Neuroprotective Effect of N-acetylcysteine in an Asphyxial Cardiac Arrest Model of Rats

Park, Seung Hyun; Choi, Chang Rak; Oh, Dong Rul; Choi, Se Min; Kim, Se Kyung

Abstract

BACKGROUND: A major pathway leading toward neuronal injury following ischemia-reperfusion of the brain involves elevation of extracellular glutamate and activation of glutamate receptors, with a subsequent increase in intracellular calcium, resulting in a generation of free radicals. Oxygen free radicals cause brain injury following resuscitation from cardiac arrest. Oxyradicals produce strand breakage in DNA, which triggers energy-consuming DNA repair mechanisms and activates the nuclear enzyme poly(ADP-ribose) synthetase(PARS). However, excessive PARS activation leads to energy depletion and exacerbation of neuronal damage in cerebral ischemia.
METHODS
We investigated the effect of a potent, free-radical scavenger, N-acetylcysteine(NAC), on hippocampal neuronal death in an asphyxial cardiac arrest model of rats. The effect of NAC on hippocampal neuronal death was studied in 32 rats which were subjected to asphyxial cardiac arrest for 7 minutes, followed by resuscitation. The animals were divided into four group(8 rats in each group) as follows: Group I was saline treated for 3 days, Group II was NAC treated for 3 days, Group III was saline treated for 6 days, and Group IV was NAC treated for 6 days. In the NAC-treated groups, NAC(150 mg/kg) was intravenously injected after return of spontaneous circulation. The coronal sections with hippocampus levels were stained with hematoxylin-eosin(H-E) and PARS antibodies at 3 and 6 days after survival. In addition, the levels of myeloperoxidase(MPO) and malondialdehyde(MDA) were determined in the brains of each group.
RESULTS
The results are as follows: 1. MPO and MDA levels were significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III. 2. The histologic damage score(HDS), as determined by H-E staining, was significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III. 3. In PARS immunohistochemical staining, the HDS was significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III.
CONCLUSION
These results suggest that a free-radical scavenger, N-acetylcysteine, may effectively prevent neuronal damages after reperfusion from asphyxial cardiac arrest in rats. Further studies will be required to examine both the mechanism of the action and the clinical application of NAC in patients with cardiac arrest.