There is increasing evidence that erythropoietin (Epo) has a protective function in cerebral ischemia. When used for treatment, high Epo plasma levels associated with increases in blood viscosity, however, may counteract beneficial effects of Epo in brain ischemia. The authors generated two transgenic mouse lines that overexpress human Epo preferentially, but not exclusively, in neuronal cells. In mouse line tg21, a fourfold increase of Epo protein level was found in brain only, whereas line tg6 showed a dramatic increase of cerebral and systemic transgene expression resulting in hematocrit levels of 80%. Cerebral blood flow (CBF), as determined by bolus tracking magnetic resonance imaging, was not altered in the tg6 line. The time-to-peak interval for the tracer, however, increased approximately threefold in polyglobulic tg6 mice. Immunohistochemical analysis revealed an increase in dilated vessels in tg6 mice, providing an explanation for unaltered CBF in polyglobulic animals. Permanent occlusion of the middle cerebral artery (pMCAO) led to similar perfusion deficits in wild-type, tg6, and tg21 mice. Compared with wild-type controls, infarct volumes were not significantly smaller (22%) in tg21 animals 24 hours after pMCAO, but were 49% enlarged (P < 0.05) in polyglobulic tg6 mice. In the latter animals, elevated numbers of Mac-1 immunoreactive cells in infarcted tissue suggested that leukocyte infiltration contributed to enlarged infarct volume. The current results indicate that moderately increased brain levels of Epo in tg21 transgenic mice were not sufficient to provide significant tissue protection after pMCAO. The results with tg6 mice indicate that systemic chronic treatment with Epo associated with elevated hematocrit might deteriorate outcome after stroke either because of the elevated hematocrit or other chronic effects.

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We studied the development of visual processing in 58 children, ranging from 1 d to 12 y of age (median age 29 mo), using functional magnetic resonance imaging. All but nine children had either been sedated using chloral hydrate (n = 12) or pentobarbital (n = 28). Nine children were studied under a full halothane/ N2O:O2 anesthesia. In the first postnatal month, 30% of the neonates showed a positive blood oxygenation level-dependent (BOLD) contrast signal, whereas, for infants between the ages of 1 mo and 1 y, 27% did so. Thirty-one percent of children between 1 and 6 y of age and 71% of children aged 6 y and above showed a positive BOLD contrast signal change to our visual stimulation paradigm. Besides the usual positive BOLD contrast signal change, we also noted that a large portion of the children measured displayed a negative BOLD contrast signal change. This negative BOLD contrast signal change was observed in 30% of children up to 1 mo of age, in 27% between 1 mo and 1 y of age, in 47% between 1 and 6 y of age, and in 14% of children 6 y and older. In the children in which we observed a negative correlating BOLD contrast signal change, the locus was more anterior and more lateral than the positive BOLD contrast signal, placing it in the secondary visual cortical area. The results indicate that when using functional magnetic resonance imaging on children, the primary visual cortical area does not respond functionally in the same manner as that of the adult until 1.5 y of age. This supports earlier clinical and electrophysiologic findings that different cortical mechanisms seem to contribute to visual perception at different times postnatally.

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