TY - JOUR
T1 - Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy
AU - Cao, Rui
AU - Zhang, Chenchu
AU - Mitkin, Vladimir V.
AU - Lankford, Miles F.
AU - Li, Jun
AU - Zuo, Zhiyi
AU - Meyer, Craig H.
AU - Goyne, Christopher P.
AU - Ahlers, Stephen T.
AU - Stone, James R.
AU - Hu, Song
N1 - Publisher Copyright:
Copyright © 2019, Mary Ann Liebert, Inc.
PY - 2019/5/15
Y1 - 2019/5/15
N2 - Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebral hemodynamics and metabolism - including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen - 4 h post-injury. Moreover, we assessed the effect of blast exposure on cerebrovascular reactivity (CVR) to vasodilatory stimulation. With vessel segmentation, we extracted these changes at the single-vessel level, revealing their dependence on vessel type (i.e., artery vs. vein) and diameter. We found that bTBI at this pressure level did not induce pronounced baseline changes in cerebrovascular diameter, blood perfusion, oxygenation, flow, oxygen extraction, and metabolism, except for a slight sO 2 increase in small veins (<45 μm) and blood flow increase in large veins (≥45 μm). In contrast, this blast exposure almost abolished CVR, including arterial dilation, flow upregulation, and venous sO 2 increase. This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.
AB - Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebral hemodynamics and metabolism - including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen - 4 h post-injury. Moreover, we assessed the effect of blast exposure on cerebrovascular reactivity (CVR) to vasodilatory stimulation. With vessel segmentation, we extracted these changes at the single-vessel level, revealing their dependence on vessel type (i.e., artery vs. vein) and diameter. We found that bTBI at this pressure level did not induce pronounced baseline changes in cerebrovascular diameter, blood perfusion, oxygenation, flow, oxygen extraction, and metabolism, except for a slight sO 2 increase in small veins (<45 μm) and blood flow increase in large veins (≥45 μm). In contrast, this blast exposure almost abolished CVR, including arterial dilation, flow upregulation, and venous sO 2 increase. This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.
KW - blast traumatic brain injury
KW - cerebrovascular reactivity
KW - hemodynamics
KW - oxygen metabolism
KW - photoacoustic microscopy
UR - http://www.scopus.com/inward/record.url?scp=85065550992&partnerID=8YFLogxK
U2 - 10.1089/neu.2018.6062
DO - 10.1089/neu.2018.6062
M3 - Article
C2 - 30501547
AN - SCOPUS:85065550992
SN - 0897-7151
VL - 36
SP - 1526
EP - 1534
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 10
ER -