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The involvement of NMDA-type glutamate receptor in neuronal injury established in experimental stroke and neurotrauma models has been recently challenged by failures in treatment of stroke/neurotrauma patients with NMDA receptor antagonists. NMDA receptor activity is known to be essential for mediating a multitude of physiological functions. However, how NMDA receptors are recruited to cause neuronal injury remains unclear. Here we report that the time period during which initial NMDA receptor up-regulation occurs is critical for the recruitment of NMDA receptors causing neuronal injury during extracellular calcium (Ca2+) reperfusion in cultured hippocampal neurons, and represents the key period for neuronal protection by NMDA receptor antagonists. Furthermore, we identified that via intracellular sodium (Na+), extracellular Ca2+ depletion induces the up-regulation of NMDA receptor gating. Taken together, our study provides direct experimental evidence suggesting that determination of when and how NMDA receptors are recruited to cause neurotoxicity is essential for guiding treatment via antagonism of NMDA receptor functions.

A study on the relation between urinary cations and blood pressure was conducted in Wuhan, China. A total of 148 boys aged 7-8 years entered the study from November 23, 1984, to January 13, 1985. Seven consecutive 24-hour urine specimens were collected and blood pressure was measured on the seven successive days corresponding to urine collection. The multiple regression showed that none of the sodium, potassium, calcium, and magnesium cations was statistically significantly related to blood pressure. However, the ratio of sodium/calcium or potassium/calcium in the urine was positively correlated with systolic pressure in multivariate analysis. The results suggest that there may be a complex interaction between sodium and calcium in their effects on blood pressure, and genetic background might have some influences on the sodium/calcium (or potassium/calcium)-blood pressure relation in the 7-8-year-old boys in the study.