63). All other measured parameters were also unaffected in the AD brains: The mean fiber length density was 248 km/cm(3) in the AD group and 247 km/cm(3) in the control group; the volume of white

matter was 329 cm(3) (AD) and 321 cm(3) (control) and the volume density of myelinated fibers to white matter tissue volume was 0.30 in AD group and 0.31 in the control group. This is the first study of subcortical brain white matter fiber length using a stereological method on postmortem brains from AD patients and control subjects. (C) 2008 IBRO. Published P-gp inhibitor by Elsevier Ltd. All rights reserved.”
“The rapid and irreversible brain injury produced by anoxia when stroke occurs is well known. Cumulative evidence suggests that the activation of neuronal ATP-sensitive potassium (K(ATP)) channels may have inherent protective effects during cerebral hypoxia, yet little information regarding the therapeutic effects of K(ATP) channel openers is available. We hypothesized that pretreatment AG-014699 chemical structure with a K(ATP) channel opener might protect against brain injury induced by cerebral hypoxia. In this study, adult Wistar rats were treated with iptakalim, a new K(ATP) channel opener, which is selective for SUR2 type K(ATP) channels, by intragastric administration at doses of 2, 4, or 8 mg/kg/day for 7 days before being exposed to simulated high altitude equivalent to 8000 m in a decompression chamber

for 8 h leading to hypoxic brain injury. By light and electron microscopic images, we observed that hypobaric hypoxia-induced brain injury could be prevented by pretreatment secondly with iptakalim. It was also observed that the permeability of the blood-brain barrier, water content, Na(+) and Ca(2+) concentration, and activities of Na(+),K(+)-ATPase,

Ca(2+)-ATPase and Mg(2+)-ATPase in rat cerebral cortex were increased and the gene expression of the occludin or aquaporin-4 was down- or upregulated respectively, which could also be prevented by the pretreatment with iptakalim at doses of 2, 4, or 8 mg/kg in a dose-dependent manner. Furthermore, we found that in an oxygen-and-glucose-deprived model in ECV304 cells and rat cortical astrocytes, pretreatment with iptakalim significantly increased survived cell rates and decreased lactate dehydrogenate release, which were significantly antagonized by glibenclamide, a K(ATP) channel blocker. We conclude that iptakalim is a promising drug that may protect against brain injury induced by acute hypobaric hypoxia through multiple pathways associated with SUR2-type K(ATP) channels, suggesting a new therapeutic strategy for stroke treatment. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The CNS can be activated by both local and systemic inflammation, resulting in the manifestation of sickness symptoms. The pathways by which the CNS is activated under these two conditions, however, may differ. In this study, we injected casein into the peritoneal cavity (i.p.) or into an s.c.