The grantee previously found screened that the combination of minocycline (MINO) and N- acetyl cysteine ( NAC ) synergistically improved brain function... acetylcysteine (MINO/ NAC ) synergistically improved cognition and memory in a mild controlled cortical impact (mCCI) model of TBI. mCCI induced a long...W81XWH-10-2-0171 TITLE: Minocycline and N- acetylcysteine : a synergistic drug combination to treat traumatic brain injury PRINCIPAL INVESTIGATOR
Cardenas, VA; Meyerhoff, DJ; Studholme, C; Kornak, J; Rothlind, J; Lampiris, H; Neuhaus, J; Grant, RM; Chao, LL; Truran, D; Weiner, MW
Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus–positive (HIV+) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV− controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P < .05) greater rates of white matter volume loss than HIV− control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals—even in the presence of viral suppression in the periphery—are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered. PMID:19499454
... Questions Glossary Contact Us Visitor Feedback mild Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity ... most common deployment injuries is a mild Traumatic Brain Injury (TBI). A mild TBI is an injury ...
Stelmaschuk, Stephanie; Will, Mary Colleen; Meyers, Tamara
Traumatic brain injury (TBI) is a leading cause of injury, disability, and death in the United States. Amantadine is an established dopamine agonist that supports neurological function. The purpose of this literature review was to determine whether amantadine improves cognitive function post-TBI. PubMed and CINAHL were used to search the literature for articles using amantadine to treat TBI from 1994 to 2004. Outcomes were summarized and the evidence was appraised. Although earlier studies from 1994 to 2003 were lower-level studies and recommended further research on treatment of cognitive dysfunction in TBI, the literature from 2004 to present generally concluded that amantadine improved cognitive function related to arousal, memory, and aggression. It can be started days to months postinjury and still produces benefits.
Kota, Daniel J.; Prabhakara, Karthik S.; van Brummen, Alexandra J.; Bedi, Supinder; Xue, Hasen; DiCarlo, Bryan; Cox, Charles S.
More than 6.5 million patients are burdened by the physical, cognitive, and psychosocial deficits associated with traumatic brain injury (TBI) in the U.S. Despite extensive efforts to develop neuroprotective therapies for this devastating disorder, there have been no successful outcomes in human clinical trials to date. Retrospective studies have shown that β-adrenergic receptor blockers, specifically propranolol, significantly decrease mortality of TBI through mechanisms not yet fully elucidated but are thought to counterbalance a hyperadrenergic state resulting from a TBI. Conversely, cellular therapies have been shown to improve long-term behavior following TBI, likely by reducing inflammation. Given the nonredundancy in their therapeutic mechanisms, we hypothesized that a combination of acute propranolol followed by mesenchymal stem cells (MSCs) isolated from human bone marrow would have additive effects in treating a rodent model of TBI. We have found that the treatments are well-tolerated individually and in combination with no adverse events. MSCs decrease BBB permeability at 96 hours after injury, inhibit a significant accumulation of activated microglia/macrophage in the thalamic region of the brain both short and long term, and enhance neurogenesis short term. Propranolol decreases edema and reduces the number of fully activated microglia at 7 days and the number of semiactivated microglia at 120 days. Combinatory treatment improved cognitive and memory functions 120 days following TBI. Therefore, the results here suggest a new, efficacious sequential treatment for TBI may be achieved using the β-blocker propranolol followed by MSC treatment. Significance Despite continuous efforts, traumatic brain injury (TBI) remains the leading cause of death and disability worldwide in patients under the age of 44. In this study, an animal model of moderate-severe TBI was treated with an acute dose of propranolol followed by a delayed dose of human mesenchymal stem
Bouvy, P F; van de Wetering, B J; Meerwaldt, J D; Bruijn, J B
A case of organic brain syndrome occurring in relation to psychological stress 2 years after a severe head injury is described. Treatment with haloperidol resulted only in slight improvement. A dramatic improvement was achieved with carbamazepine.
This report addresses comments and recommendations of parents of children with traumatic brain injury (TBI) as well as those of professionals. The report is in two sections: (1) What Parents Say about the Time of Injury; and (2) What Emergency Personnel Should Know. The first section presents quotes from five parents about reactions and…
Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...
Belavić, M; Jančić, E; Mišković, P; Brozović-Krijan, A; Bakota, B; Žunić, J
Traumatic brain injury (TBI) is divided into primary and secondary brain injury. Primary brain injury occurs at the time of injury and is the direct consequence of kinetic energy acting on the brain tissue. Secondary brain injury occurs several hours or days after primary brain injury and is the result of factors including shock, systemic hypotension, hypoxia, hypothermia or hyperthermia, intracranial hypertension, cerebral oedema, intracranial bleeding or inflammation. The aim of this retrospective analysis of a prospective database was to determine the prevalence of secondary stroke and stroke-related mortality, causes of secondary stroke, treatment and length of stay in the ICU and hospital. This study included patients with TBI with or without other injuries who were hospitalised in a general ICU over a five-year period. The following parameters were assessed: demographics (age, sex), scores (Glasgow Coma Score, APACHE II, SOFA), secondary stroke (prevalence, time of occurrence after primary brain injury, causes of stroke and associated mortality), length of stay in the ICU and hospital, vital parameters (state of consciousness, cardiac function, respiration, circulation, thermoregulation, diuresis) and laboratory values (leukocytes, C-reactive protein [CRP], blood glucose, blood gas analysis, urea, creatinine). Medical data were analysed for 306 patients with TBI (median age 56 years, range 18-93 years) who were treated in the general ICU. Secondary stroke occurred in 23 patients (7.5%), 10 of whom died, which gives a mortality rate of 43.4%. Three patients were excluded as the cause of the injury was missile trauma. The study data indicate that inflammation is the most important cause of secondary insults. Levels of CRP were elevated in 65% of patients with secondary brain injury; leukocytosis was present in 87% of these patients, and blood glucose was elevated in 73%. The lungs and urinary tract were the most common sites of infection. In conclusion
grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function when... function following TBI. Three tasks will be done to achieve this objective: 1) Differing doses of MINO/NAC will be tested for the ability to improve...between injury and drug dosing will be tested. 3) A restoration of cognitive function will be tested three months after CHI. The grantee has shown that
El Maaytah, Mohammed; Jerjes, Waseem; Upile, Tahwinder; Swinson, Brian; Hopper, Colin; Ayliffe, Peter
We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A). On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required. PMID:17123443
and may increase the risk for Alzheimer‟ s disease and Parkinson ‟ s disease as the person ages (Traumatic Brain Injury: Hope Through Research, 2002...severity of the TBI, which assesses a patient‟ s eye opening, motor , and verbal response. Two other measures for TBI severity are the length of loss of...the constant support and advice from Major Shay Capehart was fundamental in moving this research along. Lt Col Eric Unger‟ s guidance and wisdom was
Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. PMID:20707892
McCutcheon, Victoria; Park, Eugene; Liu, Elaine; Wang, Youdong; Wen, Xiao-Yan; Baker, Andrew J
Traumatic brain injury (TBI) is a leading cause of death and morbidity with no effective therapeutic treatments for secondary injury. Preclinical drug evaluation in rodent models of TBI is a lengthy process. In this regard, the zebrafish has numerous advantages to address the technical and time-dependent obstacles associated with drug evaluation. We developed a reproducible brain injury using glutamate excitoxicity in zebrafish larvae, a known initiator of delayed cell death in TBI. Glutamate challenge resulted in dose-dependent lethality over an 84-h observation period. We report significant decrease in locomotion (p < 0.0001) and mean velocity (p < 0.001) with 10 μM glutamate application as measured through automated 96-well plate behavioral analysis. Application of the NMDA receptor antagonist MK-801 (400 nM) or the calpain inhibitor, MDL-28170 (20 μM), resulted in significant recovery of locomotor function. A secA5-YFP transgenic line was used to visualize the localization of cell death due to glutamate exposure in vivo using confocal fluorescence microscopy. Our results indicate that zebrafish larvae exhibit responses to excitotoxic injury and pharmacotherapeutic intervention with pathophysiological relevance to mammalian excitotoxic brain injury. This system has potential to be applied as a high-throughput drug screening model to quickly identify candidate lead compounds for further evaluation.
