PhD Scientific Days 2021

TT_III_L: Theoretical and Translational Medicine III. Lectures

Roles of Nitric Oxide and Prostanoid Mediators in the Adaptation of the Cerebrocortical Microcirculation

Text of the abstract

Introduction: The understanding of cerebral autoregulation has become of notable importance due to the increased incidence of carotid artery stenosis in the elderly population which entails an increased risk of stroke, the 2nd most common cause of mortality worldwide. Multiple mechanisms are debated in the literature, including the role of nitric oxide synthases (NOS) and prostanoid mediators. As we found earlier endothelial NOS (eNOS), surprisingly, does not seem to play an important role in the autoregulation. Now we aimed to determine the relevance of the simultaneous lack of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) and prostanoid mediators (PMs).
Aims and Methods: We aimed to analyze the combined lack of eNOS and nNOS (double knock-out mice) and the role of prostanoid mediators (1 mg/kg indomethacin, TPR knock-out mice) in cerebrovascular autoregulation by analyzing the changes of cerebrocortical blood flow (CoBF) with the high temporal and spatial resolution of laser-speckle imaging after reducing the cerebral perfusion pressure by unilateral (left) common carotid artery occlusion (CAO).
Results: In eNOS/nNOS double KO animals the acute CoBF reduction after CAO was unaltered, but the recovery of CoBF was worsened as compared to controls. Indomethacin treatment resulted in a faster recovery in the temporal region. In TPR-KO animals, the recovery of the CoBF was diminished.
Conclusion: These results indicate that (1) the combined lack of eNOS and nNOS impairs only the subacute phase of the recovery after unilateral CAO and (2) indomethacin treatment results in a faster recovery, probably by inhibiting the release of a vasoconstrictor prostanoid, which is not thromboxane A2.
Grant and financial support: EFOP-3.6.3-VEKOP-16-2017-00009, OTKA K-125174, OTKA K-112964, NVKP_16-1-2016-0042, ÚNKP-20-4-I-SE-19.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine