title: Ultrasound prevents renal ischemia-reperfusion injury by stimulating the splenic cholinergic anti-inflammatory pathway.
abstract: AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b(+)Ly6G(high) neutrophils and CD11b(+)F4/80(high) myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4(+) T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the α7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway.
authors.affiliation: Department of Medicine, Division of Nephrology, Daejeon St. Mary’s Hospital, The Catholic University of Korea, Daeheungdong, Chungku, South Korea.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gigliotti
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Amandeep
authors.initials: A
authors.lastname: Bajwa
authors.forename: Kryt
authors.initials: K
authors.lastname: Chattrabhuti
authors.forename: Sangju
authors.initials: S
authors.lastname: Lee
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.forename: Kambiz
authors.initials: K
authors.lastname: Kalantari
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011950:Receptors, Cholinergic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000502:physiology* / Q000601:surgery; D013156:Splenectomy; D014464:Ultrasonic Therapy; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D039481:CD11b Antigen; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor
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