Doarn, Charles R; McVeigh, Francis; Poropatich, Ronald
Traumatic brain injury (TBI) has become the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. The use of improvised explosive devices has seen an exponential increase in both Iraq and Afghanistan. In previous conflicts prior to Iraq, survivability of such an injury was far less. Today, technological improvements in trauma care have increased an injured warfighter's chance of survival. A reduction in severe TBI has been achieved but an increase in mild or moderate TBI has been observed. The consequences of this kind of injury can be both physical and mental and can often be hidden or even misdiagnosed. The U.S. Army is interested in pursuing technological solutions for early detection and treatment of TBI to reduce its lasting impact on the warfighter. Such technological breakthroughs have benefit beyond the military, as TBI is a high probable event in nonmilitary settings as well. To gauge what technologies or methods are currently available, the U.S. Army's Telemedicine and Advanced Technology Research Center partnered with the American Telemedicine Association to organize and conduct a discipline-specific symposium entitled "Innovative New Technologies to Identify and Treat Traumatic Brain Injuries: Crossover Technologies and Approaches Between Military and Civilian Applications." This symposium was held in Palm Springs, CA, in September 2009. The purpose of the meeting was to provide a unique opportunity for leaders from disparate organizations involved in telemedicine and related other activities to meet and explore opportunities to collaborate in new partnership models. The meeting was designed to help Telemedicine and Advanced Technology Research Center identify opportunities to expand strategic operations and form new alliances. This report summarizes this symposium while raising awareness for collaboration into better ways of adapting and adopting technologies to address this growing health issue.
Colorado State Dept. of Education, Denver. Special Education Services Unit.
This paper on traumatic brain injuries begins with statistics on the incidence of the disorder, especially as they relate to Colorado. Traumatic brain injury is then defined, and problems caused by traumatic brain injury are discussed. The components of effective programming for students with traumatic brain injuries are described, followed by the…
Traumatic Brain Injury & Dystonia Traumatic brain injury (TBI) occurs when a sudden trauma damages to the brain. TBI can occur when the head suddenly and violently hits an object, or when an object pierces the skull and ...
combination of minocycline (MINO) and N- acetyl cysteine ( NAC ) synergistically improved brain function when dosed one hour following closed cortical...combination of minocycline and N- acetylcysteine (MINO/ NAC ) synergistically 10 improved cognition and memory in a mild controlled cortical impact...MINO, 45 mg/kg) and N- acetylcysteine ( NAC , 150 mg/kg) were previously show to improve cognition and memory in rats when dosed one hour after a
Bass, Cameron R; Panzer, Matthew B; Rafaels, Karen A; Wood, Garrett; Shridharani, Jay; Capehart, Bruce
Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is
... Hits since January 2003 RADIATION INJURY TO THE BRAIN Radiation treatments affect all cells that are targeted. ... fractions, duration of therapy, and volume of [healthy brain] nervous tissue irradiated influence the likelihood of injury. ...
Schwartz, Stacey Hunter
This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…
Greig, Nigel H; Tweedie, David; Rachmany, Lital; Li, Yazhou; Rubovitch, Vardit; Schreiber, Shaul; Chiang, Yung-Hsiao; Hoffer, Barry J; Miller, Jonathan; Lahiri, Debomoy K; Sambamurti, Kumar; Becker, Robert E; Pick, Chaim G
Traumatic brain injury (TBI), either as an isolated injury or in conjunction with other injuries, is an increasingly common event. An estimated 1.7 million injuries occur within the USA each year and 10 million people are affected annually worldwide. Indeed, nearly one third (30.5%) of all injury-related deaths in the USA are associated with TBI, which will soon outpace many common diseases as the major cause of death and disability. Associated with a high morbidity and mortality and no specific therapeutic treatment, TBI has become a pressing public health and medical problem. The highest incidence of TBI occurs in young adults (15-24 years age) and in the elderly (≥75 years of age). Older individuals are particularly vulnerable to these types of injury, often associated with falls, and have shown increased mortality and worse functional outcome after lower initial injury severity. In addition, a new and growing form of TBI, blast injury, associated with the detonation of improvised explosive devices in the war theaters of Iraq and Afghanistan, are inflicting a wave of unique casualties of immediate impact to both military personnel and civilians, for which long-term consequences remain unknown and may potentially be catastrophic. The neuropathology underpinning head injury is becoming increasingly better understood. Depending on severity, TBI induces immediate neuropathologic effects that, for the mildest form, may be transient; however, with increasing severity, these injuries cause cumulative neural damage and degeneration. Even with mild TBI, which represents the majority of cases, a broad spectrum of neurologic deficits, including cognitive impairments, can manifest that may significantly influence quality of life. Further, TBI can act as a conduit to longer term neurodegenerative disorders. Prior studies of glucagon-like peptide-1 (GLP-1) and long-acting GLP-1 receptor agonists have demonstrated neurotrophic/neuroprotective activities across a broad
Greig, Nigel H.; Tweedie, David; Rachmany, Lital; Li, Yazhou; Rubovitch, Vardit; Schreiber, Shaul; Chiang, Yung-Hsiao; Hoffer, Barry J.; Miller, Jonathan; Lahiri, Debomoy K.; Sambamurti, Kumar; Becker, Robert E.; Pick, Chaim G.
Traumatic brain injury (TBI), either as an isolated injury or in conjunction with other injuries, is an increasingly common occurring event. An estimated 1.7 million injuries occur within the US each year and 10 million people are affected annually worldwide. Indeed, some one-third (30.5%) of all injury-related deaths in the U.S. are associated with TBI, which will soon outstrip many common diseases as the major cause of death and disability. Associated with a high morbidity and mortality, and no specific therapeutic treatment, TBI has become a pressing public health and medical problem. The highest incidence of TBI occurs among young adults (15 to 24 years age) as well as in the elderly (75 years and older) who are particularly vulnerable as injury, often associated with falls, carries an increased mortality and worse functional outcome following lower initial injury severity. Added to this, a new and growing form of TBI, blast injury, associated with the detonation of improvised explosive devices in the war theaters of Iraq and Afghanistan, are inflicting a wave of unique casualties of immediate impact to both military personnel and civilians, for which long-term consequences remain unknown and may potentially be catastrophic. The neuropathology underpinning head injury is becoming increasingly better understood. Depending on severity, TBI induces immediate neuropathological effects that for the mildest form may be transient but with increasing severity cause cumulative neural damage and degeneration. Even with mild TBI, which represents the majority of cases, a broad spectrum of neurological deficits, including cognitive impairments, can manifest that may significantly influence quality of life. In addition, TBI can act as a conduit to longer-term neurodegenerative disorders. Prior studies of glucagon-like peptide-1 (GLP-1) and long-acting GLP-1 receptor agonists have demonstrated neurotrophic/neuroprotective activities across a broad spectrum of cellular and
Shin, Samuel S; Dixon, C Edward; Okonkwo, David O; Richardson, R Mark
Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.
Blennow, Kaj; Brody, David L; Kochanek, Patrick M; Levin, Harvey; McKee, Ann; Ribbers, Gerard M; Yaffe, Kristine; Zetterberg, Henrik
Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury - the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators.
Risdall, Jane E.; Menon, David K.
There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilcian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad. PMID:21149359
Persons who have suffered traumatic injury to the brain may subsequently display aggressive behavior. Three main syndromes of aggression following traumatic brain injury are described: (1) episodic dyscontrol; (2) frontal lobe disinhibition; and (3) exacerbation of premorbid antisociality. The neuropsychological substrates of these syndromes are…
Trudel, Tina M.; Halper, James; Pines, Hayley; Cancro, Lorraine
It is important to determine if a traumatic brain injury (TBI) has occurred when an individual is assessed in a hospital emergency room after a car accident, fall, or other injury that affects the head. This determination influences decisions about treatment. It is essential to screen for the injury, because the sooner they begin appropriate…
Zhao, Wenli; Wang, Chao; Li, Zhongzheng; Chen, Lei; Li, Jianbo; Cui, Weidong; Ding, Shasha; Xi, Qiang; Wang, Fan; Jia, Fei; Xiao, Shuhua; Guo, Yi; Zhao, Ye
Objective This study was aimed at evaluating the clinical efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) to treat muscle spasticity after brain injury (Chinese Clinical Trial Registry: ChiCTR-TRC-11001310). Methods A total of 60 patients with muscle spasticity after brain injury were randomized to the following 3 groups: 100, 2, and 0 Hz (sham) TEAS. The acupoints Hegu (LI4)—Yuji (LU10) and Zusanli (ST36)—Chengshan (BL57) on the injured side were stimulated at 0, 2, or 100 Hz, 5 times per week for 4 weeks. The patients were followed up for 1 and 2 months after the treatments. The effects of the treatments on muscle spasticity at the wrist, thumb, the other 4 fingers, elbow, shoulder, knee, and ankle were evaluated by the Modified Ashworth Scale, and the effects on disability were assessed by the Disability Assessment Scale. The walking capability was evaluated by the Holden functional ambulation classification score. The overall performance was assessed by the Global Assessment Scale score and the improved Barthel Index. The safety of the treatments administered was also monitored. Results The wrist spasticity was significantly reduced from baseline at weeks 2, 3, and 4 of treatment and at the 1- and 2-month follow-up visits in the 100 Hz group (P < 0.01). Compared with 2 Hz or sham TEAS, 100 Hz TEAS decreased wrist spasticity at weeks 2, 3, and 4 of treatment and 1 month after treatment (P < 0.001). The other endpoints were not affected by the treatments. No treatment-emergent adverse events were reported during treatments and follow-up visits. Conclusions TEAS appears to be a safe and effective therapy to relieve muscle spasticity after brain injury, although large-scale studies are required to further verify the findings. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-11001310 http://www.chictr.org PMID:25643051
Connor, Karen; Dettmer, Judy; Dise-lewis, Jeanne E.; Murphy, Mary; Santistevan, Barbette; Seckinger, Barbara
This manual provides Colorado educators with guidelines for serving students with brain injuries. Following an introductory chapter, chapter 2 provides basic information on the brain including definitions of brain injury and its severity, incidence of brain injury, and characteristics of students with brain injury. Chapter 3 considers…
Jenkins, Peter O.; Mehta, Mitul A.
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296
Jackson, Edwin K; Boison, Detlev; Schwarzschild, Michael A; Kochanek, Patrick M
Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI.
... of Directors Adopts Position on Rehabilitation Outcomes 27-Mar-2017 On March 21, 2017, BIAA’s Board of ... Brain Injury Awareness Day on Capitol Hill 23-Mar-2017 Reps. Pascrell (D-N.J.) and Rooney ( ...
... brain to bump against the inside of your skull. Common TBIs, such as concussions, can happen during ... an object, like a bullet or piece of skull, pierces your brain. Symptoms of a traumatic brain ...
brain slices were treated after injury with either a nootropic agent (aniracetam, cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...pharmacological approach. 15. SUBJECT TERMS traumatic brain injury, cell necrosis, neuroprotection, nootropics , epilepsy, long-term potentiation...render their use problematic in an effective brain tourniquet system. We chose to focus our investigations on the nootropic (cognition enhancing) drugs
Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen
Traumatic brain injuries (TBI) can cause multiple medical and functional problems. As the brain is involved in regulating nearly every bodily function, a TBI can affect any part of the body and aspect of cognitive, behavioral, and physical functioning. However, TBI affects each individual differently. Optimal management requires understanding the…
KIRK, KATHERINE A; SHOYKHET, MICHAEL; JEONG, JONG H; TYLER-KABARA, ELIZABETH C; HENDERSON, MARYANNE J; BELL, MICHAEL J; FINK, ERICKA L
AIM Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of brain-injured adults and is associated with poor outcome. We hypothesized that brain-injured children with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features. METHOD We developed a database of children (n=249, 154 males, 95 females; mean (SD) age 11y 10mo [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted to The Children’s Institute of Pittsburgh for rehabilitation between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia. RESULTS Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001). INTERPRETATION Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes. PMID:22712762
Elliott, Melanie B; Jallo, Jack J; Gaughan, John P; Tuma, Ronald F
The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.
