Summary: Near-infrared spectroscopy (NIRS) was used to monitor human visual cortical function during and after photic stimulation (PS) in five adult volunteers. Cerebral blood volume (CBV) increased on the occipital surface during PS, but NIRS parameters did not change on the frontal surface. The increase in CBV was caused by a rapid increase in oxyhemoglobin with but a small increase in deoxyhemoglobin, suggesting cerebral vascular dilata tion with decreased oxygen consumption. After PS A study of human subjects using positron emis sion tomography (PET) indicated that photic stim ulation (PS) raises blood flow and glucose consump tion in the visual cortex by about 50%, whereas oxygen consumption increases only 5% (Fox et al., 1988). Using proton magnetic resonance spectros copy, Prichard et al. (1991) demonstrated that PS causes an increase in brain lactate in the human visual cortex. However, the mechanism of PS ac tion on human visual cortical function is still not clear. Near-infrared spectroscopy (NIRS) is a non invasive tool for the continuous monitoring of changes in cerebral blood volume (CBV), oxyhemo globin (Hb02), deoxyhemoglobin (HbR) and redox state of cytochrome aa3 (Cyt). Voluntary hypervenReceived February 11, 1992; final revision received October 27, 1992; accepted October 27, 1992.Address correspondence and reprint requests to Dr. Toshinori Kato, Mental Retardation and Birth Defect Research Division, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi cho, Kodaira, Tokyo, Japan.Abbreviations used: CBV, cerebral blood volume; Cyt, cy tochrome aa3; DPF, differential path length factor; HbR, de oxyhemoglobin; Hb02, oxyhemoglobin; HbT, total hemoglobin (Hb02 + HbR); MRI, magnetic resonance imaging; NIRS, near infrared spectroscopy; PET, positron emission tomography; PC, photon count; PS, photic stimulation. 516stopped, CBV promptly decreased and then slightly in creased again. Cytochrome aa3 did not show any change during and after PS. These phenomena reappeared fol lowing repeated PS in all five subjects. These results may represent the first step in the development of NIRS im aging.

We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D-aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.

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Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx circulating in the blood is a major causative factor of these complications, the development of a Stx neutralizer that functions in the circulation holds promise as a viable therapy. Here we developed a series of carbosilane dendrimers, in which trisaccharides of globotriaosyl ceramide, a receptor for Stx, were variously oriented at their termini (referred to as SUPER TWIG), and identified a SUPER TWIG with six trisaccharides as a Stx neutralizer functioning in the circulation. This SUPER TWIG specifically bound to Stx with high affinity (Kd ‫؍‬ 1.1 ؋ 10 ؊6 M) and inhibited the incorporation of the toxin into target cells. Intravenous administration of the SUPER TWIG along with Stx to mice substantially reduced the fatal brain damage and completely suppressed the lethal effect of Stx. Moreover, the SUPER TWIG protected mice from challenge with a fatal dose of E. coli O157:H7, even when administered after the establishment of the infection. The SUPER TWIG neutralized Stx in vivo by a mechanism in which the accumulation and immediate degradation of Stx by phagocytic macrophages present in the reticuloendothelial system were induced. Taken together, our findings indicate that this SUPER TWIG is therapeutic agent against infections by Stx-producing E. coli.