New and Future Endovascular Treatment Strategies for Acute Ischemic Stroke

doi:10.1097/01.RVI.0000112578.95689.66

Journal of Vascular and Interventional Radiology

Volume 15, Issue 1, Part 2, January 2004, Pages S103-S110

https://doi.org/10.1097/01.RVI.0000112578.95689.66 Get rights and content

Cerebral revascularization strategies for acute ischemic stroke have been developed during the past decade. Many of these strategies are currently being evaluated and gaining in popularity, offering hope to those with an otherwise nihilistic disease. Herein, the authors discuss the current progress toward these goals and the efforts being made to develop a safe and efficacious method of clot removal in the treatment of acute ischemic stroke. Three endovascular treatment strategies are presented: endovascular thrombectomy with suction or snaring devices, mechanical clot disruption with mechanical or photoacoustic devices, and augmented fibrinolysis with mechanical or ultrasonic devices. Most of these devices are currently undergoing phase I or II trial or are approved for other uses.

Section snippets

ENDOVASCULAR THROMBECTOMY

Endovascular thrombectomy involves the extraction of the thrombus through a catheter and should provide rapid recanalization and reduce the risk of distal embolic complications seen with mechanical clot disruption. This method may be used as a standalone technique or in conjunction with a markedly reduced dose of thrombolytic drug. The technical challenges of thrombectomy include intracranial navigation of these devices, capture of occlusive material within the tortuous and dividing cerebral

MECHANICAL CLOT DISRUPTION

Mechanical clot disruption includes any technique by which the interventionalist mechanically fragments or completely destroys the thrombus within the artery. This may be accomplished simply by using guide wire manipulation or in a more complex fashion such as laser shock-wave devices. The goal of mechanical clot disruption is to rapidly establish blood flow and cerebral perfusion. As the thrombus is disrupted and flow reestablished, small emboli are created and carried into distal branches. If

AUGMENTED FIBRINOLYSIS

In a broad sense, augmented fibrinolysis can use any method with a fibrinolytic to more rapidly recanalize and reperfuse the brain. Microcatheters, guide wires, or any of the embolectomy or mechanical devices mentioned earlier, when used in addition to fibrinolytics, should, in some sense, help accomplish this goal. The use of snares, nets, balloons, or other mechanical devices to fragment or disrupt a thrombolytic-laden embolus may greatly increase the rapidity of reperfusion. In a recent

CONCLUSION

At the present time, the mainstay of treatment for acute ischemic stroke is intravenous or intraarterial fibrinolysis. Other endovascular treatment strategies that can be applied in the treatment of acute stroke are now undergoing feasibility and safety studies.

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Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases
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In addition, there is a high threshold for cardiac pain, with the possibility of developing myocardial infarction with minimum symptoms or even without pain, and that creates the opportunity of using ASIC3 agonists (Benson et al., 1999; Immke & McCleskey, 2001b; Sutherland et al., 2001) and heteromeric ASIC3/2A agonists (Hattori et al., 2009) as heart pain modulators. The main mechanism of ischemic brain injuries is represented by vascular thrombosis, and three major therapeutic approaches have been developed, including endovascular thrombectomy, mechanical clot disruption, and augmented fibrinolysis (Nesbit, Luh, Tien, & Barnwell, 2004). There have been various attempts to delay the negative effects of ischemia, due to difficulties of thrombolytic treatment (Wardlaw et al., 2012) as soon as the occurrence of thrombosis.
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Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke.
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Microsnares (eg, Amplatz Goose Neck microsnare [ev3 Neurovascular, Irvine, CA, USA]) can be used for thrombus retrieval and maceration and are preferentially used in combination with thrombolytic drugs.17 They may be most useful in the treatment of basilar artery occlusion.18 This Alligator Retriever device (ev3 Neurovascular, Irvine, CA, USA) has microforceps in the shape of claws that can be advanced through a microcatheter and used for thrombus retrieval.
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The current treatment for acute ischemic stroke is limited to restoring the blood supply to the affected area. Reperfusion therapy consists of administering the thrombolytic agent recombinant tissue plasminogen activator (rtPA), and endovascular mechanical clot extraction (Nesbit et al., 2004). However, rtPA has a narrow therapeutic timeframe of 3–4.5 h (Hacke et al., 2004; Wardlaw et al., 2012) because of the high risk of intracranial hemorrhage after thrombolysis beyond the window, especially in patients with severe strokes or increased age (van der Worp and van Gijn, 2007).
Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. Disruption of ionic homeostasis plays an important role in cell death following cerebral ischemia. Glutamate receptor-mediated ionic imbalance and neurotoxicity have been well established in cerebral ischemia after stroke. However, non-NMDA receptor-dependent mechanisms, involving acid-sensing ion channel 1a (ASIC1a), transient receptor potential melastatin 7 (TRPM7), and Na⁺/H⁺ exchanger isoform 1 (NHE1), have recently emerged as important players in the dysregulation of ionic homeostasis in the CNS under ischemic conditions. These H⁺-sensitive channels and/or exchangers are expressed in the majority of cell types of the neurovascular unit. Sustained activation of these proteins causes excessive influx of cations, such as Ca²⁺, Na⁺, and Zn²⁺, and leads to ischemic reperfusion brain injury. In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention.
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Presented at the 2003 SIR Annual Meeting.

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New and Future Endovascular Treatment Strategies for Acute Ischemic Stroke

Section snippets

ENDOVASCULAR THROMBECTOMY

MECHANICAL CLOT DISRUPTION

AUGMENTED FIBRINOLYSIS

CONCLUSION

JVIR

J Am Coll Cardiol

Tissue plasminogen activator for acute ischemic stroke: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

N Engl J Med

Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke

AJNR

Intracranial intraarterial thrombolysis facilitated by microcatheter navigation through an occluded cervical internal carotid artery

J Neurosurg

Intra-arterial prourokinase for acute ischemic stroke: The PROACT II Study—a randomized controlled trial

JAMA

Rheolytic thrombectomy of the occluded internal carotid artery in the setting of acute ischemic stroke

AJNR