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Glutamate-Induced Brain Damage in Infant Primates

John W. Olney M.D., Lawrence G. Sharpe Ph.D., Ralph D. Feigin M.D.
DOI: http://dx.doi.org/10.1097/00005072-197207000-00006 464-488 First published online: 1 July 1972

Abstract

The brains of 9 infant rhesus monkeys were examined for acute cytopathology following treatment with monosodium L-glutamate (MSG) (6 infants) or NaCl (3 infants). Hypothalamie lesions identical to those described elsewhere in MSG-treated rodents were identified by light microscopy and verified with the electron microscope in each infant monkey given MSG. No cellular pathology was detected in the hypothalami of NaCl-treated controls. Infants given relatively low oral doses of MSG (1 and 2 g/kg) sustained small focal lesions confined primarily to the rostro-ventral aspect of the infundibular nucleus. Those treated with high subcutaneous doses developed lesions which spread throughout and sometimes beyond the infundibular nucleus. At all doses tested (1–4 g/kg) and by either route of administration, rapid necrosis of neurons (within 5 hours) was a striking feature of the MSG-induced reaction pattern. Blood glutamate curves from time of treatment to time of sacrifice (5 hours) suggest that the threshold for lesion formation in 1-week-old rhesus monkeys may be in the range of 20 mg%. Differences in research approach which might account for the failure of others to locate the lesions we describe are discussed as are some of the toxicological implications of our findings.