Identification of persistent neurological complications after eclampsia and discovery of novel neuroprotective treatments to improve maternal outcomes

Introduction

The goal of this project is to define neurological outcomes after eclampsia and to determine underlying pathophysiological pathways to eclampsia, which will lead to new drugs for neuroprotection of the maternal brain.

Background

Preeclampsia and eclampsia are the most common causes of direct maternal death globally. Magnesium sulphate is the only treatment in use, but it has serious side effects, only protects from seizures in 50% of cases, and neuroprotection in the long term is not established. Women with eclampsia run an increased risk of long-term neurological sequelae, but causality with the acute insult is not proven.

There is an urgent need to understand this relationship and the underlying pathophysiological pathways to identify how the acute injury affects the chronic sequelae and to identify new targets for neuroprotective drugs.

Research Objectives

I want to respond to this need by determining recovery from the acute cerebral complications of eclampsia to follow up 6 months postpartum. The objectives include:

1. Characterizing and identifying pathways for neurological injury secondary to eclampsia.
2. Investigating mechanisms of:
   • Blood-brain barrier injury
   • Cerebral blood flow autoregulation
   • Neuroinflammation
   • Cognitive function deficits
   • White matter scarring in the brain

Methodology

I will make use of a cohort of women with eclampsia from my site at Stellenbosch University, South Africa, as well as a rat model of preeclampsia and an in vitro model of preeclampsia in my lab at the University of Gothenburg, Sweden, to evaluate these outcomes.

I will use anti-diabetic and anti-epileptic drugs commonly used in pregnancy and test these in a rat model of preeclampsia to find new neuroprotective treatments that improve maternal outcomes. This could enable us to protect the maternal brain, save lives, and reduce morbidity globally.

Unique Qualifications

My position as a fully trained obstetrician conducting translational research, focusing on cerebral complications, makes me unique in the field and very well fitted to conduct this research project.