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Translational Stroke Research

Erschienen in:

01.06.2015 | Original Article

Comparative Analysis of Different Methods of Ischemia/Reperfusion in Hyperglycemic Stroke Outcomes: Interaction with tPA

verfasst von: Sherif Hafez, Md Nasrul Hoda, Xinyue Guo, Maribeth H. Johnson, Susan C. Fagan, Adviye Ergul

Erschienen in: Translational Stroke Research | Ausgabe 3/2015

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Abstract

Acute hyperglycemia (HG) exacerbates reperfusion injury and aggravates tissue plasminogen activator (tPA)-induced hemorrhagic transformation (HT). Previous experimental hyperglycemic stroke studies employed very high blood glucose levels and exclusively used suture occlusion model to induce ischemia. Only few studies evaluated HG in embolic stroke and mostly involving the use of 10-fold higher dose of tPA than that is used in patients. However, the interaction between acute HG and low (human) dose tPA in different experimental models of stroke has never been reported. We first tested the impact of the severity of acute HG on stroke outcome. Building upon our findings, we then compared the impact of mild acute HG on neurovascular injury in rats subjected to suture or thromboembolic occlusion with and without low dose tPA. We assessed cerebral blood flow, neurobehavioral outcomes, infarction, hemorrhage, and edema. tPA did not change the infarct size in either control or hyperglycemic animals when compared to no tPA groups. HG increased HT and worsened functional outcomes in both suture and embolic occlusion models. The combination of HG and tPA exacerbated the vascular injury and worsened the neurological deficits more than each individual treatment in both models. Our findings show that the interaction between HG and even low dose tPA has detrimental effects on the cerebrovasculature and functional outcomes independent of the method of reperfusion.

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.CrossRefPubMed

Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32(10):2426–32.CrossRefPubMed

Quast MJ, Wei J, Huang NC, Brunder DG, Sell SL, Gonzalez JM, et al. Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury in hyperglycemic rats. J Cereb Blood Flow Metab. 1997;17(5):553–9.CrossRefPubMed

Yip PK, He YY, Hsu CY, Garg N, Marangos P, Hogan EL. Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Neurology. 1991;41(6):899–905.CrossRefPubMed

Suh SW, Shin BS, Ma H, Van Hoecke M, Brennan AM, Yenari MA, et al. Glucose and NADPH oxidase drive neuronal superoxide formation in stroke. Ann Neurol. 2008;64(6):654–63.CrossRefPubMedCentralPubMed

Wei J, Huang NC, Quast MJ. Hydroxyl radical formation in hyperglycemic rats during middle cerebral artery occlusion/reperfusion. Free Radic Biol Med. 1997;23(7):986–95.CrossRefPubMed

Hafez S, Coucha M, Bruno A, Fagan SC, Ergul A. Hyperglycemia, acute ischemic stroke, and throhrombolytic therapy. Transl Stroke Res. 2014;5(4):442–53.CrossRefPubMedCentralPubMed

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.CrossRefPubMedCentralPubMed

Elgebaly MM, Ogbi S, Li W, Mezzetti EM, Prakash R, Johnson MH, et al. Neurovascular injury in acute hyperglycemia and diabetes: a comparative analysis in experimental stroke. Transl Stroke Res. 2011;2(3):391–8.CrossRefPubMedCentralPubMed

10.

Cipolla MJ, Huang Q, Sweet JG. Inhibition of protein kinase Cbeta reverses increased blood-brain barrier permeability during hyperglycemic stroke and prevents edema formation in vivo. Stroke. 2011;42(11):3252–7.CrossRefPubMedCentralPubMed

11.

Xing Y, Hua Y, Keep RF, Xi G. Effects of deferoxamine on brain injury after transient focal cerebral ischemia in rats with hyperglycemia. Brain Res. 2009;1291:113–21.CrossRefPubMedCentralPubMed

12.

Kumari R, Willing LB, Patel SD, Krady JK, Zavadoski WJ, Gibbs EM, et al. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010;30(2):352–60.CrossRefPubMedCentralPubMed

13.

Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375(9727):1695–703.CrossRefPubMed

14.

Poppe AY, Majumdar SR, Jeerakathil T, Ghali W, Buchan AM, Hill MD. Admission hyperglycemia predicts a worse outcome in stroke patients treated with intravenous thrombolysis. Diabetes Care. 2009;32(4):617–22.CrossRefPubMedCentralPubMed

15.

