Development of a new militarily-relevant whole-body low-intensity blast model for mild and subconcussive traumatic brain injury: Examination of acute neurological and multi-organ pathological outcomes

Mapping Intimacies ◽

10.1101/2021.09.15.460417 ◽

2021 ◽

Author(s):

Sarah C Hellewell ◽

Ibolja Cernak

Keyword(s):

Shock Tube ◽

Brain Injuries ◽

Neuronal Damage ◽

Clinical Findings ◽

Neurological Dysfunction ◽

Whole Body ◽

Bipedal Stance ◽

Low Intensity ◽

Realistic Representation ◽

Blast Induced Neurotrauma

This work describes a newly developed experimental mouse model reproducing features of blast-induced neurotrauma (BINT), induced in operationally relevant manner using a compressed air-driven shock tube. Mild BINT (smBINT) was induced by one exposure to a low-intensity blast (LIB), whereas subconcussive BINT (rscBINT) was caused by repeated exposures to LIB. To mimic an operational scenario when a soldier is standing when exposed to blast using a quadruped experimental animal (mouse), a whole-body holder was developed to position mice in a bipedal stance, face-on toward the pressure wave generated in a shock tube. This restraint avoids bobble head movement, thus prevents tertiary blast effects, and allows administration of fast-acting inhaled anesthetics via nose cone. Using this model, we established and validated paradigms for primary blast-induced mild and repetitive traumatic brain injuries Our results showed that a single exposure to 69 kPa (10 psi) was capable of inducing smBINT, whereas three-rounds of exposure to 41 kPa (6 psi) caused rscBINT. Mice recovered rapidly from both types of BINT without prolonged neurological dysfunction. Mild superficial pathology was found predominantly in the lungs 24h after injury, with equivalent pathology after smBINT or repetitive rscBINT. The Purkinje layer of the cerebellum exhibited neuronal damage persisting up to 7d. Similar to some other models as well as clinical findings, this model reproduces blast-induced cerebellar pathology. In conclusion, this model positioning mice in a bipedal stance and facing front-on toward the shockwave provides realistic representation of operational scenarios and reproduces militarily-relevant smBINT and rscBINT in the laboratory.

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Long-wavelength Low-intensity Photon Therapy (LLPT) for Traumatic Brain Injuries

10.21236/ada534712 ◽

2010 ◽

Author(s):

Harry T. Whelan ◽

Michel T. Torbey ◽

Brendan J. Quirk

Keyword(s):

Brain Injuries ◽

Traumatic Brain Injuries ◽

Long Wavelength ◽

Low Intensity

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Langat virus encephalitis in mice II. The effect of irradiation

Journal of Hygiene ◽

10.1017/s002217240004122x ◽

1968 ◽

Vol 66 (3) ◽

pp. 355-364 ◽

Cited By ~ 12

Author(s):

H. E. Webb ◽

D. G. D. Wight ◽

G. Wiernik ◽

G. S. Platt ◽

C. E. G. Smith

Keyword(s):

Technical Assistance ◽

Neuronal Damage ◽

Preceding Paper ◽

Virus Multiplication ◽

Whole Body ◽

Virus Concentration ◽

Langat Virus ◽

The Central Nervous System ◽

Intraperitoneal Infection ◽

Inflammatory Changes

Summary1. Irradiation in a whole body dose of 200 rads or more increased the sensitivity of mice to intraperitoneal infection with Langat virus so that the LD 50 was increased to about the intracerebral LD 50.2. In mice given 500 rads before infection: (a) viraemia was prolonged by about 5 days; (b) the IgM response was depressed; (c) the IgG response was delayed by about 3 days and depressed in titre; (d) virus concentration in the brain rose continuously until death on about the tenth day while in the controls it reached a peak on the fifth day then subsided; (e) histological changes in the CNS were delayed and minimal even at death; (f) irradiated mice died with little evidence of paralysis while the controls died with severe paralysis.3. In irradiated mice, protection was observed when antibody was administered on the third day following infection. Antibody given on the 3 days after infection to control mice aggravated the disease.4. The results in this and the preceding paper are discussed in relation to the pathogenesis of encephalitis. It is concluded that neuronal damage is caused both by virus multiplication in neurones and by damage superimposed by inflammatory changes with associated oedema and hypoxia. The inflammatory changes appear to be due to an allergic reaction to virus-antibody complexes formed in the circulation and in the central nervous system.We are grateful to Miss S. J. Illavia, B.Sc., and Miss G. E. Fairbairn for their skilled technical assistance; to the Department of Radiotherapy at St Thomas's Hospital for providing time and staff to help with the irradiation experiments; and to Mr S. Peto of the Microbiological Research Establishment for statistical advice.This work was made possible by a generous grant from the Wellcome Trust and the Endowment Funds of St Thomas's Hospital.

