Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI.

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Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats

Journal of Neurotrauma ◽

10.1089/neu.2013.2862 ◽

2013 ◽

Vol 30 (11) ◽

pp. 920-937 ◽

Cited By ~ 68

Author(s):

Patrick M. Kochanek ◽

C. Edward Dixon ◽

David K. Shellington ◽

Samuel S. Shin ◽

Hülya Bayır ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Molecular Mechanisms ◽

Secondary Injury ◽

Injury And Repair ◽

The Brain

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

Medico-Biological and Socio-Psychological Problems of Safety in Emergency Situations ◽

10.25016/2541-7487-2020-0-2-32-43 ◽

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.

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Neuroprotective agents in critical illness

10.1093/med/9780199600830.003.0048 ◽

2016 ◽

Author(s):

Jerrold L. Perrott ◽

Steven C. Reynolds

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Future Research ◽

Secondary Injury ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Neuroprotective Agents ◽

Important Goal ◽

Risk Of Mortality ◽

Increased Risk ◽

Neuroprotective Strategies

The prevention and reduction of secondary injury following primary CNS insult is an important goal in critically-ill patients. Numerous pharmacological therapies have been studied as potential neuroprotective agents with few translating from research to clinical benefit. These are nimodipine and statins in aneurysmal subarachnoid haemorrhage and phenytoin in traumatic brain injury. Additionally, in traumatic brain injury, clinical studies have identified that corticosteroids and albumin colloid resuscitation are associated with increased risk of mortality, and as such should be avoided. Future research into new pharmacological neuroprotective strategies is warranted.

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Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood–Brain Barrier Breakdown

Cells ◽

10.3390/cells10051009 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1009

Author(s):

Delong Qin ◽

Junmin Wang ◽

Anh Le ◽

Tom J. Wang ◽

Xuemei Chen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Blood Brain Barrier ◽

Glial Cells ◽

Cascade Reactions ◽

Brain Barrier ◽

Ultrastructural Changes ◽

Future Research ◽

Secondary Injury ◽

Blood Brain

The secondary injury process after traumatic brain injury (TBI) results in motor dysfunction, cognitive and emotional impairment, and poor outcomes. These injury cascades include excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance, inflammation, and increased vascular permeability. Electron microscopy is an irreplaceable tool to understand the complex pathogenesis of TBI as the secondary injury is usually accompanied by a series of pathologic changes at the ultra-micro level of the brain cells. These changes include the ultrastructural changes in different parts of the neurons (cell body, axon, and synapses), glial cells, and blood–brain barrier, etc. In view of the current difficulties in the treatment of TBI, identifying the changes in subcellular structures can help us better understand the complex pathologic cascade reactions after TBI and improve clinical diagnosis and treatment. The purpose of this review is to summarize and discuss the ultrastructural changes related to neurons (e.g., condensed mitochondrial membrane in ferroptosis), glial cells, and blood–brain barrier in the existing reports of TBI, to deepen the in-depth study of TBI pathomechanism, hoping to provide a future research direction of pathogenesis and treatment, with the ultimate aim of improving the prognosis of patients with TBI.

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Modern Phineas Gage: A Man with a Knife in the Brain

International Journal of Human and Health Sciences (IJHHS) ◽

10.31344/ijhhs.v5i0-2.345 ◽

2021 ◽

Vol 5 (0-2) ◽

pp. 27

Author(s):

Chon Sum Ong ◽

Nur Amalina Binti Che Din ◽

Celine Mien Er Fong ◽

Amira Nabiha Binti Jamalludin

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

External Ventricular Drain ◽

Sella Turcica ◽

Tertiary Hospital ◽

Future Research ◽

Brain Penetration ◽

Gcs Score ◽

The Brain ◽

Multiple Antibiotics

An accident with a tamping iron made Phineas Gage a historically famous brain-injury survivor. (1) Each year, approximately 1.6 million people sustain traumatic brain injury, leading to 52,000 deaths annually. (2) However, there is limited literature regarding traumatic brain penetration injury that could be found. A 42-year-old male with psychosis forcefully inserted a butter knife through nostril, traversed via sella turcica into posterior corpus callosum in a mental health facility. He was intubated in his local hospital and transferred over to a tertiary hospital for neurosurgical intervention. Radiological imaging showed impingement of knife against the posterior cerebral artery (PCA), multiple brain infarcts, intraventricular, and subarachnoid haemorrhage. The knife was removed after securing the PCA with the collaboration between neurosurgery and interventional radiology team. Sinus repair was immediately performed by the otorhinolaryngologists. External ventricular drain was inserted due to hydrocephalus secondary to brain haemorrhage. He eventually developed ventriculitis leading to sepsis and was treated with multiple antibiotics. The traumatic brain injury led to anterior hypopituitarism and diabetes insipidus which was treated using hormone therapy. He not only survived the fatal brain injury but also regained his Glasgow Coma Scale (GCS) score. This case demonstrates the potential of a multi-disciplinary and specialty approach to achieve outcomes a single specialty team could not. The outcome of a case which was deemed to be a non-survivable brain injury was made different due to the bold decision making, experience and innovative surgical strategy. Future research is needed to better understand and manage brain penetration injury.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S27

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

Brain Sciences ◽

10.3390/brainsci8060113 ◽

2018 ◽

Vol 8 (6) ◽

pp. 113 ◽

Cited By ~ 29

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.

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Head trauma: treatment and diagnostic aids

Companion Animal ◽

10.12968/coan.2020.0033 ◽

2020 ◽

Vol 25 (11) ◽

pp. 283-288

Author(s):

Mark Lowrie

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Best Practice ◽

Treatment Options ◽

Brain Parenchyma ◽

Primary Lesion ◽

Trauma Treatment ◽

Secondary Injury ◽

Irreversible Damage ◽

The Brain

Traumatic brain injury occurs frequently in dogs and cats. The primary lesion occurs at the time of injury and causes direct, irreversible damage to the brain parenchyma and vasculature. Secondary lesions occur in the minutes following the trauma as a result of a combination of physical and biochemical changes that lead to intracranial hypertension. It is this secondary injury that veterinarians are able to reduce. This article outlines the treatment options for patients with traumatic brain injury. There remains controversy over what constitutes best practice. This article addresses the main points regarding the clinical therapeutic options currently available.

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Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_persp-19-00092 ◽

2020 ◽

Vol 5 (1) ◽

pp. 88-96

Author(s):

Mary R. T. Kennedy

Keyword(s):

College Students ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Sense Of Self ◽

Scientific Evidence ◽

Sudden Onset ◽

Lessons Learned ◽

Speech Language Pathologists ◽

The Brain ◽

Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

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