Wharton’s jelly mesenchymal stem cells attenuate global hypoxia-induced learning and memory impairment via preventing blood-brain barrier breakdown

Objective(s): Intracerebroventricular (ICV) injections of mesenchymal stem cells (MSCs) may improve the function and structure of blood-brain barrier (BBB), possibly by preserving the BBB integrity. This study examined the impact of Wharton’s jelly (WJ)-MSCs on cognitive dysfunction and BBB disruption following a protracted hypoxic state.Materials and Methods: Twenty-four male Wistar rats were randomly studied in four groups: Control (Co): Healthy animals, Sham (Sh): Rats were placed in the cage without hypoxia induction and with ICV injection of vehicle, Hypoxic (Hx)+vehicle: Hypoxic rats with ICV injection of vehicle (۵ μl of PBS), and Hx+MSCs: Hypoxic rats with ICV injection of MSCs. Spatial learning and memory were evaluated one week after WJ-MSCs injection, and then animals were sacrificed for molecular research.Results: Hypoxia increased latency and lowered the time and distance required reaching the target quarter, according to the findings. Furthermore, hypoxic rats had lower gene expression and protein levels of hippocampus vascular endothelial (VE)-cadherin, claudin ۵, and tricellulin gene expression than Co and Sh animals (P<۰.۰۵). Finally, administering WJ-MSCs after long-term hypoxia effectively reversed the cognitive deficits and prevented the BBB breakdown via the upregulation of VE-cadherin, claudin ۵, and tricellulin genes (P<۰.۰۵).Conclusion: These findings suggest that prolonged hypoxia induces spatial learning and memory dysfunction and increases BBB disruption, the potential mechanism of which might be via reducing VE-cadherin, claudin ۵, and tricellulin genes. Hence, appropriate treatment with WJ-MSCs could reverse ischemia adverse effects and protect the BBB integrity following prolonged hypoxia.

Keywords:

Blood-brain barrier , Hippocampus , Hypoxia , Intraventricular , Mesenchymal stem cells , Wharton jelly