Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2019

Open Access 01-12-2019 | Research article

Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats

Authors: Beibei Dong, Yongyan Yang, Zhishen Zhang, Keliang Xie, Lin Su, Yonghao Yu

Published in: BMC Anesthesiology | Issue 1/2019

Login to get access

Abstract

Background

Ischemia-reperfusion (I/R) is a critical pathophysiological basis of cognitive dysfunction caused by ischemia stroke. Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme for the elimination of excessive free heme by combining with hemopexin (HPX), a plasma protein that contributes to eliminating excessive free heme during ischemia stroke. This study aimed to elucidate whether HPX could alleviate cognitive dysfunction in rats subjected to cerebral I/R.

Methods

Rats were randomly divided into five groups: sham, MCAO, Vehicle, HPX and HPX + protoporphyrin IX (ZnPPIX). Cerebral I/R was induced by MCAO. Saline, vehicle, HPX and HPX + ZnPPIX were injected intracerebroventricularly at the moment after reperfusion. Morris water maze (MWM) test was used to detect the learning and cognitive function. Western blot was used to detect the expression of HO-1 in ischemic penumbra. CD31/vWF double labeling immunofluorescence was used to detect the neovascularization in the penumbra hippocampus. The structure and function of blood-brain barrier (BBB) was detected by the permeability of Evans Blue (EB), water content of the brain tissue, the Ang1/Ang2 and VE-cadherin expression.

Results

Our study verified that HPX improved the learning and memory capacity. Hemopexin up-regulated HO-1 protein expression, the average vessel density in the penumbra hippocampus and the VE- cadherin expression but decreased the permeability of EB, the water content of brain tissue and the ratio of Ang1/Ang2. The effects were reversed by ZnPPIX, an inhibitor of HO-1.

