Abstract P263: Interleukin-17 Infusion Promotes Cerebral Edema and Increased Blood Brain Barrier Permeability in Pregnant Rats

Abstract

While cerebrovascular abnormalities such as cerebral edema and increased blood-brain barrier (BBB) permeability are a common complication of (pre)eclampsia, the exact mechanisms underlying these abnormalities remain unclear. One potential mechanism could be increased Interleukin-17 (IL-17), a pro-inflammatory cytokine that is increased in both preeclampsia patients and the rat model of placental ischemia created by reducing uterine perfusion pressure. While IL-17 has been linked to the pathogenesis of preeclampsia, its effect on cerebrovascular function during pregnancy is unknown. Thus, we tested the hypothesis that increasing circulating IL-17 during pregnancy promotes regional increases in brain water content and BBB permeability. Recombinant mouse IL-17 (150 pg/day) was infused via mini-osmotic pump (i.p) from gestational day 14 to 19 in pregnant rats (n = 5-7 per group). Brain water content was assessed using the dry weight to wet weight ratio and BBB permeability was assessed by quantifying Evans blue extravasation into the anterior cerebrum, hippocampus, cortex, striatum, posterior cerebrum, and cerebrum. As reported previously, IL-17 infusion resulted in a significant increase in mean arterial pressure (119 ± 3 vs. 104 ± 4 mmHg in normal pregnant group; p = 0.010). Water content tended to be increased in the cortex (80.5 ± 0.2 vs. 79.5 ± 0.4%, p = 0.054) and striatum (77.6 ± 0.8 vs. 75.1 ± 1.4%, p = 0.062) and was significantly increased in the posterior cerebrum (79.7 ± 0.4 vs. 77.8 ± 0.5%, p = 0.007) and cerebrum (79.8 ± 0.3 vs. 78.8 ± 0.1%, p = 0.005) of the IL-17 treated group. BBB permeability was increased only in the cortex (0.017 ± 0.002 vs 0.012 ± 0.002, p = 0.046) of rats receiving IL-17 infusion. These data suggest that increased IL-17 during pregnancy contributes to edema formation and increased BBB permeability in the cerebral cortex and may be a therapeutic target in preeclampsia. Future studies will determine whether reducing IL-17 levels in placental ischemic rats will prevent these cerebrovascular changes.