Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats

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dc.citation.articleNumber199en_US
dc.citation.journalTitleFrontiers in Neurologyen_US
dc.citation.volumeNumber9en_US
dc.contributor.authorFabian, Roderic H.en_US
dc.contributor.authorDerry, Paul J.en_US
dc.contributor.authorRea, Harriett Charmaineen_US
dc.contributor.authorDalmeida, William V.en_US
dc.contributor.authorNilewski, Lizanne G.en_US
dc.contributor.authorSikkema, William K.A.en_US
dc.contributor.authorMandava, Pitchaiahen_US
dc.contributor.authorTsai, Ah-Limen_US
dc.contributor.authorMendoza, Kimberlyen_US
dc.contributor.authorBerka, Vladimiren_US
dc.contributor.authorTour, James M.en_US
dc.contributor.authorKent, Thomas A.en_US
dc.date.accessioned2018-11-15T17:16:12Zen_US
dc.date.available2018-11-15T17:16:12Zen_US
dc.date.issued2018en_US
dc.description.abstractINTRODUCTION: While oxidative stress can be measured during transient cerebral ischemia, antioxidant therapies for ischemic stroke have been clinically unsuccessful. Many antioxidants are limited in their range and/or capacity for quenching radicals and can generate toxic intermediates overwhelming depleted endogenous protection. We developed a new antioxidant class, 40 nm × 2 nm carbon nanoparticles, hydrophilic carbon clusters, conjugated to poly(ethylene glycol) termed PEG-HCCs. These particles are high-capacity superoxide dismutase mimics, are effective against hydroxyl radical, and restore the balance between nitric oxide and superoxide in the vasculature. Here, we report the effects of PEG-HCCs administered during reperfusion after transient middle cerebral artery occlusion (tMCAO) by suture in the rat under hyperglycemic conditions. Hyperglycemia occurs in one-third of stroke patients and worsens clinical outcome. In animal models, this worsening occurs largely by accelerating elaboration of reactive oxygen species (ROS) during reperfusion. METHODS: PEG-HCCs were studied for their protective ability against hydrogen peroxide in b.End3 brain endothelial cell line and E17 primary cortical neuron cultures. In vivo, hyperglycemia was induced by streptozotocin injection 2 days before tMCAO. 58 Male Sprague-Dawley rats were analyzed. They were injected IV with PBS or PEG-HCCs (4 mg/kg 2×) at the time of recanalization after either 90- or 120-min occlusion. Rats were survived for up to 3 days, and infarct volume characteristics and neurological functional outcome (modified Bederson Score) were assessed. RESULTS: PEG-HCCs were protective against hydrogen peroxide in both culture models. In vivo improvement was found after PEG-HCCs with 90-min ischemia with reduction in infarct size (42%), hemisphere swelling (46%), hemorrhage score (53%), and improvement in Bederson score (70%) (p = 0.068-0.001). Early high mortality in the 2-h in the PBS control group precluded detailed analysis, but a trend was found in improvement in all factors, e.g., reduction in infarct volume (48%; p = 0.034) and a 56% improvement in Bederson score (p = 0.055) with PEG-HCCs. CONCLUSION: This nano-antioxidant showed some improvement in several outcome measures in a severe model of tMCAO when administered at a clinically relevant time point. Long-term studies and additional models are required to assess potential for clinical use, especially for patients hyperglycemic at the time of their stroke, as these patients have the worst outcomes.en_US
dc.identifier.citationFabian, Roderic H., Derry, Paul J., Rea, Harriett Charmaine, et al.. "Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats." <i>Frontiers in Neurology,</i> 9, (2018) Frontiers: https://doi.org/10.3389/fneur.2018.00199.en_US
dc.identifier.digitalfneur-09-00199en_US
dc.identifier.doihttps://doi.org/10.3389/fneur.2018.00199en_US
dc.identifier.urihttps://hdl.handle.net/1911/103341en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordantioxidantsen_US
dc.subject.keyworddiabetes mellitusen_US
dc.subject.keywordhyperglycemiaen_US
dc.subject.keywordnanomedicineen_US
dc.subject.keywordrat modelen_US
dc.subject.keywordstrokeen_US
dc.subject.keywordtransient middle cerebral artery occlusionen_US
dc.titleEfficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Ratsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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