Hossmann KA. The hypoxic brain. Insights from ischemia research. Adv Exp Med Biol. 1999;474:155–69.

Article  CAS  PubMed  Google Scholar 

Varvarousis D, Varvarousi G, Iacovidou N, D’Aloja E, Gulati A, Xanthos T. The pathophysiologies of asphyxial vs dysrhythmic cardiac arrest: implications for resuscitation and post-event management. Am J Emerg Med. 2015;33(9):1297–304.

Article  PubMed  Google Scholar 

Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model | Critical Care | Full Text [Internet]. [cited 2022 Oct 31]. Available from: https://ccforum.biomedcentral.com/articles/https://doi.org/10.1186/s13054-017-1670-9

CDC. Centers for Disease Control and Prevention. 2022 [cited 2022 Dec 31]. About Stroke | cdc.gov. Available from: https://www.cdc.gov/stroke/about.htm

Shin TH, Lee DY, Basith S, Manavalan B, Paik MJ, Rybinnik I, et al. Metabolome changes in cerebral ischemia. Cells. 2020;9(7):1630.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dalessio L. Post-cardiac arrest syndrome. AACN Adv Crit Care. 2020;31(4):383–93.

Article  PubMed  Google Scholar 

Sandroni C, Cronberg T, Sekhon M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis. Intensive Care Med. 2021;47(12):1393–414.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greco P, Nencini G, Piva I, Scioscia M, Volta CA, Spadaro S, et al. Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future. Acta Neurol Belg. 2020;120(2):277–88.

Article  CAS  PubMed  Google Scholar 

Madden LK, Hill M, May TL, Human T, Guanci MM, Jacobi J, et al. The implementation of targeted temperature management: an evidence-based guideline from the neurocritical care society. Neurocrit Care. 2017;27(3):468–87.

Article  PubMed  Google Scholar 

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial | ADC Fetal & Neonatal Edition [Internet]. [cited 2022 Dec 31]. Available from: https://fn.bmj.com/content/105/4/405

Gulati A, Hornick MG, Briyal S, Lavhale MS. A novel neuroregenerative approach using ET(B) receptor agonist, IRL-1620, to treat CNS disorders. Physiol Res. 2018;67(Suppl 1):S95-113.

Article  CAS  PubMed  Google Scholar 

Rincon F. Targeted temperature management in brain injured patients. Neurosurg Clin N Am. 2018;29(2):231–53.

Article  PubMed  Google Scholar 

Carloni S, Facchinetti F, Pelizzi N, Buonocore G, Balduini W. Melatonin acts in synergy with hypothermia to reduce oxygen-glucose deprivation-induced cell death in rat hippocampus organotypic slice cultures. Neonatology. 2018;114(4):364–71.

Article  CAS  PubMed  Google Scholar 

Ramos MD, Briyal S, Prazad P, Gulati A. Neuroprotective effect of sovateltide (IRL 1620, PMZ 1620) in a neonatal rat model of hypoxic-ischemic encephalopathy. Neuroscience. 2022;1(480):194–202.

Article  Google Scholar 

Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332(6163):411–5.

Article  CAS  PubMed  Google Scholar 

Puppala B, Awan I, Briyal S, Mbachu O, Leonard M, Gulati A. Ontogeny of endothelin receptors in the brain, heart, and kidneys of neonatal rats. Brain Develop. 2015;37(2):206–15.

Article  Google Scholar 

Gulati A. Understanding neurogenesis in the adult human brain. Indian J Pharmacol. 2015;47(6):583.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990;348(6303):730–2.

Article  CAS  PubMed  Google Scholar 

Cardiovascular effects of centrally administered endothelin-1 in rats - PubMed [Internet]. [cited 2023 Feb 12]. Available from: https://pubmed.ncbi.nlm.nih.gov/8587377/

Castañeda MM, Cubilla MA, López-Vicchi MM, Suburo AM. Endothelinergic cells in the subependymal region of mice. Brain Res. 2010;19(1321):20–30.

Article  Google Scholar 

Bhalla S, Leonard M, Briyal S, Gulati A. Distinct alteration in brain endothelin A and B receptor characteristics following focal cerebral ischemia in rats. Drug Res (Stuttg). 2015;66(04):189–95.

