Objective To investigate the effect of dexmedetomidine (Dex) on neural injury in rats with kainic acid (KA)-induced epilepsy and its possible mechanism.

Methods Rats were randomly divided into Sham group, model group, Dex low-dose (Dex-L) group, Dex high-dose (Dex-H) group, and Dex-H+recombinant high mobility group box 1 (rHMGB1) group using a random number table method, with 10 rats in each group. Except for the Sham group, epilepsy modeling was performed in the other groups. The seizure conditions of rats in each group were observed. The Morris water maze test was used to assess the spatial learning and memory abilities (latency, time spent in the target quadrant, and the number of platform crossings) of the rats. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), and γ-aminobutyric acid (GABA) in the hippocampal tissue of the rats. Nissl staining was used to observe the morphological changes in the hippocampal tissue. The TUNEL method was applied to detect the apoptosis rate of hippocampal neurons. Western blotting was used to measure the expression levels of proteins related to the high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE)/nuclear factor κB (NF-κB) pathway.

Results Compared with the Sham group, the model group had higher seizure scores and hippocampal neuronal apoptosis rates, elevated levels of TNF-α, IL-18, IL-6, and cleaved caspase-3, HMGB1, RAGE, and phosphorylated (p)-NF-κB/NF-κB proteins in the hippocampal tissue, prolonged seizure duration and latency, decreased hippocampal neuronal numbers and platform crossings, shortened time spent in the target quadrant, and reduced GABA levels, with statistically significant differences (P < 0.05). Compared with the model group, the Dex-L and Dex-H groups had lower seizure scores and hippocampal neuronal apoptosis rates, reduced levels of TNF-α, IL-18, IL-6, and cleaved-caspase-3, HMGB1, RAGE, and p-NF-κB/NF-κB proteins in the hippocampal tissue, shortened seizure duration and latency, increased hippocampal neuronal numbers and platform crossings, prolonged time spent in the target quadrant, and elevated GABA levels, with statistically significant differences (P < 0.05). The rHMGB1 could weaken the ameliorative effect of Dex on neural injury in KA-induced epileptic rats.

Conclusion Dex can alleviate inflammatory responses, oxidative stress, and neuronal apoptosisin KA-induced epileptic rats, and improve neurological function, possibly by inhibiting the HMGB1/RAGE/NF-κB pathway.