The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model

Stem Cells International
Yaohui NiJin-Hua Gu

Abstract

Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3β-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO) until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3β-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cer...Continue Reading

References

Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·B H JiangP K Vogt
Sep 11, 2002·Journal of the Neurological Sciences·Simone WagnerMarkus Schwaninger
Apr 9, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Moritz GrögerNikolaus Plesnila
May 19, 2007·Experimental Neurology·Agnieszka A ArdeltRaymond C Koehler
May 13, 2008·Lancet·Geoffrey A DonnanStephen M Davis
Jul 17, 2008·Biological Chemistry·Robert S SmithJulie Chao
Nov 8, 2008·Stroke; a Journal of Cerebral Circulation·Madeleine AustinatChristoph Kleinschnitz
Nov 5, 2011·Stroke; a Journal of Cerebral Circulation·Liping LiuYongjun Wang

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Methods Mentioned

BETA
Protein Assay
electrophoresis

Software Mentioned

ImageJ
Multi Gauge
Graphpad Prism
ARRIVE

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