NDLI: Nafamostat Mesilate Improves Neurological Outcome and Axonal Regeneration after Stroke in Rats

Content Provider	Springer Nature Link
Author	Liu, Yuan Li, Chenhui Wang, Jing Fang, Yinquan Sun, Hao Tao, Xia Zhou, Xin Fu Liao, Hong
Copyright Year	2016
Abstract	Disability including deficiency in sensorimotor and cognition functions is a dominant consequence after stroke. Evidence suggests that serine proteases play an important role in the physiology and pathology of the brain. Previous studies reported that nafamostat mesilate (NM), a synthetic serine protease inhibitor, attenuates neuronal damage in the acute phase after stroke. However, its efficacy in the chronic phase and the mechanism underlying its beneficial effect are not fully known. Here, we have studied whether NM improves long-term functional recovery after ischemic stroke. Experimental ischemic stroke was induced by transient middle cerebral artery occlusion (tMCAO). NM treatment attenuated the brain infarct volume and the loss of body weight and improved the recovery of sensorimotor and cognitive functions. One month after tMCAO, neuronal axons and dendrites were preserved in the NM group, accompanied by increasedsynaptic proteins and structures in the ipsilateral hippocampus. The expression of brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 was increased in the contralateral sensorimotor cortex and ipsilateral hippocampus by the administration of NM. Furthermore, NM activated tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinas1/2(ERK1/2) and cAMP-response element binding protein (CREB) and inhibited the activity of Cyclin-dependent Kinase 5 (Cdk5) in the contralateral sensorimotor cortex and ipsilateral hippocampus. These results demonstrated that NM treatment could improve neurological outcome and axonal regeneration, which might be correlated with down-regulating Cdk5 activity and up-regulating TrkB-ERK1/2-CREB pathway.
Starting Page	4217
Ending Page	4231
Page Count	15
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	54
Issue Number	6
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2016-06-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Nafamostat mesilate Brain ischemia Functional recovery Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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