Contribution of excess inflammation to a possible rat model of eclamptic reversible posterior leukoencephalopathy syndrome induced by lipopolysaccharide and pentylenetetrazol: A preliminary study.

Background: Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical-imaging syndrome as well as a critical maternal complication. The precise pathophysiological mechanism remains controversial, mostly due to the lack of a reliable experimental animal model. Because women with eclampsia almost always present with RPLS as a complication, we hypothesize that seizures induced by preeclampsia may lead to RPLS in rats.

Methods: Pregnant Sprague-Dawley rats received pentylenetetrazol (PTZ, 40 mg/kg, intraperitoneal injection) after lipopolysaccharide (LPS, 1 µg/kg, tail vein injection) to induce eclampsia-like seizures. An anatomical view and brain water content were used to ascertain the success of the model. Moreover, blood pressure, serum biochemical indicators, serum and cerebrospinal fluid (CSF) inflammatory factors, neuroinflammation markers (Iba-1 for microglia and GFAP for astrocytes by immunofluorescence) and blood brain barrier (BBB) injury markers (VE-cadherin and ZO-1 protein by Western blotting) were measured to determine the possible mechanism.

Results: The rat cerebral cortex was congested and oedematous, and water contents were significantly higher following LPS and PTZ treatments. Additionally, the BP, serum and CSF inflammatory factors and neuroinflammation markers were significantly elevated, while the expression levels of VE-cadherin and ZO-1 protein were significantly decreased by LPS and PTZ treatments.

Conclusions: Excess inflammation may account for the phenotypes observed in this possible eclamptic RPLS rat model induced by LPS and PTZ, providing a better understanding of mechanism of RPLS. Specifically, excess inflammation leads to BBB dysfunction and subsequently results in fluid leakage that causes lesions and increases the entrance of inflammatory factors into the brain, thus increasing the neuronal excitability that triggers seizures.