Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage

Abstract

Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice. Permeability of BBB was measured with Evans Blue assay and brain oedema was detected by measurement of brain water content. Expressions of NF-κB, TLR4, occludin, ZO-1, IL-1β, TNF-α, Bax, and Bcl-2 were determined by Western Blot. Neutrophils, microglia were measured by immunohistochemistry staining, neuronal apoptosis was measured by TUNEL and NeuN co-stained. Administration of MPSS post-ICH significantly reduced permeability of the BBB and brain oedema and upregulated expression of ZO-1 and Occludin. MPSS inhibited inflammatory responses, including reducing proinflammatory cytokines (IL-1β, TNF-α), suppressing infiltration of neutrophils and activation of microglia. This was accompanied by attenuated activation of the TLR4/NF-κB signalling pathway. In addition, MPSS reduced neuronal apoptosis through increasing Bcl-2 expression and reducing Bax expression. MPSS suppressed inflammatory responses, attenuated disruption of the BBB and reduced neuronal apoptosis, contributing to reduction of secondary brain injury after ICH. These results suggest that MPSS may be a potential therapy for ICH.

Keywords: Blood-brain barrier; ICH; Inflammation; Methylprednisolone sodium succinate; Mouse model; Oedema.