Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular and systemic administration, are unsuitable for translation to humans; in the latter case because AT2receptor agonists are blood brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the blood brain barrier and deliver the selective AT2receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1-induced ischemic stroke. The results obtained from this study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 mins in amounts that are therapeutically relevant (8.4 - 9nM), regardless of whether the BBB was intact or disintegrated. C21 first applied N2B at 1.5 hours after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, then N2B application of AT2receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.
Pharmacology, Toxicology and Pharmaceutical Science
5
17%
Medicine and Dentistry
5
17%
Agricultural and Biological Sciences
3
10%
Biochemistry, Genetics and Molecular Biology
1
3%
Psychology
1
3%
Other
2
7%
Unknown
13
43%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 17 March 2018.
All research outputs
#24,253,629
of 34,560,275 outputs
Outputs from Clinical Science
#2,631
of 3,445 outputs
Outputs of similar age
#256,296
of 381,078 outputs
Outputs of similar age from Clinical Science
#17
of 29 outputs
Altmetric has tracked 34,560,275 research outputs across all sources so far. This one is in the 28th percentile – i.e., 28% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,445 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
