Combination of endothelial progenitor cells and BB-94 significantly alleviates brain damage in a mouse model of diabetic ischemic stroke

by Selleckchem | May 25 2023

Ischemic stroke is a complication of chronic macrovascular disease in type 2 diabetes. However, the pathogenesis of diabetic ischemic stroke has not yet been fully clarified. The aim of the present study was to investigate the underlying effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic stroke. In vitro experiments were performed using oxygen-glucose deprivation/reoxygenation (OGD/R) model cells, established using HT22 mouse hippocampal cells. MTT assays and flow cytometry revealed that BB-94 prominently induced the proliferation of the OGD/R model cells and prevented their apoptosis. When EPCs and BB-94 were applied to the OGD/R model cells in combination, proliferation was further accelerated and oxidative damage was attenuated. In vivo experiments were also performed using a middle cerebral artery occlusion (MCAO) mouse model. The results of modified neurological severity scoring and oxidative stress marker analysis demonstrated that EPCs and BB-94 prominently alleviated cerebral ischemia/reperfusion injury in the MCAO model mice. Furthermore, reverse transcription-quantitative PCR and western blot assays revealed that EPCs in combination with BB-94 significantly downregulated the expression of matrix metalloproteinases (MMPs) and upregulated the expression of tissue inhibitor of metalloproteinases 1 in OGD/R cells and MCAO model mice. The results suggest that EPCs were successfully isolated and identified, and the OGD/R cell and MCAO mouse models were successfully established. They also indicate that EPCs alone or in combination with BB-94 may exert protective effects against ischemic stroke via the reduction of MMP expression.

Comments：

The present study aimed to investigate the underlying effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic ischemic stroke. The study utilized both in vitro and in vivo experiments to assess the potential protective effects of these agents.

The in vitro experiments were performed using an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 mouse hippocampal cells. The results showed that BB-94 induced cell proliferation and prevented apoptosis. When EPCs and BB-94 were applied in combination, proliferation was further accelerated, and oxidative damage was attenuated.

The in vivo experiments were conducted using a middle cerebral artery occlusion (MCAO) mouse model. The results showed that EPCs and BB-94 alleviated cerebral ischemia/reperfusion injury in the MCAO model mice, as demonstrated by modified neurological severity scoring and oxidative stress marker analysis.

Further analysis using reverse transcription-quantitative PCR and western blot assays revealed that EPCs in combination with BB-94 significantly downregulated the expression of matrix metalloproteinases (MMPs) and upregulated the expression of tissue inhibitor of metalloproteinases 1 in OGD/R cells and MCAO model mice.

Overall, these results suggest that EPCs and BB-94 may exert protective effects against ischemic stroke, possibly through the reduction of MMP expression.