Cross, Donna J.; Garwin, Gregory G.; Cline, Marcella M.; Richards, Todd L.; Yarnykh, Vasily; Mourad, Pierre D.; Ho, Rodney J.Y.; Minoshima, Satoshi
Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2 mm3 for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury. PMID:26086366
Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Bernabeu, Montserrat; Tormos, Jose M.; Pascual-Leone, Alvaro
Brain stimulation techniques have evolved in the last few decades with more novel methods capable of painless, noninvasive brain stimulation. While the number of clinical trials employing noninvasive brain stimulation continues to increase in a variety of medication-resistant neurological and psychiatric diseases, studies evaluating their diagnostic and therapeutic potential in traumatic brain injury (TBI) are largely lacking. This review introduces different techniques of noninvasive brain stimulation, which may find potential use in TBI. We cover transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), low-level laser therapy (LLLT) and transcranial doppler sonography (TCD) techniques. We provide a brief overview of studies to date, discuss possible mechanisms of action, and raise a number of considerations when thinking about translating these methods to clinical use. PMID:21691215
Viola-Saltzman, Mari; Musleh, Camelia
Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626
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... head injury) or by an object penetrating the skull (called a penetrating injury). Some TBIs result in ... to) several types of injury to the brain: Skull fracture occurs when the skull cracks. Pieces of ...
Mazwi, Nicole L; Fusco, Heidi; Zafonte, Ross
Sleep disturbances affect more than half of survivors of traumatic brain injury (TBI) and have the potential to undermine rehabilitation, recovery, and outcomes. Normal sleep architecture has been well-described and the neurophysiology of sleep is becoming better understood in recent years, though this complex process continues to be dissected for better appreciation. There are numerous types of sleep disorder, most of which fall under two categories: dyssomnias and parasomnias. In more challenging scenarios patients may be plagued with more than one dyssomnia and/or parasomnia simultaneously, complicating the diagnostic and therapeutic approach. Objective and subjective methods are used to evaluate sleep disorders and help distinguish them from psychiatric and environmental contributors to poor sleep. There are several pharmacologic and nonpharmacologic treatments options for sleep disturbances after TBI, many of which have been particularly helpful in restoring adequate quantity and quality of sleep for survivors. However, to date no consensus has been established regarding how to treat this entity, and it may be that a multimodal approach is ultimately best.
Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon
Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI.
Ernst, William J.; Gallo, Adrienne B.; Sellers, Amanda L.; Mulrine, Jessica; MacNamara, Luciana; Abrahamson, Allison; Kneavel, Meredith
The purpose of this study is to determine knowledge of traumatic brain injury among educators. Few studies have examined knowledge of traumatic brain injury in this population and fewer still have included a substantial proportion of general education teachers. Examining knowledge of traumatic brain injury in educators is important as the vast…
Chesire, David J.; Buckley, Valerie A.; Canto, Angela I.
The incidence of brain injuries, as well as their impact on individuals who sustain them, has received growing attention from American media in recent years. This attention is likely the result of high profile individuals suffering brain injuries. Greater public awareness of traumatic brain injuries (TBIs) has also been promoted by sources such as…
... Eye Injuries Reviewed by: Brenda Pagan-Duran MD Mar. 01, 2016 When an eye injury does occur, ... Fireworks Eye Safety Jun 10, 2016 Protective Eyewear Mar 01, 2016 Scleritis Symptoms Mar 01, 2015 What ...
Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W. Dalton; Bullock, M. Ross
Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury, have been shown to induce consequent protection against post-TBI neuronal death. This concept termed “preconditioning” is achieved by exposure to different pre-injury stressors, to achieve the induction of “tolerance” to the effect of the TBI. However, the precise mechanisms underlying this “tolerance” phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditionng studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible futureclinical situation, in which pre-TBI preconditioning could be considered. PMID:24323189
Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W Dalton; Bullock, M Ross
Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury have been shown to induce consequent protection against post-TBI neuronal death. This concept termed "preconditioning" is achieved by exposure to different pre-injury stressors to achieve the induction of "tolerance" to the effect of the TBI. However, the precise mechanisms underlying this "tolerance" phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review, we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditioning studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible future clinical situations, in which pre-TBI preconditioning could be considered.
Sahler, Christopher S.; Greenwald, Brian D.
Traumatic brain injury (TBI) is a clinical diagnosis of neurological dysfunction following head trauma, typically presenting with acute symptoms of some degree of cognitive impairment. There are an estimated 1.7 to 3.8 million TBIs each year in the United States, approximately 10 percent of which are due to sports and recreational activities. Most brain injuries are self-limited with symptom resolution within one week, however, a growing amount of data is now establishing significant sequelae from even minor impacts such as headaches, prolonged cognitive impairments, or even death. Appropriate diagnosis and treatment according to standardized guidelines are crucial when treating athletes who may be subjected to future head trauma, possibly increasing their likelihood of long-term impairments. PMID:22848836
Baumann, Christian R
Post-traumatic sleep-wake disturbances are frequent and often chronic complications after traumatic brain injury. The most prevalent sleep-wake disturbances are insomnia, excessive daytime sleepiness, and pleiosomnia, (i.e., increased sleep need). These disturbances are probably of multifactorial origin, but direct traumatic damage to key brain structures in sleep-wake regulation is likely to contribute. Diagnosis and treatment consist of standard approaches, but because of misperception of sleep-wake behavior in trauma patients, subjective testing alone may not always suffice.
Flower, Oliver; Hellings, Simon
Several different classes of sedative agents are used in the management of patients with traumatic brain injury (TBI). These agents are used at induction of anaesthesia, to maintain sedation, to reduce elevated intracranial pressure, to terminate seizure activity and facilitate ventilation. The intent of their use is to prevent secondary brain injury by facilitating and optimising ventilation, reducing cerebral metabolic rate and reducing intracranial pressure. There is limited evidence available as to the best choice of sedative agents in TBI, with each agent having specific advantages and disadvantages. This review discusses these agents and offers evidence-based guidance as to the appropriate context in which each agent may be used. Propofol, benzodiazepines, narcotics, barbiturates, etomidate, ketamine, and dexmedetomidine are reviewed and compared. PMID:23050154
The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is one of the organs most vulnerable to the inflammatory cascade triggered by TBI. HMGB1 is an alarm in that can be released from activated immune cells in response to tissue injury. Increased systemic HMGB1 concentration correlates with poor lung function before and after lung transplant, confirming its role in acute ALI after TBI. HMGB1 exerts its influence by interacting with several receptors, including the RAGE receptor. RAGE also plays an important role in the onset of innate immune inflammatory responses, and systemic levels of RAGE are strongly associated with ALI and clinical outcomes in ventilator-induced lung injury. RAGE ligation to HMGB1 triggers the amplification of the inflammatory cascade involving nuclear factor-κB (NF-κB) activation. Identifying early biomarkers that mediate pulmonary dysfunction will improve outcomes not only in lung transplantation, but also in other scenarios. These novel findings show that upregulation of the HMGB1-RAGE axis plays an important role in brain-lung crosstalk. PMID:26046092
Jinadasa, Sayuri; Boone, M Dustin
Traumatic brain injury (TBI) is a physical insult (a bump, jolt, or blow) to the brain that results in temporary or permanent impairment of normal brain function. TBI describes a heterogeneous group of disorders. The resulting secondary injury, namely brain swelling and its sequelae, is the reason why patients with these vastly different initial insults are homogenously treated. Much of the evidence for the management of TBI is poor or conflicting, and thus definitive guidelines are largely unavailable for clinicians at this time. A substantial portion of this article focuses on discussing the controversies in the management of TBI.
