Featured
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Review Article |
From spreading depolarization to blood–brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy
Overall survival rates for traumatic brain injury have improved, but affected individuals often experience persistent and debilitating long-term complications. In this Review, the authors discuss recent evidence for the role of spreading depolarization in the initiation of long-term pathology in traumatic brain injury, including effects on blood–brain barrier dysfunction and neuroinflammation.
- Gerben van Hameren
- , Refat Aboghazleh
- & Alon Friedman
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Review Article |
Insights into epileptogenesis from post-traumatic epilepsy
Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications.
- Matthew Pease
- , Kunal Gupta
- & James F. Castellano
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Perspective |
Forensic neurology: a distinct subspecialty at the intersection of neurology, neuroscience and law
In this Perspective, the authors discuss the need for neurologists to assist in court cases involving criminal behaviour that was potentially influenced by a neurological disorder. The authors review evidence linking neurological disorders with criminal activity, and advocate for the development of forensic neurology as a subspecialty of the field.
- R. Ryan Darby
- , Ciaran Considine
- & William C. Darby
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Review Article |
Inflammasomes in neurological disorders — mechanisms and therapeutic potential
Increasing evidence suggests that inflammasome activation contributes to disease progression in a wide variety of neurological conditions. In this Review, Ravichandran and Heneka discuss current understanding of inflammasome activation in neurological disorders and consider interventional strategies that target inflammasome activation.
- Kishore Aravind Ravichandran
- & Michael T. Heneka
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News & Views |
Clinical outcomes evolve years after traumatic brain injury
The TRACK-TBI LONG study has shown that outcomes are highly variable in the 7 years after traumatic brain injury (TBI). Although many patients remain stable, almost one-third experience declines in cognitive, psychiatric and functional state. These findings suggest that TBI is a chronic disease and that its management should change accordingly.
- David J. Sharp
- & Neil S. N. Graham
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Review Article |
Psychiatric sequelae of traumatic brain injury — future directions in research
Understanding of the psychiatric and behavioural consequences of traumatic brain injury (TBI) remains limited. In this Review, Li and colleagues highlight ways to progress research in this field and discuss neuropsychiatric sequelae of TBI that affect long-term health outcomes and functional recovery.
- Lucia M. Li
- , Alan Carson
- & Kristen Dams-O’Connor
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Review Article |
Cell-based therapies for neurological disorders — the bioreactor hypothesis
In this Review, Savitz and Cox consider the evidence for a model of cell-based therapy referred to as the bioreactor hypothesis, in which exogenous cells migrate to peripheral organs and reprogramme host immune cells to generate an anti-inflammatory, regenerative environment.
- Sean I. Savitz
- & Charles S. Cox Jr
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Research Highlight |
Sodium channelopathy could underlie concussion symptoms
A new study indicates that concussion leads to sodium channel loss at the nodes of Ranvier, which could contribute to neurological dysfunction.
- Sarah Lemprière
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Comment |
Heading in the right direction
Responding to increasing concerns around adverse brain health outcomes among former football (soccer) players, the Football Association of England recently announced a trial ban on heading in matches for players aged under 12 years. This is a step in the right direction, but wider interventions to preserve brain health should not be forgotten.
- William Stewart
- & Alan Carson
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Perspective |
Neuroprognostication: a conceptual framework
In this Perspectives article, David Fischer and colleagues present a stepwise conceptual framework for neuroprognostication after severe brain injury, with the aim of providing structure and guidance to supplement clinical judgement and direct future investigation.
- David Fischer
- , Brian L. Edlow
- & David M. Greer
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Review Article |
Blood GFAP as an emerging biomarker in brain and spinal cord disorders
In this Review, the authors provide an overview of the evidence regarding the use of blood levels of glial fibrillary acidic protein as a biomarker in a range of neurological diseases, including traumatic brain injury, stroke, multiple sclerosis and Alzheimer disease.
