Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart-brain dysfunctions in adulthood

AimRetrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of cardiac events. However, the exact functional and temporal dynamics and the associations between heart and brain pathophysiological trajectories are not understood. MethodsA single impact to the left somatosensory cortical area of the intact skull was performed on juvenile mice (17 days postnatal). Cerebral 3D photoacoustic imaging was used to measure the oxygen saturation (sO(2)) in the impacted area 4 h after mTBI followed by 2D and 4D echocardiography at days 7, 30, 90, and 190 post-impact. At 8 months, we performed a dobutamine stress test to evaluate cardiac function. Lastly, behavioral analyses were conducted 1 year after initial injury. ResultsWe report a rapid and transient decrease in cerebrovascular sO(2) and increased hemoglobin in the impacted left brain cortex. Cardiac analyses showed long-term diastolic dysfunction and a diminished systolic strain response under stress in the mTBI group. At the molecular level, cardiac T-p38MAPK and troponin I expression was pathologic modified post-mTBI. We found linear correlations between brain sO(2) measured immediately post-mTBI and long-term cardiac strain after 8 months. We report that initial cerebrovascular hypoxia and chronic cardiac dysfunction correlated with long-term behavioral changes hinting at anxiety-like and memory maladaptation. ConclusionExperimental juvenile mTBI induces time-dependent cardiac dysfunction that corresponds to the initial neurovascular sO(2) dip and is associated with long-term behavioral modifications. These imaging biomarkers of the heart-brain axis could be applied to improve clinical pediatric mTBI management.

Automated summary

Retrospective studies have shown that mild traumatic brain injury (mTBI) in pediatric patients may increase the risk of cardiac events, but the precise functional and temporal dynamics and associations between heart and brain pathophysiological trajectories are not well understood. In this study, a single impact was performed on the left somatosensory cortical area of juvenile mice, and various imaging techniques were used to measure the changes in brain and heart function over time. The results showed that mTBI caused a transient decrease in brain oxygen saturation and long-term cardiac dysfunction, which was correlated with behavioral changes. These imaging biomarkers could potentially be used to improve the management of pediatric mTBI.