Reactive astrogliosis and microgliosis in animal models of focally induced seizures: A systematic review and multivariate multilevel meta-analysis

Abstract

Reactive astrogliosis and microgliosis are hallmarks of various central nervous system (CNS) diseases, including epilepsy. Both are observed following seizures in various models of epilepsy. We conducted a systematic meta-analysis to synthesize current knowledge on reactive astrogliosis and microgliosis in animal models involving experimentally induced seizures using a multilevel approach to analyze 260 comparisons from 52 studies. Results revealed significant elevations in both astrogliosis (Standardized Mean Difference (SMD) = 1.90, 95 % Confidence Interval (CI): 1.39–2.40) and microgliosis (SMD = 2.02, 95 % CI: 1.39–2.66) with distinct model-specific temporal profiles. Models using chemoconvulsants demonstrated progressive astrocytic activation and pronounced microglial surge during the chronic phase, while electrical stimulation models showed temporally distinct glial activation patterns. Infection models induced acute microglial responses and progressive astrogliosis. Significant methodological heterogeneity was observed, with evidence of publication bias (including inconsistent definitions of seizure phases and limited use of EEG or blinding) and notable effects of a priori power analyses on reported outcomes. These findings provide a framework for understanding model-specific seizures induced glial responses and identify critical methodological considerations for enhancing translational value, including optimal windows for targeted interventions.