title: Melanocortin MC4 receptor agonists alleviate brain damage in abdominal compartment syndrome in the rat.
abstract: Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality in surgical departments and ICUs. However, its specific pathophysiology is unclear. IAH not only leads to intra-abdominal tissue damage but also causes dysfunction in distal organs, such as the brain. In this study, we explore the protective effects of melanocortin 4 receptor agonists in IAH-induced brain injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air was injected into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4 receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were observed, which indicated that RO27-3225 could reduce brain edema, the expressions of the IL-1β and TNF-α inflammatory cytokines, the blood-brain barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9 (MMP9) levels. Moreover, the nicotinic acetylcholine receptor antagonist chlorisondamine and the selective melanocortin 4 receptor antagonist HS024 can negate the protective effects of the RO27-3225. The MC4R agonist can effectively reduce the intracerebral proinflammatory cytokine gene expression and alleviate the brain injury caused by blood-brain barrier damage following IAH.
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Zhang
authors.affiliation: Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zi-Ai
authors.initials: ZA
authors.lastname: Zhao
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Ming-Tao
authors.initials: MT
authors.lastname: Chang
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Trauma Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. Electronic address: dpzhangly@163.com.
authors.forename: Lian-Yang
authors.initials: LY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D059325:Intra-Abdominal Hypertension / Q000150:complications / Q000188:drug therapy*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D016207:Cytokines; D010455:Peptides; D044105:Receptor, Melanocortin, Type 4; C560214:butir-His-Phe-Arg-Trp-Sar-NH2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Intra-abdominal hypertension; Ischemia/reperfusion; Melanocortin 4 receptor