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Targeting the Cerebrovascular System: Next-Generation Biomarkers and Treatment for Mild Traumatic Brain Injury

The Neuroscientist ◽

10.1177/10738584211012264 ◽

2021 ◽

pp. 107385842110122

Author(s):

Tamara L. Baker ◽

Denes V. Agoston ◽

Rhys D. Brady ◽

Brendan Major ◽

Stuart J. McDonald ◽

...

Keyword(s):

Brain Function ◽

Brain Injuries ◽

Neurological Dysfunction ◽

Clinical Approach ◽

Cerebral Vasculature ◽

Review Of The Literature ◽

Cerebrovascular Injury ◽

Medical Issues ◽

And Function ◽

Cerebrovascular System

The diagnosis, prognosis, and treatment of mild traumatic brain injuries (mTBIs), such as concussions, are significant unmet medical issues. The kinetic forces that occur in mTBI adversely affect the cerebral vasculature, making cerebrovascular injury (CVI) a pathophysiological hallmark of mTBI. Given the importance of a healthy cerebrovascular system in overall brain function, CVI is likely to contribute to neurological dysfunction after mTBI. As such, CVI and related pathomechanisms may provide objective biomarkers and therapeutic targets to improve the clinical management and outcomes of mTBI. Despite this potential, until recently, few studies have focused on the cerebral vasculature in this context. This article will begin by providing a brief overview of the cerebrovascular system followed by a review of the literature regarding how mTBI can affect the integrity and function of the cerebrovascular system, and how this may ultimately contribute to neurological dysfunction and neurodegenerative conditions. We then discuss promising avenues of research related to mTBI biomarkers and interventions that target CVI, and conclude that a clinical approach that takes CVI into account could result in substantial improvements in the care and outcomes of patients with mTBI.

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Built to Last: Functional and Structural Mechanisms in the Moth Olfactory Network Mitigate Effects of Neural Injury

Brain Sciences ◽

10.3390/brainsci11040462 ◽

2021 ◽

Vol 11 (4) ◽

pp. 462

Author(s):

Charles B. Delahunt ◽

Pedro D. Maia ◽

J. Nathan Kutz

Keyword(s):

Brain Injuries ◽

Hebbian Learning ◽

Neuronal Damage ◽

Neural Systems ◽

Network Motifs ◽

Neural Firing ◽

Neural Injury ◽

Axonal Pathology ◽

Structural Mechanisms ◽

Axonal Swellings

Most organisms suffer neuronal damage throughout their lives, which can impair performance of core behaviors. Their neural circuits need to maintain function despite injury, which in particular requires preserving key system outputs. In this work, we explore whether and how certain structural and functional neuronal network motifs act as injury mitigation mechanisms. Specifically, we examine how (i) Hebbian learning, (ii) high levels of noise, and (iii) parallel inhibitory and excitatory connections contribute to the robustness of the olfactory system in the Manduca sexta moth. We simulate injuries on a detailed computational model of the moth olfactory network calibrated to data. The injuries are modeled on focal axonal swellings, a ubiquitous form of axonal pathology observed in traumatic brain injuries and other brain disorders. Axonal swellings effectively compromise spike train propagation along the axon, reducing the effective neural firing rate delivered to downstream neurons. All three of the network motifs examined significantly mitigate the effects of injury on readout neurons, either by reducing injury’s impact on readout neuron responses or by restoring these responses to pre-injury levels. These motifs may thus be partially explained by their value as adaptive mechanisms to minimize the functional effects of neural injury. More generally, robustness to injury is a vital design principle to consider when analyzing neural systems.

