NDLI: Anti-apoptotic activity of ET<sub>B</sub> receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia.

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Anti-apoptotic activity of ET_B receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia.

Content Provider	Europe PMC
Author	Briyal, Seema Ranjan, Amaresh K. Hornick, Mary G. Puppala, Anupama K. Luu, Thanh Gulati, Anil
Abstract	Endothelin-B receptor agonist, IRL-1620, provides significant neuroprotection following cerebral ischemia in rats. Whether this neuroprotection is due to inhibition of apoptosis is unknown. IRL-1620-treated rats following permanent middle cerebral artery occlusion (MCAO) showed significant improvement in neurological and motor functions along with a decrease in infarct volume at 24 h (-81.3%) and day 7 (-73.0%) compared to vehicle group. Cerebral blood flow (CBF) significantly improved in IRL-1620-treated animals compared to vehicle by day 7 post MCAO. IRL-1620-treated rats showed an increase in phospho-Akt and decrease in Bad level 7 h post-occlusion compared to vehicle, while Akt and Bad expression was similar in cerebral hemispheres at 24 h post-MCAO. The phospho-Bad level was lower in vehicle- but not in IRL-1620-treated rats at 24 h. Anti-apoptotic Bcl-2 expression decreased, while pro-apoptotic Bax expression increased in vehicle-treated MCAO rats, these changes were attenuated (P < 0.01) by IRL-1620. Mitochondrial membrane-bound Bax intensity significantly decreased in IRL-1620 compared to vehicle-treated MCAO rats. IRL-1620 treatment reduced (P < 0.001) the number of TUNEL-positive cells compared to vehicle at 24 h and day 7 post MCAO. The results demonstrate that IRL-1620 is neuroprotective and attenuates neural damage following cerebral ischemia in rats by increasing CBF and reducing apoptosis.
Journal	Scientific Reports [Sci Rep]
Volume Number	9
DOI	10.1038/s41598-019-46203-x
PubMed Central reference number	PMC6639304
Issue Number	1
PubMed reference number	31320660
e-ISSN	20452322
Language	English
Publisher	Nature Publishing Group
Publisher Date	2019-07-18
Publisher Place	London
Access Restriction	Open
Subject Keyword	Preclinical research Stroke
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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