Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats

Huong L. Moldthan, Aaron C. Hirko, Jeffrey S. Thinschmidt, Maria B. Grant, Zhimin Li, Joanna Peris, Yuanqing Lu, Ahmed S. Elshikha, Michael A. King, Jeffrey A. Hughes, Sihong Song

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Our objective is to develop a new therapy for the treatment of stroke. Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin (AAT), a serine proteinase inhibitor with potent anti-inflammatory, anti-apoptotic, antimicrobial, and cytoprotective activities, could be beneficial in stroke. The goal of this study is to test whether AAT can improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial (i.c.) microinjection of endothelin-1. Five to 10 minutes after stroke induction, rats received either i.c. or intravenous delivery of human AAT. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours, the infarct volumes of the human AAT treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (P

Original languageEnglish (US)
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

alpha 1-Antitrypsin
Stroke
Middle Cerebral Artery Infarction
Therapeutics
Vibrissae
Serine Proteinase Inhibitors
Fibrinolytic Agents
Microinjections
Endothelin-1
Tissue Plasminogen Activator
Anti-Inflammatory Agents
Magnetic Resonance Imaging
Injections

Keywords

  • alpha 1-antitrypsin
  • anti-inflammation
  • endothelin-1-induced MCAO
  • inflammation
  • Ischemic stroke
  • neuroprotection

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Moldthan, H. L., Hirko, A. C., Thinschmidt, J. S., Grant, M. B., Li, Z., Peris, J., ... Song, S. (2014). Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats. Journal of Stroke and Cerebrovascular Diseases, 23(5). https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.029

Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats. / Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria B.; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed S.; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 5, 2014.

Research output: Contribution to journalArticle

Moldthan, HL, Hirko, AC, Thinschmidt, JS, Grant, MB, Li, Z, Peris, J, Lu, Y, Elshikha, AS, King, MA, Hughes, JA & Song, S 2014, 'Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats', Journal of Stroke and Cerebrovascular Diseases, vol. 23, no. 5. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.029
Moldthan, Huong L. ; Hirko, Aaron C. ; Thinschmidt, Jeffrey S. ; Grant, Maria B. ; Li, Zhimin ; Peris, Joanna ; Lu, Yuanqing ; Elshikha, Ahmed S. ; King, Michael A. ; Hughes, Jeffrey A. ; Song, Sihong. / Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats. In: Journal of Stroke and Cerebrovascular Diseases. 2014 ; Vol. 23, No. 5.
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