Abstract
BackgroundImpairment of the blood–brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). Mesenchymal stem cells (MSCs) have been widely adopted in clinical research because of their pleiotropic functions. The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects.MethodsSprague-Dawley rats were randomly assigned to the control, SAP and SAP+MSCs groups. Pancreatic impairment was assessed. The serum levels of amylase, TNF-α and IL-10, expression levels of claudin-5, Bax, Bcl-2 and MMP-9, and the BBB permeability were measured. Endothelial cell apoptosis was evaluated.ResultsSAP rats showed BBB impairment with increased permeability and secondary cerebral edema, which was confirmed using the Evans blue assay and the calculation of the brain dry/wet ratio. Treatment with MSCs decreased the serum levels of amylase and TNF-α, increased the serum levels of IL-10, attenuated the apoptosis of brain microvascular endothelial cells, upregulated claudin-5 expression and downregulated MMP-9 expression. This treatment attenuated the increased BBB permeability in SAP rats.ConclusionsMSCs attenuated the impairment of the BBB and decreased its permeability, producing protective effects in SAP rats.
Highlights
Impairment of the blood–brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP)
Flow cytometry analysis showed that CD29, CD34, CD45- and CD90-positive cells respectively accounted for approximately 99.28, 0.94, 1.44 and 97.79% of the cells, which met the requirements for further experiments (Fig. 1b)
Mesenchymal stem cell (MSC) alleviated pancreatic impairment and decreased BBB permeability in SAP rats The typical manifestations of SAP, including ascites and scattered saponification spots on the mesenterium and the greater omentum, were observed when the rats were euthanized
Summary
Impairment of the blood–brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects. The underlying pathogenesis remains to be explored, but the main promising hypothesis suggests that PE development is closely related to a blood–brain barrier (BBB) impairment that causes increased permeability. The BBB protects the central nervous system from pathogens [2]. It is mainly composed of brain microvascular endothelial cells (BMECs), paracellular junctions, astrocytes, pericytes and the basement membrane [3]. BMECs and paracellular junctions are the structural and functional components of the BBB.
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