sb-3ct-compound and Brain-Edema

Topics: Animals; Aquaporin 4; Blood-Brain Barrier; Brain Edema; Claudin-5; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hallucinogens; Heterocyclic Compounds, 1-Ring; Low Density Lipoprotein Receptor-Related Protein-1; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9; N-Methyl-3,4-methylenedioxyamphetamine; Permeability; Plasminogen; Rats; Sulfones; Time Factors

Blood-brain-barrier (BBB) breakdown and cerebral edema result from postischemic inflammation and contribute to mortality and morbidity after ischemic stroke. A functional role for the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the regulation of reperfusion injury has not yet been demonstrated.. We sought to identify and characterize the relevance of CEACAM1-expressing inflammatory cells in BBB breakdown and outcome after ischemic stroke in Ceacam1(-/-) and wild-type mice.. Focal ischemia was induced by temporary occlusion of the middle cerebral artery with a microfilament. Using MRI and Evans blue permeability assays, we observed increased stroke volumes, BBB breakdown and edema formation, reduction of cerebral perfusion, and brain atrophy in Ceacam1(-/-) mice. This translated into poor performance in neurological scoring and high poststroke-associated mortality. Elevated neutrophil influx, hyperproduction, and release of neutrophil-related matrix metalloproteinase-9 in Ceacam1(-/-) mice were confirmed by immune fluorescence, flow cytometry, zymography, and stimulation of neutrophils. Importantly, neutralization of matrix metalloproteinase-9 activity in Ceacam1(-/-) mice was sufficient to alleviate stroke sizes and improve survival to the level of CEACAM1-competent animals. Immune histochemistry of murine and human poststroke autoptic brains congruently identified abundance of CEACAM1(+)matrix metalloproteinase-9(+) neutrophils in the ischemic hemispheres.. CEACAM1 controls matrix metalloproteinase-9 secretion by neutrophils in postischemic inflammation at the BBB after stroke. We propose CEACAM1 as an important inhibitory regulator of neutrophil-mediated tissue damage and BBB breakdown in focal cerebral ischemia.

Topics: Animals; Antigens, CD; Atrophy; Behavior, Animal; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Carcinoembryonic Antigen; Cell Adhesion Molecules; Disease Models, Animal; Flow Cytometry; Heterocyclic Compounds, 1-Ring; Humans; Infarction, Middle Cerebral Artery; Inflammation Mediators; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Motor Activity; Neurologic Examination; Neutrophil Activation; Neutrophil Infiltration; Neutrophils; Sulfones; Time Factors