Obesity As a Limiting Factor for Remote Ischemic Postconditioning-Mediated Neuroprotection After Stroke

Overview

Journal J Obes Metab Syndr

Date 2023 Dec 4

PMID 38049179

Authors

Klaudia Kotorova

Jana Koncekova

Miroslav Gottlieb

Martin Bona

Petra Bonova

Affiliations

Soon will be listed here.

Abstract

Background: Remote ischemic postconditioning (RIPostC) may protect the brain from ischemia/reperfusion (I/R) injury. The association between RIPostC and obesity has not yet been extensively studied.

Methods: Twelve-week-old male Zucker diabetic fatty (ZDF; n=68) and Zucker diabetic lean (ZDL; n=51) rats were subjected to focal cerebral ischemia for 90 minutes, followed by 24 hours of reperfusion. RIPostC was performed with 5-minute I/R cycles using a tourniquet on the right hind limb.

Results: The results showed a negative association between obesity and neurological impairment in ischemic animals. We observed a 70% greater infarct size in ZDF rats compared with their lean counterparts, as evaluated by 2,3,5-triphenyltetrazolium chloride staining. To measure the total fragmented DNA in peripheral lymphocytes, comet assay was performed. Obese rats exhibited higher levels of DNA damage (by approximately 135%) in peripheral blood lymphocytes even before the induction of stroke. RIPostC did not attenuate oxidative stress in the blood in obese rats subjected to ischemia. Focal cerebral ischemia increased core and penumbra tissue glutamate release in the brain and decreased it in the blood of ischemic ZDL rats, and these changes improved following RIPostC treatment. However, changes in blood and tissue glutamate content were not detected in ischemic ZDF rats or after RIPostC intervention.

Conclusion: Our findings suggest that obese animals respond more severely to ischemia-reperfusion brain injury. However, obese animals did not achieve neuroprotective benefits of RIPostC treatment.

Citing Articles

New alternative approaches to stroke treatment: the blood cell-derived secretome shows promise in individuals with obesity.

Kotorova K, Koncekova J, Bona M, Bonova P Metab Brain Dis. 2024; 40(1):56.

PMID: 39641824 PMC: 11624225. DOI: 10.1007/s11011-024-01491-9.

Effectiveness of remote ischaemic conditioning is not affected by hyper-inflammation in a rat model of stroke.

Koncekova J, Kotorova K, Nemethova M, Bona M, Bonova P Sci Rep. 2024; 14(1):20750.

PMID: 39237655 PMC: 11377586. DOI: 10.1038/s41598-024-71328-z.

References

Lu M, Wang Y, Yin X, Li Y, Li H . Cerebral protection by remote ischemic post-conditioning in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials. Front Neurol. 2022; 13:905400. PMC: 9532592. DOI: 10.3389/fneur.2022.905400. View

Goth L . A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta. 1991; 196(2-3):143-51. DOI: 10.1016/0009-8981(91)90067-m. View

Osmond J, Mintz J, Stepp D . Preventing increased blood pressure in the obese Zucker rat improves severity of stroke. Am J Physiol Heart Circ Physiol. 2010; 299(1):H55-61. PMC: 2904128. DOI: 10.1152/ajpheart.01111.2009. View

Matsuda M, Shimomura I . Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract. 2014; 7(5):e330-41. DOI: 10.1016/j.orcp.2013.05.004. View

Maltais-Payette I, Boulet M, Prehn C, Adamski J, Tchernof A . Circulating glutamate concentration as a biomarker of visceral obesity and associated metabolic alterations. Nutr Metab (Lond). 2018; 15:78. PMC: 6219091. DOI: 10.1186/s12986-018-0316-5. View

Schmued L, Albertson C, Slikker Jr W . Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res. 1997; 751(1):37-46. DOI: 10.1016/s0006-8993(96)01387-x. View

Bouhidel O, Pons S, Souktani R, Zini R, Berdeaux A, Ghaleh B . Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol. 2008; 295(4):H1580-6. PMC: 2759460. DOI: 10.1152/ajpheart.00379.2008. View

Osborne K, Shigeno T, Balarsky A, Ford I, McCulloch J, Teasdale G . Quantitative assessment of early brain damage in a rat model of focal cerebral ischaemia. J Neurol Neurosurg Psychiatry. 1987; 50(4):402-10. PMC: 1031873. DOI: 10.1136/jnnp.50.4.402. View

Zhao H, Ren C, Chen X, Shen J . From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia. Curr Drug Targets. 2011; 13(2):173-87. PMC: 3346695. DOI: 10.2174/138945012799201621. View

10.

Singh N, McCoy M, Tice R, Schneider E . A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988; 175(1):184-91. DOI: 10.1016/0014-4827(88)90265-0. View

11.

Tsao C, Aday A, Almarzooq Z, Alonso A, Beaton A, Bittencourt M . Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022; 145(8):e153-e639. DOI: 10.1161/CIR.0000000000001052. View

12.

Bonova P, Jachova J, Nemethova M, Bona M, Kollarova P, Gottlieb M . Accelerated capacity of glutamate uptake via blood elements as a possible tool of rapid remote conditioning mediated tissue protection. Neurochem Int. 2020; 142:104927. DOI: 10.1016/j.neuint.2020.104927. View

13.

Callaway J, Knight M, Watkins D, Beart P, Jarrott B, Delaney P . A novel, rapid, computerized method for quantitation of neuronal damage in a rat model of stroke. J Neurosci Methods. 2000; 102(1):53-60. DOI: 10.1016/s0165-0270(00)00278-8. View

14.

Sun Y, Oberley L, Li Y . A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988; 34(3):497-500. View

15.

Ashwal S, Tone B, Tian H, Cole D, Pearce W . Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke. 1998; 29(5):1037-46; discussion 1047. View

16.

Marseglia L, Manti S, DAngelo G, Nicotera A, Parisi E, Di Rosa G . Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014; 16(1):378-400. PMC: 4307252. DOI: 10.3390/ijms16010378. View

17.

Avraham Y, Dayan M, Lassri V, Vorobiev L, Davidi N, Chernoguz D . Delayed leptin administration after stroke induces neurogenesis and angiogenesis. J Neurosci Res. 2012; 91(2):187-95. DOI: 10.1002/jnr.23147. View

18.

Zhao Z, Corvera J, Halkos M, Kerendi F, Wang N, Guyton R . Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003; 285(2):H579-88. DOI: 10.1152/ajpheart.01064.2002. View

19.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

20.

Longa E, Weinstein P, Carlson S, Cummins R . Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20(1):84-91. DOI: 10.1161/01.str.20.1.84. View