Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening.
The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent polyethylene glycol telomere B immediately after decompression, were rendered thrombocytopenic, or were treated with an inhibitor of nitric oxide synthase-2 (iNOS) prior to decompression, or in knockout (KO) mice lacking myeloperoxidase or iNOS. If MPs were harvested from control (no decompression) mice and injected into naive mice, no AP broadening occurred, but AP broadening was observed with injections of equal numbers of MPs from either wild-type or iNOS KO mice subjected to decompression stress. Although not required for AP broadening, MPs from decompressed mice, but not control mice, exhibit NADPH oxidase activation. We conclude that inherent differences in MPs from decompressed mice, rather than elevated MPs numbers, mediate neurological injury and that a component of the perivascular response to MPs involves iNOS. Additional study is needed to determine the mechanism of AP broadening and also mechanisms for MP generation associated with exposure to elevated gas pressure.
Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
Ming
M
Yang
Paul
P
Kosterin
Brian M
BM
Salzberg
Tatyana N
TN
Milovanova
Veena M
VM
Bhopale
Stephen R
SR
Thom
D000200:Action Potentials; D000818:Animals; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D003664:Decompression / Q000009:adverse effects*; D003665:Decompression Sickness / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D009195:Peroxidase / Q000172:deficiency / Q000235:genetics; D010900:Pituitary Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010904:Pituitary Gland, Posterior / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D013921:Thrombocytopenia / Q000378:metabolism / Q000503:physiopathology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019255:NADPH Oxidases
NADPH oxidase; decompression sickness; leukocytes; nitric oxide synthase; platelets