We did not restrict eligibility according to kidney function

l Origin v5.0 software and presented as linear transformations using a LineweaverBurk plot. Errors in the values were within 1015%. The results are reported as mean6S.E. of at least three independent experiments. MALDI-TOF analysis Ab-dependent hydrolysis of OPs In all cases the products of OP hydrolysis were analysed by MALDI-TOF mass spectrometry using a ReflexIII system equipped with a 337-nm nitrogen laser, 3 ns pulse duration. ~~ ~~ The involvement of immature cells in the normal function and repair capacity of the adult brain is becoming increasingly appreciated. Since the initial observations that new neurons can be generated in certain areas of the adult mammalian brain, populations of stem cells have been described in various brain and spinal cord regions. It was soon recognized that insults such as ischemic stroke and epilepsy were able to mobilize these endogenous cells, suggesting their readiness to respond to various challenges. Enriched environments and physical exercise are also able to promote adult neurogenesis. Additional work has identified genes that are prominently expressed in these cells and help with their identification. Culture systems and in vivo validation experiments are generating strategies for the manipulation of these cells in situ. The aim, in many of these approaches, is the replacement of lost cells from endogenous sources. However, a more recent Endogenous Hes3+ Cells in the Adult Hippocampus phorylation in the absence of STAT3-tyrosine phosphorylation also induce the transcription of the transcription factor Hairy and Enhancer of Split 3 . Hes3 is expressed in the developing brain where it regulates the timing of the differentiation of the neural precursor population. We have reported that Hes3 expression persists in the adult, where it identifies putative neural stem cell populations in many areas of the brain. In fact, established fetal and adult rodent neural stem cell cultures express Hes3 and Hes3 expression is lost following induced differentiation. Hes3 null mice show a generally normal phenotype. Neural stem cell cultures from adult Hes3 null mice can be established, suggesting that the role of Hes3 is not essential for their maintenance. However, Hes3 null cultures exhibit a much reduced response to treatments with Delta4 and insulin. These results show that Hes3 mediates functions that are directly relevant to the regenerative response after injury. In this work, we focused on Hes3 expression in order to measure the effects of treatments on the putative endogenous neural stem cell/progenitor cell population in the adult mouse and rat brains. In the adult brain, Delta4 and Angiopoietin 2 are produced by vascular endothelial cells, with which Hes3+ cells physically associate, suggesting that the activation of Hes3+ cells by the exogenous factors used here may reflect a natural regenerative response of the adult brain to injury. Our previous work has presented a therapeutic strategy that relies on the SB-590885 site neuroprotective effects of endogenous neural stem cells, presumably through their trophic support on injured neurons. There is no evidence that neuronal replacement is involved in this process. Here we show that soluble factors can also increase the numbers of Hes3+ cells in the adult rodent hippocampus, a neurogenic zone of the adult brain. Future work may reveal if in this area, neurogenesis as well as learning and memory functions can also be affected by our treatments. Results Our experimen