scholarly journals A Review of Traumatic Brain Injury and the Gut Microbiome: Insights into Novel Mechanisms of Secondary Brain Injury and Promising Targets for Neuroprotection

2018 ◽  
Vol 8 (6) ◽  
pp. 113 ◽  
Author(s):  
Caroline Zhu ◽  
Ramesh Grandhi ◽  
Thomas Patterson ◽  
Susannah Nicholson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gut Microbiome ◽  
The Body ◽  
Secondary Brain Injury ◽  
Major Focus ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

The gut microbiome and its role in health and disease have recently been major focus areas of research. In this review, we summarize the different ways in which the gut microbiome interacts with the rest of the body, with focus areas on its relationships with immunity, the brain, and injury. The gut–brain axis, a communication network linking together the central and enteric nervous systems, represents a key bidirectional pathway with feed-forward and feedback mechanisms. The gut microbiota has a central role in this pathway and is significantly altered following injury, leading to a pro-inflammatory state within the central nervous system (CNS). Herein, we examine traumatic brain injury (TBI) in relation to this axis and explore potential interventions, which may serve as targets for improving clinical outcomes and preventing secondary brain injury.

Use of hemoglobin-based oxygen-carrying solution–201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage

2008 ◽  
Vol 108 (3) ◽  
pp. 575-587 ◽  
Author(s):  
Guy Rosenthal ◽  
Diane Morabito ◽  
Mitchell Cohen ◽  
Annina Roeytenberg ◽  
Nikita Derugin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mr Imaging ◽  
Swine Model ◽  
Secondary Brain Injury ◽  
Large Animal ◽  
Fluoro Jade B ◽  
Significant Difference ◽  
Impact Injury ◽  
The Brain

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

scholarly journals Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats

2019 ◽  
Author(s):  
Solomon M. Adams ◽  
Fanuel T. Hagos ◽  
Jeffrey P. Cheng ◽  
Robert S. B. Clark ◽  
Patrick M. Kochanek ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mrna Expression ◽  
Neurovascular Unit ◽  
Post Injury ◽  
Adult Rats ◽  
Order Of Magnitude ◽  
Liver And Kidney ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTTraumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.Significance StatementBaseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.

scholarly journals Clinical and epidemiological analysis of severe traumatic brain injury: the role of nutritional support to the injured with a prolonged state of impaired consciousness

2020 ◽  
pp. 32-43
Author(s):  
M. V. Nikiforov ◽  
A. A. Korolev
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nutritional Support ◽  
The Body ◽  
Medical Rehabilitation ◽  
Impaired Consciousness ◽  
Epidemiological Analysis ◽  
The Brain

Relevance. Patients with prolonged impaired consciousness due to traumatic brain injury are the most difficult category of patients in inpatient medical rehabilitation units. Despite the experience gained in managing this complex category of patients, the problem of nutrition status and trophological insufficiency, as well as practical issues regarding the organization of optimal nutrition at this stage of medical rehabilitation remain unresolved.Intention. To study the role of nutritional support for patients with long-term impaired consciousness on the basis of a clinical and epidemiological analysis of severe traumatic brain injury.Methodology. The data of an epidemiological analysis of traumatic brain injuries and features of ongoing nutritional support in patients with long-term impaired consciousness are presented, based on a study of domestic and foreign publications from 2005 to 2019.Results and Discussion. Timely and adequate nutritional support optimizes the structural-functional and metabolic systems of the body, adaptive reserves interfere with rapidly progressive depletion and chronic catabolic processes, contribute to positive changes in the functional state of the brain, reduce infectious complications, and increase the effectiveness of rehabilitation measures and the rate of recovery of consciousness.Conclusion. The analysis revealed the ambiguity of the interpreted data on clinical recommendations and approaches to the use of nutritional support in patients with long-term impaired consciousness due to traumatic brain injury. Considering the fact that in most cases such patients need continuous long-term comprehensive rehabilitation measures, accompanied by significant energy costs of the body, an essential component of the rehabilitation process, in our opinion, is the inclusion of adequate nutritional support that prevents fast-progressing exhaustion and chronic catabolic processes. In this regard, such an urgent task is to optimize the algorithms of nutritional support in patients with long-term impaired consciousness after a traumatic brain injury, the solution of which will improve the functional state of the brain and, therefore, the rehabilitation prognosis and quality of their life.

scholarly journals Analysis of Neuron Specific Enolase Serum Levels in Traumatic Brain Injury

2021 ◽  
Vol 5 (4) ◽  
pp. 1218-1222
Author(s):  
Yuliarni Syafrita ◽  
Nora Fitri
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Injuries ◽  
Neuron Specific Enolase ◽  
Serum Levels ◽  
Pathological Process ◽  
P Value ◽  
Secondary Brain Injury ◽  
Post Injury ◽  
The Brain

