Title:Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain
Injury in the Females
Volume: 23
Issue: 7
Author(s): Mohammad I. Yatoo, Ghaith A. Bahader, Shafayat A. Beigh, Adil M. Khan, Antonisamy William James, Maleha R. Asmi and Zahoor A. Shah*
Affiliation:
- Department of Medicinal and
Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614,
USA
Keywords:
Traumatic brain injury, biomarkers, female, sex differences, protective response, BDNF, mitochondrial.
Abstract: Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality
and morbidity. Clinical and preclinical research suggests sex-related differences in short- and longterm
outcomes following TBI; however, males have been the main focus of TBI research. Females
show a protective response against TBI. Female animals in preclinical studies and women in clinical
trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a
favorable protective nature of the females compared to the males, primarily attributed to various protective
mechanisms that provide better prognosis and recovery in the females after TBI. Understanding
the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive
goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological,
hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the
protective nature of females compared to males. Furthermore, we sought to outline the evidence of
multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology,
and treatment and which can serve as objective measures and novel targets for individualized therapeutic
interventions in TBI treatment. Implementations from this review are important for the understanding
of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response
in females. It also emphasizes the critical need to include females as a biological variable and in sufficient
numbers in future TBI studies.