In vivo imaging of nitric oxide in the male rat brain exposed to a shock wave

Abstract

While numerous studies have suggested the involvement of cerebrovascular dysfunction in the pathobiology of blast‐induced traumatic brain injury (bTBI), its exact mechanisms and how they affect the outcome of bTBI are not fully understood. Our previous study showed the occurrence of cortical spreading depolarization (CSD) and subsequent long‐lasting oligemia/hypoxemia in the rat brain exposed to a laser‐induced shock wave (LISW). We hypothesized that this hemodynamic abnormality is associated with shock wave‐induced generation of nitric oxide (NO). In this study, to verify this hypothesis, we used an NO‐sensitive fluorescence probe, diaminofluorescein‐2 diacetate (DAF‐2 DA), for real‐time in vivo imaging of male Sprague–Dawley rats' brain exposed to a mild‐impulse LISW. We observed the most intense fluorescence, indicative of NO production, along the pial arteriolar walls during the period of 10–30 min post‐exposure, parallel with CSD occurrence. This post‐exposure period also coincided with the early phase of hemodynamic abnormalities. While the changes in arteriolar wall fluorescence measured in rats receiving pharmacological NO synthase inhibition by nitro‐L‐arginine methyl ester (L‐NAME) 24 h before exposure showed a temporal profile similar to that of changes observed in LISW‐exposed rats with CSD, their intensity level was considerably lower; this suggests partial involvement of NOS in shock wave‐induced NO production. To the best of our knowledge, this is the first real‐time in vivo imaging of NO in rat brain, confirming the involvement of NO in shock‐wave‐induced hemodynamic impairments. Finally, we have outlined the limitations of this study and our future research directions.

Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging

“…Examining the long-term ramifications of exposure to LLB is particularly significant due to its potential to contribute to chronic deficits in cerebral perfusion by accelerating aging-related mechanisms in cerebrovascular dysfunction, such as reductions in nitric oxide (NO) availability and neurovascular oxidative stress [ 108 ]. Notably, preclinical investigations have demonstrated that blast exposure triggers acute oxidative stress [ 21 , 44 , 60 , 109 , 110 ] and alters NO production [ 60 , 111 , 112 ], linking both to disruptions in BBB permeability [ 44 , 109 , 111 , 112 , 113 ]. Intriguingly, similar patterns of neurovascular dysfunction are apparent in neurodegenerative diseases, such as AD, dementia, and PD [ 100 ].…”