- Ahmed Abdelhak
- , Matteo Foschi
- & Hayrettin Tumani
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News & Views |
Defining traumatic encephalopathy syndrome — advances and challenges
Chronic traumatic encephalopathy (CTE) is presumed to be associated with a clinical condition termed traumatic encephalopathy syndrome (TES). A new set of research diagnostic criteria for TES might be an improvement over previous guidelines, but many questions surrounding the putative link between head impacts, CTE neuropathology and neurobehavioural symptoms remain unanswered.
- C. Munro Cullum
- & Christian LoBue
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Review Article |
White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies
Intraventricular haemorrhage (IVH) is a complication of preterm birth associated with neurodevelopmental sequelae. Here, Ballabh and de Vries review the mechanisms underlying IVH-induced white matter injury, focusing on its effects on oligodendrocyte progenitor cells, and discuss promising novel treatments for IVH-induced white matter injury.
- Praveen Ballabh
- & Linda S. de Vries
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Review Article |
Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies
In this Review, the authors discuss recent progress in the detection and prediction of recovery of consciousness in patients with disorders of consciousness caused by severe brain injuries. They describe the ongoing development of pharmacological and electrophysiological therapies designed to enhance recovery.
- Brian L. Edlow
- , Jan Claassen
- & David M. Greer
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News & Views |
Making headway — a role for CGRP in post-traumatic headache
Although common, post-traumatic headache remains poorly understood and poorly treated. New data have implicated calcitonin gene-related peptide and the trigeminovascular system in this disorder, opening up new avenues for research into its pathophysiology and treatment.
- Dimos D. Mitsikostas
- & Michael A. Moskowitz
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Research Highlight |
Meningeal lymphatic flow slows after mild traumatic brain injury
- Sarah Lemprière
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News & Views |
Towards improving care for disorders of consciousness
Disorders of consciousness (DOCs), including vegetative and minimally conscious states, represent a financial, medical and ethical conundrum. Recently published guidelines for the diagnosis, prognosis and treatment of DOCs should lead us to reconsider our management strategies for these challenging disorders.
- Caroline Schnakers
- & Martin M. Monti
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News & Views |
Genetic interplay with soccer ball heading
Mortality from neurodegenerative disease is high among professional soccer players, potentially associated with repeated head impacts during routine gameplay. New data suggest that the apolipoprotein E ε4 allele might exacerbate the effects of soccer ball heading on cognition. However, genotyping of athletes to determine their dementia risk remains a distant prospect.
- Douglas H. Smith
- & William Stewart
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In Brief |
Interneuron transplants elicit hippocampal repair after traumatic brain injury in mice
- Heather Wood
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Review Article |
Post-traumatic headache: epidemiology and pathophysiological insights
Post-traumatic headache (PTH) is a common disabling consequence of mild traumatic brain injury. In this Review, Ashina et al. discuss possible pathogenic mechanisms of PTH, the research needed to improve our understanding, and drugs for prevention and treatment of persistent PTH.
- Håkan Ashina
- , Frank Porreca
- & David W. Dodick
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Review Article |
Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury
In this Review, the authors discuss the evidence that exosomes could be used as a neurorestorative therapy after stroke or traumatic brain injury and how engineering of their microRNA cargo could optimize this approach.
- Zheng Gang Zhang
- , Benjamin Buller
- & Michael Chopp
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News & Views |
Concussion and risk of suicide: who, when and under what circumstances?
A new analysis has found that concussion and mild traumatic brain injury (mTBI) are linked to an increased risk of suicidal behaviours and thoughts. However, a host of risk factors might influence this correlation, and careful investigation is required to establish which individuals with mTBI might be most at risk of suicide.
- Lisa A. Brenner
- & Nazanin H. Bahraini
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Perspective |
Chronic traumatic encephalopathy — confusion and controversies
In this Perspectives article, Smith et al. address the misconceptions about the clinical and pathological features of chronic traumatic encephalopathy that cause confusion and controversy not only in the public but also among health-care professionals.
