Editorial: Revisiting mouse models of traumatic brain injuries: a focus on intracellular mechanisms

Abstract

Traumatic brain injury (TBI) continues to be a critical health condition, especially for the newly born, the elderly, and victims of motor vehicle accidents, sports concussions, war blasts, etc. Due to the extremely complicated nature of primary and secondary sequelae following injury and the complexity of research on the human brain, little can be inferred from human clinical studies concerning TBI pathogenesis and progression (Maas et al., 2017). Instead, mouse models have overwhelmed the in vivo research on TBI. Drivers for the dominance of TBI studies in mice range from minimally serious ethical concerns of experimenting with the mouse brain, to the homogeneous genetic background of mouse strains, to the advantages of employing a larger statistically relevant sample size. Studies on rodents are nonetheless burdened with several limitations, such as non-standardized categorization of severity, use of neuroprotective anesthetics, and a different time-course of progression post-TBI damage compared to humans (Siebold et al., 2018, Radabaugh et al., 2023). More importantly, short- and long-term dysregulation of neuronal and glial cells at the perilesional region are often neglected at the expense of studying biomarkers that are more readily detected in the bloodstream (Sabirov et al., 2022). This research topic aimed to highlight the relevance and shortcomings of existing TBI mouse models (CCI, FPI, blast TBI, CHIMERA, etc.) and to investigate the intracellular mechanisms dysregulated in the injured brain (Petersen et al., 2021, Xiong et al., 2013). The dysregulated processes could include rapid short-term changes of molecular signatures or persistent long-term sequelae such as those linked to neurodegeneration. Moreover, several studies in mice have attempted pharmacological and neurotherapeutic interventions that can ameliorate TBI defects, but these await the proper assessment of their potential translation into human studies (Kabadi and Faden, 2014). There are also recent methodological interventions that can expand our knowledge of how distinct cell populations are involved in TBI etiology, progression, and treatment. As such, a reference addressing these issues would help resolve much of the concerns In review on reproducibility and translation of basic molecular phenomena into the clinical manifestation of TBI.