Article  PubMed  Google Scholar 

Gulati A. Endothelin receptors, mitochondria and neurogenesis in cerebral ischemia. Curr Neuropharmacol. 2016;14(6):619–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gulati A, Agrawal N, Vibha D, Misra UK, Paul B, Jain D, et al. Safety and efficacy of sovateltide (IRL-1620) in a multicenter randomized controlled clinical trial in patients with acute cerebral ischemic stroke. CNS Drugs. 2021;35(1):85–104.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pharmazz, Inc. A prospective, multicentric, randomized, double-blind, parallel, phase III clinical study to assess efficacy of PMZ-1620 along with standard treatment in patients of acute ischemic stroke [Internet]. clinicaltrials.gov; 2022 Feb [cited 2023 Jan 1]. Report No.: NCT04047563. Available from: https://clinicaltrials.gov/study/NCT04047563

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;29:n71.

Article  Google Scholar 

Friedrich J, Lindauer U, Höllig A. Procedural and methodological quality in preclinical stroke research-a cohort analysis of the rat MCAO model comparing periods before and after the publication of STAIR/ARRIVE. Front Neurol. 2022;30(13):834003.

Article  Google Scholar 

Evans NJ. Assessing the practical differences between model selection methods in inferences about choice response time tasks. Psychon Bull Rev. 2019;26(4):1070–98.

Article  PubMed  PubMed Central  Google Scholar 

Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, et al. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke. 2009;40(6):2244–50.

Article  PubMed  PubMed Central  Google Scholar 

Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14(1):43.

Article  PubMed  PubMed Central  Google Scholar 

Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019;22(4):153–60.

Article  PubMed  PubMed Central  Google Scholar 

Schwarzer G. meta: An R package for meta-analysis. R news. 2007;7:40.

Google Scholar 

Cifuentes EG, Hornick MG, Havalad S, Donovan RL, Gulati A. Neuroprotective effect of IRL-1620, an endothelin B receptor agonist, on a pediatric rat model of middle cerebral artery occlusion. Front Pediatr. 2018;23(6):310.

Article  Google Scholar 

Ranjan AK, Briyal S, Khandekar D, Gulati A. Sovateltide (IRL-1620) affects neuronal progenitors and prevents cerebral tissue damage after ischemic stroke. Can J Physiol Pharmacol. 2020;98(9):659–66.

Article  CAS  PubMed  Google Scholar 

Briyal S, Ranjan AK, Hornick MG, Puppala AK, Luu T, Gulati A. Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia. Sci Rep. 2019;9(1):10439.

Article  PubMed  PubMed Central  Google Scholar 

Ranjan AK, Briyal S, Gulati A. Sovateltide (IRL-1620) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke. Sci Rep. 2020;10(1):12737.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leonard MG, Gulati A. Endothelin B receptor agonist, IRL-1620, enhances angiogenesis and neurogenesis following cerebral ischemia in rats. Brain Res. 2013;1528:28–41.

Article  CAS  PubMed  Google Scholar 

Leonard MG, Briyal S, Gulati A. Endothelin B receptor agonist, IRL-1620, reduces neurological damage following permanent middle cerebral artery occlusion in rats. Brain Res. 2011;28(1420):48–58.

Article  Google Scholar 

Integrative cerebral blood flow regulation in ischemic stroke - PMC [Internet]. [cited 2023 Jan 9]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985438/

Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol Neurodegener. 2011;6(1):11.

Article  PubMed  PubMed Central  Google Scholar 

Rogers SD, Demaster E, Catton M, Ghilardi JR, Levin LA, Maggio JE, et al. Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans. Exp Neurol. 1997;145(1):180–95.

Article  CAS  PubMed  Google Scholar 

Koyama Y, Endothelin ETB. Receptor-mediated astrocytic activation: pathological roles in brain disorders. Int J Mol Sci. 2021;22(9):4333.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Repeated administration of centhaquin to pregnant rats did not affect postnatal development and expression of endothelin receptors in the brain, heart or kidney of pups - PubMed [Internet]. [cited 2023 Feb 21]. Available from: https://pubmed.ncbi.nlm.nih.gov/23154885/

Davidson JO, Wassink G, van den Heuij LG, Bennet L, Gunn AJ. Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy—Where to from Here? Front Neurol. 2015;14(6):198.

Google Scholar 

Hypoxic-Ischemic Encephalopathy - Pharmazz, Inc. [Internet]. [cited 2022 Oct 31]. Available from: https://www.pharmazz.com/hypoxic-ischemic-encephalopathy.php

Animals in scientific research - Environment - European Commission [Internet]. [cited 2023 Jan 9]. Available from: