Rapidly Increased Neuronal Mitochondrial Biogenesis After Hypoxic-Ischemic Brain Injury

Yin, Wei; Signore, Armando P.; Iwai, Masanori; Cao, Guodong; Gao, Yanqin; Chen, Jun

doi:10.1161/strokeaha.108.520114

Cited by 207 publications

(178 citation statements)

References 32 publications

(37 reference statements)

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“…In the ischemic groups with SA treatment, a significant increase was observed. In accordance with our study, in the literature the increase in NRF1 values in the ischemia/ reperfusion groups was in proportion with the reperfusion time and was shown to increase further with the use of neuroprotective agents (12,13,25,26) (Table 1).…”

Section: Discussionsupporting

confidence: 92%

The protective effect of syringic acid on ischemia injury in rat brain

Güven¹,

Aras²,

Topaloğlu³

et al. 2015

Turk J Med Sci

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IntroductionBrain ischemia is still a serious clinical problem that may lead to permanent neurological deficits and serious complications. Contusion, the initial mechanical damage, may cause edema and pressure causes brain cell death and produces permanent damage. If pressure is removed or continues after the primary injury, the capillary permeability of the damaged area and surroundings increases; with the effect of reactive oxygen species (ROS) and inflammation, more dramatic results may occur due to secondary damage (1). To prevent ischemia and later damage, current studies have been and continue to be conducted on many chemopreventive agents.Polyphenols, naturally found in many plants, have antiinflammatory and immunomodulatory effects and are known to show antioxidant effects, cleaning out ROS formed by cellular damage and oxidative stress. Simonyi et al. (2) showed the neuroprotective effect of polyphenols on cerebral ischemic lesions. Studies on a polyphenolic derivative of benzoic acid (2,3), syringic acid (SA), have shown it to have chemoprotective (4) and antimicrobial (5) activity. In addition, Morton et al. (6) showed that SA was a strong inhibitor of low-density lipoprotein oxidation, supporting the scavenging of free radicals, reducing production of malondialdehyde, and thus slowing atherosclerosis.There are no studies on the effects of SA on brain ischemia found in the literature. The aim of this study was to investigate the preventive effect of the active ingredient in SA, a member of the polyphenol group with known antioxidant properties, on injury due to brain ischemia. SA may provide a novel and promising therapeutic strategy for treatment of human cerebral ischemia via antioxidants and antiapoptotic effects.Background/aim: Brain ischemia and treatment are important topics in neurological science. Free oxygen radicals and inflammation formed after ischemia are accepted as the most significant causes of damage. Currently there are studies on many chemopreventive agents to prevent cerebral ischemia damage. Our aim is to research the preventive effect of the active ingredient in syringic acid, previously unstudied, on oxidative damage in cerebral ischemia. Materials and methods:The rats were randomly divided into 4 groups: control group (no medication or surgical procedure), sham group (artery occlusion), artery occlusion + syringic acid group sacrificed at 6 h, and artery occlusion + syringic acid group sacrificed at 24 h. Obtained brain tissue from the right hemisphere was investigated histopathologically and for tissue biochemistry.Results: Superoxide dismutase and nuclear respiratory factor 1 values decreased after ischemia and they increased after syringic acid treatment, while increased malondialdehyde levels after ischemia were reduced after treatment. Caspase-3 and caspase-9 values increased after ischemia and decreased after treatment; this reduction was more pronounced at 24 h. Conclusion:Our study revealed that syringic acid treatment in cerebral ischemia reduced oxidative stress and n...

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Section: Discussionsupporting

confidence: 92%

The protective effect of syringic acid on ischemia injury in rat brain

Güven¹,

Aras²,

Topaloğlu³

et al. 2015

Turk J Med Sci

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“…Initiation of mitochondrial biogenesis occurs in acute injury models (26,27,36,41). We assessed expression of several known mediators of mitochondrial biogenesis by PCR and immunoblot analysis.…”

Section: Resultsmentioning

confidence: 99%

“…However, the role of mitochondrial fission and fusion following initial injury and during the recovery and maintenance phase is still not completely understood. Mitochondrial biogenesis is initiated after acute organ injuries (27,41), including cellular models of AKI (26). There is an immediate induction of the transcriptional co-activator peroxisome proliferator-activated receptor ␥ co-activator 1-␣ (PGC-1␣) in experimental models of stroke, liver damage, heart failure, and neuromuscular disorders in response to the increased energy demand in such tissues (27,36,38,41).…”

mentioning

confidence: 99%

“…Mitochondrial biogenesis is initiated after acute organ injuries (27,41), including cellular models of AKI (26). There is an immediate induction of the transcriptional co-activator peroxisome proliferator-activated receptor ␥ co-activator 1-␣ (PGC-1␣) in experimental models of stroke, liver damage, heart failure, and neuromuscular disorders in response to the increased energy demand in such tissues (27,36,38,41). PGC-1␣ is a primary regulator of mitochondrial biogenesis and is known to associate with transcription factors responsible for mitochondrial gene expression, including the nuclear respiratory factors (NRFs) and mitochondrial transcription factor A (Tfam) (40).…”

