Effects and mechanisms of dexmedetomidine on apoptosis of hippocampal neurons in rats with cerebral ischemia-reperfusion injury

Objective: The aim of this study was to examine the effects of dexmedetomidine on apoptosis of hippocampal neurons in rats with cerebral ischemia-reperfusion injury (IRI). Methods: A total of 45 mice were randomly and equally (n = 15/each) divided into the sham (S) group, model (M) group, and dexmedetomidine (D) group. Nerve injuries were evaluated using Purdy scores and cerebral infarct area was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The content of water and glutamate and gamma-aminobutyric acid was detected using the wet-dry weighting method and HPLC-mass spectrometer, respectively. In addition, apoptosis of hippocampal neurons was detected by TUNEL staining and flow cytometry. Moreover, mRNA and protein expression of cleaved caspase-3, Bcl-2, and Bax was detected via real-time quantitative PCR and Western blotting, respectively. Results: Compared with Group S, Group M displayed significantly increased Purdy scores, cerebral infarct area, and water content (P < 0.01). These were significantly lower or smaller in Group D than those in Group M (P < 0.01). However, the content of y-aminobutyric acid in Group M was significantly lower than that in Group S (P < 0.01), but significantly higher in Group D than in Group M (P < 0.01). In addition, apoptosis of hippocampal neurons in Group M was obviously increased (P < 0.01), lower in Group D than in Group M (P < 0.01). Furthermore, cleaved caspase-3 protein levels in hippocampal tissues in Group M were significantly increased (P < 0.01), with decreased Bcl-2/Bax mRNA and protein levels (P < 0.01). However, cleaved caspase-3 protein levels in Group D were obviously lower than those in Group M (P < 0.01), with higher Bcl-2/Bax mRNA and protein levels (P < 0.01). Conclusion: Dexmedetomidine improves nerve function after cerebral IRI in rats, reduces cerebral infarct area, and decreases apoptosis of hippocampal neurons. These effects may be through upregulation of gamma-aminobutyric acid, decrease of caspase-3 levels, and increase of Bcl-2/Bax ratios.