Research ArticleColivelin Rescues Ischemic Neuron and Axons Involving JAK/STAT3 Signaling Pathway
Section snippets
INTRODUCTION
Cerebral ischemia and subsequent neurological deficits gravely afflict stroke patients. Current therapies for acute ischemic stroke are limited to intravenous administration of tissue plasminogen activator (tPA) which is further restricted by a short therapeutic window and strict inclusion criteria(Hacke et al., 2008, Ahmad and Graham, 2010, Lees et al., 2010, Chamorro et al., 2012). Endovascular thrombectomy (EVT), with the aid of CT/MRI perfusion imaging, show significant outcome improvement
Animals
Male C57BL/6 mice were purchased from Taconic (Oxnard, CA, USA). For all experiments, 10- to 12-week-old, 20 to 25 g, age-matched male littermates were used between experimental groups. All mice were randomly assigned to each experiment. Mice were housed no more than 5 animals per cage under standardized light–dark cycle conditions with access to food and water ad libitum. All animal experiments were performed in accordance with the recommendations of the Guide for the Care and Use of
Colivelin reduces infarct volume and improves neurological deficits after MCAO
Wild type C57BL/6 mice were intraperitoneally injected with Colivelin (1 mg/kg) or vehicle (20% ethyl alcohol) 30 min prior to sham or MCAO procedures, and continuous 6 days with daily administration. To determine the impact of Colivelin on ischemic brain injury, neurodeficits, infarct lesion volume and brain edema of MCAO mice receiving Colivelin or vehicle were examined. From day 1 to day 14 post ischemia and reperfusion, Colivelin administration resulted in improved motor and cognitive
Discussion
In this study, we describe the beneficial effect of Colivelin in mouse model of ischemic stroke as evidenced by improved neurodeficits, reduced lesion size and attenuated neuronal apoptosis. Colivelin treatment results in accelerated growth of midline-crossing axons, which is highly correlated with improved clinical outcome. Moreover, activation of STAT3 signaling might be involved in the beneficial mechanism of Colivelin.
The use of neuroprotective agents in stroke has been a notable failure of
Declarations of interest
None.
Funding
This study was supported in part by National Science Foundation of China grant 81771274, 91642205, and 81830038.
Acknowledgments
We would like to thank Samuel Xiang-Yu Shi (Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA) for editorial assistance.
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