Enhanced Neuroprotection by Local Intra-Arterial Infusion of Human Albumin Solution and Local Hypothermia

Chen, Jian; Fredrickson, Vance L; Ding, Yuchuan; Cheng, Huakun; Wang, Ning; Li, Feng; Ji, Xunming

doi:10.1161/strokeaha.112.675462

Cited by 46 publications

(45 citation statements)

References 13 publications

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“…The present study demonstrated that transarterial regional hypothermia exerts robust neuroprotective effects in the pMCAO with tCHP model, as well as the typical tMCAO model, as reported previously (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Kurisu et al, 2015;Luan et al, 2004;Zhao et al, 2009). This therapy significantly improved neurological deficits and decreased infarct/edema volumes.…”

Section: Discussionsupporting

confidence: 90%

“…Consistent with previous findings (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Luan et al, 2004;Zhao et al, 2009), we also clarified that transarterial regional hypothermia exerts strong neuroprotective effects on ischemia-reperfusion (I/R) injury (Kurisu et al, 2015). However, the effects of this therapy have only been examined in a typical ischemic stroke model, the transient middle cerebral artery occlusion (tMCAO) model (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Kurisu et al, 2015;Luan et al, 2004;Zhao et al, 2009), which is a complete reperfusion model (Fluri et al, 2015;Takahashi et al, 2012;Zhao and Steinberg, 2011). The effects of this therapy have not yet been investigated in other ischemic stroke models, even though ischemic stroke in humans is extremely diverse in its pattern of occlusion and reperfusion in actual clinical settings.…”

Section: Introductionsupporting

confidence: 93%

“…Thus, further studies that focus on how a delay in the initiation of therapy affects its effects are warranted. In order to prolong the therapeutic time window, another strategy may be required, such as the effective supply of oxygen with cooled artificial oxygen carriers (Shimbo et al, 2014) or cooled neuroprotective agents (Chen et al, 2013). Furthermore, we need to establish acceptable and appropriate therapeutic conditions in terms of, for example, timing, infusion volumes, and infusion routes for successful clinical applications.…”

Section: Discussionmentioning

confidence: 99%

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Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

et al. 2016

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(248 words)The robust neuroprotective effects of transarterial regional hypothermia have been demonstrated in the typical transient middle cerebral artery occlusion (tMCAO) model, but have not yet been tested in other ischemic stroke models, even though clinical ischemic conditions are diverse. In order to clarify these effects in a different ischemic stroke model, we employed a rat model of permanent MCAO (pMCAO) with transient collateral hypoperfusion (tCHP), which was achieved by direct MCA ligation through craniotomy and 1-hour bilateral common carotid artery occlusion at the beginning of pMCAO. The infusion of 20 ml/kg of 4°C cold saline (CS) or 37°C warm saline (WS) into the ipsilateral internal carotid artery (ICA) was performed for 15 minutes in intraor post-tCHP. Neurological scores, infarct/edema volumes, and neuronal apoptosis and reactive gliosis were compared between the CS and WS groups and a non-infusion control group after 48 hours of reperfusion. Although brain temperatures were only reduced by 2-3°C for 15 minutes, the CS group had significantly better neurological scores, smaller infarct/edema volumes, and less penumbral neuronal apoptosis and reactive gliosis than the control and WS groups. The post-tCHP CS group exhibited prominent neuroprotective effects, even though infarct volumes and neuronal apoptosis were reduced less than those in the intra-tCHP CS group. In conclusion, we demonstrated the neuroprotective effects of transarterial regional hypothermia in an ischemic model of pMCAO with tCHP. Even though MCAO is persistent, cold infusion via the ICA is neuroprotective for the penumbra, suggesting the wider therapeutic application of this therapy.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

et al. 2016

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“…Preliminary studies using LEVI with neuroprotective drugs have shown exceptional promise; a 2012 study by Song et al found that LEVI of a magnesium sulfate solution at 15°C caused a 65% reduction in infarct volumes compared to a 48% reduction from LEVI alone [51]. Similar results were found following LEVI of a 20% human albumin solution cooled to 0°C [52]. Normothermic local infusion of drugs has shown potential as well, as LEVI of erythropoietin at room temperature reduced infarct volumes by 21% (signiicant compared to control), decreased apoptosis in the ischemic core and penumbra, and signiicantly preserved neurological scores [53].…”

Section: Drug Delivery Into Ischemic Territory Through Levimentioning

confidence: 88%

Hypothermia in Stroke Therapy: Systemic versus Local Application

Huber¹,

Duan²,

Chandra³

et al. 2017

Hypoxia and Human Diseases

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Presently, there are no efective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective beneits of hypothermia, and surfacecooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and eicacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identiies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well.

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“…Serum albumin is a unique multifunctional protein and has been shown to be neuroprotective [2][3][4][5][6]. Several studies have demonstrated the obvious protective influence of serum albumin in many diseases, such as myocardial infarction and cardiovascular diseases [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Serum albumin level is associated with the recurrence of acute ischemic stroke

Zhang

Lei

Wang

et al. 2016

The American Journal of Emergency Medicine

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Enhanced Neuroprotection by Local Intra-Arterial Infusion of Human Albumin Solution and Local Hypothermia

Abstract: The local low-dose cold albumin infusion into the ischemic area offered a combination of regional brain hypothermia and albumin administration, which enhanced neuroprotection and would be beneficial in the clinical setting.

Cited by 46 publications

References 13 publications

Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

Hypothermia in Stroke Therapy: Systemic versus Local Application

Serum albumin level is associated with the recurrence of acute ischemic stroke

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