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Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats.

Publication ,  Journal Article
Li, X; Duan, W; Du, L; Chu, D; Wang, P; Yang, Z; Qu, X; Yang, Z; Batinic-Haberle, I; Spasojevic, I; Warner, DS; Crapo, JD; Treggiari, MM; Sheng, H
Published in: Antioxidants (Basel)
October 13, 2023

Endovascular mechanical thrombectomy, combined with a tissue plasminogen activator (t-PA), is efficacious as a standard care for qualifying ischemic stroke patients. However, > 50% of thrombectomy patients still have poor outcomes. Manganese porphyrins, commonly known as mimics of superoxide dismutases, are potent redox-active catalytic compounds that decrease oxidative/nitrosative stress and in turn decrease inflammatory responses, mitigating therefore the secondary injury of the ischemic brain. This study investigates the effect of intracarotid MnTnBuOE-2-PyP5+ (BMX-001) administration on long-term, 28-day post-stroke recovery in a clinically relevant setting. The 90 min of transient middle cerebral artery occlusion was performed in young, aged, male, female, and spontaneous hypertension rats. All physiological parameters, including blood pressure, blood gas, glucose, and temperature, were well controlled during ischemia. Either BMX-001 or a vehicle solution was infused through the carotid artery immediately after the removal of filament, mimicking endovascular thrombectomy, and was followed by 7 days of subcutaneous injection. Neurologic deficits and infarct volume were assessed at 28 days in a blinded manner. The effects of BMX-001 on the carotid arterial wall and blood-brain barrier permeability and its interaction with t-PA were assessed in normal rats. There were no intra-group differences in physiological variables. BMX-001-treated stroke rats regained body weight earlier, performed better in behavioral tests, and had smaller brain infarct size compared to the vehicle-treated group. No vascular wall damage and blood-brain barrier permeability changes were detected after the BMX-001 infusion. There was no drug interaction between BMX-001 and t-PA. Intracarotid BMX-001 infusion was safe, and it significantly improved stroke outcomes in rats. These findings indicate that BMX-001 is a candidate drug as an adjunct treatment for thrombectomy procedure to further improve the neurologic outcomes of thrombectomy patients. This study warrants further clinical investigation of BMX-001 as a new stroke therapy.

Duke Scholars

Published In

Antioxidants (Basel)

DOI

ISSN

2076-3921

Publication Date

October 13, 2023

Volume

12

Issue

10

Location

Switzerland

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

Citation

APA
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ICMJE
MLA
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Li, X., Duan, W., Du, L., Chu, D., Wang, P., Yang, Z., … Sheng, H. (2023). Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats. Antioxidants (Basel), 12(10). https://doi.org/10.3390/antiox12101861
Li, Xuan, Weina Duan, Li Du, Dongmei Chu, Peng Wang, Zhong Yang, Xingguang Qu, et al. “Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats.Antioxidants (Basel) 12, no. 10 (October 13, 2023). https://doi.org/10.3390/antiox12101861.
Li, Xuan, et al. “Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats.Antioxidants (Basel), vol. 12, no. 10, Oct. 2023. Pubmed, doi:10.3390/antiox12101861.
Li X, Duan W, Du L, Chu D, Wang P, Yang Z, Qu X, Batinic-Haberle I, Spasojevic I, Warner DS, Crapo JD, Treggiari MM, Sheng H. Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats. Antioxidants (Basel). 2023 Oct 13;12(10).

Published In

Antioxidants (Basel)

DOI

ISSN

2076-3921

Publication Date

October 13, 2023

Volume

12

Issue

10

Location

Switzerland

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology