This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knuckey, N. W. Articles by Johanson, C. E. Search for Related Content PubMed PubMed Citation Articles by Knuckey, N. W. Articles by Johanson, C. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLCYSTEINE Medline Plus Health Information Transient Ischemic Attack

(Stroke. 1995;26:305-311.)
© 1995 American Heart Association, Inc.

Articles

N-Acetylcysteine Enhances Hippocampal Neuronal Survival After Transient Forebrain Ischemia in Rats

Neville W. Knuckey, FRACS; Donald Palm, PhD; Michael Primiano, BS; Mel H. Epstein, MD Conrad E. Johanson, PhD

From the Department of Clinical Neuroscience, Program in Neurosurgery, Rhode Island Hospital/Brown University, Providence, RI.

Correspondence to Neville W. Knuckey, 110 Lockwood St, Providence, RI 02903.

Background and Purpose Free radical scavengers enhance neuronal survival in some models of transient forebrain ischemia. Recent experiments have suggested that N-acetylcysteine prevents cellular injury after a reperfusion injury. No information is available regarding the neuroprotective potential of the free radical scavenger N-acetylcysteine after transient forebrain ischemia. In this study we evaluated the potential of N-acetylcysteine to improve hippocampal neuronal survival after transient forebrain ischemia in the rat.

Methods In series A and B, ventilated, paralyzed, normothermic rats had 10 minutes of transient forebrain ischemia induced by bilateral carotid occlusion with hypotension induced by blood withdrawal (mean arterial blood pressure, 45 mm Hg). In series A, animals were administered N-acetylcysteine (163 mg/kg) 30 minutes and 5 minutes before transient forebrain ischemia. In series B, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia. In series C, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia in animals with a mean arterial blood pressure of 30 mm Hg during transient forebrain ischemia. All series had normal control, sham, and vehicle treatment groups. In all series, the rats were allowed to recover and were killed at 7 days after ischemia. The effect of forebrain ischemia was assessed by evaluating the number of viable neurons at bregma sections -3.3, -3.8, and -4.3 of the CA1 region of the hippocampus.

Results The results demonstrated no physiological difference among the various treatment groups. There were no differences in the number of viable neurons between the transient forebrain ischemia with no treatment group and the vehicle (saline)-treated transient forebrain ischemic groups. Animals pretreated with N-acetylcysteine (mean number of neurons, 84±6) had a significant increase (P<.05) in neuronal survival compared with vehicle-treated animals (mean number of neurons, 43±4). Animals posttreated with N-acetylcysteine (mean number of neurons, 89±9) had a significant increase in neuronal survival compared with vehicle-treated animals (mean number of neurons, 7±1). However, N-acetylcysteine protection was only partial at 45 mm Hg and did not improve neuronal survival (mean number of neurons, 22±3) in animals with a more severe ischemic insult (mean arterial blood pressure, 30 mm Hg during transient forebrain ischemia) compared with vehicle-treated animals (mean number of neurons, 10±1).

Conclusions N-Acetylcysteine partially improved neuronal survival when administered before or after ischemia following transient cerebral ischemia (mean arterial blood pressure, 45 mm Hg) but not with a more severe ischemic insult of 10 minutes of transient cerebral ischemia with a mean arterial blood pressure of 30 mm Hg.

Key Words: acetylcysteine • cerebral ischemia, transient • free radicals • hippocampus • rats

This article has been cited by other articles:

				M. Tanito, A. Nishiyama, T. Tanaka, H. Masutani, H. Nakamura, J. Yodoi, and A. Ohira Change of Redox Status and Modulation by Thiol Replenishment in Retinal Photooxidative Damage Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2392 - 2400. [Abstract] [Full Text] [PDF]

				Y. Gilgun-Sherki, Z. Rosenbaum, E. Melamed, and D. Offen Antioxidant Therapy in Acute Central Nervous System Injury: Current State Pharmacol. Rev., June 1, 2002; 54(2): 271 - 284. [Abstract] [Full Text] [PDF]

				Y. Numagami and S. T. Ohnishi S-Allylcysteine Inhibits Free Radical Production, Lipid Peroxidation and Neuronal Damage in Rat Brain Ischemia J. Nutr., March 1, 2001; 131(3): 1100S - 1105. [Abstract] [Full Text]

				C. Y. I. Yan and L. A. Greene Prevention of PC12 Cell Death by N-Acetylcysteine Requires Activation of the Ras Pathway J. Neurosci., June 1, 1998; 18(11): 4042 - 4049. [Abstract] [Full Text] [PDF]

				J. T. Henderson, M. Javaheri, S. Kopko, and J. C. Roder Reduction of Lower Motor Neuron Degeneration in wobbler Mice by N-Acetyl-L-Cysteine J. Neurosci., December 1, 1996; 16(23): 7574 - 7582. [Abstract] [Full Text] [PDF]