... The NIH has also funded research to develop sensors to determine the type of acceleration and rotation ... can lead to brain injuries. Researchers hope these sensors can help determine the effect of head injuries ...
Ray, Bradley; Sapp, Dona; Kincaid, Ashley
Research on traumatic brain injury among inmates has focused on comparing the rate of traumatic brain injury among offenders to the general population, but also how best to screen for traumatic brain injury among this population. This study administered the short version of the Ohio State University Traumatic Brain Injury Identification Method to all male inmates admitted into Indiana state prisons were screened for a month (N = 831). Results indicate that 35.7% of the inmates reported experiencing a traumatic brain injury during their lifetime and that these inmates were more likely to have a psychiatric disorder and a prior period of incarceration than those without. Logistic regression analysis finds that a traumatic brain injury predicts the likelihood of prior incarceration net of age, race, education, and psychiatric disorder. This study suggests that brief instruments can be successfully implemented into prison screenings to help divert inmates into needed treatment.
Wu, C. W.; Zhu, Z. D.; Zhang, W.
It has long been recognized that woodpecker is an excellent anti-shock organism, as its head and brain can bear high deceleration up to 1500 g under fast pecking. To investigate the mechanism of brain protection of woodpecker, we built a finite element model of a whole woodpecker using computed topography scanning technique and geometry modeling. Numerical results show that the periodical changing Young's modulus around the skull affects the stress wave propagation in head and makes the stress lowest at the position of the brain. Modal analysis reveals the application of pre-tension force to the hyoid bone can increase the natural frequency of woodpecker's head. The large gap between the natural and working frequencies enable the woodpecker to effectively protect its brain from the resonance injury. Energy analyses indicate the majority of the impact energy (99.7%) is stored in the bulk of body and is utilized in the next pecking. There is only a small fraction of it enters into the head (0.3%). The whole body of the woodpecker gets involved in the energy conversion and forms an efficient anti-shock protection system for the brain.
Fernandez-Rodriguez, Eva; Bernabeu, Ignacio; Castro, Ana I; Casanueva, Felipe F
The prevalence of hypopituitarism after traumatic brain (TBI) injury is widely variable in the literature; a meta-analysis determined a pooled prevalence of anterior hypopituitarism of 27.5%. Growth hormone deficiency is the most prevalent hormone insufficiency after TBI; however, the prevalence of each type of pituitary deficiency is influenced by the assays used for diagnosis, severity of head trauma, and time of evaluation. Recent studies have demonstrated improvement in cognitive function and cognitive quality of life with substitution therapy in GH-deficient patients after TBI.
Degeneffe, Charles Edmund; Tucker, Mark
Objective: to examine the perspectives of brain injury professionals concerning family members' feelings about the quality of life experienced by individuals with brain injuries. Participants: participating in the study were 28 individuals in leadership positions with the state affiliates of the Brain Injury Association of America (BIAA). Methods:…
Mrozek, Ségolène; Vardon, Fanny; Geeraerts, Thomas
The regulation of brain temperature is largely dependent on the metabolic activity of brain tissue and remains complex. In intensive care clinical practice, the continuous monitoring of core temperature in patients with brain injury is currently highly recommended. After major brain injury, brain temperature is often higher than and can vary independently of systemic temperature. It has been shown that in cases of brain injury, the brain is extremely sensitive and vulnerable to small variations in temperature. The prevention of fever has been proposed as a therapeutic tool to limit neuronal injury. However, temperature control after traumatic brain injury, subarachnoid hemorrhage, or stroke can be challenging. Furthermore, fever may also have beneficial effects, especially in cases involving infections. While therapeutic hypothermia has shown beneficial effects in animal models, its use is still debated in clinical practice. This paper aims to describe the physiology and pathophysiology of changes in brain temperature after brain injury and to study the effects of controlling brain temperature after such injury. PMID:23326261
Corps, Kara N.; Roth, Theodore L.; McGavern, Dorian B.
IMPORTANCE Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI. OBJECTIVES To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI. EVIDENCE REVIEW We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. FINDINGS Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning
Bigler, Erin D.
This review explores the cellular pathology associated with traumatic brain injury (TBI) and its relation to neurobehavioral outcomes, the relationship of brain imaging findings to underlying pathology, brain imaging techniques, various image analysis procedures and how they relate to neuropsychological testing, and the importance of brain imaging…
Yi, Ho Sung; Seo, Mi Ri
Bruxism is a diurnal or nocturnal parafunctional activity that includes tooth clenching, bracing, gnashing, and grinding. The dopaminergic system seems to be the key pathophysiology of bruxism and diminution of dopaminergic transmission at the prefrontal cortex seems to induce it. We report two patients with diurnal bruxism in whom a bilateral frontal lobe injury resulted from hemorrhagic stroke or traumatic brain injury. These patients' bruxism was refractory to bromocriptine but responded to low-dose metoclopramide therapy. We propose that administering low doses of metoclopramide is possibly a sound method for treating bruxism in a brain injury patient with frontal lobe hypoperfusion on positron emission tomography imaging. PMID:24466522
The purpose of this resource guide on traumatic brain injury (TBI) is to provide assistance to educators, families, and professionals who may be striving to increase their knowledge and understanding of brain injury. This guide will hopefully become an initial resource. It provides: a glossary of TBI Terms; contact information for and brief…
Bullock, Lyndal M.; Gable, Robert A.; Mohr, J. Darrell
In this article, the authors provide information designed to enhance the knowledge and understanding of school personnel about traumatic brain injury (TBI). The authors specifically define TBI and enumerate common characteristics associated with traumatic brain injury, discuss briefly the growth and type of services provided, and offer some…
National Information Center for Children and Youth with Disabilities, Washington, DC.
