Guanosine Protects Against Traumatic Brain Injury-Induced Functional Impairments and Neuronal Loss by Modulating Excitotoxicity, Mitochondrial Dysfunction, and Inflammation

2016 ◽  
Vol 54 (10) ◽  
pp. 7585-7596 ◽  
Author(s):  
Rogério da Rosa Gerbatin ◽  
Gustavo Cassol ◽  
Fernando Dobrachinski ◽  
Ana Paula O. Ferreira ◽  
Caroline B. Quines ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Neuronal Loss ◽  
Functional Impairments

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

NEURONAL LOSS AND CYTOSKELETAL PERTURBATION AFTER TRAUMATIC BRAIN INJURY (TBI) IN THE NFH/LacZ TRANSGENIC MOUSE

1998 ◽  
Vol 57 (5) ◽  
pp. 475
Author(s):  
J. E. Galvin ◽  
V. M. -Y. Lee ◽  
M. Nakamura ◽  
K. E. Saatman ◽  
R. Raghupathi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Transgenic Mouse ◽  
Neuronal Loss

scholarly journals Enhancement of Neurogenesis and Memory by a Neurotrophic Peptide in Mild to Moderate Traumatic Brain Injury

Neurosurgery ◽  
2014 ◽  
Vol 76 (2) ◽  
pp. 201-215 ◽  
Author(s):  
Muhammad Omar Chohan ◽  
Olga Bragina ◽  
Syed Faraz Kazim ◽  
Gloria Statom ◽  
Narjes Baazaoui ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Parietal Cortex ◽  
Saline Solution ◽  
Neuronal Loss ◽  
Synaptic Density ◽  
Moderate Traumatic Brain Injury ◽  
Long Term Treatment ◽  
Newborn Neurons

ABSTRACT BACKGROUND: Traumatic brain injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. OBJECTIVE: To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. METHODS: TBI was induced in adult C57Bl6 mice using controlled cortical impact with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/d of Peptide 6 or saline solution for 30 days. Dentate gyrus neurogenesis, dendritic and synaptic density, and AD biomarkers were quantitatively analyzed, and behavioral tests were performed. RESULTS: Ipsilateral neuronal loss in CA1 and the parietal cortex and increase in Alzheimer-type hyperphosphorylated tau and A-β were seen in TBI mice. Compared with saline solution, Peptide 6 treatment increased the number of newborn neurons, but not uncommitted progenitor cells, in dentate gyrus by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. CONCLUSION: Long-term treatment with Peptide 6 enhances the pool of newborn neurons in the dentate gyrus, prevents neuronal loss in CA1 and parietal cortex, preserves the dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into the therapeutic potential of small molecules based on neurotrophic factors.

Mesenchymal stem cell therapy for the treatment of traumatic brain injury: progress and prospects

2019 ◽  
Vol 30 (8) ◽  
pp. 839-855 ◽  
Author(s):  
Mahasweta Das ◽  
Karthick Mayilsamy ◽  
Shyam S. Mohapatra ◽  
Subhra Mohapatra
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Neuronal Loss ◽  
Tumor Formation ◽  
Functional Improvement ◽  
Preclinical Research ◽  
Mortality And Morbidity ◽  
Mesenchymal Stem Cell Therapy ◽  
Beneficial Effects

Abstract Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and memory deficits, vision and hearing loss, movement disorders, and different psychological problems. The primary insult causes neuronal damage and activates astrocytes and microglia which evokes immune responses causing further damage to the brain. Clinical trials of drugs to recover the neuronal loss are not very successful. Regenerative approaches for TBI using mesenchymal stem cells (MSCs) seem promising. Results of preclinical research have shown that transplantation of MSCs reduced secondary neurodegeneration and neuroinflammation, promoted neurogenesis and angiogenesis, and improved functional outcome in the experimental animals. The functional improvement is not necessarily related to cell engraftment; rather, immunomodulation by molecular factors secreted by MSCs is responsible for the beneficial effects of this therapy. However, MSC therapy has a few drawbacks including tumor formation, which can be avoided by the use of MSC-derived exosomes. This review has focused on the research works published in the field of regenerative therapy using MSCs after TBI and its future direction.

scholarly journals Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Jing-Ya Wang ◽  
Ya-Ni Huang ◽  
Chong-Chi Chiu ◽  
David Tweedie ◽  
Weiming Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Loss ◽  
Behavioral Impairments

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.

scholarly journals Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration

2019 ◽  
Vol 36 (14) ◽  
pp. 2246-2259 ◽  
Author(s):  
Randhall B. Carteri ◽  
Afonso Kopczynski ◽  
Marcelo Salimen Rodolphi ◽  
Nathan Ryzewski Strogulski ◽  
Mônia Sartor ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Testosterone Administration
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