Gestational treatment of folic acid attenuates blood–brain barrier leakage in pregnant- and prepubertal rats after pentylenetetrazole-induced seizure

Abstract

Objectives: Folic acid (FA) is physiologically important in mammals and is a common vitamin supplement used during pregnancy and lactation. Numerous studies have reported that FA significantly improves endothelial function. The blood–brain barrier (BBB) plays an important role in maintaining the microenvironment required for neuronal function, but its unique structure is damaged by epileptic seizures. The aim of this study was to evaluate the potential protective role of FA on BBB leakage, as well as on the reactive astrogliosis in pregnant rats and their prepubertal offspring during pentylenetetrazole (PTZ)-induced epileptic seizure.

Methods: Pregnant rats were treated with FA (5 mg/kg) and PTZ on gestational days 0–19 and 19, respectively. The pups were treated with PTZ at puberty. Evans blue was used to evaluate BBB integrity. Reactive astrogliosis was defined using immunohistochemical analysis for glial fibrillary acidic protein (GFAP). Mean arterial blood pressure (MABP) was measured at the femoral artery.

Results: A moderate decrease in BBB leakage was observed in FA-treated pregnant and prepubertal animals (P < 0.05). MABP was decreased significantly in pregnant rats (P < 0.05). The epilepsy-induced increase in MABP was less prominent in pregnant animals (P < 0.05). GFAP intensity decreased in PTZ-treated pregnant animals (P < 0.01) and FA-treated prepubertal rats.

Discussion: Our findings suggest that FA, which is used as a maternal vitamin to promote normal fetus development, may be beneficial against seizure-induced neuronal damage by decreasing BBB leakage and reactive astrogliosis in pregnant and prepubertal rats.

Keywords:

• Blood–brain barrier
• Epilepsy
• Folic acid
• Glial fibrillary acidic protein
• Pregnancy

Acknowledgments

This study was supported by Istanbul University Scientific Research Projects Unit (Project No: T-836) and Halic University, Istanbul, Turkey.

Disclaimer statements

Contributors

Dr. Burcu Şeker and Prof. Dr. Baria Oztas were responsible for the organization of structural and scientific background of this study. Dr. Hatice Yorulmaz fully participated in the animal experiments. Dr. Engin Kaptan was responsible for the GFAP immunostaining. Berrak Caglayan helped for preparing and writing process of the manuscript.

Funding

Istanbul University Scientific Research Projects Unit and Halic University.

Conflicts of interest

None.

Ethics approval

Our study has an ethical approval from Istanbul University Experimental Animal Ethics Committee (Protocol no: 01/12.12.06).