Objective To investigate the effect of dexmedetomidine (DEX) on cognitive function in rats with cerebral ischemic stroke (CIS) and analyze its potential underlying mechanisms.
Methods A rat model of CIS was established using the middle cerebral artery occlusion (MCAO) method. The rats were randomly divided into sham-operation group, model group, low-dose DEX group (25 mg/kg DEX solution, administered by gavage), high-dose DEX group (50 mg/kg DEX solution, administered by gavage), and edaravone group (3.2 mg/kg edaravone solution, administered by gavage). After treatment, cognitive function was assessed using the neurological deficit score and the novel object recognition test. Brain infarction area and histopathological damage in brain tissue were detected using triphenyltetrazolium chloride (TTC) staining and hematoxylin and eosin (HE) staining, respectively. The expression of the microglial marker ionized calcium-binding adapter molecule 1 (Iba-1) was analyzed using immunohistochemical staining. The levels of interleukin (IL)-6, IL-18, and IL-1β in brain tissue were measured using ELISA kits. The expression of proteins related to the toll-like receptor 4/nuclear factor κB/NOD-like receptor thermal protein domain-containing protein 3 (TLR4/NF-κB/NLRP3) signaling pathway was detected using western blot.
Results Compared with the sham-operation group, the model group exhibited increased or enlarged neurological scores, brain infarction area, levels of IL-6, IL-1β, IL-18, Iba-1, TLR4, p-NF-κB, NLRP3, Cleaved Caspase-1, and GSDMD-N, as well as a decreased novel object discrimination index. Compared with the model group, the low-dose DEX, high-dose DEX, and edaravone groups showed decreased or shrinked neurological scores, brain infarction area, levels of IL-6, IL-1β, IL-18, Iba-1, TLR4, p-NF-κB, NLRP3, Cleaved Caspase-1, and GSDMD-N, along with an increased novel object discrimination index. Compared with the low-dose DEX and edaravone groups, the high-dose DEX group demonstrated further decreases in neurological scores, brain infarction area, levels of IL-6, IL-1β, IL-18, Iba-1, TLR4, p-NF-κB, NLRP3, Cleaved Caspase-1, and GSDMD-N-terminal domain (GSDMD-N), as well as an increased novel object discrimination index. The differences among the aforementioned groups were all statistically significant (P < 0.05).
Conclusion DEX improves cognitive function in rats with CIS by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway, thereby suppressing neuronal pyroptosis and microglial activation and alleviating the inflammatory response.
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