Abstract TP014: Experimental preeclampsia increases MPO expression and is associated with increased stroke severity in rat neonates

Introduction: Emerging evidence has demonstrated that myeloperoxidase (MPO), a neutrophilic peroxidase enzyme, reduces nitric oxide bioavailability and contributes to poor placentation and vascular impairment during preeclampsia. Experimental preeclampsia (ePE) has been shown to impair myogenic tone and sensitivity to nitric oxide in the cerebral blood vessels of rat offspring. Given the role of MPO in neutrophil extracellular traps (NET) and its role in acute stroke injury, we sought to evaluate the role of MPO in pial collateral function in neonatal rats during stroke. Hypothesis: Experimental preeclampsia induces penumbral MPO activity, which is associated with impaired pial collateral recruitment and aggravates perinatal stroke outcomes. Methods: Experimental preeclampsia was induced by a high cholesterol diet in Sprague Dawley pregnant rats. Male and female pups (10-11 days) born to normal pregnancies (NP) were transcardially perfused with latex/ink (30%/70%) to determine the coordinates of pial collaterals. Laser speckle contrast imaging (LSCI) was used to measure pial blood flow in the collateral territory during 3-hour awake intraluminal middle cerebral artery occlusion (MCAO). At 72 h post-MCAO, pups were euthanized, brains were collected, and TTC staining was performed for infarct volume measurement. Plasma and brain tissue were also collected to perform molecular analyses. Result: Analysis of LSCI data demonstrated robust recruitment of pial collaterals in NP-pups but not in ePE-pups. Experimental preeclampsia increased systemic inflammation as well as cerebral infarction in newborn offspring at 72h post-MCAO, with a more prominent effect in males. This concurred with a significant rise in MPO, citrullinated histone-3 (Cit-H3), IL-1β, TNF-α, P-selectin, VCAM-1, and eNOS protein expression in ischemic tissue (Table 1). Conclusion: The present findings indicate that ePE aggravates stroke-induced brain injury and impairs collateral recruitment during arterial stroke in newborn rats. These effects were more significant in male stroke pups. MPO and Cit-H3 overexpression in ischemic neonatal brains is suggestive of NET formation and represents a promising therapeutic target to improve cerebral perfusion and mitigate stroke outcomes in neonates born to preeclamptic mothers.