Intravenous infusion of mesenchymal stem cells reduces epileptogenesis in a rat model of status epilepticus.

ABSTRACT

OBJECTIVE: Status epilepticus (SE) causes neuronal cell death, aberrant mossy fiber sprouting (MFS), and cognitive deteriorations. The present study tested the hypothesis that systemically infused mesenchymal stem cells (MSCs) reduce epileptogenesis by inhibiting neuronal cell death and suppressing aberrant MFS, leading to cognitive function preservation in a rat model of epilepsy. METHODS: SE was induced using the lithium-pilocarpine injection model. The seizure frequency was scored using a video-monitoring system and the Morris water maze test was carried out to evaluate cognitive function. Comparisons were made between MSCs- and vehicle-infused rats. Immunohistochemical staining was performed to detect Green fluorescent protein (GFP)+ MSCs and to quantify the number of GAD67+ and NeuN+ neurons in the hippocampus. Manganese-enhanced magnetic resonance imaging (MEMRI) and Timm staining were also performed to assess the MFS. RESULTS: MSC infusion inhibited epileptogenesis and preserved cognitive function after SE. The infused GFP+ MSCs were accumulated in the hippocampus and were associated with the preservation of GAD67+ and NeuN+ hippocampal neurons. Furthermore, the MSC infusion suppressed the aberrant MFS in the hippocampus as evidenced by MEMRI and Timm staining. CONCLUSIONS: This study demonstrated that the intravenous infusion of MSCs mitigated epileptogenesis, thus advancing MSCs as an effective approach for epilepsy in clinical practice.