scholarly journals A new EPOR/CD131 heteroreceptor agonist EP-11-1: a neuroprotective effect in experimental traumatic brain injury

2021 ◽  
Vol 7 (4) ◽  
pp. 1-9
Author(s):  
Oleg V. Antsiferov ◽  
Roman F. Cherevatenko ◽  
Mikhail V. Korokin ◽  
Vladimir V. Gureev ◽  
Anastasia V. Gureeva ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Locomotor Activity ◽  
Neurological Deficit ◽  
Biochemical Study ◽  
Neuroprotective Effect ◽  
Morphological Examination ◽  
Combined Administration ◽  
Male Wistar Rats ◽  
Weight Method

Introduction: EP-11-1 (UEHLERALNSS) is a short-chain erythropoietin derivative without have erythropoietic activity. It was created by modifying a peptide mimicking the spatial structure of the erythropoietin a-helix B pHBSP. One of the promising directions of its administration is the correction of morphofunctional disorders that occur in traumatic brain injury (TBI). Materials and methods: The study was performed in 160 male Wistar rats, weighing 180–200 g.TBI was simulated using the drop-weight method. To assess the emerging morphofunctional disorders and a degree of their correction, we used the severity of neurological deficit, indicators of locomotor activity and exploration, a marker of brain injury S100B and morphological examination. Results and discussion: The combined administration of a new EPOR/CD131 heteroreceptor agonist EP-11-1 with citicoline and trimetazidine led to a more pronounced correction of the neurological deficit when compared not only to the group of the ”untreated” animals, but also to the groups of animals to which these drugs had been administered as monotherapy (p < 0.05). The same tendency was also observed in the study of locomotor activity and exploration. A biochemical study showed that the administration of all three combinations led to a statistically significant (p < 0.05) decrease in the S-100B concentration compared not only to the group of “untreated” animals, but also to the groups of animals to which these drugs had been administered as a monotherapy. Conclusion: The results of the conducted experiments prove the most pronounced positive dynamics in the combined administration of the new EPOR/CD131 heteroreceptor agonist EP-11-1with citicoline and trimetazidine.

scholarly journals Neuroprotective effect of nerolidol in traumatic brain injury associated behavioural comorbidities in rats

2021 ◽  
Author(s):  
Amandeep Kaur ◽  
Gagandeep Jaiswal ◽  
Jasdeep Brar ◽  
Puneet Kumar
Keyword(s):  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Locomotor Activity ◽  
Ache Activity ◽  
Motor Coordination ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Weight Drop

Abstract Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to temporary/permanent secondary injuries, i.e. impairment of cognitive, physical, and psycho-social functions with altered consciousness. The leading mechanism responsible for neuronal damage following TBI is an increase in oxidative reactions initiated by free radicals generated by the injury along with various other mechanisms. Nerolidol is reported to have potent antioxidant and anti-neuroinflammatory properties. The present study was designed to explore the neuroprotective effect of nerolidol in weight-drop-induced TBI in rats. Animals were injured on the 1st day by dropping a free-falling weight of 200 gm from a height of 1 m through a guide pipe onto the exposed skull. After 14 days of injury, nerolidol (25, 50, and 100 mg/kg, i.p.) treatment was given for the next 14 days. Locomotor activity and motor coordination were evaluated using an actophotometer and rotarod, respectively. Cognitive impairment was observed through the Morris Water Maze and Object Recognition Test. On the 29th day, animals were sacrificed, and their brains were collected for the biochemical estimation. The weight drop model significantly decreased locomotor activity, motor coordination, increased Acetylcholinesterase (AChE) activity, oxidative stress, and induced cognitive deficits in TBI rats. Nerolidol significantly improved locomotor activity, reversed motor incoordination and cognitive impairment, and reduced the AChE activity and oxidative/nitrosative stress. The present study demonstrates the promising neuroprotective effects of nerolidol, which might improve the quality of life of TBI patients.

