Osteopontin inhibitor alleviates neuroinflammation after subarachnoid hemorrhage in rats via TLR4/NF-κB pathway

Subarachnoid haemorrhage (SAH) has a high mortality and morbidity rate. In the early stages of subarachnoid haemorrhage, neuroinflammation is one of the important mechanisms leading to brain damage.The aim of this study was to investigate the protective effect of Osteobridging protein (OPN) inhibitors against subarachnoid haemorrhage in rats. The temporal lobe tissues of rats showed a significant increase in SPP1 (OPN) in the SAH group by single-cell RNA sequencing, differential gene expression. Brain stereotactic ventricular injection of 250 umol/L OPN inhibitor was used to observe cognition 24 hours after SAH rat model. The permeability of the blood-brain barrier was detected and the activation degree of microglia was observed by immunofluorescence. The results showed that OPN inhibitor improved cognitive impairment and reduced the permeability of the blood-brain barrier in rats, as well as reduced microglia activation while inhibiting the expression of inflammatory factors, which may be related to the inhibition of the TLR4/NF-κB pathway. These findings suggest that OPN inhibitors may be promising agents for the treatment of SAH by modulating blood-brain barrier permeability and inhibiting neuroinflammation. • OPN inhibitors alleviate cognitive impairment caused by early brain injury in rat SAH. • Microglia were significantly activated in the right temporal lobe after 24 hours of SAH in rats. • OPN inhibitors reduce inflammation through the TLR4/NF-κB pathway. • Using single-cell RNA sequencing to screen for early brain injury drivers after subarachnoid hemorrhage (SAH) provides a solid basis for subsequent pharmacological studies.