Salvianolic Acid B Attenuates Excitotoxic Neuronal Injury After Transient Cerebral Ischemia

Excitotoxic neuronal injury plays a central role in the pathological cascade which follows cerebral ischemia. Excessive glutamatergic signaling leads to calcium overload and the activation of apoptotic pathways, ultimately triggering neuronal death. Salvianolic acid B (Sal B), a water-soluble polyphenolic compound derived from Salvia miltiorrhiza, exhibits neuroprotective properties; however, its effects on excitotoxic neuronal injury following cerebral ischemia remain unclear. The present study used both in vitro and in vivo models of ischemic injury to investigate whether Sal B attenuated excitotoxic neuronal damage.

Primary cortical neurons were exposed to cobalt chloride (CoCl₂) to induce hypoxia-like injury, after which neuronal viability and apoptotic markers were evaluated. A middle cerebral artery occlusion (MCAO) rat model was constructed to examine the ischemia-induced alterations in excitatory neurotransmission-related proteins. Protein expression was analyzed using western blotting and immunofluorescence, while gene expression was assessed using quantitative real-time PCR.

Sal B significantly improved neuronal viability and reduced CoCl₂-induced apoptotic signaling, as indicated by the decreased cleavage of caspase-3 and PARP-1. In the MCAO model, ischemia altered the expression of glutamatergic markers, including glutamate receptor-1 (GluA1), vesicular glutamate transporter-2 (VGLUT2), and N-methyl-D-aspartate receptor-1 (NMDAR1). Sal-B treatment attenuated these alterations, reducing the GluA1 and VGLUT2 intensities in NeuN-positive cortical neurons. Furthermore, Sal B decreased mRNA expression of the hypoxia marker HIF1α and the pro-apoptotic factor Noxa, while increasing expression of the anti-apoptotic Bcl2 family members, Bcl-2 and Bcl-xL.

SalB attenuates hypoxia- and ischemia-induced neuronal injury and modulates excitatory neurotransmission in the ischemic cortex. These findings indicate that Sal B exerts neuroprotective effects partly through the regulation of excitatory synaptic signaling following cerebral ischemia.