Targeting Neuroinflammation in the Piriform Cortex-Amygdala: Enhanced Efficacy of Niosome-Based Sodium Butyrate in Ischemic Stroke.

Ischemic stroke induces extensive neuronal damage in multiple brain regions, including the piriform cortex-amygdala (PCA), critical for olfaction and emotional regulation. The present study evaluated the efficacy of sodium butyrate (SB) as a neuroprotective agent against the stroke-induced damage in the PCA. SB possesses poor pharmacokinetic properties. Therefore, to overcome this obstacle, the niosome nanoparticles, containing SB, were formulated and analyzed for physicochemical features. A particle size of 85.82 nm, polydispersity index (PDI) of 0.277, zeta potential of -39.8 mV, and a controlled release pattern were determined for nio-SB. To evaluate the treatment efficacy of SB and nio-SB on PCA, male Wistar rats were assigned to four groups of sham, MCAO, SB, and nio-SB. Ischemia was induced by middle cerebral artery occlusion (MCAO). Following 24 h reperfusion, neurological deficiencies, infarct volume, blood-brain barrier (BBB) permeability, histopathological status, biochemical parameters, and relative mRNA expression of proinflammatory and the BBB tight junction proteins were assessed. SB and nio-SB improved the neurological deficiency score, stroke volume, BBB leakage, and neuronal death in the PCA. However, the effects of nio-SB were significantly more pronounced. Nio-SB also increased the superoxide dismutase and glutathione peroxidase activity, and decreased malondialdehyde levels. Furthermore, nio-SB declined the mRNA expression of interleukin-1β and tumor necrosis factor-α in the PCA and preserved the BBB integrity by attenuating matrix metalloproteinase-9 and upregulating claudin-5 and zonula occludens-1 mRNA levels. In conclusion, the study underscores the SB efficacy in alleviating the stroke-derived injuries in the PCA, and the niosome nanoparticles probably improve its effectiveness.