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Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats

Nonaka, Shigeyuki1; Chuang, De-Maw1,2

Neuropharmacology

WE have recently shown that long-term, but not acute, treatment with lithium robustly protects cultured CNS neurons against excitotoxicity mediated by NMDA receptors. Since NMDA receptor over-excitation has been strongly implicated in the ischemic brain injury, we examined the effects of chronic lithium treatment on neurological deficit and brain infarct induced by occlusion of the left middle cerebral artery in rats. Subcutaneous injection of LiCl for 16 days significantly improved neurological deficits, including abnormal posture and hemiplegia, measured 24 h after artery occlusion. Importantly, the size of ischemic infarct was reduced by 56% after lithium pretreatment. These results raise the possibility that lithium may be useful for reducing focal ischemia-induced brain damage and neurological abnormalities.

1Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive MSC 1272, Bethesda, MD 20892-1272, USA.

2Corresponding Author: De-Maw Chuang

ACKNOWLEDGEMENTS: The authors would like to thank Huafeng Wei, Christopher Hough, Paul Saunders and Peter Leeds of NIMH for their invaluable discussion and assistance in the course of this study.

Website publication 10 June 1998

Received 30 March 1998; accepted 22 April 1998

© Lippincott-Raven Publishers.