• Mohammad Amin Rajizadeh, Mohammad Khaksari, Mohammad Abbas Bejeshk, Ladan Amirkhosravi, Elham Jafari, Zahra Jamalpoor, and Akram Nezhadi.
• Cognitive and Neuroscience Research Center, AJA University of Medical Sciences, Tehran, Iran.
• Neurocrit Care. 2023 Oct 1; 39 (2): 478498478-498.

BackgroundTraumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI.MethodsEighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50 mg/kg and E2 33.3 μg/kg via inhalation for 30 min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals.ResultsVeterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations.ConclusionsOur results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.

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