Qin Hu1, Anatol Manaenko1, Hetao Bian1, Zongduo Guo1, Jun-Long Huang1, Zhen-Ni Guo1, Peng Yang1, Jiping Tang1, John H Zhang2. 1. From the Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China (Q.H., J.-L.H.); Departments of Physiology and Pharmacology (Q.H., H.B., Z.G., Z.-N.G., P.Y., J.T., J.H.Z.) and Department of Anesthesiology (J.H.Z.), Loma Linda University School of Medicine, CA; and Department of Neurology, University of Erlangen-Nuremberg, Germany (A.M.). 2. From the Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China (Q.H., J.-L.H.); Departments of Physiology and Pharmacology (Q.H., H.B., Z.G., Z.-N.G., P.Y., J.T., J.H.Z.) and Department of Anesthesiology (J.H.Z.), Loma Linda University School of Medicine, CA; and Department of Neurology, University of Erlangen-Nuremberg, Germany (A.M.). johnzhang3910@yahoo.com.
Abstract
BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).
BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. RESULTS:Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusionrats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusionrats. HBO might be promising approach for treatment of acute ischemic strokepatients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).
Authors: Björn Reuter; Claus Rodemer; Saskia Grudzenski; Stephen Meairs; Peter Bugert; Michael G Hennerici; Marc Fatar Journal: Transl Stroke Res Date: 2014-12-05 Impact factor: 6.829
Authors: Yongzhen Guo; Lingdi Dong; Ao Gong; Jingwen Zhang; Li Jing; Tomas Ding; Ping-An Andy Li; Jian-Zhong Zhang Journal: Int J Mol Med Date: 2021-06-03 Impact factor: 4.101