The Neuroprotective Effect of Pyrroloquinoline Quinone on Traumatic Brain Injury

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

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Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

Critical Care ◽

10.1186/s13054-020-03373-9 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Rita Campos-Pires ◽

Haldis Onggradito ◽

Eszter Ujvari ◽

Shughoofa Karimi ◽

Flavia Valeo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Outcome ◽

Neuroprotective Effect ◽

Neuronal Loss ◽

Brain Trauma ◽

Lesion Volume ◽

Oxygen Balance ◽

Sprague Dawley ◽

Locomotor Deficits

Abstract Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

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Reduction of Traumatic Brain Damage by Tspo Ligand Etifoxine

International Journal of Molecular Sciences ◽

10.3390/ijms20112639 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2639 ◽

Cited By ~ 6

Author(s):

Mona Shehadeh ◽

Eilam Palzur ◽

Liat Apel ◽

Jean Francois Soustiel

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Damage ◽

Neuroprotective Effect ◽

Experimental Studies ◽

Potential Effect ◽

Translocator Protein ◽

Male Rats ◽

Lesion Volume ◽

Sprague Dawley

Experimental studies have shown that ligands of the 18 kDa translocator protein can reduce neuronal damage induced by traumatic brain injury by protecting mitochondria and preventing metabolic crisis. Etifoxine, an anxiolytic drug and 18 kDa translocator protein ligand, has shown beneficial effects in the models of peripheral nerve neuropathy. The present study investigates the potential effect of etifoxine as a neuroprotective agent in traumatic brain injury (TBI). For this purpose, the effect of etifoxine on lesion volume and modified neurological severity score at 4 weeks was tested in Sprague–Dawley adult male rats submitted to cortical impact contusion. Effects of etifoxine treatment on neuronal survival and apoptosis were also assessed by immune stains in the perilesional area. Etifoxine induced a significant reduction in the lesion volume compared to nontreated animals in a dose-dependent fashion with a similar effect on neurological outcome at four weeks that correlated with enhanced neuron survival and reduced apoptotic activity. These results are consistent with the neuroprotective effect of etifoxine in TBI that may justify further translational research.

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The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury

Stem Cells International ◽

10.1155/2017/4782820 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Yongqi Ye ◽

Pengju Zhang ◽

Yuhang Qian ◽

Baoxin Yin ◽

Meijuan Yan

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Caspase 3 ◽

Negative Control Group ◽

Pyrroloquinoline Quinone ◽

Protective Role ◽

Negative Control ◽

Control Group ◽

Protective Effects ◽

Si Rna

WISP1, as a member of the CCN4 protein family, has cell protective effects of promoting cell proliferation and inhibiting cell apoptosis. Although some studies have confirmed that WISP1 is concerned with colon cancer and lung cancer, there is little report about the influence of WISP1 in traumatic brain injury. Here, we found that the expression of WISP1 mRNA and protein decreased at 3 d and then increased at 5 d after traumatic brain injury (TBI). Meanwhile, immunofluorescence demonstrated that there was little colocation of WISP1 with GFAP, Iba1, and WISP1 colocalized with NeuN partly. WISP1 colocalized with LC3, but there was little of colocation about WISP1 with cleaved caspase-3. Subsequent study displayed that the expression ofβ-catenin protein was identical to that of WISP1 after TBI. WISP1 was mainly located in cytoplasm of PC12 or SHSY5Y cells. Compared with the negative control group, WISP1 expression reduced obviously in SHSY5Y cells transfected with WISP1 si-RNA. CCK-8 assay showed that pyrroloquinoline quinone (PQQ) had little influence on viability of PC12 and SHSY5Y cells. These results suggested that WISP1 played a protective role after traumatic brain injury in rats, and this effect might be relative to autophagy caused by traumatic brain injury.

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Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury

Inflammation ◽

10.1007/s10753-021-01520-0 ◽

2021 ◽

Author(s):

Pınar Kuru Bektaşoğlu ◽

Türkan Koyuncuoğlu ◽

Selin Akbulut ◽

Dilek Akakın ◽

İrem Peker Eyüboğlu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Plasminogen Activator ◽

Mild Traumatic Brain Injury ◽

Rat Model ◽

Neuroprotective Effect ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

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Propofol effects in rodent models of traumatic brain injury: a systematic review

Asian Biomedicine ◽

10.2478/abm-2021-0032 ◽

2021 ◽

Vol 15 (6) ◽

pp. 253-265

Author(s):

Riyadh Firdaus ◽

Sandy Theresia ◽

Ryan Austin ◽

Rani Tiara

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuroprotective Effect ◽

Head Injuries ◽

Inflammatory Factors ◽

Lesion Volume ◽

Rodent Models ◽

Neuroprotective Effects ◽

Traumatic Lesion ◽

Neurotoxic Effects

Abstract Background Traumatic brain injury (TBI) causes high mortality and disability worldwide. Animal models have been developed to explore the complex processes in TBI. Propofol is used to manage head injuries during surgical intervention and mechanical ventilation in patients with TBI. Many studies have investigated the neuroprotective effect of propofol on TBI. However, other studies have shown neurotoxic effects. Objectives To review systematically the literature regarding the neuroprotective and neurotoxic effects of propofol in rodent models of TBI. Methods Data from rodents as models of TBI with propofol as one of the intervention agents, and/or comparing the neuroprotective effects of propofol with the other substances in rodent models of TBI, were obtained from PubMed, EBSCO Host, and ProQuest databases. The PRISMA 2020 statement recommendations were followed and research questions were developed based on PICOS guidelines. Data was extracted from the literature using a standardized Cochrane method. Results We analyzed data from 12 articles on physiological changes of experimental animals before and after trauma, the effects of propofol administration, and the observed neurotoxic effects. The effects of propofol administration were observed in terms of changes in traumatic lesion volume, the release of antioxidants and inflammatory factors, and the neurological function of rodent models of TBI. Conclusion Propofol has neuroprotective and neurotoxic effects via several mechanisms, and various doses have been used in research to determine its effects. The timing of administration, the dose administered, and the duration of administration contribute to determine the effect of propofol in rodent models of TBI. However, the doses that produce neuroprotective and neurotoxic effects are not yet clear and further research is needed to determine them.

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