Umut Ocak1,2, Pinar Eser Ocak2,3, Lei Huang2, John H Zhang2. 1. University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Department of Emergency Medicine, Bursa, Turkey. 2. Loma Linda University School of Medicine, Department of Physiology and Pharmacology, Loma Linda, California, USA 3. Uludag University, School of Medicine, Department of Neurosurgery, Bursa, Turkey
Abstract
AIM: To evaluate the effect of FSLLRY-NH2, a protease-activated receptor 2 (PAR2) inhibitor, on neurocognitive impairment and hippocampal neuronal degeneration in the setting of asphyxial cardiac arrest (ACA)-induced global cerebral ischemia (GCI) in rats. MATERIAL AND METHODS: A total of 43 Sprague-Dawley male rats were used. Shams and rats resuscitated from 9 minutes of ACA were randomized to two separate experiments including time course and short-term neurological outcomes. FSLLRY-NH2 (50 microgram [μg] per rat) was administered intranasally at 1 hour postresuscitation. Neurological function and hippocampal neuronal degeneration were evaluated after ACA. RESULTS: Significant neurological function decline and hippocampal neuron degeneration were observed in ACA animals as compared with the shams. Treatment with FSLLRY-NH2 significantly improved neurological outcome and reduced the number of degenerating hippocampal neurons after ACA. CONCLUSION: Targeting PAR2 may be a novel therapeutic approach in the management of neurological dysfunction after cardiac arrest-associated ischemic injury.
AIM: To evaluate the effect of FSLLRY-NH2, a protease-activated receptor 2 (PAR2) inhibitor, on neurocognitive impairment and hippocampal neuronal degeneration in the setting of asphyxial cardiac arrest (ACA)-induced global cerebral ischemia (GCI) in rats. MATERIAL AND METHODS: A total of 43 Sprague-Dawley male rats were used. Shams and rats resuscitated from 9 minutes of ACA were randomized to two separate experiments including time course and short-term neurological outcomes. FSLLRY-NH2 (50 microgram [μg] per rat) was administered intranasally at 1 hour postresuscitation. Neurological function and hippocampal neuronal degeneration were evaluated after ACA. RESULTS: Significant neurological function decline and hippocampal neuron degeneration were observed in ACA animals as compared with the shams. Treatment with FSLLRY-NH2 significantly improved neurological outcome and reduced the number of degenerating hippocampal neurons after ACA. CONCLUSION: Targeting PAR2 may be a novel therapeutic approach in the management of neurological dysfunction after cardiac arrest-associated ischemic injury.
Authors: Umut Ocak; Pinar Eser Ocak; Lei Huang; Weilin Xu; Yuchun Zuo; Peng Li; Marcin Gamdzyk; Gang Zuo; Jun Mo; Guangyu Zhang; John H Zhang Journal: J Neuroinflammation Date: 2020-05-04 Impact factor: 8.322