Placental ischemia in pregnant rats impairs cerebral blood flow autoregulation and increases blood–brain barrier permeability

Abstract

Cerebrovascular events contribute to ~40% of preeclampsia/eclampsia‐related deaths, and neurological symptoms are common among preeclamptic patients. We previously reported that placental ischemia, induced by reducing utero‐placental perfusion pressure, leads to impaired myogenic reactivity and cerebral edema in the pregnant rat. Whether the impaired myogenic reactivity is associated with altered cerebral blood flow (CBF) autoregulation and the edema is due to altered blood–brain barrier (BBB) permeability remains unclear. Therefore, we tested the hypothesis that placental ischemia leads to impaired CBF autoregulation and a disruption of the BBB. CBF autoregulation, measured in vivo by laser Doppler flowmetry, was significantly impaired in placental ischemic rats. Brain water content was increased in the anterior cerebrum of placental ischemic rats and BBB permeability, assayed using the Evans blue extravasation method, was increased in the anterior cerebrum. The expression of the tight junction proteins: claudin‐1 was increased in the posterior cerebrum, while zonula occludens‐1, and occludin, were not significantly altered in either the anterior or posterior cerebrum. These results are consistent with the hypothesis that placental ischemia mediates anterior cerebral edema through impaired CBF autoregulation and associated increased transmission of pressure to small vessels that increases BBB permeability leading to cerebral edema.

Abstract

Preeclampsia is associated with an increased risk for developing encephalopathies. A prevailing theory is that impaired cerebral blood flow autoregulation contributes to this process. Whether placental ischemia, commonly thought to be a major underlying factor in the development of preeclampsia, can cause impaired cerebral blood flow autoregulation is not clear. In this study, placental ischemia is experimentally induced to test this directly. The results show that placental ischemia in the pregnant rat causes marked impairment of cerebral blood flow autoregulation.