Skip to main content

Advertisement

SpringerLink
Log in

Nicotine Treatment Ameliorates Blood-Brain Barrier Damage After Acute Ischemic Stroke by Regulating Endothelial Scaffolding Protein Pdlim5

  • Research
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Analysis of a National Institutes of Health (NIH) trial shows that cigarette smoking protected tissue plasminogen activator (tPA)-treated patients from hemorrhage transformation (HT); however, the underlying mechanism is not clear. Damage to the integrity of the blood-brain barrier (BBB) is the pathological basis of HT. Here, we investigated the molecular events of BBB damage after acute ischemic stroke (AIS) using in vitro oxygen-glucose deprivation (OGD) and in vivo mice middle cerebral artery occlusion (MCAO) models. Our results showed that the permeability of bEND.3 monolayer endothelial cells was significantly increased after being exposed to OGD for 2 h. Mice were subjected to 90-min ischemia with 45-min reperfusion, and BBB integrity was significantly damaged, accompanied by tight junction protein occludin degradation, downregulation of microRNA-21 (miR-21), transforming growth factor-β (TGF-β), phosphorylated Smad (p-Smad), plasminogen activator inhibitor-1 (PAI-1), and the upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that has been shown to regulate TGF-β-Smad3 pathway. In addition, pretreatment with two-week nicotine significantly reduced AIS-induced BBB damage and its associated protein dysregulation via downregulating Pdlim5. Notably, AIS did not significantly induce BBB damage in Pdlim5 deficit mice, but overexpression of Pdlim5 in the striatum with adeno-associated virus produced BBB damage and associated protein dysregulation which could be ameliorated by two-week nicotine pretreatment. More important, AIS induced a significant miR-21 decrease, and miR-21 mimics treatment decreased AIS-induced BBB damage by decreasing Pdlim5. Together, these results demonstrate that nicotine treatment alleviates the AIS-compromised integrity of BBB by regulating Pdlim5.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

References

  1. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581–7.

    Article  Google Scholar 

  2. NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke. 1997;28(11):2109–18.

    Article  Google Scholar 

  3. Jin X, Liu J, Liu W. Early ischemic blood brain barrier damage: a potential indicator for hemorrhagic transformation following tissue plasminogen activator (tPA) thrombolysis? Curr Neurovasc Res. 2014;11(3):254–62.

    Article  CAS  PubMed  Google Scholar 

  4. Liu C, Xie J, Sun S, Li H, Li T, Jiang C, Chen X, Wang J, Le A, Wang J, Li Z, Wang J, Wang W. Hemorrhagic transformation after tissue plasminogen activator treatment in acute ischemic stroke. Cell Mol Neurobiol. 2022;42(3):621–46.

    Article  CAS  PubMed  Google Scholar 

  5. Yang SH, Liu R. Four decades of ischemic penumbra and its implication for ischemic stroke. Transl Stroke Res. 2021;12(6):937–45.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jin X, Liu J, Yang Y, Liu KJ, Liu W. Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset. Neurobiol Dis. 2012;48(3):309–16.

    Article  PubMed  Google Scholar 

  7. Liu J, Jin X, Liu KJ, Liu W. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage. J Neurosci. 2012;32(9):3044–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Leigh R, Jen SS, Hillis AE, Krakauer JW, Barker PB. Pretreatment blood-brain barrier damage and post-treatment intracranial hemorrhage in patients receiving intravenous tissue-type plasminogen activator. Stroke. 2014;45(7):2030–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Leigh R, Christensen S, Campbell BC, Marks MP, Albers GW, Lansberg MG. Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology. 2016;87(3):263–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen S, Sun Y, Li F, Zhang X, Hu X, Zhao X, Li Y, Li H, Zhang J, Liu W, Zheng GQ, Jin X. Modulation of alpha7nAchR by melatonin alleviates ischemia and reperfusion-compromised integrity of blood-brain barrier through inhibiting HMGB1-mediated microglia activation and CRTC1-mediated neuronal loss. Cell Mol Neurobiol. 2022;42(7):2407–22.

    Article  CAS  PubMed  Google Scholar 

  11. Naik P, Fofaria N, Prasad S, Sajja RK, Weksler B, Couraud PO, Romero IA, Cucullo L. Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe? BMC Neurosci. 2014;15:51.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zidovetzki R, Chen P, Fisher M, Hofman FM, Faraci FM. Nicotine increases plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-associated pathway. Stroke. 1999;30(3):651–5.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou J, Zhang J. Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. Mol Med Rep. 2014;10(2):971–6.

    Article  CAS  PubMed  Google Scholar 

  14. Momi N, Kaur S, Rachagani S, Ganti AK, Batra SK. Smoking and microRNA dysregulation: a cancerous combination. Trends Mol Med. 2015;20(1):36–47.

