Abstract
Hemorrhagic transformation occurs in as many as 48 % of stroke patients and is a major contributor to post-insult morbidity and mortality. Experimental models of hemorrhagic transformation are utilized for understanding the mechanisms behind its development, as well as for investigating potential therapeutics for prevention and reduction of bleeding. Thoroughly studying animal models of hemorrhagic transformation is critically important for testing novel treatments. Thus far, no study has examined the progression of brain swelling and hemorrhagic transformation after transient middle cerebral artery occlusion (MCAO). Herein, we investigate the development of infarction, brain swelling, and hemorrhagic transformation following MCAO in hyperglycemic rats. Twenty-five Sprague-Dawley rats were subjected to either 1.5 h of MCAO or sham surgery 15 min after induction of hyperglycemia. Animals were sacrificed at 0.25, 1, 3, or 24 h after reperfusion for measurement of infarct volume, brain swelling, and hemoglobin volume. Within 15 min of reperfusion, the infarct volume was significantly larger than in sham animals and did not increase in size over the 24 h. However, both brain swelling and hemorrhagic transformation, which began immediately after reperfusion, increase over 24 h after reperfusion.
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References
Alvarez-Sabin J, Maisterra O, Santamarina E, Kase CS (2013) Factors influencing haemorrhagic transformation in ischaemic stroke. Lancet Neurol 12:689–705
Arnould MC, Grandin CB, Peeters A, Cosnard G, Duprez TP (2004) Comparison of CT and three MR sequences for detecting and categorizing early (48 hours) hemorrhagic transformation in hyperacute ischemic stroke. Am J Neuroradiol 25:939–944
Asahi M, Asahi K, Wang X, Lo EH (2000) Reduction of tissue plasminogen activator-induced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats. J Cereb Blood Flow Metab 20:452–457
Bruno A, Biller J, Adams HP, Clarke WR, Woolson RF, Williams LS, Hansen MD, Investigators T (1999) Acute blood glucose level and outcome from ischemic stroke. Neurology 52:280–284
Chen C, Ostrowski RP, Zhou C, Tang J, Zhang JH (2010) Suppression of hypoxia-inducible factor-1 alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia. J Neurosci Res 88:2046–2055
Choudhri TF, Hoh BL, Solomon RA, Connolly ES Jr, Pinsky DJ (1997) Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice. Stroke 28:2296–2302
Ergul A, Elgebaly MM, Middlemore M-L, Li W, Elewa H, Switzer JA, Hall C, Kozak A, Fagan SC (2007) Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes. BMC Neurol 7:33
Fagan SC, Lapchak PA, Liebeskind DS, Ishrat T, Ergul A (2013) Recommendations for preclinical research in hemorrhagic transformation. Transl Stroke Res 4:322–327
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2013) Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 127:e6–e245
Hafez S, Coucha M, Bruno A, Fagan SC, Ergul A (2014) Hyperglycemia, acute ischemic stroke, and thrombolytic therapy. Transl Stroke Res 5:442–453
Hornig CR, Dorndorf W, Agnoli AL (1986) Hemorrhagic cerebral infarction–a prospective study. Stroke 17:179–185
Kawamura S, Yasui N, Shirasawa M, Fukasawa H (1991) Rat middle cerebral artery occlusion using an intraluminal thread technique. Acta Neurochir 109:126–132
Khanna A, Kahle KT, Walcott BP, Gerzanich V, Simard JM (2014) Disruption of ion homeostasis in the neurogliovascular unit underlies the pathogenesis of ischemic cerebral edema. Transl Stroke Res 5:3–16
Kissela BM, Ewing I, Khoury J, Moomaw CJ, Kleindorfer D, Szaflarski JP, Woo D, Gebel J, Schneider A, Shukla R, Alwell K, Broderick JP, Miller R (2005) Epidemiology of ischemic stroke in patients with diabetes – the greater Cincinnati/Northern Kentucky Stroke Study. Diabetes Care 28:355–359
Lapchak PA (2002) Hemorrhagic transformation following ischemic stroke: significance, causes, and relationship to therapy and treatment. Curr Neurol Neurosci Rep 2:38–43
Mandava P, Martini SR, Munoz M, Dalmeida W, Sarma AK, Anderson JA, Fabian RH, Kent TA (2014) Hyperglycemia worsens outcome after rt-PA primarily in the large-vessel occlusive stroke subtype. Transl Stroke Res 5:519–525
Marinescu M, Bouley J, Chueh J, Fisher M, Henninger N (2014) Clot injection technique affects thrombolytic efficacy in a rat embolic stroke model: implications for translaboratory collaborations. J Cereb Blood Flow Metab 34:677–682
Morgenstern LB, Frankowski RF, Shedden P, Pasteur W, Grotta JC (1998) Surgical treatment for intracerebral hemorrhage (STICH) – a single-center, randomized clinical trial. Neurology 51:1359–1363
Orso F, Baldasseroni S, Maggioni AP (2008) The role of thrombolysis in acute ischemic stroke. Herz 33:498–506
Pulsinelli WA, Waldman S, Rawlinson D, Plum F (1982) Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology 32:1239–1246
Song M, Yu SP (2014) Ionic regulation of cell volume changes and cell death after ischemic stroke. Transl Stroke Res 5:17–27
Sumii T, Lo EH (2002) Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 33:831–836
Tejima E, Katayama Y, Suzuki Y, Kano T, Lo EH (2001) Hemorrhagic transformation after fibrinolysis with tissue plasminogen activator: evaluation of role of hypertension with rat thromboembolic stroke model. Stroke 32:1336–1340
Thanvi B, Treadwell S, Robinson T (2008) Early neurological deterioration in acute ischaemic stroke: predictors, mechanisms and management. Postgrad Med J 84:412–417
Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH (2003) Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab 23:855–864
Yip PK, He YY, Hsu CY, Garg N, Marangos P, Hogan EL (1991) Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Neurology 41:899–905
Zhang Z, Yan J, Shi H (2013) Hyperglycemia as a risk factor of ischemic stroke. J Drug Metab Toxicol 4:1000153
Acknowledgments
This work was supported by National Institutes of Health grant R01 NS043338 (JHZ).
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McBride, D.W. et al. (2016). Acute Hyperglycemia Is Associated with Immediate Brain Swelling and Hemorrhagic Transformation After Middle Cerebral Artery Occlusion in Rats. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_42
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DOI: https://doi.org/10.1007/978-3-319-18497-5_42
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