Conclusion

HPX can maintain the integrity of the blood-brain barrier and alleviate cognitive dysfunction after cerebral I/R through the HO-1 pathway.
Literature
1.
Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES et al: Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation 2011, 123(4):e18-e209.
2.
Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391–401.CrossRef
3.
Panahpour H, Nekooeian AA, Dehghani GA. Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats. Iran Biomed J. 2014;18(4):232–8.PubMedPubMedCentral
4.
Petrov VI, Ponomarev EA, Maskin SS, Strepetov NN. Pharmacological neuroprotection against brain damage in ischemiai/reperfusion experiment. Eksp Klin Farmakol. 2011;74(8):13–6.PubMed
5.
Chen-Roetling J, Regan RF. Effect of heme oxygenase-1 on the vulnerability of astrocytes and neurons to hemoglobin. Biochem Biophys Res Commun. 2006;350(1):233-7. 
6.
Dong B, Cai M, Fang Z, Wei H, Zhu F, Li G, Dong H, Xiong L. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia. BMC Neurosci. 2013;14:58.CrossRef
7.
Immenschuh S, Vijayan V, Janciauskiene S, Gueler F. Heme as a Target for Therapeutic Interventions. Front Pharmacol. 2017;8:146.
8.
Brzica H, Abdullahi W, Ibbotson K, Ronaldson PT. Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke. J Cent Nerv Syst Dis. 2017;9:595446934.
9.
Wu BJ, Midwinter RG, Cassano C, Beck K, Wang Y, Changsiri D, Gamble JR, Stocker R. Heme oxygenase-1 increases endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2009;29(10):1537–42.CrossRef
10.
Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11(1):47–60.CrossRef
11.
Liddell JR, Lehtonen S, Duncan C, Keksa-Goldsteine V, Levonen AL, Goldsteins G, Malm T, White AR, Koistinaho J, Kanninen KM. Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes. J Neuroinflammation. 2016;13:49.CrossRef
12.
KA E, Jasper H. Measurement of experimentally induced brain swelling and shrinkage. Am J Phys. 1949;157(1):122–9.
13.
Prakash R, Carmichael ST. Blood-brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury. Curr Opin Neurol. 2015;28(6):556–64.CrossRef
14.
Bentley K, Franco CA, Philippides A, Blanco R, Dierkes M, Gebala V, Stanchi F, Jones M, Aspalter IM, Cagna G, et al. The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nat Cell Biol. 2014;16(4):309–21.CrossRef
15.
The burden of disease in Russia from 1980 to 2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2018.
16.
van Ierssel SH, Conraads VM, Van Craenenbroeck EM, Liu Y, Maas AI, Parizel PM, Hoymans VY, Vrints CJ, Jorens PG. Endothelial dysfunction in acute brain injury and the development of cerebral ischemia. J Neurosci Res. 2015;93(6):866–72.CrossRef
17.
Ohnishi M, Katsuki H, Unemura K, Izumi Y, Kume T, Takada-Takatori Y, Akaike A. Heme oxygenase-1 contributes to pathology associated with thrombin-induced striatal and cortical injury in organotypic slice culture. Brain Res. 2010;1347:170–8.CrossRef
18.
Kaluza J, Wolk A, Larsson SC. Heme iron intake and risk of stroke: a prospective study of men. STROKE. 2013;44(2):334–9.CrossRef
19.
Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ, Figdor CG. Different faces of the heme-heme oxygenase system in inflammation. Pharmacol Rev. 2003;55(3):551–71.CrossRef
20.
Li RC, Saleem S, Zhen G, Cao W, Zhuang H, Lee J, Smith A, Altruda F, Tolosano E, Dore S. Heme-hemopexin complex attenuates neuronal cell death and stroke damage. J Cereb Blood Flow Metab. 2009;29(5):953–64.CrossRef
21.
Lu X, Gu R, Hu W, Sun Z, Wang G, Wang L, Xu Y. Upregulation of heme oxygenase-1 protected against brain damage induced by transient cerebral ischemia-reperfusion injury in rats. Exp Ther med. 2018;15(6):4629-36.
22.
Zeng B, Lin G, Ren X, Zhang Y, Chen H. Over-expression of HO-1 on mesenchymal stem cells promotes angiogenesis and improves myocardial function in infarcted myocardium. J Biomed Sci. 2010;17:80.CrossRef
23.
Liu C, Zhong L, Tian XL, Han YC. Protective effects of 8-MOP on blood-brain barrier via the Nrf-2/HO-1 pathway in mice model of cerebral infarction. Eur Rev Med Pharmacol Sci. 2018;22(13):4278–87.PubMed
24.
Zhao YJ, Nai Y, Ma QS, Song DJ, Ma YB, Zhang LH, Mi LX. Dl-3-n-butylphthalide protects the blood brain barrier of cerebral infarction by activating the Nrf-2/HO-1 signaling pathway in mice. Eur Rev Med Pharmacol Sci. 2018;22(7):2109–18.PubMed
25.
Thomsen MS, Routhe LJ, Moos T. The vascular basement membrane in the healthy and pathological brain. J Cereb Blood Flow Metab. 2017;37(10):3300-17.
26.
Barrionuevo G, Brown TH. Associative long-term potentiation in hippocampal slices. Proc Natl Acad Sci U S A. 1983;80(23):7347–51.CrossRef
Metadata
Title
Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats
Authors
Beibei Dong
Yongyan Yang
Zhishen Zhang
Keliang Xie
Lin Su
Yonghao Yu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2019
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-019-0681-2

Other articles of this Issue 1/2019

BMC Anesthesiology 1/2019 Go to the issue

Research article

The oculocardiac reflex and depth of anesthesia measured by brain wave

Research article

Adverse events associated with continuous interscalene block administered using the catheter-over-needle method: a retrospective analysis

Research article

Effects of a metabolic optimized fast track concept (MOFA) on bowel function and recovery after surgery in patients undergoing elective colon or liver resection: a randomized controlled trial

Research article

Lack of association between intraoperative handoff of care and postoperative complications: a retrospective observational study

Research article

The influences of morphine or ketamine pre-treatment on hemodynamic, acid-base status, biochemical markers of brain damage and early survival in rats after asphyxial cardiac arrest

Research article

Minimally invasive spinal anesthesia for cesarean section in maternal anticoagulation therapy: a randomized controlled trial