    Article  Google Scholar 

  15. Ge X, Han Z, Chen F, Wang H, Zhang B, Jiang R, Lei P, Zhang J. MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain injury in rats. Brain Res. 2015;1603:150–7.

    Article  CAS  PubMed  Google Scholar 

  16. Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, Holzmann A, Just A, Remke J, Zimmer K, Zeug A, Ponimaskin E, Schmiedl A, Yin X, Mayr M, Halder R, Fischer A, Engelhardt S, Wei Y, Schober A, et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014;124(5):2136–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ito J, Iijima M, Yoshimoto N, Niimi T, Kuroda S, Maturana AD. Scaffold protein enigma homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes. Cell Signal. 2015;27(12):2425–33.

    Article  CAS  PubMed  Google Scholar 

  18. Huang J, Cai C, Zheng T, Wu X, Wang D, Zhang K, Xu B, Yan R, Gong H, Zhang J, Shi Y, Xu Z, Zhang X, Zhang X, Shang T, Zhou J, Guo X, Zeng C, Lai EY, et al. Endothelial scaffolding protein ENH (enigma homolog protein) promotes PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2)-mediated dephosphorylation of AKT1 and eNOS (endothelial NO synthase) promoting vascular remodeling. Arterioscler Thromb Vasc Biol. 2020;40(7):1705–21.

    Article  CAS  PubMed  Google Scholar 

  19. Chen T, Zhou G, Zhou Q, Tang H, Ibe JC, Cheng H, Gou D, Chen J, Yuan JX, Raj JU. Loss of microRNA-17 approximately 92 in smooth muscle cells attenuates experimental pulmonary hypertension via induction of PDZ and LIM domain 5. Am J Respir Crit Care Med. 2015;191(6):678–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cai Y, Liu X, Chen W, Wang Z, Xu G, Zeng Y, Ma Y. TGF-beta1 prevents blood-brain barrier damage and hemorrhagic transformation after thrombolysis in rats. Exp Neurol. 2015;266:120–6.

    Article  CAS  PubMed  Google Scholar 

  21. Cheng H, Kimura K, Peter AK, Cui L, Ouyang K, Shen T, Liu Y, Gu Y, Dalton ND, Evans SM, Knowlton KU, Peterson KL, Chen J. Loss of enigma homolog protein results in dilated cardiomyopathy. Circ Res. 2010;107(3):348–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Murrin LC, Ferrer JR, Zeng WY, Haley NJ. Nicotine administration to rats: methodological considerations. Life Sci. 1987;40(17):1699–708.

    Article  CAS  PubMed  Google Scholar 

  23. Ryan RE, Ross SA, Drago J, Loiacono RE. Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in alpha4 nicotinic receptor subunit knockout mice. Br J Pharmacol. 2001;132(8):1650–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, Cheng J, Jia J, Zhen X. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun. 2015;49:75–85.

    Article  CAS  PubMed  Google Scholar 

  25. Liu Y, Liu WC, Sun Y, Shen X, Wang X, Shu H, Pan R, Liu CF, Liu W, Liu KJ, Jin X. Normobaric hyperoxia extends neuro- and vaso-protection of N-acetylcysteine in transient focal ischemia. Mol Neurobiol. 2017;54(5):3418–27.

    Article  CAS  PubMed  Google Scholar 

  26. Wang X, Liu Y, Sun Y, Liu W, Jin X. Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO. J Neurol Sci. 2016;363:63–8.

    Article  CAS  PubMed  Google Scholar 

  27. Sun Y, Chen X, Zhang X, Shen X, Wang M, Wang X, Liu WC, Liu CF, Liu J, Liu W, Jin X. β2-adrenergic receptor-mediated HIF-1alpha upregulation mediates blood brain barrier damage in acute cerebral ischemia. Front Mol Neurosci. 2017;10:257.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Eckle T, Faigle M, Grenz A, Laucher S, Thompson LF, Eltzschig HK. A2B adenosine receptor dampens hypoxia-induced vascular leak. Blood. 2008;111(4):2024–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang Y, Wang X, Zhang X, Chen S, Sun Y, Liu W, Jin X, Zheng G. D1 receptor-mediated endogenous tPA upregulation contributes to blood-brain barrier injury after acute ischaemic stroke. J Cell Mol Med. 2020;24(16):9255–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shu H, Wang M, Song M, Sun Y, Shen X, Zhang J, Jin X. Acute nicotine treatment alleviates LPS-induced impairment of fear memory reconsolidation through AMPK activation and CRTC1 upregulation in hippocampus. Int J Neuropsychopharmacol. 2020;23(10):687–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nicaise C, Mitrecic D, Demetter P, De Decker R, Authelet M, Boom A, Pochet R. Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS rat. Brain Res. 2009;1301:152–62.

    Article  CAS  PubMed  Google Scholar 

  32. Yao X, Wang Y, Zhang D. microRNA-21 confers neuroprotection against cerebral ischemia-reperfusion injury and alleviates blood-brain barrier disruption in rats via the MAPK signaling pathway. J Mol Neurosci. 2018;65(1):43–53.

    Article  CAS  PubMed  Google Scholar 

  33. Hawkins BT, Brown RC, Davis TP. Smoking and ischemic stroke: a role for nicotine? Trends Pharmacol Sci. 2002;23(2):78–82.

    Article  CAS  PubMed  Google Scholar 

  34. Zou D, Luo M, Han Z, Zhan L, Zhu W, Kang S, Bao C, Li Z, Nelson J, Zhang R, Su H. Activation of alpha-7 nicotinic acetylcholine receptor reduces brain edema in mice with ischemic stroke and bone fracture. Mol Neurobiol. 2017;54(10):8278–86.

    Article  CAS  PubMed  Google Scholar 

  35. Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH. Alpha7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3beta inhibition in a mouse model of intracerebral hemorrhage. Stroke. 2012;43(3):844–50.

    Article  CAS  PubMed  Google Scholar 

  36. Krafft PR, Caner B, Klebe D, Rolland WB, Tang J, Zhang JH. PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice. Stroke. 2013;44(6):1743–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Duris K, Manaenko A, Suzuki H, Rolland WB, Krafft PR, Zhang JH. alpha7 nicotinic acetylcholine receptor agonist PNU-282987 attenuates early brain injury in a perforation model of subarachnoid hemorrhage in rats. Stroke. 2011;42(12):3530–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dash PK, Zhao J, Kobori N, Redell JB, Hylin MJ, Hood KN, Moore AN. Activation of alpha 7 cholinergic nicotinic receptors reduce blood-brain barrier permeability following experimental traumatic brain injury. J Neurosci. 2016;36(9):2809–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Elahy M, Lam V, Pallebage-Gamarallage MM, Giles C, Mamo JC, Takechi R. Nicotine attenuates disruption of blood-brain barrier induced by saturated-fat feeding in wild-type mice. Nicotine Tob Res. 2015;17(12):1436–41.

    Article  CAS  PubMed  Google Scholar 

  40. Uzum G, Diler AS, Ziylan YZ. Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat. Pharmacol Res. 1999;40(3):263–9.

    Article  CAS  PubMed  Google Scholar 

  41. Beinat C, Banister SD, Herrera M, Law V, Kassiou M. The therapeutic potential of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) agonists for the treatment of the cognitive deficits associated with schizophrenia. CNS Drugs. 2015;29(7):529–42.

    Article  CAS  PubMed  Google Scholar 

  42. Shah KK, Boreddy PR, Abbruscato TJ. Nicotine pre-exposure reduces stroke-induced glucose transporter-1 activity at the blood-brain barrier in mice. Fluids Barriers CNS. 2015;12:10.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Li C, Sun H, Arrick DM, Mayhan WG. Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury. J Appl Physiol. 2016;120(3):328–33.

    Article  CAS  PubMed  Google Scholar 

  44. Wang L, Kittaka M, Sun N, Schreiber SS, Zlokovic BV. Chronic nicotine treatment enhances focal ischemic brain injury and depletes free pool of brain microvascular tissue plasminogen activator in rats. J Cereb Blood Flow Metab. 1997;17(2):136–46.

    Article  CAS  PubMed  Google Scholar 

  45. Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, Campos CR, Davis TP. Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res. 2004;1027(1-2):48–58.

    Article  CAS  PubMed  Google Scholar 

  46. Paulson JR, Yang T, Selvaraj PK, Mdzinarishvili A, Van der Schyf CJ, Klein J, Bickel U, Abbruscato TJ. Nicotine exacerbates brain edema during in vitro and in vivo focal ischemic conditions. J Pharmacol Exp Ther. 2010;332(2):371–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. d'Adesky N, Diaz F, Zhao W, Bramlett HM, Perez-Pinzon MA, Dave KR, Raval AP. Nicotine exposure along with oral contraceptive treatment in female rats exacerbates post-cerebral ischemic hypoperfusion potentially via altered histamine metabolism. Transl Stroke Res. 2021;12(5):817–28.

    Article  CAS  PubMed  Google Scholar 

  48. Gonzalez CL, Gharbawie OA, Kolb B. Chronic low-dose administration of nicotine facilitates recovery and synaptic change after focal ischemia in rats. Neuropharmacology. 2006;50(7):777–87.

    Article  CAS  PubMed  Google Scholar 

  49. Kume T, Takada-Takatori Y. Nicotinic acetylcholine receptor signaling: roles in neuroprotection. In: Akaike A, Shimohama S, Misu Y, editors. Nicotinic acetylcholine receptor signaling in neuroprotection. Springer, Singapore; 2018. p. 59–71.

  50. Chen S, Bennet L, McGregor AL. Delayed varenicline administration reduces inflammation and improves forelimb use following experimental stroke. J Stroke Cerebrovasc Dis. 2017;26(12):2778–87.

    Article  PubMed  Google Scholar 

  51. Seyedaghamiri F, Hosseini L, Kazmi S, Mahmoudi J, Shanehbandi D, Ebrahimi-Kalan A, Rahbarghazi R, Sadigh-Eteghad S, Farhoudi M. Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: the possible roles of inflammation, apoptosis, and synaptic factors. Brain Res Bull. 2022;181:36–45.

    Article  CAS  PubMed  Google Scholar 

  52. Huo K, Wei M, Zhang M, Wang Z, Pan P, Shaligram SS, Huang J, Prado LBD, Wong J, Su H. Reduction of neuroinflammation alleviated mouse post bone fracture and stroke memory dysfunction. J Cereb Blood Flow Metab. 2021;41(9):2162–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li ZL, Gou CY, Wang WH, Li Y, Cui Y, Duan JJ, Chen Y. A novel effect of PDLIM5 in alpha7 nicotinic acetylcholine receptor upregulation and surface expression. Cell Mol Life Sci. 2022;79, (1):64.

    Article  Google Scholar 

  54. Macias MJ, Martin-Malpartida P, Massague J. Structural determinants of Smad function in TGF-beta signaling. Trends Biochem Sci. 2015;40(6):296–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, Tsuruo T, Sawada Y, Niwa M, Kataoka Y. Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production. Brain Res. 2005;1038(2):208–15.

    Article  CAS  PubMed  Google Scholar 

  56. Ronaldson PT, Demarco KM, Sanchez-Covarrubias L, Solinsky CM, Davis TP. Transforming growth factor-beta signaling alters substrate permeability and tight junction protein expression at the blood-brain barrier during inflammatory pain. J Cereb Blood Flow Metab. 2009;29(6):1084–98.

    Article  CAS  PubMed  Google Scholar 

  57. Kim JS. tPA helpers in the treatment of acute ischemic stroke: are they ready for clinical use? J Stroke. 2019;21(2):160–74.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ren B, Li X, Zhang J, Fan J, Duan J, Chen Y. PDLIM5 mediates PKCepsilon translocation in PMA-induced growth cone collapse. Cell Signal. 2015;27(3):424–35.

    Article  CAS  PubMed  Google Scholar 

  59. Lopez MS, Morris-Blanco KC, Ly N, Maves C, Dempsey RJ, Vemuganti R. MicroRNA miR-21 decreases post-stroke brain damage in rodents. Transl Stroke Res. 2022;13(3):483–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Key R&D Program of China (2022YFC3602805). This work was also supported by the National Natural Science Foundation of China (81671145, 81870973).

Author information

Author notes

  1. Xiaoyan Hu, Jiali Dong, Panpan Geng and Yanyun Sun contributed equally to this work.

Authors and Affiliations

  1. Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100069, People’s Republic of China

    Xiaoyan Hu, Panpan Geng, Weihong Du, Xiaoyun Zhao, Qian Wang & Xinchun Jin

  2. Institute of Neuroscience, the second affiliated hospital of Soochow University, Suzhou, 215004, China

    Jiali Dong, Yanyun Sun, Xiaona Wang, Yushan Liu & Xinchun Jin

  3. Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China

    Changqing Liu

  4. The Central Laboratory, Shenzhen Second People’s Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen University School of Medicine, Shenzhen, 518035, China

    Wenlan Liu

  5. Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China

    Hongqiang Cheng

  6. Department of Physiology, Capital Medical University, Beijing, 100069, People’s Republic of China

    Wei Wang

Authors
  1. Xiaoyan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiali Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Panpan Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanyun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weihong Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoyun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Changqing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaona Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yushan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wenlan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hongqiang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xinchun Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XH, JD, PG, YS, WD, XZ, QW, CL, XW, and YL performed experiments and analyzed the data.WW, HC, and WL provided advice on the experimental design and interpretation of the manuscript. XH, PG, YS, QW, and CL made the figures and drafted the manuscript. HC, WW, and XJ finalized the manuscript.

Corresponding authors

Correspondence to Hongqiang Cheng, Wei Wang or Xinchun Jin.

Ethics declarations

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. All the animal experiments were approved by the Laboratory Animal Welfare and Ethics Committee of Soochow University (IACUC-201611A355).

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, X., Dong, J., Geng, P. et al. Nicotine Treatment Ameliorates Blood-Brain Barrier Damage After Acute Ischemic Stroke by Regulating Endothelial Scaffolding Protein Pdlim5. Transl. Stroke Res. 15, 672–687 (2024). https://doi.org/10.1007/s12975-023-01158-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-023-01158-0

Keywords

Search

Navigation