Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets

Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult i...

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Published in:Frontiers in cellular neuroscience Vol. 13; p. 528
Main Authors: Ng, Si Yun, Lee, Alan Yiu Wah
Format: Journal Article
Language:English
Published: Switzerland Frontiers Research Foundation 27.11.2019
Frontiers Media S.A
Subjects:
Apoptosis
Autophagy
Bioavailability
Biomedical materials
biopolymers
Brain damage
Cell death
cell penetrating proteins
Cellular Neuroscience
Clinical trials
CNS trauma
controlled drug release
Contusions
Drug delivery
Edema
Excitotoxicity
Head injuries
Ischemia
Life sciences
Military personnel
Mitochondria
Molecular modelling
Morbidity
Neurodegeneration
neuronal regeneration
Neuronal-glial interactions
Oxidative stress
Parenchyma
secondary injuries
Therapeutic applications
Traumatic brain injury
Malaysia
Singapore
secondary injuries
cell penetrating proteins
biopolymers
controlled drug release
neuronal regeneration
CNS trauma
ISSN:1662-5102, 1662-5102
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Abstract Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
AbstractList Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and militants military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
Author Lee, Alan Yiu Wah
Ng, Si Yun
AuthorAffiliation 1 Neurobiology/Ageing Program, Centre for Life Sciences, Department of Physiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore , Singapore , Singapore
2 School of Pharmacy, Monash University Malaysia , Bandar Sunway , Malaysia
AuthorAffiliation_xml – name: 2 School of Pharmacy, Monash University Malaysia , Bandar Sunway , Malaysia
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Author_xml – sequence: 1
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  organization: Neurobiology/Ageing Program, Centre for Life Sciences, Department of Physiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore, Singapore
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Keywords secondary injuries
cell penetrating proteins
biopolymers
controlled drug release
neuronal regeneration
CNS trauma
Language English
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Snippet Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances...
Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and militants military personnel globally. Despite...
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StartPage 528
SubjectTerms Apoptosis
Autophagy
Bioavailability
Biomedical materials
biopolymers
Brain damage
Cell death
cell penetrating proteins
Cellular Neuroscience
Clinical trials
CNS trauma
controlled drug release
Contusions
Drug delivery
Edema
Excitotoxicity
Head injuries
Ischemia
Life sciences
Military personnel
Mitochondria
Molecular modelling
Morbidity
Neurodegeneration
neuronal regeneration
Neuronal-glial interactions
Oxidative stress
Parenchyma
secondary injuries
Therapeutic applications
Traumatic brain injury
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Title Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets
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