Brain damage in neonatal mice following monosodium glutamate administration: Possible involvement of hypernatremia and hyperosmolality

Abstract

The effects of glutamic acid hydrochloride, sodium chloride and sucrose administered orally to neonatal mice at levels equimolar and hyperosmolar to those used in obtaining brain damage with a monosodium glutamate (MSG) were examined. Hypernatremia is induced in neonatal mice at the highest dosage of MSG used to elicit neuropathologic changes. Glutamic acid hydrochloride was found to elicit the same pattern of brain lesions as does MSG. High sodium levels therefore, are not necessary to open the bloodbrain barrier for glutamate-induced neuronal lesions. Sodium chloride itself, although not causing lesions in arcuate nucleus, is capable of causing a wide spectrum of damage in neonatal mouse brain at lower levels (0.02–0.05 meq 1) than previously recognized. Glutamic acid and sodium caused brain lesions often in the same structures but their pattern of damage differed, probably as a result of different routes of entry into the brain. Glutamate, or more probably one of its metabolites, damaged cells close to circulating cerebrospinal fluid (CSF), while hypertonic saline apparently egressed into brain tissue from capillaries, arterioles and venules. Neuronal damage following MSG administration tends to radiate inward within structures in contact with circulating CSF. Lesions following sodium chloride ingestion present themselves as foci or bands occurring throughout a given structure. Sometimes neuronal necrosis accompanied hemorrhagic vessels within a structure, a phenomenon not seen following MSG administration. A high rate of animal mortality followed hyperosmolality induced by sucrose loads. Brain shrinkage and extensive vascular dilatation, unaccompanied by marked neuronal dehydration were the major neurological observations. Finally, while neither hyperosmolarity nor hypernatremia is capable of eliciting the patterns of lesions correlated with MSG ingestion, either condition can result in severe vascular changes in the neonatal mouse brain.