Potassium channel activators protect the N-methyl-D-aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets

Background and Purpose-Cerebral arteriolar dilation to N-methyl-D-aspartate (NMDA) is a neuronally mediated multistep process that is sensitive to cerebral hypoxia and ischemia (H/I). We tested the hypothesis that topical pretreatment with the selective potassium channel agonists NS1619 and aprikalim preserves the vascular response to NMDA after consecutive WI. Methods-Pial arteriolar diameters were measured in anesthetized piglets with the use of a closed cranial window and intravital microscopy, Arteriolar responses to NMDA (10(-5), 5 x 10(-5), and 10(-4) mol/L) were recorded before and 1 hour after 10 minutes of hypoxia (8.5% O-2 in N-2) plus; 10 minutes of ischemia (WI), Ischemia was induced by increasing intracranial pressure, Subgroups were topically pretreated with 10(-5) mol/L NS1619, 10(-6) mol/L aprikalim, 10(-6) mol/L calcitonin gene-related peptide (CGRP), or 10(-5) mol/L papaverine. We also examined the effects of H/I on vascular responses to kainate (10(-4) mol/L) to assess specificity of neuronal injury. Results-Arteriolar responses to NMDA were significantly attenuated after WI. Baseline compared with post-WI arteriolar diameters were 9+/-4% versus 3+/-2% at 10(-5) mol/L, 22+/-4% versus 4+/-2% at 5 x 10(-5) mol/L, and 33+/-4% versus 7+/-2% at 10(-4) mol/L (mean+/-SE; all P<.05, n=7), Pretreatment with NS1619 and aprikalim preserved the arteriolar responses to NMDA after WI, For NS1619 (n=6), values were as follows: 9+/-2% versus 6+/-4% at 10(-5) mol/L, 19+/-6% versus 21+/-5% at 5x10(-5) mol/L, and 35+/-3% versus 31+/-5% at 10(-4) mol/L, For aprikalim (n=7), values were as follows: 6+/-2% versus 8+/-2% at 10(-5) mol/L, 22+/-6% versus 15+/-3% at 5x10(-5) mol/L, and 41+/-5% versus 32+/-6% at 10(-4) mol/L. In contrast, piglets pretreated with CGRP (n=6) or papaverine (n=5) showed no preservation of the vascular response to NMDA after WI, although these compounds dilated the arterioles to an extent similar to that with NS1619/aprikalim. Kainate-induced arteriolar dilation (n=6) was largely preserved after H/I compared with preischemic responses, Conclusions-(1) Vascular responses of cerebral arterioles to NMDA after H/I are preserved by pretreatment with NS1619 or aprikalim, indicating a neuroprotective effect, (2) CGRP and papaverine do not preserve the vascular response to NMDA despite causing vasodilation similar to that with NS1619 or aprikalim, This suggests that activation of potassium channels on neurons accounts for the protective effect of potassium channel agonists, (3) Preserved arteriolar dilation to kainate suggests largely intact functioning of neuronal nitric oxide synthase after H/I

Mitochondrial potassium channel opener diazoxide preserves neuronal-vascular function after cerebral ischemia in newborn pigs

Background and Purpose-N-Methyl-D-aspartate (NMDA) elicits neuronally mediated cerebral arteriolar vasodilation that is reduced by ischemia/reperfusion (I/R). This sequence has been preserved by pretreatment with the ATP-sensitive potassium (K-ATP) channel opener aprikalim, although the mechanism was unclear. In the heart, mitochondrial K-ATP channels (mitoK(ATP)) are involved in the ischemic preconditioning-like effect of K+ channel openers. We determined whether the selective mitoK(ATP) channel opener diazoxide preserves the vascular dilation to NMDA after I/R. Methods-Pial arteriolar diameters were determined with the use of closed cranial window/intravital microscopy in anesthetized piglets. Vascular responses to NMDA were assessed before and 1 hour after 10 minutes of global cerebral ischemia induced by raising intracranial pressure. Subgroups received 1 of the following pretreatments before I/R: vehicle; 1 to 10 mu mol/L diazoxide; and coapplication of 100 mu mol/L 5-hydroxydecanoic acid (5-HD), a K-ATP antagonist with diazoxide. Results-NMDA-induced dose-dependent pial arteriolar dilation was not affected by diazoxide treatment only but was severely attenuated by I/R, In contrast, diazoxide dose-dependently preserved the NMDA vascular response after I/R; at 10 mu mol/L, diazoxide arteriolar responses were unaltered by I/R. The effect of diazoxide was antagonized by coapplication of 5-HD with diazoxide. Percent preservation of 100 mu mol/L NMDA-induced vasodilation after I/R was 53 +/- 19% (mean +/- SEM, n = 8) in vehicle-treated controls versus 55 +/- 10%, 85 +/- 5%, and 99 +/- 15% in animals pretreated with 1, 5, and 10 mu mol/L diazoxide (n = 8, n = 8, and n = 12, respectively) and 60 +/- 15% in the group treated with 5-HD+diazoxide (n = 5). Conclusions-The mitoK(ATP) channel opener diazoxide in vivo preserves neuronal function after I/R, shown by pial arteriolar responses to NMDA, in a dose-dependent manner. Thus, activation of mitoK(ATP) channels may play a role in mediating the protective effect of other K+ channel openers

