Neuroprotective effects and underlying mechanism of preconditioning with MK-801 in cerebral ischemia/reperfusion injury in rats induced by cardiac arrest-cardiopulmonary resuscitation

Abstract

Objective To explore effects of dizocilpine (MK-801) preconditioning on excitatory amino acids and inflammatory response in rats induced by cardiac arrest-cardiopulmonary resuscitation (CA-CPR). Methods 18 male Sprague Dawley (SD) rats were randomly divided into three groups: control group, CA group and CA+ MK-801 group. To establish rat models of CA-CPR and keep samples of serum and specimens of brain tissues for following detection. The injury of neurons was observed by HE staining and expression of N-methyl-D-aspartic acid receptor (NMDAR) in brain tissues was detected by Western blot. The concentrations of interleukin 1 beta (IL-1β) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA). Results Neurons in CA group were disorganized, cells shrank, nuclei pyknosis, and cytoplasmic eosinophilia, accompanied by inflammatory cell infiltration. Preconditioning with MK-801 reduced the pathological damage of neuron and degree of macrophage infiltration. The relative expression of NMDAR protein in CA group were significantly higher than that in control group (907.9±24.9 vs 321.6±18.4, P<0.001). Preconditioning with MK-801 significantly decreased the expression of NMDAR in CA+ MK-801 group compared with that in CA group (512.4±21.1 vs 907.9±24.9). The CA group showed significantly increased concentrations of IL-1β and TNF-α than that in control group (P<0.001), and this effect was abolished by preconditioning with MK-801. CA rats treated with MK-801 showed higher concentrations of IL-1β and TNF-α than the control group. Conclusions Cardiac arrest causes pathological injury of neurons, up-regulates expression of NMDAR and aggravates inflammatory response. These results induce the apoptosis of nerve cells. Blocking glutamate receptor with MK-801 can inhibit expression of NMDAR, decrease level of cytokines, down-regulate inflammatory reaction degree therefore to protect the brain. Key words: Dizocilpine maleate/AD; Ischemic preconditioning; Brain ischemia; Reperfusion injury/DT; Receptors, glutamate/ME; Interleukin-1beta/ME; Tumor necrosis factor-alpha/ME; Rats