Brain microvascular damage linked to a moderate level of strain induced by controlled cortical impact

Cerebral blood vessels play an important role in brain metabolic activity in general and following traumatic brain injury (TBI) in particular. However, the extent to which TBI alters microvessel structure is not well understood. Specifically, how intracranial mechanical responses produced during impacts relate to vascular damage needs to be better studied. Therefore, the objective of this study was to investigate the biomechanical mechanisms and thresholds of brain microvascular injury. Detailed microvascular damage of mouse brain was quantified using Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI) and ex vivo Serial Two-Photon Tomography (STPT) in seven mice that had undergone controlled cortical impact. Mechanical strains were investigated through finite element (FE) modeling of the mouse brain. We then compared the post-injury vessel density map with FE-predicted strain and found a moderate correlation between the vessel length density and the predicted peak maximum principal strains (MPS) (R2 = 0.52). High MPS was observed at the impact regions with low vessel length density, supporting the mechanism of strain-triggered microvascular damage. Using logistic regression, the MPS corresponding to a 50% probability of injury was found to be 0.17. Given the literature reporting MPS of over 0.2 in the human brain for mild TBI/concussion cases, it is highly recommended to consider microvascular damage when investigating mild TBI/concussion in the future.