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Stem Cells International
Volume 2018 (2018), Article ID 1706982, 11 pages
Research Article

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

1Department of Neurology, Affiliated Hospital of Nantong University, Jiangsu 226001, China
2Department of Pathophysiology, Medical School of Nantong University, Jiangsu 26001, China
3Geriatric Department, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China
4Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu 226001, China
5Department of Neurosurgery, Affiliated Hospital of Nantong University, Jiangsu 226001, China

Correspondence should be addressed to Xing Su; moc.liamg@utngnixus and Jin-hua Gu; moc.liamtoh@ugoalugoal

Received 7 June 2017; Revised 23 September 2017; Accepted 10 October 2017; Published 5 April 2018

Academic Editor: Hailiang Tang

Copyright © 2018 Yaohui Ni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.