Coenzyme Q10 ameliorates cerebral ischemia reperfusion injury in hyperglycemic rats

Lu, Cuijie; Guo, Yongzhen; Zhang, Yang; Yang, Lingfeng; Chang, Yun Woo; Zhang, Jingwen; Li, Jing; Zhang, Jianzhong

doi:10.1016/j.prp.2017.06.005

Cited by 31 publications

(14 citation statements)

References 35 publications

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“…We examined Fis1 protein and mRNA in our study to test this hypothesis. Interestingly, some reports also confirmed our hypothesis by demonstrating that Fis1 expression increased following cerebral I/R injury [8,29].…”

Section: Discussionsupporting

confidence: 82%

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Tang

Chen

Sun

et al. 2019

Preprint

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13Mitochondrial immoderate fission induces neuronal apoptosis following focal cerebral 14 ischemia-reperfusion (I/R) injury. With fewer complications, selective brain 15 hypothermia (SBH) is considered an effective treatment against neuronal injury after 16 stroke. However, the specific mechanism by which SBH influences mitochondrial 17 fission remains unknown. Mitochondrial fission 1 protein (Fis1), a key factor of the 18 mitochondrial fission system, regulates mitochondrial dynamics. This study aimed to 19 investigate whether SBH regulates Fis1 expression in focal cerebral I/R injury. In this 20 study, rat middle cerebral artery occlusion (MCAO) models were established. After 2 21 h of occlusion, cold saline or normal saline was pumped into rats in different groups 22 through the carotid artery, followed by restoration of blood perfusion. Cortical and 23 rectal temperatures showed that the cold saline treatment achieved SBH. Cerebral I/R 24 injury increased neurological deficit scores(NDS); neuronal apoptosis; Fis1 protein 25 and mRNA expression; cytosolic cytochrome c (cyto-Cyto c) protein expression at 6, 26 24 and 48 h postreperfusion; and cerebral infarct volumes at 24 h postreperfusion. 27 Interestingly, SBH inhibited Fis1 protein and mRNA expression, blocked cyto-Cyto c 28 protein expression, preserved neuronal cell integrity, and reduced neuronal apoptosis. 29 However, normal saline treatment rarely resulted in positive outcomes. Based on 30 these results, SBH inhibited Fis1 expression, thus ameliorating focal cerebral I/R 31 injury in rats.32 3 33 Introduction 34 Stroke is one of the leading causes of death and disability in the world [1-3]. Ischemic 35 stroke caused by cerebral thrombosis or endovascular embolization accounts for a 36 major portion of strokes. Early restoration of blood perfusion is the most effective 37 treatment for stroke; this treatment provides nutrients and oxygen and removes toxic 38 metabolites [4,5]. However, vessel recanalization often exacerbates the existing tissue 39 damage [6,7]; thus, this condition is called cerebral ischemia-reperfusion (I/R) injury. 40 Recent studies have suggested that morphological changes in mitochondria might be 41 relevant to I/R injury [8,9]. Within the cell, mitochondria exist in an ever-changing 42 dynamic state-constant fission and fusion-to form mitochondrial networks and 43 maintain cellular physiological function and survival [10]. Notably, growing evidence 44 has indicated that I/R injury can break this balance to induce neuronal apoptosis 45 [11-13]. Mitochondrial fission protein 1 (Fis1), a 16-kDa protein anchored to the outer 46 membrane of the mitochondria, mediates mitochondrial fission by recruiting 47 cytoplasmic dynamin-related protein1 (Drp1) into the mitochondrial outer membrane 48 [14]. Overexpression of Fis1 increases the frequency of mitochondrial fission, 49 subsequently increasing the release of Cyto c and disrupting mitochondrial membrane 50 potential, thus inducing neuronal apoptosis [15]. In addition, in cells with th...

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Section: Discussionsupporting

confidence: 82%

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Tang

Chen

Sun

et al. 2019

Preprint

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“…After TBI, the brain mitochondria are vulnerable to secondary injury, and there is loss of cellular function due to reactive oxygen species. Ubiquinol is naturally produced in cell mitochondria, is essential for adenosine triphosphate (ATP) synthesis, and increases the cellular antioxidant capacity (Lu et al, ; Neergheen et al, ). We administered ubiquinol before and after TBI, and demonstrated a significant reduction in programmed cell death, mitochondrial damage, and serum biomarkers of TBI severity.…”

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confidence: 99%

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Pierce

Gupte

Thimmesch

et al. 2018

J of Neuroscience Research

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Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

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“…Pronounced lucency and disarray and disappearance of mitochondrial cristae were observed, suggesting that UCP2 deletion increases mitochondrial morphological damage caused by cerebral ischemia in both normo-and hyperglycemic animals. We have previously shown that hyperglycemia aggravates ischemic brain damage [49,50]. This effect is associated with increases of mitochondrial fission and mitochondrial morphological alterations [21,33,51].…”

Section: Discussionmentioning

confidence: 94%

Deletion of Mitochondrial Uncoupling Protein 2 Exacerbates Mitochondrial Damage in Mice Subjected to Cerebral Ischemia and Reperfusion Injury under both Normo- and Hyperglycemic Conditions

He¹,

Ma²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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Deletion of mitochondrial uncoupling protein 2 (UCP2) has been shown to aggravate ischemic damage in the brain. However, the underlying mechanisms are not fully understood. The objective of this study is to explore the impact of homozygous UCP2 deletion (UCP2-/-) on mitochondrial fission and fusion dynamic balance in ischemic mice under normo-and hyperglycemic conditions. UCP2-/-and wildtype mice were subjected to a 60 min middle cerebral artery occlusion (MCAO) and allowed reperfusion for 6h, 24h and 72h. Our results demonstrated that deletion of UCP2 enlarged infarct volumes and increased numbers of cell death in both normo-and hyperglycemic ischemic mice compared with their wildtype counterparts subjected to the same duration of ischemia and reperfusion. The detrimental effects of UCP deletion were associated with increased ROS production, elevated mitochondrial fission markers Drp1 and Fis1 and suppressed fusion markers Opa1 and Mfn2 in UCP2-/-mice. Electron microscopic study demonstrated a marked mitochondrial swolling after 6h of reperfusion in UCP2-/-mice, contrasting to a mild mitochondrial swolling in wildtype ischemic animals. It is concluded that the exacerbating effects of UCP2-/-on ischemic outcome in both normo-and hyperglycemic animals are associated with increased ROS production, disturbed mitochondrial dynamic balance towards fission and early damage to mitochondrial ultrastructure.

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Coenzyme Q10 ameliorates cerebral ischemia reperfusion injury in hyperglycemic rats

Cited by 31 publications

References 35 publications

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Deletion of Mitochondrial Uncoupling Protein 2 Exacerbates Mitochondrial Damage in Mice Subjected to Cerebral Ischemia and Reperfusion Injury under both Normo- and Hyperglycemic Conditions

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