Saajan Davies’s research while affiliated with Cardiff University and other places

Introduction Oestrogen has a protective effect against neurodegenerative conditions, including glaucoma and dementia. Animal models suggest that oestrogen has a vasodilatory effect, which is a possible mechanism for this. However, the full influence of oestrogen on specific cerebrovascular functions is unclear. Aims This study aims to investigate the influence of hormonal fluctuations across a healthy menstrual cycle on measures of retinal and cortical vascular functioning. Methods 27 menstruating participants (age mean[SD]=22.94[3.52] years) completed a testing session during the early-follicular, late-follicular, and mid-luteal phase of their menstrual cycle. Bloods were taken to measure circulating hormones.Retinal vasculature was assessed using a Swept-Source OCT (TOPCON healthcare), including: • Choroidal thickness – 6mm² OCT scan • Vessel density, radius, and resistance – 3mm² OCT Angiography Cortical data were acquired on a Siemens MAGNETOM Prisma 3T MRI scanner and include: • Grey matter Cerebral Blood Flow (CBF) and Arterial Arrival Time (AAT) – MPLD-pCASL scan • Global Oxygen Extraction Fraction (OEF) – TRUST sequence Linear models investigated the amount of variance explained by circulating oestradiol. Results Oestradiol significantly decreased retinal resistance (χ²(1)=6.1218, P=0.01335), an effect which was greatest in the foveal vessels. Other retinal measures were stable across the menstrual cycle. No association was found with OEF, but oestradiol did significantly increase CBF (χ²(1)=17.801; P=2.452e-5) and AAT (χ²(1)=9.5183; P=0.002034), which was a global effect. Conclusion Evidence for oestrogen’s vasodilatory influence was demonstrated across a menstrual cycle and in multiple vascular beds. This provides information into how oestrogen influences the cerebrovascular system and highlights possible mechanisms by which oestrogen has a protective effect against neurodegenerative conditions. Acknowledgements The Wellcome Trust (WT224267)

Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia (CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) are modulated by gonadal hormone activity, while insulin‐like growth factor 1 facilitates exercise‐mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ in n = 128 adolescents characterised as endurance‐exercise trained (males: n = 30, females: n = 36) or untrained (males: n = 29, females: n = 33). Participants were further categorised as pre‐ (males: n = 35, females: n = 33) or post‐ (males: n = 24, females: n = 36) peak height velocity (PHV) to determine pubertal or ‘maturity’ status. Three‐factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$. Data are reported as group means (SD). Pre‐PHV youth demonstrated elevated gCBF and slower CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response times than post‐PHV counterparts (both: P ≤ 0.001). gCBF was only elevated in post‐PHV trained males when compared to untrained counterparts (634 (43) vs. 578 (46) ml min⁻¹; P = 0.007). However, CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time was faster in pre‐ (72 (20) vs. 95 (29) s; P ≤ 0.001), but not post‐PHV (P = 0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post‐PHV youth (r² = 0.19; P ≤ 0.001) and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time in pre‐PHV youth (r² = 0.13; P = 0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.