No abstract

Although periventricular white matter injury (PWMI) is the leading cause of chronic neurological disability and cerebral palsy in survivors of premature birth, the cellular-molecular mechanisms by which ischemia-reperfusion contributes to the pathogenesis of PWMI are not well defined. To define pathophysiologic relationships among ischemia, acute cerebral white matter damage, and vulnerable target populations, we used a global cerebral ischemia-reperfusion model in the instrumented 0.65 gestation fetal sheep. We developed a novel method to make repeated measurements of cerebral blood flow using fluorescently labeled microspheres to resolve the spatial heterogeneity of flow in situ in three-dimensional space. Basal flow in the periventricular white matter (PVWM) was significantly lower than in the cerebral cortex. During global cerebral ischemia induced by carotid occlusion, flow to all regions was reduced by nearly 90%. Ischemia of 30 or 37 min duration generated selective graded injury to frontal and parietal PVWM, two regions of predilection for human PWMI. Injury was proportional to the duration of ischemia and increased markedly with 45 min of ischemia to extensively damage cortical and subcortical gray matter. Surprisingly, the distribution of PVWM damage was not uniform and not explained by heterogeneity in the degree of white matter ischemia. Rather, the extent of white matter damage coincided with the presence of a susceptible population of late oligodendrocyte progenitors. These data support that although ischemia is necessary to generate PWMI, the presence of susceptible populations of oligodendrocyte progenitors underlies regional predilection to injury.

Watermelon is rich in L-citrulline, an effective precursor of L-arginine. This study was conducted to determine whether dietary supplementation with watermelon pomace juice could ameliorate the metabolic syndrome in the Zucker diabetic fatty (ZDF) rat, an animal model of noninsulin-dependent diabetes mellitus. Nine-week-old ZDF rats were assigned randomly to receive drinking water containing 0% (control) or 0.2% L-arginine (as 0.24% L-arginine-HCl), 63% watermelon pomace juice, 0.01% lycopene, or 0.05% citrus pectin (n = 6 per treatment). At the end of the 4-wk supplementation period, blood samples, aortic rings, and hearts were obtained for biochemical and physiological analyses. Feed or energy intakes did not differ among the 5 groups of rats. However, dietary supplementation with watermelon pomace juice or L-arginine increased serum concentrations of arginine; reduced fat accretion; lowered serum concentrations of glucose, free fatty acids, homocysteine, and dimethylarginines; enhanced GTP cyclohydrolase-I activity and tetrahydrobiopterin concentrations in the heart; and improved acetylcholine-induced vascular relaxation. Compared with the control, dietary supplementation with lycopene or citrus pectin did not affect any measured parameter. These results provide the first evidence to our knowledge for a beneficial effect of watermelon pomace juice as a functional food for increasing arginine availability, reducing serum concentrations of cardiovascular risk factors, improving glycemic control, and ameliorating vascular dysfunction in obese animals with type-II diabetes.

In this chapter we have summarized our view of the subsets of murine CD4- CD8- thymocytes which can be identified with a range of monoclonal antibodies. We have shown the division rate and turnover time of the main subsets and have listed what we know of the TcR gene rearrangement, and expression at the RNA and protein levels. We have been unable to completely segregate gamma delta-TcR-expressing cells from alpha beta-TcR-expressing cells by any of the markers we have used, although the proportions of the two receptor forms vary widely in the different subsets. Experiments involving intrathymic transfer of the CD4- CD8- subsets are described, which indicate that all the TcR- subsets of the CD4- CD8- thymocytes display some precursor activity and which suggest a progression of at least five stages through the TcR- subpopulations of CD4- CD8- cells. The earliest precursor is a Thy 1 low, HSA low, Pgp-1 high cell which has unrearranged C beta and is non-dividing and which closely resembles the bone marrow prothymocyte. The later precursors are Thy 1 high, HSA high, Pgp-1 low, have rearranged C beta and are rapidly dividing. We tentatively conclude that none of the TcR+ CD4- CD8- cells are precursors of the major thymocyte subsets or of typical peripheral T cells, and we have found no evidence so far of separate precursors for the different mature subsets of thymocytes or peripheral T cells.