Document Detail


Motoneuronotrophic factor analog GM6 reduces infarct volume and behavioral deficits following transient ischemia in the mouse.
MedLine Citation:
PMID:  18789909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Motoneuronotrophic factor (MNTF) is an endogenous neurotrophin that is highly specific for the human nervous system, and some of the observed effects of MNTF include motoneuron differentiation, maintenance, survival, and reinnervation of target muscles and organs. MNTF is a neuro-signaling molecule that binds to specific receptors. Using In Silico Analysis, one of the active sites of MNTF was identified as an analog of six amino acids (GM6). The effect of chemically synthesized GM6 on ischemic stroke was studied in the middle cerebral artery occlusion (MCAo) mouse model. Mice were subjected to 1 hur of ischemia followed by 24 h of reperfusion. Mice were injected intravenously with a bolus of GM6, at various doses (1 and 5 mg/kg) immediately after the start of reperfusion and examined for changes in physiological parameters, neurological deficits and infarct volume. GM6 was able to penetrate the blood brain barrier, and at both 1 and 5 mg/kg showed a significant protection from infarct damage, which translated to improvement of neurological deficits. Administration of GM6 demonstrated no changes in HR, BP, pO(2), pCO(2), or pH. A significant increase over the control group in CBF after reperfusion was observed with GM6 administration, which helped to mitigate the ischemic effect caused by the blockage of blood flow. The time window of treatment was assessed at various times following cerebral ischemia with GM6 demonstrating a significant protective effect up to 6-12 h post ischemia. In addition, GM6 increased neurogenesis, and decreased apoptosis and inflammation in the mouse brain following cerebral ischemic injury. These data suggest that GM6 is neuroprotective to the brain following IV injection in the mouse model of MCAo.
Authors:
Jin Yu; Hong Zhu; Dorothy Ko; Mark S Kindy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-29
Journal Detail:
Title:  Brain research     Volume:  1238     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2009-02-09     Revised Date:  2012-02-13    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  143-53     Citation Subset:  IM    
Affiliation:
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Behavior, Animal / drug effects*
Brain / drug effects*,  pathology
Enzyme-Linked Immunosorbent Assay
In Situ Nick-End Labeling
Inflammation / prevention & control
Ischemic Attack, Transient / drug therapy*
Mice
Mice, Inbred C57BL
Nerve Growth Factors / pharmacology*
Neurogenesis / drug effects
Neuroprotective Agents / pharmacology*
Peptides
Grant Support
ID/Acronym/Agency:
R01 AG019323-04/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Nerve Growth Factors; 0/Neuroprotective Agents; 0/Peptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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