Abstract TP273: Multiparity is Associated with Higher Perfusion of the Transverse Sinus and Increased Peripheral Retinal Cannabinoid Receptor 1 Expression in Mice

Multiparity, the condition of giving birth to multiple offspring, is associated with increased cardiovascular risk and overall neuroprotective effects. We showed previously that retinal vascular parameters are altered in multiparous mice; however, the potential mechanisms were not assessed. Additionally, whether cerebrovascular perfusion is altered in multiparous mice, is unknown. The goal of the current study was to determine whether multiparity leads to changes in cerebral perfusion and whether the expression of retinal cannabinoid receptor 1 (CB1R), important for vascular function, is affected. We utilized female Cnr1-eGFP reporter mice that were nulliparous (n=6) or multiparous (n=8) with 3±2 litters. Cerebral perfusion was measured using Laser Speckle Imaging along with heart rate and oxygen saturation, recorded using a paw sensor. For CB1R expression, retinas were dissected, stained with GFP and CD31 (endothelial cell marker), and imaged using confocal microscopy. Mean GFP intensity in the central and peripheral retina was obtained using NIS Elements and normalized to the image area. Differences were analyzed using Unpaired T-test. Multiparous mice had higher body weight (38.4 ± 5.1g vs 29.8 ± 7.7g, p=0.026), heart weight (179.9 ± 16.4mg vs 145.2 ± 15.2mg, p=0.002), and lower brain weight as a fraction of body weight (12.5 ± 1.3 vs 16.5 ± 4.5, p=0.010) compared to nulliparous females. Multiparous females had a higher perfusion of the transverse sinus (24.9 ± 3.3pu/mm 2 vs 19.5 ± 4.3pu/mm 2 , p=0.021) with no difference in other brain regions compared to nulliparous mice (p>0.05). Mean CB1R expression was unchanged in the central retina (p=0.207), but increased in peripheral retina (p=0.087). Further analysis showed that majority of the expression occurred in the photoreceptor layer of the retina. Together, these data support the hypothesis that multiparity increases brain drainage through the sinuses, with no change in other brain regions. Additionally, higher CB1R expression in the peripheral retina could indicate improved retinal function in multiparous mice. Ongoing studies will quantify and characterize CB1R changes in the retinal layers, as well determine whether it changes in pregnancy and hypertensive pregnancy disorders.