Alvarez-Sabin J, Molina CA, Montaner J, Arenillas JF, Huertas R, Ribo M, et al. Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator-treated patients. Stroke. 2003;34(5):1235–41.CrossRefPubMed

16.

Ning R, Chopp M, Yan T, Zacharek A, Zhang C, Roberts C, et al. Tissue plasminogen activator treatment of stroke in type-1 diabetes rats. Neuroscience. 2012;222:326–32.CrossRefPubMedCentralPubMed

17.

Fan X, Lo EH, Wang X. Effects of minocycline plus tissue plasminogen activator combination therapy after focal embolic stroke in type 1 diabetic rats. Stroke. 2013;44(3):745–52.CrossRefPubMedCentralPubMed

18.

Fan X, Ning M, Lo EH, Wang X. Early insulin glycemic control combined with tPA thrombolysis reduces acute brain tissue damages in a focal embolic stroke model of diabetic rats. Stroke. 2013;44(1):255–9.CrossRefPubMedCentralPubMed

19.

Fan X, Qiu J, Yu Z, Dai H, Singhal AB, Lo EH, et al. A rat model of studying tissue-type plasminogen activator thrombolysis in ischemic stroke with diabetes. Stroke. 2012;43(2):567–70.CrossRefPubMedCentralPubMed

20.

Won SJ, Tang XN, Suh SW, Yenari MA, Swanson RA. Hyperglycemia promotes tissue plasminogen activator-induced hemorrhage by increasing superoxide production. Ann Neurol. 2011;70(4):583–90.CrossRefPubMed

21.

Hoda MN, Li W, Ahmad A, Ogbi S, Zemskova MA, Johnson MH, et al. Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. Exp Transl Stroke Med. 2011;3(1):16.CrossRefPubMedCentralPubMed

22.

Li W, Qu Z, Prakash R, Chung C, Ma H, Hoda MN, et al. Comparative analysis of the neurovascular injury and functional outcomes in experimental stroke models in diabetic Goto-Kakizaki rats. Brain Res. 2013;1541:106–14.CrossRefPubMed

23.

Ergul A, Elgebaly MM, Middlemore ML, Li W, Elewa H, Switzer JA, et al. Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes. BMC Neurol. 2007;7:33.CrossRefPubMedCentralPubMed

24.

Guan W, Kozak A, El-Remessy A, Johnson M, Pillai B, Fagan S. Acute treatment with candesartan reduces early injury after permanent middle cerebral artery occlusion. Transl Stroke Res. 2011;2(2):179–85.CrossRefPubMedCentralPubMed

25.

Kelly-Cobbs AI, Prakash R, Li W, Pillai B, Hafez S, Coucha M, 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.CrossRefPubMedCentralPubMed

26.

Prakash R, Li W, Qu Z, Johnson MA, Fagan SC, Ergul A. Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery. Stroke. 2013;44(10):2875–82.CrossRefPubMed

27.

Bruno A, Biller J, Adams Jr HP, Clarke WR, Woolson RF, Williams LS, et al. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology. 1999;52(2):280–4.CrossRefPubMed

28.

Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke. 2000;31(4):811–6.CrossRefPubMed

29.

Bruno A, Levine SR, Frankel MR, Brott TG, Lin Y, Tilley BC, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002;59(5):669–74.CrossRefPubMed

30.

Yong M, Kaste M. Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASS-II trial. Stroke. 2008;39(10):2749–55.CrossRefPubMed

31.

Piironen K, Putaala J, Rosso C, Samson Y. Glucose and acute stroke: evidence for an interlude. Stroke. 2012;43(3):898–902.CrossRefPubMed

32.

Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008;39(2):384–9.CrossRefPubMed

33.

Johnston KC, Hall CE, Kissela BM, Bleck TP, Conaway MR. Glucose regulation in acute stroke patients (GRASP) trial: a randomized pilot trial. Stroke. 2009;40(12):3804–9.CrossRefPubMedCentralPubMed

34.

Bruno A, Durkalski VL, Hall CE, Juneja R, Barsan WG, Janis S, et al. The stroke hyperglycemia insulin network effort (SHINE) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke. Int J. Stroke. 2014;9(2):246–51.CrossRef

35.

Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283–97.CrossRefPubMed

36.

Gerstein HC, Miller ME, Byington RP, Goff Jr DC, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59.CrossRefPubMed

37.

