Cranial Bone Changes Induced by Mild Traumatic Brain Injuries: A Neglected Player in Concussion Outcomes?

Abstract

Mild traumatic brain injuries (TBIs), particularly when repetitive in nature, are increasingly recognized to have a range of significant negative implications for brain health. Much of the ongoing research in the field is focused on the neurological consequences of these injuries and the relationship between TBIs and long-term neurodegenerative conditions such as chronic traumatic encephalopathy and Alzheimer's disease. However, our understanding of the complex relationship between applied mechanical force at impact, brain pathophysiology, and neurological function remains incomplete. Past research has shown that mild TBIs, even below the threshold that results in cranial fracture, induce changes in cranial bone structure and morphology. These structural and physiological changes likely have implications for the transmission of mechanical force into the underlying brain parenchyma. Here, we review this evidence in the context of the current understanding of bone mechanosensitivity and the consequences of TBIs or concussions. We postulate that heterogeneity of the calvarium, including differing bone thickness attributable to past impacts, age, or individual variability, may be a modulator of outcomes after subsequent TBIs. We advocate for greater consideration of cranial responses to TBI in both experimental and computer modeling of impact biomechanics, and raise the hypothesis that calvarial bone thickness represents a novel biomarker of brain injury vulnerability post-TBI.

The emerging importance of skull-brain interactions in traumatic brain injury

“…Currently, the interaction between age and sex on cranial thickness and strength remains unclear (20). It is worth noting here that while skull fracture can occur in severe TBI and contribute to post-injury fragility, moderate TBI has been shown to cause an increase in cranial thickness which may be protective against cranial fracture in cases of repeated TBI (21).…”

“…Preliminary research shows that this bone anabolic effect may be mediated in part by the cannabinoid-1 receptor (70). Furthermore, the underlying meninges appears to respond in a similarly localized fashion, mounting a dynamic transcriptomic response that is exacerbated with age (21). As with the potential role of the skull's immune response in modulating TBI outcome, the influence of changes to skull morphology at both the macroscopic and cellular levels following TBI may serve as another path to explore potential therapeutic interventions for recovery from TBI.…”

Approximation of bone mineral density and subcutaneous adiposity using T1-weighted images of the human head

“…The outcomes of our study suggest that skull BDM can serve as a proxy measure of a person's total BMD. In addition, the information on skull bone thickness might become relevant in studies of traumatic brain injuries as the cranium plays a vital role in protecting the brain (Semple & Panagiotopoulou, 2023). Furthermore, the thickness-based adiposity proxy measures can be included as potential confounds in functional neuroimaging studies, such as electroencephalography, functional near infrared spectroscopy, and transcranial direct current stimulation (Gorniak et al 2022).…”