| Title |
Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice
|
|---|---|
| Published in |
The AAPS Journal, December 2015
|
| DOI | 10.1208/s12248-015-9854-1 |
| Pubmed ID | |
| Authors |
Huinan Zhang, Jingru Meng, Shimeng Zhou, Yunhan Liu, Di Qu, Ling Wang, Xubo Li, Ning Wang, Xiaoxing Luo, Xue Ma |
| Abstract |
Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro- and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 29% |
| Researcher | 5 | 16% |
| Professor | 4 | 13% |
| Student > Doctoral Student | 2 | 6% |
| Student > Master | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 8 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 13% |
| Medicine and Dentistry | 4 | 13% |
| Agricultural and Biological Sciences | 3 | 10% |
| Engineering | 3 | 10% |
| Immunology and Microbiology | 2 | 6% |
| Other | 3 | 10% |
| Unknown | 12 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 January 2016.
All research outputs
#18,434,182
of 22,837,982 outputs
Outputs from The AAPS Journal
#1,101
of 1,287 outputs
Outputs of similar age
#281,173
of 389,451 outputs
Outputs of similar age from The AAPS Journal
#23
of 28 outputs
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