The Role of Free Radicals in Traumatic Brain Injury

2012 ◽  
Vol 15 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Karen M. O’Connell ◽  
Marguerite T. Littleton-Kearney
Keyword(s):  
Traumatic Brain Injury ◽  
Free Radicals ◽  
Free Radical ◽  
Brain Injury ◽  
Current Knowledge ◽  
Cellular Level ◽  
Secondary Brain Injury ◽  
Secondary Injury ◽  
The Military

Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.

Optimising the management of severe Traumatic Brain Injury in the military maritime environment

2014 ◽  
Vol 100 (3) ◽  
pp. 293-300
Author(s):  
IA Edgar ◽  
G Hadjipavlou ◽  
JE Smith
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Healthcare Systems ◽  
Secondary Brain Injury ◽  
Eye Protection ◽  
Alternative Approaches ◽  
The Military ◽  
Primary Injury ◽  
Maritime Environment

AbstractSevere Traumatic Brain Injury (sTBI) is a devastating cause of morbidity and mortality, especially among those aged less than 45 years. Advances in clinical practice continue to focus on preventing primary injury through developing ballistic head and eye protection, and through minimising secondary brain injury (secondary prevention).Managing sTBI is challenging in well-developed, well-resourced healthcare systems. Achieving management aims in the military maritime environment poses even greater challenges.Strategies for the management of sTBI in the maritime environment should be in keeping with current best evidence. Provision of specialist interventions for sTBI in military maritime environments may require alternative approaches matched to the skills of the staff and environmental restrictions.

scholarly journals Antioxidant therapies in traumatic brain injury: a review

2017 ◽  
Vol 31 (3) ◽  
pp. 319-334
Author(s):  
Hector Rolando Romero-Rivera ◽  
Marticela Cabeza-Morales ◽  
Enrique Soto-Zarate ◽  
Guru Dutta Satyarthee ◽  
Huber Padilla-Zambrano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Death ◽  
Good Alternative ◽  
Secondary Injury ◽  
Injury Management ◽  
Definitive Therapy ◽  
Unconventional Therapies

Abstract Oxidative stress constitute one of the commonest mechanism of the secondary injury contributing to neuronal death in traumatic brain injury cases. The oxidative stress induced secondary injury blockade may be considered as to be a good alternative to improve the outcome of traumatic brain injury (TBI) treatment. Due to absence of definitive therapy of traumatic brain injury has forced researcher to utilize unconventional therapies and its roles investigated in the improvement of management and outcome in recent year. Antioxidant therapies are proven effective in many preclinical studies and encouraging results and the role of antioxidant mediaction may act as further advancement in the traumatic brain injury management it may represent aonr of newer moadlaity in neurosurgical aramamentorium, this kind of therapy could be a good alternative or adjuct to the previously established neuroprotection agents in TBI.

scholarly journals Traumatic Brain Injury Patients Mortality and Serum Total Antioxidant Capacity

2020 ◽  
Vol 10 (2) ◽  
pp. 110 ◽  
Author(s):  
Leonardo Lorente ◽  
María M. Martín ◽  
Antonia Pérez-Cejas ◽  
Agustín F. González-Rivero ◽  
Pedro Abreu-González ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Injury Severity ◽  
Early Mortality ◽  
Secondary Brain Injury ◽  
Total Antioxidant ◽  
Time Of Admission

Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. Methods: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Results: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71–0.86; p < 0.001), 0.87 (0.79–0.93; p < 0.001), and 0.76 (0.67–0.84; p = 0.006) respectively. Conclusions: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI.

scholarly journals The synapse in traumatic brain injury

Brain ◽  
2020 ◽  
Author(s):  
Aimun A B Jamjoom ◽  
Jonathan Rhodes ◽  
Peter J D Andrews ◽  
Seth G N Grant
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
New Technology ◽  
Secondary Injury ◽  
Synapse Loss ◽  
Recent Developments ◽  
Mechanical Insult ◽  
And Function ◽  
The Impact

Abstract Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.

The role of NLRP3 in traumatic brain injury and its regulation by pioglitazone

2020 ◽  
Vol 133 (4) ◽  
pp. 1083-1091
Author(s):  
Ho Jun Yi ◽  
Jung Eun Lee ◽  
Dong Hoon Lee ◽  
Young Il Kim ◽  
Chul Bum Cho ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Brain Edema ◽  
Cerebral Edema ◽  
Sham Group ◽  
Secondary Brain Injury ◽  
Treatment Groups ◽  
Perilesional Edema

OBJECTIVEPerilesional edema is a predominant mechanism underlying secondary brain injury after traumatic brain injury (TBI). Perilesional edema is characterized by inflammation, production of proinflammatory cytokines, and migration of peripheral immune cells into the brain. The nucleotide-binding domain and leucine-rich repeat (NLR) family pyrin domain–containing 3 protein (NLRP3) is a key component of secondary injury. Pioglitazone regulates NLRP3 and other inflammatory cytokines. In the present study, the role of NLRP3 and the pharmacological effects of pioglitazone were investigated in animal TBI models.METHODSBrain contusion was induced in a weight drop model involving 3 groups of mice: C57 BL/6 (sham group), NLRP3 knockout (K/O group), and pioglitazone-treated mice (treatment group). The percentage of brain water content of the 3 groups of mice was compared over a period of time. Western blot, immunohistochemistry, and immunofluorescence analyses were conducted to investigate NLRP3-related inflammasomes and the effects of pioglitazone in the TBI models.RESULTSBrain edema was the highest on day 3 after TBI in the sham group. Brain edema in both the K/O and the treatment groups was lower than in the sham group. In Western blot, the expression of inflammasomes was higher after TBI in the sham group, but the expression of interleukin-1β, caspase-1, and NLRP3 was decreased significantly following treatment with pioglitazone. The expression of GFAP (glial fibrillary acidic protein) and Iba1 was decreased in both the K/O and treatment groups. In addition, confocal microscopy revealed a decrease in microglial cell and astrocyte activation following pioglitazone therapy.CONCLUSIONSThe inflammasome NLRP3 plays a pivotal role in regulating cerebral edema and secondary inflammation. Interestingly, pioglitazone reduced cerebral edema and immune response after TBI by downregulating the effects of NLRP3. These results suggest that the clinical application of pioglitazone may be a neuroprotective strategy in TBI.

scholarly journals Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Mehar Naseem ◽  
Suhel Parvez
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Brain Injury ◽  
Protective Role ◽  
Secondary Injury ◽  
Severe Injuries ◽  
Cord Injury ◽  
Injured Part

Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it.

Endogenous opioids may mediate secondary damage after experimental brain injury

1987 ◽  
Vol 253 (5) ◽  
pp. E565-E574 ◽  
Author(s):  
T. K. McIntosh ◽  
R. L. Hayes ◽  
D. S. DeWitt ◽  
V. Agura ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Traumatic Injury ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Endogenous Opioids ◽  
Secondary Brain Injury ◽  
Secondary Damage ◽  
Cord Injury

Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.

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