Modeling of the response of ptO2 in rat brain to changes in physiological parameters.

It is known that oxygen tension in tissue (ptO2) will change in response to an alteration of physiological parameters including: pCO2 in arterial blood, blood flow, capillary density, oxygen carrying capacity, and p50 of hemoglobin. We have used modeling to compute the change of PtO2 in response to changes of each physiological parameter and related these changes to experimental data. The oxygen distribution in a Krogh cylinder was computed assuming a linear decrease of hemoglobin saturation from the arterial to the venous end of the capillary. Parameters of the model were used to compute the baseline cerebral PtO2 expressed as the mean value of the PtO2 over the whole cylinder. These parameters were adjusted to derive PtO2 values close to those measured at the relevant experimental conditions. Then each desired parameter was varied to calculate the change in PtO2 related to this parameter. Effects of different factors on cerebral PtO2 were modeled and compared with experimental values obtained with various experimental interventions including: changing CBF, modifying p50 with the allosteric modifier RSR13, modification of capillary density, and hemoglobin content. An acceptable agreement of the computed and the experimental changes of the cerebral PtO2 was obtained for these experimental conditions.

Monitoring angiogenesis in brain using steady-state quantification of DeltaR2 with MION infusion.

An MRI method for quantification of cerebral blood volume (CBV) in time-course studies of angiogenesis is described. Angiogenesis was stimulated by acclimation to hypoxia. The change in relaxation rate, R2, which is relatively sensitive to the microvasculature, was quantified before and after infusion of a superparamagnetic vascular contrast agent (MION). The DeltaR2 was measured in serum and brain parenchyma with a multiecho sequence. In vitro and in vivo calibration curves of MION concentration vs. R2 were approximated by a linear function. CBV was 3.14 +/- 0.32% (mean +/- SE, n=13) and 6.42 +/- 0.54% (n=4) before and after acclimation. A second acclimated group was hemodiluted to control for polycythemia. CBV was not significantly different between hemodiluted and nonhemodiluted groups. In animals where NMR measurements were taken before and after acclimation, there was a 120% increase in CBV. The NMR technique was validated using quantitative morphometrics, which showed an increase of 147% in CBV with acclimation. We found a linear correlation between MRI and the morphometric results for CBV, as well as demonstrating a quantitative equivalence for relative changes in CBV. This article describes a simple, repeatable method of imaging brain microvascular volume using a plasma-based contrast agent that can be applied to longitudinal studies of angiogenesis.

Brain tissue and sagittal sinus pO2 measurements using the lifetimes of oxygen-quenched luminescence of a ruthenium compound.

The study was done to assess the performance of a system that measures the partial pressures of oxygen (pO2) from the lifetimes of oxygen-quenched luminescence of ruthenium compounds immobilized at the tip of fiber-optic optodes (Oxylite system). The system was used to measure the pO2 in brain tissue (thalamus and hypothalamus) and in the sagittal sinus of isoflurane-anesthetized rats at different FiO2's. The pO2 recorded in the hypothalamus (HPtO2) was consistently higher than the pO2 in the thalamus (TPtO2) at all FiO2. HPtO2 was closely related to PvO2 during normoxia but not during hypoxia. The equilibrium time of Oxylite system was found to be rapid compared to in vivo tissue response to changes in FiO2.

Antigen presentation by vaginal cells: role of TGFbeta as a mediator of estradiol inhibition of antigen presentation.

Estradiol is known to inhibit antigen presentation in the vagina. We report here that TGFbeta mediates the action of estradiol on vaginal antigen presenting cells (APC). When vaginal APC from ovariectomized rats were incubated with increasing concentrations of TGFbeta1 and TGFbeta2 in the presence of ovalbumin-specific T cells and ovalbumin, both TGFbeta1 and TGFbeta2 inhibited vaginal cell antigen presentation, whereas IL-6, IL-10, and TNFalpha had no consistent effect. In other experiments, estradiol-induced inhibition of antigen presentation by vaginal cells was partially reversed when vaginal APC were incubated with anti-TGFbeta antibody. In contrast, anti-TNFalpha, anti-IL-6, and anti-IL-10 had no effect on antigen presentation. The effect of anti-TGFbeta was seen with vaginal APC from ovariectomized rats treated with estradiol for 1 d as well as 3 d. Finally, analysis of TGFbeta in the culture media of vaginal cells from saline- and estradiol-treated rats indicated that the TGFbeta produced is biologically active. In response to estradiol, vaginal cell production of TGFbeta was significantly greater than that seen with control cells. These studies suggest that estradiol regulation of antigen presentation by vaginal cells is mediated through the local production of TGFbeta by vaginal cells.