Does sex influence basal cerebral perfusion or hypercapnic cerebrovascular reactivity in young adults?
Authors: Muer Jessica , Didier Kaylin , Wannebo Brett , Sanchez Sophie , Haley Travis , Carter Katrina , Eldridge Marlowe , Wieben Oliver , Schrage William 
Published: May 2023

Introduction: Sex differences in disease progression, prognosis, and location have been identified in stroke, aneurysms, and Alzheimer’s Disease (AD). These conditions are often associated with disturbed regional cerebral blood flow (CBF). Studies testing sex differences in CBF generally use transcranial doppler on the middle cerebral artery, leaving most brain regions unexplored. Furthermore, cerebrovascular reactivity (CVR) to a carbon dioxide (CO2) challenge might uncover functional sex differences. The purpose of this study was to assess brain regions commonly tested in pathologic states without the confounds of age, comorbidities, and pathologies. We studied healthy adults to test the hypotheses that: 1) resting regional cerebral perfusion is higher in females when compared to males and 2) CVR to CO2 is greater in females than males. Methods: Young healthy adults (M=17, F=17) were included (23 ± 4 years, BMI: 22 ± 2). Females were not taking hormonal birth control and studied on days 1-5 of menstrual cycle. Participants completed Arterial Spin Labeling (ASL) MRI scans under room air (RA) and hypercapnic (HC) conditions by breathing 21% O2 and 5% CO2, respectively. Computational Anatomy Toolbox (CAT12) program in SPM12 quantified global and regional CBF relative to gray matter volume (mL/100gm/min). Brain regions of interest were brain stem, thalamus, entorhinal area, hippocampus, and amygdala. Significance was determined using student’s t-tests. Data are presented as mean ± SD. Results: Resting regional cerebral blood flow (mL/100g/min) between sexes was significantly different in several regions: brain stem (M: 31±8, F: 42±7, p<0.001), thalamus (M: 40±10, F: 54±8, p<0.001), entorhinal area (M: 44±8, F: 57± 7, p<0.001), hippocampus (M: 46±10, F: 62±8, p<0.001) and amygdala (M: 42±9, F: 55±7 p<0.001). End tidal carbon dioxide (EtCO2) increased to HC (p<0.001) in a manner similar between sexes (M: 36±2 to 44±2mmHg; F: 35±2 to 42±2mmHg, p=0.40). CVR was significantly different between sexes (Δ mL/100g/min)/ (Δ EtCO2 mmHg) in the thalamus (M: 1.9±0.9, F: 3.2±2.2, p=0.02), and trending towards significance in the hippocampus (M: 1.7±0.7, F: 2.5±2.1, p=0.06). However, there was no significant differences in CVR in the brain stem (M: 1.7±0.9, F: 2.3±2.0, p=0.13), entorhinal area, (M: 1.6±1.1, F: 2.2±1.8, p=0.12), and amygdala (M: 1.7±0.8, F: 2.1±1.9, p=0.19). Conclusion: These data suggest fundamental differences in CBF regulation at rest, with sex differences in the brain stem, thalamus, entorhinal area, hippocampus and amygdala. CVR data suggest females exhibit a higher reactivity in the thalamus and hippocampus than males. These data uncover basic sex differences in CBF regulation, and hold implications for sex specific brain diseases in human aging.

NIH R01 HL150361

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.