scholarly journals Korean Red Ginseng Improves Astrocytic Mitochondrial Function by Upregulating HO-1-Mediated AMPKα–PGC-1α–ERRα Circuit after Traumatic Brain Injury

2021 ◽  
Vol 22 (23) ◽  
pp. 13081
Author(s):  
Minsu Kim ◽  
Joohwan Kim ◽  
Sunhong Moon ◽  
Bo Young Choi ◽  
Sueun Kim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cytochrome C ◽  
Mitochondrial Function ◽  
Heme Oxygenase 1 ◽  
O2 Consumption ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Atp Production ◽  
Injured Region

Heme oxygenase-1 (HO-1) exerts beneficial effects, including angiogenesis and energy metabolism via the peroxisome proliferator-activating receptor-γ coactivator-1α (PGC-1α)–estrogen-related receptor α (ERRα) pathway in astrocytes. However, the role of Korean red ginseng extract (KRGE) in HO-1-mediated mitochondrial function in traumatic brain injury (TBI) is not well-elucidated. We found that HO-1 was upregulated in astrocytes located in peri-injured brain regions after a TBI, following exposure to KRGE. Experiments with pharmacological inhibitors and target-specific siRNAs revealed that HO-1 levels highly correlated with increased AMP-activated protein kinase α (AMPKα) activation, which led to the PGC-1α-ERRα axis-induced increases in mitochondrial functions (detected based on expression of cytochrome c oxidase subunit 2 (MTCO2) and cytochrome c as well as O2 consumption and ATP production). Knockdown of ERRα significantly reduced the p-AMPKα/AMPKα ratio and PGC-1α expression, leading to AMPKα–PGC-1α–ERRα circuit formation. Inactivation of HO by injecting the HO inhibitor Sn(IV) protoporphyrin IX dichloride diminished the expression of p-AMPKα, PGC-1α, ERRα, MTCO2, and cytochrome c in the KRGE-administered peri-injured region of a brain subjected to TBI. These data suggest that KRGE enhanced astrocytic mitochondrial function via a HO-1-mediated AMPKα–PGC-1α–ERRα circuit and consequent oxidative phosphorylation, O2 consumption, and ATP production. This circuit may play an important role in repairing neurovascular function after TBI in the peri-injured region by stimulating astrocytic mitochondrial biogenesis.

Impaired cerebral mitochondrial function after traumatic brain injury in humans

2000 ◽  
Vol 93 (5) ◽  
pp. 815-820 ◽  
Author(s):  
Bon H. Verweij ◽  
J. Paul Muizelaar ◽  
Federico C. Vinas ◽  
Patti L. Peterson ◽  
Ye Xiong ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Oxygen Content ◽  
Mitochondrial Function ◽  
Oxygen Delivery ◽  
Neuronal Cell ◽  
Content Type ◽  
Atp Production ◽  
Fine Print

Object. Oxygen supply to the brain is often insufficient after traumatic brain injury (TBI), and this results in decreased energy production (adenosine triphosphate [ATP]) with consequent neuronal cell death. It is obviously important to restore oxygen delivery after TBI; however, increasing oxygen delivery alone may not improve ATP production if the patient's mitochondria (the source of ATP) are impaired. Traumatic brain injury has been shown to impair mitochondrial function in animals; however, no human studies have been previously reported.Methods. Using tissue fractionation procedures, living mitochondria derived from therapeutically removed brain tissue were analyzed in 16 patients with head injury (Glasgow Coma Scale Scores 3–14) and two patients without head injury. Results revealed that in head-injured patients mitochondrial function was impaired, with subsequent decreased ATP production.Conclusions. Decreased oxygen metabolism due to mitochondrial dysfunction must be taken into account when clinically defining ischemia and interpreting oxygen measurements such as jugular venous oxygen saturation, arteriovenous difference in oxygen content, direct tissue oxygen tension, and cerebral blood oxygen content determined using near-infrared spectroscopy. Restoring mitochondrial function might be as important as maintaining oxygen delivery.

Toll-like receptor 2 contributes to glial cell activation and heme oxygenase-1 expression in traumatic brain injury

2008 ◽  
Vol 431 (2) ◽  
pp. 123-128 ◽  
Author(s):  
Chanhee Park ◽  
Ik-Hyun Cho ◽  
Donghoon Kim ◽  
Eun-Kyeong Jo ◽  
Se-Young Choi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cell ◽  
Heme Oxygenase ◽  
Cell Activation ◽  
Heme Oxygenase 1 ◽  
Toll Like Receptor ◽  
Glial Cell Activation ◽  
Toll Like Receptor 2

Induction of heme oxygenase-1 (HO-1) after traumatic brain injury in the rat

1995 ◽  
Vol 199 (2) ◽  
pp. 127-130 ◽  
Author(s):  
Kazumasa Fukuda ◽  
S. Scott Panter ◽  
Frank R. Sharp ◽  
L.J. Noble
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals Cyclosporin A Preserves Mitochondrial Function after Traumatic Brain Injury in the Immature Rat and Piglet

2011 ◽  
Vol 28 (5) ◽  
pp. 763-774 ◽  
Author(s):  
Todd J. Kilbaugh ◽  
Sunita Bhandare ◽  
David H. Lorom ◽  
Manda Saraswati ◽  
Courtney L. Robertson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cyclosporin A ◽  
Mitochondrial Function ◽  
Immature Rat

Heme Oxygenase 1 in Cerebrospinal Fluid from Infants and Children after Severe Traumatic Brain Injury

2006 ◽  
Vol 28 (4-5) ◽  
pp. 342-347 ◽  
Author(s):  
J’mir L. Cousar ◽  
Yichen Lai ◽  
Christina D. Marco ◽  
Hülya Bayır ◽  
P. David Adelson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Heme Oxygenase ◽  
Severe Traumatic Brain Injury ◽  
Infants And Children ◽  
Heme Oxygenase 1

scholarly journals Changes in Local Cerebral Blood Flow, Glucose Utilization, and Mitochondrial Function Following Traumatic Brain Injury in Rats.

2000 ◽  
Vol 40 (1) ◽  
pp. 16-29 ◽  
Author(s):  
Xiao Bin JIANG ◽  
Kikuo OHNO ◽  
Liang QIAN ◽  
Ben TOMINAGA ◽  
Toshihiko KUROIWA ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Mitochondrial Function ◽  
Glucose Utilization ◽  
Local Cerebral Blood Flow

scholarly journals Neuroprotective effects of crude extract of Crataegus songarica on a rat model of traumatic brain injury

2022 ◽  
Vol 20 (2) ◽  
pp. 293-299
Author(s):  
Xueliang Gao ◽  
Zhao Wang ◽  
Peilei Jia ◽  
Yapeng Zhao ◽  
Kai Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Brain Cortex ◽  
Neuronal Survival ◽  
Underlying Mechanism ◽  
Tunel Staining ◽  
Heme Oxygenase 1 ◽  
Nissl Staining ◽  
Neuroprotective Effects

Purpose: To investigate the protective effect of Crataegus songarica extract (CSCE) against traumatic brain injury (TBI) in rats, and the underlying mechanism of action. Methods: A rat model of TBI was established via tracheal intubation procedure, and the rats were treated with graded doses of CSCE. Neuronal survival was determined by Nissl staining, while neuronal apoptosis was measured using TUNEL-staining. Neurological impairments were determined based on neurological severity score (NSS). Results: Treatment of TBI rats with CSCE enhanced neuronal survival and decreased TUNEL-positive cell fraction in the brain cortex. The treatment prevented elevation of NSS and suppressed mRNA and protein expression levels of IL-6 and TNF-α in brain cortex. Moreover, CSCE treatment prevented TBI-mediated suppression of activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and attenuated hydrogen peroxide (H2O2) levels in TBI rat brain cortex. Treatment of TBI rats with CSCE down-regulated NF-κB expression, increased Nrf2 expression and up-regulated mRNA expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1 (NQO-1). Conclusion: These results suggest that CSCE prevents TBI-mediated reduction in neuronal survival and inhibits brain cortical neuronal death in rats. It improves NSS and inhibits inflammatory response via activation of Nrf2 pathway and targeting of NF-κB expression. Therefore, CSCE is a potential therapeutic agent for TBI.

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