Universal temperature dependence of optical excitation life-time and band-gap in chirality assigned semiconducting single-wall carbon nanotubes

The temperature dependence of optical excitation life-time, Gamma, and transition energies, E_ii, were measured for bucky-papers of single-wall carbon nanotubes (SWCNTs) and inner tubes in double-wall carbon nanotubes (DWCNTs) using resonant Raman scattering. The temperature dependence of Gamma and E_ii is the same for both types of samples and is independent of tube chirality. The data proves that electron-phonon interaction is responsible for temperature dependence of E_ii(T). The temperature independent inhomogeneous contribution to Gamma is much larger in the SWCNT samples, which is explained by the different SWCNT environment in the two types of samples. Gamma of the inner tubes for the bucky-paper DWCNT sample is as low as \sim 30 meV, which is comparable to that found for individual SWCNTs

A conceptual design of an advanced 23 m diameter IACT of 50 tons for ground-based gamma-ray astronomy

A conceptual design of an advanced Imaging Air Cherenkov Telescope with a 23 m diameter mirror and of 50 tons weight will be presented. A system photon detection efficiency of 15-17%, averaged over 300-600 nm, is aimed at to lower the threshold to 10-20 GeV. Prospects for a second generation camera with Geiger-mode Avalanche Photo Diodes will be discussed.Comment: 4 pages, 1 figure, to appear in the proceedings of the 31th International Cosmic Ray Conference, Lodz, Poland, 200

Infinite disorder scaling of random quantum magnets in three and higher dimensions

Using a very efficient numerical algorithm of the strong disorder renormalization group method we have extended the investigations about the critical behavior of the random transverse-field Ising model in three and four dimensions, as well as for Erd\H os-R\'enyi random graphs, which represent infinite dimensional lattices. In all studied cases an infinite disorder quantum critical point is identified, which ensures that the applied method is asymptotically correct and the calculated critical exponents tend to the exact values for large scales. We have found that the critical exponents are independent of the form of (ferromagnetic) disorder and they vary smoothly with the dimensionality.Comment: 6 pages, 5 figure

Logarithmic delocalization of end spins in the S=3/2 antiferromagnetic Heisenberg chain

Using the DMRG method we calculate the surface spin correlation function, $C_L(l)=$, in the spin $S=3/2$ antiferromagnetic Heisenberg chain. For comparison we also investigate the $S=1/2$ chain with S=1 impurity end spins and the S=1 chain. In the half-integer spin models the end-to-end correlations are found to decay to zero logarithmically, $C_L(1)\sim (\log L)^{-2d}$, with $d=0.13(2)$. We find no surface order, in clear contrast with the behavior of the S=1 chain, where exponentially localized end spins induce finite surface correlations. The lack of surface order implies that end spins do not exist in the strict sense. However, the system possesses a logarithmically weakly delocalizing boundary excitation, which, for any chain lengths attainable numerically or even experimentally, creates the illusion of an end spin. This mode is responsible for the first gap, which vanishes asymptotically as $\Delta_1 \approx (\pi v_S d)/(L\ln L)$, where $v_S$ is the sound velocity and $d$ is the logarithmic decay exponent. For the half-integer spin models our results on the surface correlations and on the first gap support universality. Those for the second gap are less conclusive, due to strong higher-order corrections.Comment: 10 pages, 8 figure