Gray CS, Hildreth AJ, Sandercock PA, O'Connell JE, Johnston DE, Cartlidge NE, et al. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol. 2007;6(5):397–406.CrossRefPubMed

38.

Siemkowicz E, Hansen AJ, Gjedde A. Hyperglycemic ischemia of rat brain: the effect of post-ischemic insulin on metabolic rate. Brain Res. 1982;243(2):386–90.CrossRefPubMed

39.

Bemeur C, Ste-Marie L, Montgomery J. Increased oxidative stress during hyperglycemic cerebral ischemia. Neurochem Int. 2007;50(7–8):890–904.CrossRefPubMed

40.

Ste-Marie L, Hazell AS, Bemeur C, Butterworth R, Montgomery J. Immunohistochemical detection of inducible nitric oxide synthase, nitrotyrosine and manganese superoxide dismutase following hyperglycemic focal cerebral ischemia. Brain Res. 2001;918(1–2):10–9.CrossRefPubMed

41.

Bhardwaj A, Harukuni I, Murphy SJ, Alkayed NJ, Crain BJ, Koehler RC, et al. Hypertonic saline worsens infarct volume after transient focal ischemia in rats. Stroke. 2000;31(7):1694–701.CrossRefPubMed

42.

Korninger C, Collen D. Studies on the specific fibrinolytic effect of human extrinsic (tissue-type) plasminogen activator in human blood and in various animal species in vitro. Thromb Haemost. 1981;46(2):561–5.PubMed

43.

Zhu H, Fan X, Yu Z, Liu J, Murata Y, Lu J, et al. Annexin A2 combined with low-dose tPA improves thrombolytic therapy in a rat model of focal embolic stroke. J Cereb Blood Flow Metab. 2010;30(6):1137–46.CrossRefPubMedCentralPubMed

44.

Wang X, Fan X, Yu Z, Liao Z, Zhao J, Mandeville E, et al. Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke. Stroke. 2014;45(2):619–22.CrossRefPubMedCentralPubMed

45.

Meng W, Wang X, Asahi M, Kano T, Asahi K, Ackerman RH, et al. Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 1999;19(12):1316–21.CrossRefPubMed

46.

Zhang L, Chopp M, Teng H, Ding G, Jiang Q, Yang XP, et al. Combination treatment with N-acetyl-seryl-aspartyl-lysyl-proline and tissue plasminogen activator provides potent neuroprotection in rats after stroke. Stroke. 2014;45(4):1108–14.CrossRefPubMedCentralPubMed

47.

Lapergue B, Dang BQ, Desilles JP, Ortiz-Munoz G, Delbosc S, Loyau S, et al. High-density lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke. Stroke. 2013;44(3):699–707.CrossRefPubMed

48.

Shehadah A, Chen J, Cui Y, Zhang L, Roberts C, Lu M, et al. Combination treatment with low-dose niaspan and tissue plasminogen activator provides neuroprotection after embolic stroke in rats. J Neurol Sci. 2011;309(1–2):96–101.CrossRefPubMedCentralPubMed

49.

Zhang L, Zhang ZG, Buller B, Jiang J, Jiang Y, Zhao D, et al. Combination treatment with velcade and low-dose tissue plasminogen activator provides potent neuroprotection in aged rats after embolic focal ischemia. Stroke. 2010;41(5):1001–7.CrossRefPubMedCentralPubMed

50.

Berny-Lang MA, Hurst S, Tucker EI, Pelc LA, Wang RK, Hurn PD, et al. Thrombin mutant W215A/E217A treatment improves neurological outcome and reduces cerebral infarct size in a mouse model of ischemic stroke. Stroke. 2011;42(6):1736–41.CrossRefPubMedCentralPubMed

51.

Kilic E, Hermann DM, Hossmann KA. Recombinant tissue plasminogen activator reduces infarct size after reversible thread occlusion of middle cerebral artery in mice. Neuroreport. 1999;10(1):107–11.CrossRefPubMed

52.

Kent DM, Price LL, Ringleb P, Hill MD, Selker HP. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke. 2005;36(1):62–5.CrossRefPubMed

Titel: Comparative Analysis of Different Methods of Ischemia/Reperfusion in Hyperglycemic Stroke Outcomes: Interaction with tPA
verfasst von: Sherif Hafez
Md Nasrul Hoda
Xinyue Guo
Maribeth H. Johnson
Susan C. Fagan
Adviye Ergul
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 3/2015
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-015-0391-0

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