This fact sheet describes traumatic brain injury (TBI), an injury of the brain caused by the head being hit by something or being shaken violently. It discusses the incidence of TBI, and describes its symptoms as changes in thinking and reasoning, understanding words, remembering things, paying attention, solving problems, thinking abstractly,…
Mayfield, Joan; Homack, Susan
Children who sustain traumatic brain injury (TBI) can experience significant cognitive deficits. These deficits may significantly impair their functioning in the classroom, resulting in the need for academic and behavioral modifications. Behavior and social problems can be the direct or indirect result of brain injury. Difficulties in paying…
Mendieta Zerón, Hugo; Arriaga García Rendon, Julio Cesar
After a brain injury, raised temperature may be due to a regulated readjustment in the hypothalamic 'set-point' in response to inflammation. The purpose of this report is to mention possible implications related to temperature and homeostasis of morphine treatment in a patient with brain injury. During the month previous to her hospitalization in our city she was treated for fever with paracetamol and metamizol without results. After 31 days with similar results, we changed to morphine IV considering the possibility of treating pain and fever. This option was successful and afterwards we changed to fentanyl patches, keeping fever absent. After 100 days of hospitalization, the patient was discharged to her home.
Bhattacharya, Bishwajit; Maung, Adrian A
Traumatic brain injury (TBI) represents a wide spectrum of disease and disease severity. Because the primary brain injury occurs before the patient enters the health care system, medical interventions seek principally to prevent secondary injury. Anesthesia teams that provide care for patients with TBI both in and out of the operating room should be aware of the specific therapies and needs of this unique and complex patient population.
Atkins, C.M.; Kang, Y.; Furones, C.; Truettner, J.S.; Alonso, O.F.; Dietrich, W.D.
The pathology caused by traumatic brain injury (TBI) is exacerbated by the inflammatory response of the injured brain. Two pro-inflammatory cytokines that contribute to inflammation after TBI are tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In previous studies using the parasagittal fluid-percussion brain injury model, we reported that the anti-inflammatory drug rolipram, a phosphodiesterase 4 inhibitor, reduced TNF-α and IL-1β levels and improved histopathological outcome when administered 30 min prior to injury. We now report that treatment with (±)-rolipram given 30 min after injury significantly reduced TNF-α levels in the cortex and hippocampus. However, post-injury administration of (±)-rolipram significantly increased cortical contusion volume and increased atrophy of the cortex as compared to vehicle-treated animals at 10 days post-injury. Thus, despite the reduction in pro-inflammatory cytokine levels, histopathological outcome was worsened with post-TBI (±)-rolipram treatment. Further histological analysis of (±)-rolipram-treated TBI animals revealed significant hemorrhage in the contused brain. Given the well known role of (±)-rolipram to increase vasodilation, it is likely that (±)-rolipram worsened outcome after fluid-percussion brain injury by causing increased bleeding. PMID:22535545
Arciniegas, David B; Harris, Susie N; Brousseau, Kristin M
Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.
Villapol, Sonia; Balarezo, María G; Affram, Kwame; Saavedra, Juan M; Symes, Aviva J
See Moon (doi:10.1093/awv239) for a scientific commentary on this article.Traumatic brain injury frequently leads to long-term cognitive problems and physical disability yet remains without effective therapeutics. Traumatic brain injury results in neuronal injury and death, acute and prolonged inflammation and decreased blood flow. Drugs that block angiotensin II type 1 receptors (AT1R, encoded by AGTR1) (ARBs or sartans) are strongly neuroprotective, neurorestorative and anti-inflammatory. To test whether these drugs may be effective in treating traumatic brain injury, we selected two sartans, candesartan and telmisartan, of proven therapeutic efficacy in animal models of brain inflammation, neurodegenerative disorders and stroke. Using a validated mouse model of controlled cortical impact injury, we determined effective doses for candesartan and telmisartan, their therapeutic window, mechanisms of action and effect on cognition and motor performance. Both candesartan and telmisartan ameliorated controlled cortical impact-induced injury with a therapeutic window up to 6 h at doses that did not affect blood pressure. Both drugs decreased lesion volume, neuronal injury and apoptosis, astrogliosis, microglial activation, pro-inflammatory signalling, and protected cerebral blood flow, when determined 1 to 3 days post-injury. Controlled cortical impact-induced cognitive impairment was ameliorated 30 days after injury only by candesartan. The neurorestorative effects of candesartan and telmisartan were reduced by concomitant administration of the peroxisome proliferator-activated receptor gamma (PPARγ, encoded by PPARG) antagonist T0070907, showing the importance of PPARγ activation for the neurorestorative effect of these sartans. AT1R knockout mice were less vulnerable to controlled cortical impact-induced injury suggesting that the sartan's blockade of the AT1R also contributes to their efficacy. This study strongly suggests that sartans with dual AT1R blocking and
Balarezo, María G.; Affram, Kwame; Saavedra, Juan M.; Symes, Aviva J.
See Moon (doi:10.1093/awv239) for a scientific commentary on this article. Traumatic brain injury frequently leads to long-term cognitive problems and physical disability yet remains without effective therapeutics. Traumatic brain injury results in neuronal injury and death, acute and prolonged inflammation and decreased blood flow. Drugs that block angiotensin II type 1 receptors (AT1R, encoded by AGTR1) (ARBs or sartans) are strongly neuroprotective, neurorestorative and anti-inflammatory. To test whether these drugs may be effective in treating traumatic brain injury, we selected two sartans, candesartan and telmisartan, of proven therapeutic efficacy in animal models of brain inflammation, neurodegenerative disorders and stroke. Using a validated mouse model of controlled cortical impact injury, we determined effective doses for candesartan and telmisartan, their therapeutic window, mechanisms of action and effect on cognition and motor performance. Both candesartan and telmisartan ameliorated controlled cortical impact-induced injury with a therapeutic window up to 6 h at doses that did not affect blood pressure. Both drugs decreased lesion volume, neuronal injury and apoptosis, astrogliosis, microglial activation, pro-inflammatory signalling, and protected cerebral blood flow, when determined 1 to 3 days post-injury. Controlled cortical impact-induced cognitive impairment was ameliorated 30 days after injury only by candesartan. The neurorestorative effects of candesartan and telmisartan were reduced by concomitant administration of the peroxisome proliferator-activated receptor gamma (PPARγ, encoded by PPARG) antagonist T0070907, showing the importance of PPARγ activation for the neurorestorative effect of these sartans. AT1R knockout mice were less vulnerable to controlled cortical impact-induced injury suggesting that the sartan’s blockade of the AT1R also contributes to their efficacy. This study strongly suggests that sartans with dual AT1R blocking
Zetterberg, Henrik; Blennow, Kaj
Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.
... 45 Public Welfare 4 2012-10-01 2012-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an...
... 45 Public Welfare 4 2013-10-01 2013-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an...
... 45 Public Welfare 4 2014-10-01 2014-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an...
... 45 Public Welfare 4 2011-10-01 2011-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an...