Background : Traumatic brain injury is still the main cause of death and disability in productive age. Assessment the level of consciousness and imaging examinations after a brain injury can not always describe the severity of damage in the brain, this is because the pathological process is still ongoing due to secondary brain injury. Therefore, it is necessary to examine biomarkers that can describe the severity of the pathological process that occurs. The purpose of this study was to assess serum neuron-specific enolase (NSE) levels and their relationship to the severity and outcome of a traumatic brain injury. Methods : A cross sectional design was conducted in the emergency department of DR M Djamil Hospital, Padang. There were 72 patients who met the inclusion criteria. A Glasgow Coma Scale examination was performed to assess the severity of brain injury and examination of NSE serum levels at 48 hours post- injury using ELISA technique and assess the Glasgow outcome scale (GOS) at 6 weeks post-injury. Data analysis using SPSS 22 program, the results are significance if the p value <0.05  Results : The average NSE level was higher in severe brain injuries than moderate and mild brain injuries and this difference was statistically significant (p<0.05).  The NSE serum levels were higher in poor outcomes than in good outcomes and this difference was statistically significant (p<0.05).  Conclusion : High NSE serum levels in the acute phase were associated with the severity of the brain injury and poor outcome 6 weeks after the brain injury. 

scholarly journals Pathophysiology of severe traumatic brain injury and management of intracranial hypertension

2019 ◽  
Vol 18 (2) ◽  
pp. 62-71
Author(s):  
Raimondas Juškys ◽  
Vaiva Hendrixson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Hypertension ◽  
Severe Traumatic Brain Injury ◽  
Current Treatment ◽  
Secondary Brain Injury ◽  
Management Options ◽  
Treatment Protocols ◽  
Improved Outcomes ◽  
The Brain

It is well recognized that severe traumatic brain injury causes major health and socioeconomic burdens for patients their families and society itself. Over the past decade, understanding of secondary brain injury processes has increased tremendously, permitting implementation of new neurocritical methods of care that substantially contribute to improved outcomes of such patients. The main objective of current treatment protocols is to optimize different physiological measurements that prevent secondary insults and reinforce the ability of the brain to heal. The aim of this literature review is to uncover the pathophysiological mechanisms of severe traumatic brain injury and their interrelationship, including cerebral metabolic crisis, disturbances of blood flow to the brain and development of edema, putting emphasis on intracranial hypertension and its current management options.

scholarly journals Gut Microbiome Influences The Neuroinflammatory Response To Traumatic Brain Injury

2021 ◽  
Author(s):  
Akshita Jade Kumar ◽  
Supinder Singh Bedi ◽  
Naama Toledano-Furman ◽  
Louis Carrillo ◽  
Fanni Cardenas ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Gut Microbiome ◽  
Central Component ◽  
Post Injury ◽  
Probiotic Treatment ◽  
Anti Inflammatory ◽  
Microglial Response ◽  
The Brain

Abstract Background: Traumatic brain injury (TBI) is a systemic injury that disrupts a complex arrangement of interacting cells in the brain and in the gastrointestinal tract (GI). Disruption in the brain results in neuroinflammation, in which microglia are a central component along with cytokines and other soluble factors [pro and anti-inflammatory microglia (M1:M2)]. Disruption in the GI due to TBI results in a systemic inflammation which is dependent upon the gut microbiome (GM). Gut microbiome can influence microglia in the brain via the gut-brain axis. In order to determine if the microbiome-microglia connections via the gut-brain axis can be modulated, we used probiotics and antibiotics in a rodent TBI model to evaluate the microbiome-microglial connections in acute and chronic experiments.Methods: The temporal effects of treatment (probiotics or antibiotics) were used to evaluate the gut-associated lymphoid tissue (GALT) influence on the microglial response at 72 hours or 21 days after a cortical contusion injury (CCI), a rodent model of TBI. Injured animals received daily probiotics, antibiotics, or no treatment. Sham-injured animals (controls) did not receive any treatment.Results: Twenty-one days of probiotic treatment attenuated the pro-inflammatory response of microglia (M1:M2) after CCI. The post-injury inflammatory response was heightened in the GALT with antibiotic-induced dysbiosis which resulted in amplification of the pro-inflammatory microglial response. Conclusions: Probiotic treatment after TBI is a potential therapeutic in attenuating microglial activation through anti-inflammatory signaling.

scholarly journals The brain-gut axis - where are we now and how can we modulate these connections?

2020 ◽  
Vol 18 ◽  
Author(s):  
Wojciech Dabrowski ◽  
Dorota Siwicka-Gieroba ◽  
Katarzyna Kotfis ◽  
Sami Zaid ◽  
Sylwia Terpilowska ◽  
...  
Keyword(s):  
Nervous System ◽  
Brain Injury ◽  
Gut Microbiome ◽  
Microglial Activation ◽  
Molecular Processes ◽  
Protein Extravasation ◽  
The Central Nervous System ◽  
Intensive Investigation ◽  
Cytoskeletal Rearrangements ◽  
The Brain

