Thanks for posting, Cece---
Dr. Ge's info was really dense, he is very knowledgable, and a GREAT asset to the ISNVD. Wow--he and Haacke are stars in the imaging world, and they are working together to understand the vascular connection to MS. He showed some 7T images that were really scary...micro-bleeds/lesions in the MS brain, that are not detectable by weaker machines, and show up prior to demylinating lesion formation.
Dr. Steven Alexander questioned Dr. Ge's reference to nitric oxide after his presentation--since there is a big difference between eNOS (endothelial-derived NO) and iNOS (inducible NO from cytokines). I was glad Dr. Alexander dug in a bit more and asked for clarification on this with Dr. Ge, since I've been singing the praises of NO, and here was a theory stating NO was behind the damage of MS and O2 utilization (eek!) I got a look from the Hubbards
eNOS controls perfusion, is vasodilating and strenghtens the BBB. It comes from a healthy endothelium, which has shear stress and good tight junctions.
iNOS is induced by cytokines, is inflammatory and damaging to the BBB.
Here's a recent paper from Dr. Alexander--
Levels of NO+ and its metabolites are elevated in blood, urine, and CSF of MS patients,103 but it remains controversial whether NO+ plays a protective, an injurious, or both roles in pathogenesis of MS.103 In the BBB, CEC form NO+ via endothelial NO+ synthase (eNOS, NOSIII) and may decrease or increase BBB. CEC sense NO+ by a cGMP- pathway that may phosphorylate junction associated proteins (like VASP),104 which strengthen paraendothelial barrier and limits endothelial permeability. Although by scavenging oxidants NO may also serve as an important antioxidant defense in CEC,105 several reactions between oxidants and NO+ can lead to formation of highly reactive species, like peroxynitrite, which disintegrate the BBB.106 The induction of iNOS by cytokines in several cells within the BBB could release sufficient NO+ to form toxic levels of NO+ metabolites that disrupt the BBB.107
Our data demonstrate that iNOS and eNOS are differently regulated in physiologic conditions and in liver disease. While eNOS seems to be involved in the physiological regulation of hepatic perfusion, strong upregulation of iNOS might contribute to inflammatory processes in FHF.
So...endothelial health depends on the good NO.
eNOS is a sign of good brain health, BBB integrity. iNOS shows permeable BBB, unhealthy brain.http://kuscholarworks.ku.edu/dspace/bit ... 0Oxide.pdf
hope that makes sense
my brain is still crispy.