- Douglas H. Smith
- , Victoria E. Johnson
- & William Stewart
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Review Article |
Genetic drivers of cerebral blood flow dysfunction in TBI: a speculative synthesis
Impairment of cerebral autoregulation after traumatic brain injury (TBI) is associated with poor outcomes, but the reasons underlying this association are poorly understood. This Review highlights genetic polymorphisms that might be linked to cerebrovascular function after TBI that might promote improved understanding of the pathogenic mechanisms underlying impaired vascular reactivity and offer potential targets for new therapies.
- Frederick A. Zeiler
- , Eric P. Thelin
- & David K. Menon
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Review Article |
Traumatic brain injury: sex, gender and intersecting vulnerabilities
Traumatic brain injury (TBI) susceptibility and outcomes are influenced by numerous factors, many relating to sex and gender. The authors review recent research exploring the influence of sex and gender in the TBI context, focusing particularly on marginalized populations.
- Tatyana Mollayeva
- , Shirin Mollayeva
- & Angela Colantonio
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News & Views |
Risk of dementia after TBI — a cause of growing concern
Moderate and severe traumatic brain injuries (TBIs) have long been recognized as risk factors for dementia, but the relationship between mild TBI (mTBI) and dementia is unclear. New research demonstrates that even an mTBI without loss of consciousness is associated with a twofold increase in the risk of dementia.
- Cassandra L. Pattinson
- & Jessica M. Gill
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In Brief |
Minocycline reduces microglial activation but increases neurodegeneration after TBI
- Heather Wood
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Review Article |
PET imaging of the neurovascular interface in cerebrovascular disease
PET is a versatile imaging technique that is advancing our understanding of cerebrovascular disease and intracerebral pathophysiology. In this Review, Evans and colleagues describe mechanistic insights from PET studies relating to the metabolic pathophysiology of carotid atherosclerosis, salvageable penumbra after stroke, and neuroinflammatory changes associated with small vessel disease and vascular cognitive impairment.
- Nicholas R. Evans
- , Jason M. Tarkin
- & Elizabeth A. Warburton
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Review Article |
The far-reaching scope of neuroinflammation after traumatic brain injury
Neuroinflammation can cause acute secondary injury after traumatic brain injury (TBI), and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, the authors propose a new framework for targeted immunomodulation after TBI.
- Dennis W. Simon
- , Mandy J. McGeachy
- & Patrick M. Kochanek
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Research Highlight |
Remote white matter integrity influences cognitive function after stroke
- Heather Wood
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Review Article |
Fluid biomarkers for mild traumatic brain injury and related conditions
Owing to a lack of objective diagnostic tools, the diagnosis of mild traumatic brain injury (TBI) and related conditions, such as postconcussive syndrome and chronic traumatic encephalopathy must be made on clinical grounds. Here, Zetterberg and Blennow review the most recent developments in search for biomarkers for mild TBI and related conditions.
- Henrik Zetterberg
- & Kaj Blennow
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Review Article |
The Glasgow Outcome Scale — 40 years of application and refinement
The Glasgow Outcome Scale (GOS) is widely recommended as an outcome measure after traumatic brain injury. Following the 40thanniversary of its original publication, McMillan and colleagues review the development of the GOS and its extension and refinement over the past four decades, and consider how it can contribute to further understanding of brain injury.
- Tom McMillan
- , Lindsay Wilson
- & Michael Bond
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Opinion |
Sports-related concussions — media, science and policy
Participants in collision sports show a high incidence of concussion and can have deleterious long-term consequences for brain function. Here, Rebekah Mannix and colleagues discuss the benefits and risks associated with the practice of contact sports and examine how this balance affects policies regarding the practice of collision sports.
- Rebekah Mannix
- , William P. Meehan III
- & Alvaro Pascual-Leone
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Review Article |
Vascular endothelial growth factor: a neurovascular target in neurological diseases
The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, and was subsequently co-opted to regulate vascular function. Here, the authors review the roles of the VEGF family as both aetiological factors and therapeutic targets in neurological disease.
- Christian Lange
- , Erik Storkebaum
- & Peter Carmeliet
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