Sericin improves cognitive outcomes in a mouse model of cerebral ischemia: The role of Blood-Brain Barrier disruption and edema

Abstract

Purpose: Oxidative stress, edema, and blood-brain barrier (BBB) dysfunction are involved in the pathophysiology of stroke and may offer opportunities for managing its related insults. Sericin (Ser) has neuroprotective and pro-cognitive effects. This study aimed to determine whether Ser could reduce cerebral edema and its associated molecular and cognitive abnormalities in a mouse model of cortical ischemia. Methods:The mice were allocated into five cohorts: Sham, normal saline (NS), Ser200, Ser300, and Ser400. Each group received its treatment for 14 days before being subjected to cerebral ischemia or a sham surgery procedure. Spatial memory was assessed using the Lashley III maze. Brain edema, BBB permeability, malondialdehyde (MDA) level, and changes in anti-oxidant markers (total antioxidant capacity (TAC) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities) were evaluated in the brain samples. Additionally, the expression of BBB structural integrity proteins, including occludin and zonula occludens-1 (ZO-1), and matrix metalloproteinase-9 (MMP-9), were analyzed. Results: Ser300 and Ser400 improved spatial memory (at least p< 0.05). Also, Ser400 reduced brain water content (p< 0.05), Ser300 and 400 decresed BBB leakage (at least p< 0.05), and normalized anti-oxidant markers (at least p< 0.05). As well, Ser400 diminished MDA content (p< 0.05). All doses decreased MMP-9 levels (at least p< 0.01). Ser400 upregulated the expression of occludin (p< 0.01), and Ser300 and 400 increased ZO-1 proteins (at least p< 0.05). Conclusion: Ser improved cognitive dysfunction associated with BBB damage and edema induced by cerebral ischemia in a mouse model.

Keywords: Brain edema, Sericin, Blood-brain barrier, Oxidative stress, Photothrombotic stroke, Memory