: A traumatic brain injury (TBI) initiates an inflammatory response with molecular cascades triggered by the presence of necrotic debris including damaged myelin, hemorrhages and injured neuronal cells. Molecular cascades prominent in TBI-induced inflammation include the release of an excess of proinflammatory cytokines and angiogenic factors, the degradation of tight junctions (TJs), cytoskeletal rearrangements and leukocyte and protein extravasation promoted by increased expression of adhesion molecules. The brain-gut axis consists of a complex network involving neuroendocrine and immunological signaling pathways and bi-directional neural mechanisms. Importantly, modifying the gut microbiome alters this axis, and in turn may influence brain injury and neuroinflammatory processes. In recent years it has been demonstrated that the activity and composition of the gastrointestinal (GI) microbiome population influences the brain through all of above mentioned pathways affecting homeostasis of the central nervous system (CNS). The GI microbiome is involved in the modulation of cellular and molecular processes which are fundamental to the progression of TBI-induced pathologies including neuroinflammation, abnormal blood brain barrier (BBB) permeability, immune system responses, microglial activation, and mitochondrial dysfunction. It has been postulated that interaction between the brain and gut microbiome occurs mainly via the enteric nervous system and the vagus nerve through neuroactive compounds including serotonin or dopamine and activation by bacterial metabolites including endotoxin, neurotransmitters, neurotrophic factors, and cytokines. In recent years the multifactorial impact of selected immunomodulatory drugs on immune processes occurring in the CNS and involving the brain-gut axis has been under intensive investigation.

scholarly journals Effect of Soluble Complement Receptor-1 on Neutrophil Accumulation after Traumatic Brain Injury in Rats

1995 ◽  
Vol 15 (5) ◽  
pp. 860-864 ◽  
Author(s):  
Susan L. Kaczorowski ◽  
Joanne K. Schiding ◽  
Carol A. Toth ◽  
Patrick M. Kochanek
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Acute Inflammatory Response ◽  
Complement Receptor ◽  
Neutrophil Accumulation ◽  
The Central Nervous System ◽  
The Brain

As part of the acute inflammatory response, neutrophils accumulate in the central nervous system after injury. Recently, a soluble human recombinant complement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alternative pathways of complement. sCR1 attenuates the effects of the acute inflammatory response in several models of injury outside the central nervous system. The role of complement in traumatic brain injury, however, remains undefined. We hypothesized that treatment with sCR1 would attenuate neutrophil accumulation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague–Dawley rats were pretreated with sCR1 or saline (control) at both 2 h and 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCR1 (or saline) was given 6 h after trauma. Coronal brain sections centered on the site of trauma were obtained at 24 h after trauma and analyzed for myeloperoxidase (MPO) activity as a marker of neutrophil accumulation. Complete blood counts with differential were obtained before treatment with sCR1 and at 24 h after trauma. At 24 h after trauma, brain MPO activity was reduced by 41% in sCR1-treated rats compared with control rats [0.1599 ± 0.102 versus 0.27(2 ± 0.178 U/g (mean ± SD); p = 0.02]. The neutrophil count in peripheral blood increased approximately twofold in both groups. Neutrophil accumulation occurring in the brain after trauma is inhibited by sCR1 treatment. This suggests that complement activation is involved in the local inflammatory response to traumatic brain injury and plays an important role in neutrophil accumulation in the injured brain.

Role of zinc and copper ions in the pathogenetic mechanisms of traumatic brain injury and Alzheimer’s disease

2020 ◽  
Vol 31 (3) ◽  
pp. 233-243 ◽  
Author(s):  
Nickolay K. Isaev ◽  
Elena V. Stelmashook ◽  
Elisaveta E. Genrikhs
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Copper Ions ◽  
Research Data ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Β Amyloid ◽  
The Brain ◽  
Lateral Sclerosis

AbstractThe disruption of homeostasis of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of many neurodegenerative diseases, such as amyotrophic lateral sclerosis, Wilson’s, Creutzfeldt-Jakob, Parkinson’s, and Alzheimer’s diseases (AD), and traumatic brain injury (TBI). The last two pathological conditions of the brain are the most common; moreover, it is possible that TBI is a risk factor for the development of AD. Disruptions of Zn2+ and Cu2+ homeostasis play an important role in the mechanisms of pathogenesis of both TBI and AD. This review attempts to summarize and systematize the currently available research data on this issue. The neurocytotoxicity of Cu2+ and Zn2+, the synergism of the toxic effect of calcium and Zn2+ ions on the mitochondria of neurons, and the interaction of Zn2+ and Cu2+ with β-amyloid (Abeta) and tau protein are considered.

scholarly journals Developmental Dysfunction of the Central Nervous System Lymphatics Modulates the Adaptive Neuro-Immune Response in the Perilesional Cortex in a Mouse Model of Traumatic Brain Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Sara Wojciechowski ◽  
Anaïs Virenque ◽  
Maria Vihma ◽  
Barbara Galbardi ◽  
Erin Jane Rooney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Immune Response ◽  
T Cells ◽  
Nervous System ◽  
Brain Injury ◽  
T Cell ◽  
Lesion Volume ◽  
The Central Nervous System ◽  
The Brain

RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury.ConclusionsOur results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury.

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