A systematic review and meta-analysis of the relationship between neuroinflammation and blood-brain barrier based on in vitro models

The blood-brain barrier (BBB) plays a crucial role in maintaining homeostasis within the central nervous system (CNS). Neuroinflammation disrupts the integrity of the BBB. However, there is a lack of comprehensive synthesis of in vitro evidence on this topic. This study aims to systematically review in vitro research examining the effects of neuroinflammatory stimuli on the structure and function of the BBB. PubMed, EMBASE, and Web of Science were searched for studies published between November 2014 and November 2024. Included studies employed in vitro BBB models to assess effects of defined neuroinflammatory on structural and functional. Pooled standardized mean differences (SMD) with 95 % confidence intervals (CI) were calculated using random effects models. Meta-analysis was performed using R. Overall, 55 studies were included. Neuroinflammation was found to significantly decrease transendothelial electrical resistance (TEER) (-2.15, 95 % CI [-2.73, -1.56]) while increasing permeability (2.75, 95 % CI [1.71, 3.79]). Subgroup analyses showed that co-culture models exhibited more severe disruptions compared to mono-cultures measured by a significant decrease in TEER (p < 0.05). Human-derived cells displayed heightened decreases in TEER and increased permeability compared to non-human derived cells (p < 0.05). Co-cultures of endothelial cells and pericytes exhibited pronounced effects of decreased TEER compared to endothelial cells alone (p < 0.05). Stimulation periods exceeding 24 h led to significant changes. Lipopolysaccharide (LPS) caused significant disruptions. Experiments conducted with transwell systems were more sensitive to changes in TEER compared to non-transwell systems (p < 0.05). In vitro evidence confirms neuroinflammation disrupts BBB integrity through reduced TEER, increased permeability. Human-derived cells, particularly hiPSC-derived models, endothelial-pericytes co-cultures, and exposure to LPS exceeding 24 h most effectively replicate pathophysiological disruption, potentially offering optimal platforms for exploring neurological disease-related mechanisms and therapeutic strategy in the future.