Arterial recanalization and subsequent reperfusion have extensively demonstrated the ability to restore the brain function when performed shortly after acute ischemic stroke. Experimental and human studies have consistently demonstrated that early tissue reperfusion may limit ischemic tissue enlargement, leading to a reduced infarct size and favorable clinical outcome. However, arterial recanalization does not necessarily lead to brain tissue reperfusion. Lack of reperfusion after early recanalization may be caused by multiple downstream embolization, blockage of microcirculation due to non-reflow phenomenon or rapid recruitment of ischemic tissue before recanalization resulting in non-nutritional reperfusion. In some cases, sudden tissue reperfusion may be deleterious, leading to brain blood barrier disruption and hemorrhagic transformation or massive brain edema due to the so-called ‘reperfusion injury’. In spite of this, recanalization represents the powerful predictor of stroke outcome and it is being increasingly used as a surrogate efficacy measurement in thrombolytic and other revascularization trials in acute stroke. Several emerging strategies have the potential to extend cerebral reperfusion therapy to larger numbers of patients, including patients presenting beyond the current 3-hour time window. Moreover, novel reperfusion approaches may improve the efficacy and safety of thrombolysis in a larger number of stroke patients. This review highlights recent advances in reperfusion treatments for acute ischemic stroke.

Keywords:
Recanalization, Cerebral reperfusion, Acute ischemic stroke, Thrombolysis, Outcome
1.
Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S, ATLANTIS Trials Investigators, ECASS Trials Investigators, NINDS rt-PA Study Group Investigators: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768–774.
2.
Lyden P, TNK for Stroke Investigators: Pilot study of tenecteplase (TNK) in acute ischemic stroke: preliminary report. Stroke 2003;34:246A.
3.
Liberatore GT, Samson A, Bladin C, Schleuning WD, Medcalf RL: Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke 2003;34:537–543.
4.
Noble S, McTavish D: Reteplase. A review of its pharmacological properties and clinical efficacy in the management of acute myocardial infarction. Drugs 1996;52:589–605.
5.
Lapchak PA, Araujo DM, Pakola S, Song D, Wei J, Zivin JA: Microplasmin: a novel thrombolytic that improves behavioral outcome after embolic strokes in rabbits. Stroke 2002;33:2279–2284.
6.
Adams HP Jr, Leclerc JR, Bluhmki E, Clarke W, Hansen MD, Hacke W: Measuring outcomes as a function of baseline severity of ischemic stroke. Cerebrovasc Dis 2004;18:124–129.
7.
Seitz RJ, Meisel S, Moll M, Wittsack H-J, Junghans U, Siebler M: The effect of combined thrombolysis with rtPA and tirofiban on ischemic brain lesions. Neurology 2004;62:2110–2112.
8.
Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, Bammer R, Kakuda W, Lansberg MG, Shuaib A, Coplin W, Hamilton S, Moseley M, Marks MP: Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 2006;60:508–517.
9.
Davydov L, Cheng JW: Tenecteplase: a review. Clin Ther 2001;23:982–997.
10.
Qureshi AI, Ali Z, Suri MF, Kim SH, Shatla AA, Ringer AJ, Lopes DK, Guterman LR, Hopkins LN: Intra-arterial third-generation recombinant tissue plasminogen activator (reteplase) for acute ischemic stroke. Neurosurgery 2001;49:41–48.
11.
Marder VJ, Stewart D: Towards safer thrombolytic therapy. Semin Hematol 2002;39:206–216.
12.
Gahn G, Kunz A, Putz V, Becker U, Goldhagen T, Hahn G, et al: Recanalization of middle cerebral artery occlusion after either t-PA or t-PA combined with abciximab (abstract). Stroke 2004;35:287.
13.
De Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M, Davis SM, Koroshetz WJ, Rordorf G, Warach S: Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004;63:312–317.
14.
Eggers J, Koch B, Meyer K, Konig I, Seidel G: Effect of ultrasound on thrombolysis of middle cerebral artery occlusion. Ann Neurol 2003;53:797–800.
15.
Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moye LA, Hill MD, Wojner AW, CLOTBUST Investigators: Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004;351:2170–2178.
16.
Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. J Am Med Assoc 1999;282:2003–2011.
17.
Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke 2004;35:904–911.
18.
Starkman S, MERCI Investigators: Results of the combined MERCI I-II (Mechanical Embolus Removal in Cerebral Ischemia) Trials. Stroke 2004;35:A240.
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2009
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