US Department of Defense
Advancing Blast Injury Research to Protect and Heal Those Who Serve

Mild Traumatic Brain Injury Induces Time - and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability

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The response of individuals with blast-related TBI to a stroke was explored using a mouse model, showing that vascular dysfunction due to mTBI persists to four (4) weeks in female mice but not in males.

Mild traumatic brain injury (mTBI) is a well-known condition prevalent with military personnel returning from deployment and is associated with subtle cerebrovascular impairments that persist over time. This animal study was motivated by known increases in susceptibility to strokes in Service members with mTBI. In this study, a standardized mTBI exposure protocol was applied to mice, and a mid-cerebral artery occlusion (simulating a stroke) was applied for 1 hour, at seven (7) or 28 days after blast exposure in the experimental group. The resulting tissue damage to the mouse brain was studied using histological methods to determine the volume of infarcted lesions, the presence of several physiological indicators, and the status of the blood-brain barrier.

The data suggests that mTBI may result in persistent cerebrovascular dysfunction and increased susceptibility to worsened ischemic outcomes, although these dysfunctions occur differently in male and female mice. Compared to non-mTBI groups, both the male and female mTBI groups had larger infarct volumes if the infarct was applied 7 days after blast exposure. However, if the infarct was applied 28 days after blast exposure, the infarct volumes for the female mTBI groups were larger than the non-exposed, but the infarct volumes for the male mTBI groups were not statistically significantly different as compared to the male non-exposed groups (p < 0.05). Similar measurements were performed in this study to assess changes in intravascular coagulation, blood-brain barrier permeability, and angiogenesis in response to a stroke after a mTBI. These showed substantive changes in vascular physiology consistent with less effective recovery from ischemia.

These results increased attention to vascular-related neurological conditions in Veterans with mTBI especially with female warfighters who have experienced a mTBI. Similar studies could lead to advances in treatment for these conditions based on the vascular responses that were observed.

MRI technologist conducts an MRI scan of a patient's brain
Figure 1. SAN DIEGO (Aug. 3, 2020) Lorie Falaminiano, an MRI technologist assigned to Naval Medical Center San Diego (NMCSD), conducts an MRI scan of a patient's brain at the hospital Aug. 3. NMCSD continues to treat patients during the coronavirus (COVID-19) pandemic while its Sailors and staff adhere to social-distancing guidelines. NMCSD's mission is to prepare service members to deploy in support of operational forces, deliver high quality healthcare services, and shape the future of military medicine through education, training, and research. NMCSD employs more than 6,000 active duty military personnel, civilians, and contractors in Southern California to provide patients with world-class care anytime, anywhere. (U.S. Navy photo by Mass Communication Specialist Seaman Luke Cunningham)


Bailey Whitehead, Ruth Velazquez-Cruz, Ali Albowaidey, Ning Zhang, Kate Karelina, and Zachary M. Weil. Mild Traumatic Brain Injury Induces Time- and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability. Journal of Neurotrauma. ahead of print


This study was supported by the National Institutes of Neurological Disorders and Stroke (P30-NS045758), as well as the West Virginia University Stroke and Alzheimer's Related Dementias Training Program (T32AG052375), and the National Institute of General Medicine Sciences (P20 GM109098).

Last modified: 26-Jan-2023