Three years ago this was reported;
GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice
yet we are no farther along in this because why?
DOI: 10.1111/jnc.13169
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Issue
Abstract
Traumatic
brain injury (TBI), a brain dysfunction for which there is no present
effective treatment, is often caused by a concussive impact to the head
and affects an estimated 1.7 million Americans annually. Our laboratory
previously demonstrated that exendin-4, a long-lasting glucagon-like
peptide 1 receptor (GLP-1R) agonist, has neuroprotective effects in
cellular and animal models of TBI. Here, we demonstrate neurotrophic and
neuroprotective effects of a different GLP-1R agonist, liraglutide, in
neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide
promoted dose-dependent proliferation in SH-SY5Y cells and in a GLP-1R
over-expressing cell line at reduced concentrations. Pretreatment with
liraglutide rescued neuronal cells from oxidative stress- and glutamate
excitotoxicity-induced cell death. Liraglutide produced neurotrophic and
neuroprotective effects similar to those of exendin-4 in vitro.
The cAMP/PKA/pCREB pathway appears to play an important role in this
neuroprotective activity of liraglutide. Furthermore, our findings in
cell culture were well-translated in a weight-drop mTBI mouse model.
Post-treatment with a clinically relevant dose of liraglutide for 7 days
in mice ameliorated memory impairments caused by mTBI when evaluated 7
and 30 days post trauma. These data cross-validate former studies of
exendin-4 and suggest that liraglutide holds therapeutic potential for
the treatment of mTBI.
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