naa a22 4500 510776264 CHVBK 20180411083231.0 cr unu---uuuuu 180411e20130401xx s 000 0 eng 10.1007/s12975-012-0239-9 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0239-9 Splenic Immune Cells in Experimental Neonatal Hypoxia-Ischemia [Elektronische Daten] [Nancy Fathali, Robert Ostrowski, Yu Hasegawa, Tim Lekic, Jiping Tang, John Zhang] Neuroimmune processes contribute to hypoxic-ischemic damage in the immature brain and may play a role in the progression of particular variants of neonatal encephalopathy. The present study was designed to elucidate molecular mediators of interactions between astrocytes, neurons, and infiltrating peripheral immune cells after experimental neonatal hypoxia-ischemia (HI). Splenectomy was performed on postnatal day 7 Sprague-Dawley rats 3days prior to HI surgery, in which the right common carotid artery was permanently ligated followed by 2h of hypoxia (8% O2). Quantitative analysis showed that natural killer (NK) and T cell expression was reduced in spleen but increased in the brain following HI. Elevations in cyclooxygenase-2 (COX-2) expression after HI by immune cells promoted interleukin-15 (IL-15) expression in astrocytes and infiltration of inflammatory cells to site of injury; additionally, these downregulated the prosurvival protein, phosphoinositide-3-kinase (PI3K), resulting in caspase 3-mediated neuronal death. The removal of the largest pool of peripheral immune cells in the body by splenectomy and COX-2 inhibitors as well as rendering NK cells inactive by CD161 knockdown significantly ameliorated cerebral infarct volume at 72h, diminished body weight loss and brain and systemic organ atrophy, and reduced neurobehavioral deficits at 3weeks. Herein, we demonstrate with the use of surgical approach (splenectomy) and with pharmacological loss-gain function approach using COX-2 inhibitors/agonists as well as with NK cell-type-specific siRNA that after neonatal HI, the infiltrating peripheral immune cells may modulate downstream targets of cell death and neuroinflammation by COX-2-regulated signals. Springer Science+Business Media New York, 2012 NK cells nationallicence Neuroinflammation nationallicence Hypoxia-ischemia nationallicence Neonatal nationallicence Cyclooxygenase-2 nationallicence Fathali Nancy Department of Human Anatomy and Pathology, Loma Linda University, Loma Linda, CA, USA aut Ostrowski Robert Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut Hasegawa Yu Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut Lekic Tim Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut Tang Jiping Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut Zhang John Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 208-219 1868-4483 4:2<208 2013 4 12975 https://doi.org/10.1007/s12975-012-0239-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0239-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fathali Nancy Department of Human Anatomy and Pathology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 700 1- Ostrowski Robert Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 700 1- Hasegawa Yu Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 700 1- Lekic Tim Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 700 1- Tang Jiping Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 700 1- Zhang John Department of Physiology, Loma Linda University, Loma Linda, CA, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 208-219 1868-4483 4:2<208 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer