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Cerebral Vascular Injury in Diabetic Ischemia and Reperfusion

  • Wenlu Li
  • Haibin Dai
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

About 30% of stroke patients are diabetic and more than 90% of them comprise type 2 diabetes (T2D). Diabetic stroke patients have higher mortality and worse neurological outcomes. Emerging clinical and experimental data suggest that blood-brain barrier (BBB) disruption, neuroinflammation, and stroke recovery impairment are exacerbated in diabetic patients. Hence, finding therapeutic approaches that can target these specific diabetic mechanisms in stroke is the thrust of the present translational study. Here, we summarize the ischemia-reperfusion injury in stroke, presenting the clinical evidence for involvement of hyperglycemia in severe damage of cerebral ischemia-reperfusion. We go on to consider the mechanisms that underlie such pathology, and highlight areas for future basic research and clinical studies into diabetic ischemia and reperfusion.

Keywords

Vascular Cerebral ischemia-reperfusion Stroke Diabetes 

References

  1. 1.
    Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391–401.CrossRefPubMedGoogle Scholar
  2. 2.
    Turc G, Isabel C, Calvet D. Intravenous thrombolysis for acute ischemic stroke. Diagn Interv Imaging. 2014;95(12):1129–33.CrossRefPubMedGoogle Scholar
  3. 3.
    Shi J, Liu Y, Duan Y, et al. A new idea about reducing reperfusion injury in ischemic stroke: gradual reperfusion. Med Hypotheses. 2013;80(2):134–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Nour M, Scalzo F, Liebeskind DS. Ischemia-reperfusion injury in stroke. Interv Neurol. 2013;1(3-4):185–99.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Luitse MJ, Biessels GJ, Rutten GE, Kappelle LJ. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol. 2012;11(3):261–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Bejot Y, Giroud M. Stroke in diabetic patients. Diabetes Metab. 2010;36(Suppl 3):S84–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Kissela B, Air E. Diabetes: impact on stroke risk and poststroke recovery. Semin Neurol. 2006;26(1):100–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Hill MD. Stroke and diabetes mellitus. Handb Clin Neurol. 2014;126:167–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22.CrossRefPubMedGoogle Scholar
  10. 10.
    Liao CC, Shih CC, Yeh CC, et al. Impact of diabetes on stroke risk and outcomes: two nationwide retrospective cohort studies. Medicine (Baltimore). 2015;94(52):e2282.CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Kaarisalo MM, Raiha I, Sivenius J, et al. Diabetes worsens the outcome of acute ischemic stroke. Diabetes Res Clin Pract. 2005;69(3):293–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16(2):434–44.CrossRefPubMedGoogle Scholar
  13. 13.
    Shou J, Zhou L, Zhu S, Zhang X. Diabetes is an independent risk factor for stroke recurrence in stroke patients: a meta-analysis. J Stroke Cerebrovasc Dis. 2015;24(9):1961–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Kruyt ND, Biessels GJ, Devries JH, Roos YB. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management. Nat Rev Neurol. 2010;6(3):145–55.CrossRefPubMedGoogle Scholar
  15. 15.
    Kelly-Cobbs AI, Prakash R, Li W, et al. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes. Am J Physiol Heart Circ Physiol. 2013;304(6):H806–15.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Demchuk AM, Morgenstern LB, Krieger DW, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999;30(1):34–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Masrur S, Cox M, Bhatt DL, et al. Association of Acute and Chronic Hyperglycemia with acute ischemic stroke outcomes post-thrombolysis: findings from get with the guidelines-stroke. J Am Heart Assoc. 2015;4(10):e002193.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Alvarez-Sabin J, Molina CA, Montaner J, et al. Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator--treated patients. Stroke. 2003;34(5):1235–41.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ribo M, Molina C, Montaner J, et al. Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke. 2005;36(8):1705–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29.CrossRefPubMedGoogle Scholar
  21. 21.
    del Zoppo GJ. Inflammation and the neurovascular unit in the setting of focal cerebral ischemia. Neuroscience. 2009;158(3):972–82.CrossRefPubMedGoogle Scholar
  22. 22.