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confidence: 99%

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Persistent disruption of mitochondrial homeostasis after acute kidney injury

Funk

Schnellmann

2012

American Journal of Physiology-Renal Physiology

204

192

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Funk JA, Schnellmann RG. Persistent disruption of mitochondrial homeostasis after acute kidney injury. Am J Physiol Renal Physiol 302: F853-F864, 2012. First published December 7, 2011 doi:10.1152/ajprenal.00035.2011.-While mitochondrial dysfunction is a pathological process that occurs after acute kidney injury (AKI), the state of mitochondrial homeostasis during the injury and recovery phases of AKI remains unclear. We examined markers of mitochondrial homeostasis in two nonlethal rodent AKI models. Myoglobinuric AKI was induced by glycerol injection into rats, and mice were subjected to ischemic AKI. Animals in both models had elevated serum creatinine, indicative of renal dysfunction, 24 h after injury which partially recovered over 144 h postinjury. Markers of proximal tubule function/injury, including neutrophil gelatinase-associated lipocalin and urine glucose, did not recover during this same period. The persistent pathological state was confirmed by sustained caspase 3 cleavage and evidence of tubule dilation and brush-border damage. Respiratory proteins NDUFB8, ATP synthase ␤, cytochrome c oxidase subunit I (COX I), and COX IV were decreased in both injury models and did not recover by 144 h. Immunohistochemical analysis confirmed that COX IV protein was progressively lost in proximal tubules of the kidney cortex after ischemia-reperfusion (I/R). Expression of mitochondrial fission protein Drp1 was elevated after injury in both models, whereas the fusion protein Mfn2 was elevated after glycerol injury but decreased after I/R AKI. LC3-I/II expression revealed that autophagy increased in both injury models at the later time points. Markers of mitochondrial biogenesis, such as PGC-1␣ and PRC, were elevated in both models. These findings reveal that there is persistent disruption of mitochondrial homeostasis and sustained tubular damage after AKI, even in the presence of mitochondrial recovery signals and improved glomerular filtration.

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“…Increased mitochondrial biogenesis has also been reported in neurons of the cortical infarct border zone after hypoxic-ischemic brain injury. 48 Some of the normal reactive mitochondria display transformation of the matrix to a dense ''twisted'' conformation. This morphotype represents an intermediate, reversible stage of mitochondrial swelling.…”

Section: Discussionmentioning

confidence: 99%

Cellular Alterations in Human Traumatic Brain Injury: Changes in Mitochondrial Morphology Reflect Regional Levels of Injury Severity

Balan

Saladino

Aarabi

et al. 2013

Journal of Neurotrauma

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Mitochondrial dysfunction may be central to the pathophysiology of traumatic brain injury (TBI) and often can be recognized cytologically by changes in mitochondrial ultrastructure. This study is the first to broadly characterize and quantify mitochondrial morphologic alterations in surgically resected human TBI tissues from three contiguous cortical injury zones. These zones were designated as injury center (Near), periphery (Far), and Penumbra. Tissues from 22 patients with TBI with varying degrees of damage and time intervals from TBI to surgical tissue collection within the first week post-injury were rapidly fixed in the surgical suite and processed for electron microscopy. A large number of mitochondrial structural patterns were identified and divided into four survival categories: normal, normal reactive, reactive degenerating, and end-stage degenerating profiles. A tissue sample acquired at 38 hours post-injury was selected for detailed mitochondrial quantification, because it best exhibited the wide variation in cellular and mitochondrial changes consistently noted in all the other cases. The distribution of mitochondrial morphologic phenotypes varied significantly between the three injury zones and when compared with control cortical tissue obtained from an epilepsy lobectomy. This study is unique in its comparative quantification of the mitochondrial ultrastructural alterations at progressive distances from the center of injury in surviving TBI patients and in relation to control human cortex. These quantitative observations may be useful in guiding the translation of mitochondrial-based neuroprotective interventions to clinical implementation.

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Rapidly Increased Neuronal Mitochondrial Biogenesis After Hypoxic-Ischemic Brain Injury

Cited by 207 publications

References 32 publications

The protective effect of syringic acid on ischemia injury in rat brain

The protective effect of syringic acid on ischemia injury in rat brain

Persistent disruption of mitochondrial homeostasis after acute kidney injury

Cellular Alterations in Human Traumatic Brain Injury: Changes in Mitochondrial Morphology Reflect Regional Levels of Injury Severity

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