Bigler, Erin D; Brooks, Michael
As part of a special issue of The Journal of Head Trauma Rehabilitation, forensic neuropsychology is reviewed as it applies to traumatic brain injury (TBI) and other types of acquired brain injury in which clinical neuropsychologists and rehabilitation psychologists may be asked to render professional opinions about the neurobehavioral effects and outcome of a brain injury. The article introduces and overviews the topic focusing on the process of forensic neuropsychological consultation and practice as it applies to patients with TBI or other types of acquired brain injury. The emphasis is on the application of scientist-practitioner standards as they apply to legal questions about the status of a TBI patient and how best that may be achieved. This article introduces each topic area covered in this special edition.
persons, and leaves 99,000 persons permanently disabled . The total cost for treatment and rehabilitation of patients with brain injuries is...registry based or retrospective or include only secondary insults that occur in the intensive care unit ( ICU ) setting. Most prior investigations have...in the surgical and neurosurgical ICU diagnosed with a traumatic brain injury requiring a diagnostic procedure were eligible for the study. The study
and a tracking of these measures over time both as a means to document and understand the normal recovery process and response to treatment and to...N, Macdonald R, Rutks I, Sayer NA, Dobscha SK and Wilt TJ. Prevalence, assessment, and treatment of mild traumatic brain injury and posttraumatic...potentially modifiable factors. 0078 Chiropractic Sacro Occipital Technique (SOT) and Cranial Treatment Model for Traumatic Brain Injury Along with
Wei, Jing; Xiao, Guo-min
Traumatic brain injury is the leading cause of morbidity and mortality in young adults. The secondary injury in traumatic brain injury consists of a complex cascade of processes that simultaneously react to the primary injury to the brain. This cascade has been the target of numerous therapeutic agents investigated over the last 30 years, but no neuroprotective treatment option is currently available that improve neurological outcome after traumatic brain injury. Progesterone has long been considered merely a female reproductive hormone. Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans. Here, we review the increasing evidence that progesterone can act as a neuroprotective agent to treat traumatic brain injury and the mechanisms underlying these effects. Additionally, we discuss the current progress of clinical studies on the application of progesterone in the treatment of traumatic brain injuries. PMID:24241345
Bartlett, Sue; Lorenz, Laura; Rankin, Theresa; Elias, Eileen; Weider, Katie
This article is the eighth of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received limited national attention and support. However, since it is the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained attention of elected officials, military leaders, policymakers, and the public. The…
Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen
This article is the first of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received very limited national public policy attention and support. However since it has become the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained the attention of elected officials, military leaders,…
Oudeman, Eline A; Martins Jarnalo, Carine O; van Ouwerkerk, Willem J R
We present a 41-year-old man with severe traumatic brain injury. Cranial imaging studies revealed cerebral contusion and a longitudinal fracture of the temporal bone. Several days later brain herniated into the left external auditory canal. Imaging studies showed the known skull fracture with a direct connection between the external acoustic meatus and the intracranial structures.
02139 D. Moore Defense and Veterans Brain Injury Center (WRAMC) 6900 Georgia Ave. NW, Washington, DC 20307 L. Noels University of Liege Chemin des...chevreuils 1, B4000 Liege , Belgium ABSTRACT Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain in
Lucke-Wold, Brandon P; Nguyen, Linda; Turner, Ryan C; Logsdon, Aric F; Chen, Yi-Wen; Smith, Kelly E; Huber, Jason D; Matsumoto, Rae; Rosen, Charles L; Tucker, Eric S; Richter, Erich
Post-traumatic epilepsy continues to be a major concern for those experiencing traumatic brain injury. Post-traumatic epilepsy accounts for 10-20% of epilepsy cases in the general population. While seizure prophylaxis can prevent early onset seizures, no available treatments effectively prevent late-onset seizure. Little is known about the progression of neural injury over time and how this injury progression contributes to late onset seizure development. In this comprehensive review, we discuss the epidemiology and risk factors for post-traumatic epilepsy and the current pharmacologic agents used for treatment. We highlight limitations with the current approach and offer suggestions for remedying the knowledge gap. Critical to this pursuit is the design of pre-clinical models to investigate important mechanistic factors responsible for post-traumatic epilepsy development. We discuss what the current models have provided in terms of understanding acute injury and what is needed to advance understanding regarding late onset seizure. New model designs will be used to investigate novel pathways linking acute injury to chronic changes within the brain. Important components of this transition are likely mediated by toll-like receptors, neuroinflammation, and tauopathy. In the final section, we highlight current experimental therapies that may prove promising in preventing and treating post-traumatic epilepsy. By increasing understanding about post-traumatic epilepsy and injury expansion over time, it will be possible to design better treatments with specific molecular targets to prevent late-onset seizure occurrence following traumatic brain injury.
It has been well known that alcohol consumption affects traumatic brain injury. The mechanism of detrimental effect of ethanol on traumatic brain injury has not been clarified. This review focused on the relationship among traumatic brain injury, ethanol and aquaporin-4. We have reported that ethanol increased brain edema after brain contusion and decreased survival rates in rats. It was suggested that increasing brain edema by ethanol after brain contusion may be caused by oxidative stress. Brain edema consists of cytotoxic brain edema, vasogenic brain edema, interstitial brain edema and osmotic edema. Ethanol mainly increases cytotoxic brain edema. Both alcohol consumption and brain contusion cause oxidative stress. Antioxidant treatment decreases cytotoxic brain edema. Aquaporin-4, an water channel, was increased by ethanol 24 hr after traumatic brain injury in rat. The aquaporin-4 inhibitor decreased brain edema after brain contusion and increased survival rates under ethanol consumption. Aquaporin-4 may have strict relation between ethanol and brain edema increasing after brain contusion.
An 8 yr old spayed female Yorkshire terrier was referred for evaluation of progressive neurological signs after a routine dental prophylaxis with tooth extractions. The patient was circling to the left and blind in the right eye with right hemiparesis. Neurolocalization was to the left forebrain. MRI revealed a linear tract extending from the caudal oropharynx, through the left retrobulbar space and frontal lobe, into the left parietal lobe. A small skull fracture was identified in the frontal bone through which the linear tract passed. Those findings were consistent with iatrogenic trauma from slippage of a dental elevator during extraction of tooth 210. The dog was treated empirically with clindamycin. The patient regained most of its normal neurological function within the first 4 mo after the initial injury. Although still not normal, the dog has a good quality of life. Traumatic brain injury is a rarely reported complication of extraction. Care must be taken while performing dental cleaning and tooth extraction, especially of the maxillary premolar and molar teeth to avoid iatrogenic damage to surrounding structures.
Hannawi, Yousef; Stevens, Robert D
There is a paucity of accurate and reliable biomarkers to detect traumatic brain injury, grade its severity, and model post-traumatic brain injury (TBI) recovery. This gap could be addressed via advances in brain mapping which define injury signatures and enable tracking of post-injury trajectories at the individual level. Mapping of molecular and anatomical changes and of modifications in functional activation supports the conceptual paradigm of TBI as a disorder of large-scale neural connectivity. Imaging approaches with particular relevance are magnetic resonance techniques (diffusion weighted imaging, diffusion tensor imaging, susceptibility weighted imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, and positron emission tomographic methods including molecular neuroimaging). Inferences from mapping represent unique endophenotypes which have the potential to transform classification and treatment of patients with TBI. Limitations of these methods, as well as future research directions, are highlighted.