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

The Neuroprotective Effect of Salubrinal in a Mouse Model of Traumatic Brain Injury

2015 ◽  
Vol 17 (1) ◽  
pp. 58-70 ◽  
Author(s):  
Vardit Rubovitch ◽  
Shani Barak ◽  
Lital Rachmany ◽  
Renana Baratz Goldstein ◽  
Yael Zilberstein ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Neuroprotective Effect

scholarly journals Regulatory T cells exhibit neuroprotective effect in a mouse model of traumatic brain injury

2016 ◽  
Vol 14 (6) ◽  
pp. 5556-5566 ◽  
Author(s):  
Yunhu Yu ◽  
Fang Cao ◽  
Qishan Ran ◽  
Xiaochuan Sun
Keyword(s):  
Traumatic Brain Injury ◽  
T Cells ◽  
Brain Injury ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Neuroprotective Effect

scholarly journals Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 943 ◽  
Author(s):  
Helene Ismail ◽  
Zaynab Shakkour ◽  
Maha Tabet ◽  
Samar Abdelhady ◽  
Abir Kobaisi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Free Radical Scavenger ◽  
Health Concern ◽  
Radical Scavenger ◽  
History Of ◽  
Ionic Imbalance

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.

Reduction of the Neurological Deficit in Mice with Traumatic Brain Injury by Nitric Oxide Synthase Inhibitors

1996 ◽  
Vol 13 (4) ◽  
pp. 209-214 ◽  
Author(s):  
CHRISTIAN MÉSENGE ◽  
CATHERINE VERRECCHIA ◽  
MONIQUE ALLIX ◽  
ROGER R. BOULU ◽  
MICHEL PLOTKINE
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nitric Oxide Synthase ◽  
Neurological Deficit ◽  
Nitric Oxide Synthase Inhibitors ◽  
Oxide Synthase

scholarly journals Metallothionein-II Inhibits Lipid Peroxidation and Improves Functional Recovery after Transient Brain Ischemia and Reperfusion in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Araceli Diaz-Ruiz ◽  
Patricia Vacio-Adame ◽  
Antonio Monroy-Noyola ◽  
Marisela Méndez-Armenta ◽  
Alma Ortiz-Plata ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Frontal Cortex ◽  
Neurological Deficit ◽  
Neuroprotective Effect ◽  
Treated Group ◽  
Neurological Deficits ◽  
Control Group ◽  
Ischemia And Reperfusion ◽  
Male Wistar Rats ◽  
Neuroprotective Treatment

After transient cerebral ischemia and reperfusion (I/R), damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II) protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 μg per rat i.p.) or vehicle after ischemia. Lipid peroxidation (LP) was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7%) and hippocampus (26.4%), as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P<0.05) reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

scholarly journals Treatment of traumatic brain injury with thymosin β4 in rats

2011 ◽  
Vol 114 (1) ◽  
pp. 102-115 ◽  
Author(s):  
Ye Xiong ◽  
Asim Mahmood ◽  
Yuling Meng ◽  
Yanlu Zhang ◽  
Zheng Gang Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sham Group ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Saline Group ◽  
Lesion Volume ◽  
Male Wistar Rats ◽  
Left Parietal Cortex ◽  
First Time

Object This study was designed to investigate the efficacy of delayed thymosin β4 (Tβ4) treatment of traumatic brain injury (TBI) in rats. Methods Young adult male Wistar rats were divided into the following groups: 1) sham group (6 rats); 2) TBI + saline group (9 rats); 3) and TBI + Tβ4 group (10 rats). Traumatic brain injury was induced by controlled cortical impact over the left parietal cortex. Thymosin β4 (6 mg/kg) or saline was administered intraperitoneally starting at Day 1 and then every 3 days for an additional 4 doses. Neurological function was assessed using a modified neurological severity score (mNSS), foot fault, and Morris water maze tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemistry to assess angiogenesis, neurogenesis, and oligodendrogenesis after Tβ4 treatment. Results Compared with the saline treatment, delayed Tβ4 treatment did not affect lesion volume but significantly reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, increased oligodendrogenesis in the CA3 region, and significantly improved sensorimotor functional recovery and spatial learning. Conclusions These data for the first time demonstrate that delayed administration of Tβ4 significantly improves histological and functional outcomes in rats with TBI, indicating that Tβ4 has considerable therapeutic potential for patients with TBI.

scholarly journals 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 ◽  
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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