Ischemic Post-conditioning is Neuroprotective Even at Delayed TPA Administration After Embolic Stroke in Female Rats

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2022 Apr 18

PMID 35432799

Authors

Mohadeseh Mohammadi

Masoud Mobini

Fatemeh Mashayekhi

Mohammad Allahtavakoli

Ayat Kaeidi

Jalal Hassanshahi

Ali Shamsizadeh

Elham Hakimizadeh

Mahsa Hassanipour

Affiliations

Soon will be listed here.

Abstract

Objectives: Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats.

Materials And Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated.

Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (<0.05). The combination of PC and tPA reduced the infarct volume, brain edema, and protected BBB. tPA+PC could alleviate neurobehavioral disorders compared with control or tPA. Moreover, PC had the capability of MMP-9 reduction when combined with delayed tPA (<0.05).

Conclusion: Conduction of PC not only alleviated some stroke complications but also enhanced the therapeutic time window of tPA in female rats under embolic stroke.

Citing Articles

Neuroprotective effect of ischemic postconditioning against hyperperfusion and its mechanisms of neuroprotection.

Bagheri S, Allahtavakoli M, Hakimizadeh E J Res Med Sci. 2024; 29:31.

PMID: 39239075 PMC: 11376715. DOI: 10.4103/jrms.jrms_341_22.

References

Yao G, Zhu Q, Xia J, Chen F, Huang M, Liu J . Ischemic postconditioning confers cerebroprotection by stabilizing VDACs after brain ischemia. Cell Death Dis. 2018; 9(10):1033. PMC: 6180002. DOI: 10.1038/s41419-018-1089-5. View

Meirhaeghe A, Cottel D, Cousin B, Dumont M, Marecaux N, Amouyel P . Sex Differences in Stroke Attack, Incidence, and Mortality Rates in Northern France. J Stroke Cerebrovasc Dis. 2018; 27(5):1368-1374. DOI: 10.1016/j.jstrokecerebrovasdis.2017.12.023. View

Emberson J, Lees K, Lyden P, Blackwell L, Albers G, Bluhmki E . Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014; 384(9958):1929-35. PMC: 4441266. DOI: 10.1016/S0140-6736(14)60584-5. View

Hill M, Barber P, Takahashi J, Demchuk A, Feasby T, Buchan A . Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. CMAJ. 2000; 162(9):1281-4. PMC: 1232409. View

Liu R, Wen Y, Perez E, Wang X, Day A, Simpkins J . 17beta-Estradiol attenuates blood-brain barrier disruption induced by cerebral ischemia-reperfusion injury in female rats. Brain Res. 2005; 1060(1-2):55-61. DOI: 10.1016/j.brainres.2005.08.048. View

Zakeri M, Fatemi I, Kaeidi A, Zakeri M, Hakimizadeh E, Hassanipour M . Pro-neurocognitive and anti-sarcopenic benefits of one-year metformin therapy in ovariectomized aged mice. Clin Exp Pharmacol Physiol. 2019; 46(12):1133-1140. DOI: 10.1111/1440-1681.13149. View

Dela Pena I, Borlongan C, Shen G, Davis W . Strategies to Extend Thrombolytic Time Window for Ischemic Stroke Treatment: An Unmet Clinical Need. J Stroke. 2017; 19(1):50-60. PMC: 5307939. DOI: 10.5853/jos.2016.01515. View

El-Hakim Y, Mani K, Eldouh A, Pandey S, Grimaldo M, Dabney A . Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats. Biol Sex Differ. 2021; 12(1):14. PMC: 7811247. DOI: 10.1186/s13293-020-00352-1. View

Sacco R, Kasner S, Broderick J, Caplan L, Connors J, Culebras A . An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 44(7):2064-89. PMC: 11078537. DOI: 10.1161/STR.0b013e318296aeca. View

10.

Morancho A, Rosell A, Garcia-Bonilla L, Montaner J . Metalloproteinase and stroke infarct size: role for anti-inflammatory treatment?. Ann N Y Acad Sci. 2010; 1207:123-33. DOI: 10.1111/j.1749-6632.2010.05734.x. View

11.

Guo H, Yang J, Liu M, Wang L, Hou W, Zhang L . Selective activation of estrogen receptor β alleviates cerebral ischemia neuroinflammatory injury. Brain Res. 2019; 1726:146536. DOI: 10.1016/j.brainres.2019.146536. View

12.

Bonkhoff A, Schirmer M, Bretzner M, Hong S, Regenhardt R, Brudfors M . Outcome after acute ischemic stroke is linked to sex-specific lesion patterns. Nat Commun. 2021; 12(1):3289. PMC: 8172535. DOI: 10.1038/s41467-021-23492-3. View

13.

Carcel C, Woodward M, Wang X, Bushnell C, Sandset E . Sex matters in stroke: A review of recent evidence on the differences between women and men. Front Neuroendocrinol. 2020; 59:100870. DOI: 10.1016/j.yfrne.2020.100870. View

14.

Zhao H . The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain. J Neuroimmune Pharmacol. 2007; 2(4):313-8. DOI: 10.1007/s11481-007-9089-8. View

15.

Joachim E, Barakat R, Lew B, Kim K, Ko C, Choi H . Single intranasal administration of 17β-estradiol loaded gelatin nanoparticles confers neuroprotection in the post-ischemic brain. Nanomedicine. 2020; 29:102246. DOI: 10.1016/j.nano.2020.102246. View

16.

Purroy F, Vicente-Pascual M, Arque G, Baraldes-Rovira M, Begue R, Gallego Y . Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack. Stroke. 2021; 52(2):424-433. PMC: 7834662. DOI: 10.1161/STROKEAHA.120.032814. View

17.

Shen F, Jiang L, Han F, Degos V, Chen S, Su H . Increased Inflammatory Response in Old Mice is Associated with More Severe Neuronal Injury at the Acute Stage of Ischemic Stroke. Aging Dis. 2019; 10(1):12-22. PMC: 6345332. DOI: 10.14336/AD.2018.0205. View

18.

Rezazadeh H, Hoseini Kahnuee M, Roohbakhsh A, Shamsizadeh A, Rahmani M, Bidaki R . Neuroprotective consequences of postconditioning on embolic model of cerebral ischemia in rat. Iran J Basic Med Sci. 2013; 16(2):144-9. PMC: 3843857. View

19.

Esposito E, Hayakawa K, Ahn B, Chan S, Xing C, Liang A . Effects of ischemic post-conditioning on neuronal VEGF regulation and microglial polarization in a rat model of focal cerebral ischemia. J Neurochem. 2018; 146(2):160-172. PMC: 6105375. DOI: 10.1111/jnc.14337. View

20.

Esmaeeli-Nadimi A, Kennedy D, Allahtavakoli M . Opening the window: Ischemic postconditioning reduces the hyperemic response of delayed tissue plasminogen activator and extends its therapeutic time window in an embolic stroke model. Eur J Pharmacol. 2015; 764:55-62. DOI: 10.1016/j.ejphar.2015.06.043. View