    Tureyen K, Bowen K, Liang J, Dempsey RJ, Vemuganti R. Exacerbated brain damage, edema and inflammation in type-2 diabetic mice subjected to focal ischemia. J Neurochem. 2011;116(4):499–507.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Strecker JK, Minnerup J, Gess B, Ringelstein EB, Schabitz WR, Schilling M. Monocyte chemoattractant protein-1-deficiency impairs the expression of IL-6, IL-1beta and G-CSF after transient focal ischemia in mice. PLoS One. 2011;6(10):e25863.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Strecker JK, Minnerup J, Schutte-Nutgen K, Gess B, Schabitz WR, Schilling M. Monocyte chemoattractant protein-1-deficiency results in altered blood-brain barrier breakdown after experimental stroke. Stroke. 2013;44(9):2536–44.CrossRefPubMedGoogle Scholar
  25. 25.
    Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV. Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury. J Cereb Blood Flow Metab. 2006;26(6):797–810.CrossRefPubMedGoogle Scholar
  26. 26.
    El-Sahar AE, Safar MM, Zaki HF, Attia AS, Ain-Shoka AA. Neuroprotective effects of pioglitazone against transient cerebral ischemic reperfusion injury in diabetic rats: modulation of antioxidant, anti-inflammatory, and anti-apoptotic biomarkers. Pharmacol Rep. 2015;67(5):901–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Li W, Chen Z, Yan M, He P, Chen Z, Dai H. The protective role of isorhamnetin on human brain microvascular endothelial cells from cytotoxicity induced by methylglyoxal and oxygen-glucose deprivation. J Neurochem. 2016;136(3):651–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Panes J, Kurose I, Rodriguez-Vaca D, et al. Diabetes exacerbates inflammatory responses to ischemia-reperfusion. Circulation. 1996;93(1):161–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Enzmann G, Mysiorek C, Gorina R, et al. The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injury. Acta Neuropathol. 2013;125(3):395–412.CrossRefPubMedGoogle Scholar
  30. 30.
    Jing L, Wang JG, Zhang JZ, et al. Upregulation of ICAM-1 in diabetic rats after transient forebrain ischemia and reperfusion injury. J Inflamm. 2014;11(1):35.CrossRefGoogle Scholar
  31. 31.
    Ding C, He Q, Li PA. Diabetes increases expression of ICAM after a brief period of cerebral ischemia. J Neuroimmunol. 2005;161(1-2):61–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Das Evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res. 2007;55(6):498–510.CrossRefPubMedGoogle Scholar
  33. 33.
    Booth G, Stalker TJ, Lefer AM, Scalia R. Mechanisms of amelioration of glucose-induced endothelial dysfunction following inhibition of protein kinase C in vivo. Diabetes. 2002;51(5):1556–64.CrossRefPubMedGoogle Scholar
  34. 34.
    Yi JH, Park SW, Kapadia R, Vemuganti R. Role of transcription factors in mediating post-ischemic cerebral inflammation and brain damage. Neurochem Int. 2007;50(7-8):1014–27.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. Int J Endocrinol. 2014;2014:674987.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Russo MA, Sansone L, Carnevale I, et al. One special question to start with: can HIF/NFkB be a target in inflammation? Endocr Metab Immune Disord Drug Targets. 2015;15(3):171–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Iwata N, Okazaki M, Nakano R, Kasahara C, Kamiuchi S, Suzuki F, Iizuka H, Matsuzaki H, Hibino Y. Diabetes-mediated exacerbation of neuronal damage and inflammation after cerebral ischemia in rat: protective effects of water-soluble extract from culture medium of ganodermalucidum mycelia. In: Advances in the preclinical study of ischemic stroke. Rijeka, Croatia: InTech; 2012.Google Scholar
  38. 38.
    Jian Liu K, Rosenberg GA. Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med. 2005;39(1):71–80.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Yang Y, Rosenberg GA. Matrix metalloproteinases as therapeutic targets for stroke. Brain Res. 2015;1623:30–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kamada H, Yu F, Nito C, Chan PH. Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood-brain barrier dysfunction. Stroke. 2007;38(3):1044–9.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Elgebaly MM, Prakash R, Li W, et al. Vascular protection in diabetic stroke: role of matrix metalloprotease-dependent vascular remodeling. J Cereb Blood Flow Metab. 2010;30(12):1928–38.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Li W, Xu H, Hu Y, et al. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress. PLoS One. 2013;8(9):e76025.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Li W, Liu J, He P, et al. Hydroxysafflor yellow A protects methylglyoxal-induced injury in the cultured human brain microvascular endothelial cells. Neurosci Lett. 2013;549:146–50.CrossRefPubMedGoogle Scholar
  44. 44.
    Fang L, Li X, Zhong Y, et al. Autophagy protects human brain microvascular endothelial cells against methylglyoxal-induced injuries, reproducible in a cerebral ischemic model in diabetic rats. J Neurochem. 2015;135(2):431–40.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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