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Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20170001 ◽

2017 ◽

Vol 75 (2) ◽

pp. 92-95 ◽

Cited By ~ 3

Author(s):

Yara Dadalti Fragoso ◽

Tarso Adoni ◽

Joseph Bruno Bidin Brooks ◽

Sidney Gomes ◽

Marcus Vinicius Magno Goncalves ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Disease Onset ◽

Clinical Findings ◽

Neurological Dysfunction ◽

Superficial Siderosis ◽

Blood Products ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri ◽

Intermittent Bleeding

ABSTRACT Superficial siderosis (SS) of the central nervous system (CNS) is a rare and possibly underdiagnosed disorder resulting from chronic or intermittent bleeding into the subarachnoid space, leading to deposition of blood products in the subpial layers of the meninges. Magnetic resonance imaging (MRI) shows a characteristic curvilinear pattern of hypointensity on its blood-sensitive sequences. Methods Series of cases collected from Brazilian centers. Results We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset. Conclusion SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

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Acute reversible toxic encephalopathy during capecitabine and oxaliplatin treatment

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217739686 ◽

2017 ◽

Vol 25 (2) ◽

pp. 497-501 ◽

Cited By ~ 2

Author(s):

João Godinho ◽

Mafalda Casa-Nova ◽

Teresa Mesquita ◽

Maria João Baptista ◽

Francisco Araújo ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Findings ◽

Neurological Dysfunction ◽

Toxic Encephalopathy ◽

Central Nervous System Toxicity ◽

Cerebellar Dysfunction ◽

Oxaliplatin Treatment ◽

Tumor Involvement ◽

The Central Nervous System

Introduction Capecitabine is a fluoropyrimidine commonly used in the treatment of colorectal cancer which may cause central nervous system toxicity, namely cerebellar dysfunction. Case report We describe a 77-year-old man undergoing adjuvant treatment of colon cancer with capecitabine and oxaliplatin who presented with acute cerebellar ataxia and encephalopathy that progressed to coma. Diagnosis of toxic encephalopathy was made after the exclusion of alternative causes of neurological dysfunction and complete resolution of clinical findings with permanent discontinuation of chemotherapy. Discussion When patients with cancer develop symptoms and signs of central nervous dysfunction, metabolic and infectious causes plus tumor involvement of central nervous system must be sought. However, chemotherapy may also cause toxicity to the central nervous system. Capecitabine is no exception, although cerebellar dysfunction is rarely reported. Conclusion Although rare, capecitabine-induced encephalopathy may be severe and physicians should be aware of this possible side effect.

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Prevalence of Traumatic Brain Injuries and Comparison of Its Clinical Findings from Mild to Severe Grade on Computed Tomography

EAS Journal of Radiology and Imaging Technology ◽

10.36349/easjrit.2021.v03i02.014 ◽

2021 ◽

Vol 3 (2) ◽

pp. 119-125

Author(s):

Ayesha Umar ◽

Akash John ◽

Muhammad Ahmad Naeem ◽

Hussnain Rashid Butt ◽

Abid Ali

Keyword(s):

Computed Tomography ◽

Brain Injuries ◽

Traumatic Brain Injuries ◽

Clinical Findings ◽

Severe Grade

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Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome

Neuropediatrics ◽

10.1055/s-0041-1736179 ◽

2021 ◽

Author(s):

Kingthong Anurat ◽

Chaiyos Khongkhatithum ◽

Thipwimol Tim-Aroon ◽

Chanin Limwongse ◽

Lunliya Thampratankul

Keyword(s):

Sleep Disorder ◽

Developmental Delay ◽

Daytime Sleepiness ◽

Glucose Transporter ◽

Focal Epilepsy ◽

Deficiency Syndrome ◽

Clinical Findings ◽

Whole Body ◽

Global Developmental Delay

AbstractGlucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.

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Military-Relevant Rodent Models of Blast-Induced Traumatic Brain Injuries

Neurotrauma ◽

10.1093/med/9780190279431.003.0024 ◽

2018 ◽

pp. 285-302

Author(s):

Ibolja Cernak

Keyword(s):

Brain Injuries ◽

Traumatic Brain Injuries ◽

Blast Waves ◽

Terrorist Attacks ◽

Rodent Models ◽

Blast Injuries ◽

Chronic Health ◽

Specific Factors ◽

Blast Induced Neurotrauma ◽

Health Impairments

Explosive weaponry is the main cause of injuries in current military actions and terrorist attacks. Blast injuries and blast-induced neurotrauma (BINT) are caused by blast waves generated during an explosion. In both civilian and military environments, exposure to a blast may cause instant death, injuries with immediate manifestation of symptoms, and latent injuries that are initiated at the time of exposure and may manifest over a period of hours, months, or even years. Chronic health impairments due to blast often remain un- or underdiagnosed and represent significant challenges for treatment and rehabilitation. We need to advance our understanding of the mechanisms of these injuries to develop better preventive, diagnostic and treatment approaches. This could be achieved through research using clinically and militarily relevant and scientifically reliable models. This chapter provides an overview on rodent BINT models and discusses the generalizable and blast-specific factors that every rodent BINT model should fulfill.

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