects of melatonin on the ABI and its subgroups.

Keywords: Brain injury, Melatonin, Mitochondria, Oxidative stress