INTRODUCTION: The ketogenic diet (KD) is a high-fat, low-carbohydrate nutritional regimen with moderate protein content that induces a metabolic state of ketosis, in which fats replace glucose as the primary energy source. Over the past century, the therapeutic role of KD in the treatment of epilepsy has been widely recognized. However, its impact on early development of nervous system remains unknown. Given the rising non-medical popularity of KD and its increasing use among healthy individuals, it is essential to evaluate its potential adverse consequences. Hippocampal astrocytes play essential roles in brain development, including participation in neurogenesis and ketone body transport across the blood–brain barrier (BBB).

AIM(S): The aim of the present study was to evaluate the effects of KD on hippocampal astrocytes during nervous system development using a rat model.

METHOD(S): Pregnant Wistar females were divided according to diet into a ketogenic diet group (KD) and a normal diet group (ND), as well as a group in which the diet was switched from KD to ND on the second postnatal day (KDND). On postnatal day 60 (P60), offspring were perfused, and their brains were collected, sectioned, and processed using immunohistochemical staining technique.

RESULTS: To assess astrocytic reactivity within the hippocampus, GFAP immunostaining was performed followed by quantitative microscopic analysis. Based on acquired hippocampal images, the immunoreactive area of GFAP-positive cells was quantified using ImageJ.

CONCLUSIONS: By examining how maternal ketogenic diet influences astrocyte development, this study addresses an important gap in our understanding of the diet’s potential impact on the maturation of the offspring’s nervous system.