Viola-Saltzman, Mari; Watson, Nathaniel F.
SYNOPSIS Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. Two types of TBI negatively impact sleep: contact injuries causing focal brain damage and acceleration/deceleration injuries causing more generalized brain damage. Diagnosis of sleep disorders after TBI may involve polysomnography, multiple sleep latency testing and/or actigraphy. Treatment is disorder specific and may include the use of medications, continuous positive airway pressure (or similar device) and/or behavioral modifications. Unfortunately, treatment of sleep disorders associated with TBI often does not improve sleepiness or neuropsychological function. PMID:23099139
McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A
Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.
Nudo, Randolph J.
The past 20 years have represented an important period in the development of principles underlying neuroplasticity, especially as they apply to recovery from neurological injury. It is now generally accepted that acquired brain injuries, such as occur in stroke or trauma, initiate a cascade of regenerative events that last for at least several weeks, if not months. Many investigators have pointed out striking parallels between post-injury plasticity and the molecular and cellular events that take place during normal brain development. As evidence for the principles and mechanisms underlying post-injury neuroplasticity has been gleaned from both animal models and human populations, novel approaches to therapeutic intervention have been proposed. One important theme has persisted as the sophistication of clinicians and scientists in their knowledge of neuroplasticity mechanisms has grown: behavioral experience is the most potent modulator of brain plasticity. While there is substantial evidence for this principle in normal, healthy brains, the injured brain is particularly malleable. Based on the quantity and quality of motor experience, the brain can be reshaped after injury in either adaptive or maladaptive ways. This paper reviews selected studies that have demonstrated the neurophysiological and neuroanatomical changes that are triggered by motor experience, by injury, and the interaction of these processes. In addition, recent studies using new and elegant techniques are providing novel perspectives on the events that take place in the injured brain, providing a real-time window into post-injury plasticity. These new approaches are likely to accelerate the pace of basic research, and provide a wealth of opportunities to translate basic principles into therapeutic methodologies. PMID:24399951
Jantz, Paul B.; Coulter, Gail A.
More than five million children suffer from brain injuries each year. While the majority of these children are treated and released without permanent consequences, many children return to the classroom with lasting effects. Symptoms of brain injury can be misconstrued as common behaviour or academic problems. Therefore, teachers need to recognize…
Browning, Megan; Shear, Deborah A; Bramlett, Helen M; Dixon, C Edward; Mondello, Stefania; Schmid, Kara E; Poloyac, Samuel M; Dietrich, W Dalton; Hayes, Ronald L; Wang, Kevin K W; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M
Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C-terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT.
Solmaz, Berkan; Tunç, Birkan; Parker, Drew; Whyte, John; Hart, Tessa; Rabinowitz, Amanda; Rohrbach, Morgan; Kim, Junghoon; Verma, Ragini
Many of the clinical and behavioral manifestations of traumatic brain injury (TBI) are thought to arise from disruption to the structural network of the brain due to diffuse axonal injury (DAI). However, a principled way of summarizing diffuse connectivity alterations to quantify injury burden is lacking. In this study, we developed a connectome injury score, Disruption Index of the Structural Connectome (DISC), which summarizes the cumulative effects of TBI-induced connectivity abnormalities across the entire brain. Forty patients with moderate-to-severe TBI examined at 3 months postinjury and 35 uninjured healthy controls underwent magnetic resonance imaging with diffusion tensor imaging, and completed behavioral assessment including global clinical outcome measures and neuropsychological tests. TBI patients were selected to maximize the likelihood of DAI in the absence of large focal brain lesions. We found that hub-like regions, with high betweenness centrality, were most likely to be impaired as a result of diffuse TBI. Clustering of participants revealed a subgroup of TBI patients with similar connectivity abnormality profiles who exhibited relatively poor cognitive performance. Among TBI patients, DISC was significantly correlated with post-traumatic amnesia, verbal learning, executive function, and processing speed. Our experiments jointly demonstrated that assessing structural connectivity alterations may be useful in development of patient-oriented diagnostic and prognostic tools. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Wu, Qiuhe; Huang, Ying-Ying; Dhital, Saphala; Sharma, Sulbha K.; Chen, Aaron C.-H.; Whalen, Michael J.; Hamblin, Michael R.
Low level laser (or light) therapy (LLLT) has been clinically applied for many indications in medicine that require the following processes: protection from cell and tissue death, stimulation of healing and repair of injuries, and reduction of pain, swelling and inflammation. One area that is attracting growing interest is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may have beneficial effects in the acute treatment of brain damage injury by increasing respiration in the mitochondria, causing activation of transcription factors, reducing key inflammatory mediators, and inhibiting apoptosis. We tested LLLT in a mouse model of TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with 660-nm, 810-nm or 980-nm laser (36 J/cm2) four hours post-injury and were followed up by neurological performance testing for 4 weeks. Mice with moderate to severe TBI treated with 660- nm and 810-nm laser had a significant improvement in neurological score over the course of the follow-up and histological examination of the brains at sacrifice revealed less lesion area compared to untreated controls. Further studies are underway.
Fleminger, Simon; Oliver, Donna L; Williams, W Huw; Evans, Jonathan
Biological aspects of depression after brain injury, in particular traumatic brain injury (TBI) and stroke, are reviewed. Symptoms of depression after brain injury are found to be rather non-specific with no good evidence of a clear pattern distinguishing it from depression in those without brain injury. Nevertheless symptoms of disturbances of interest and concentration are particularly prevalent, and guilt is less evident. Variabilitiy of mood is characteristic. The prevalence of depression is similar after both stroke and TBI with the order of 20-40% affected at any point in time in the first year, and about 50% of people experience depression at some stage. There is no good evidence for areas of specific vulnerability in terms of lesion location, and early suggestions of a specific association with injury to the left hemisphere have not been confirmed. Insight appears to be related to depressed mood with studies of TBI indicating that greater insight over time post-injury may be associated with greater depression. We consider that this relationship may be due to depression appearing as people gain more awareness of their disability, but also suggest that changes in mood may result in altered awareness. The risk of suicide after TBI is reviewed. There appears to be about a three to fourfold increased risk of suicide after TBI, although much of this increased risk may be due to pre-injury factors in terms of the characteristics of people who suffer TBI. About 1% of people who have suffered TBI will commit suicide over a 15-year follow-up. Drug management of depression is reviewed. There is little specific evidence to guide the choice of antidepressant medication and most psychiatrists would start with a selective serotonin reuptake inhibitor (SSRI). It is important that the drug management of depression after brain injury is part of a full package of care that can address biological as well as psychosocial factors in management.
Feng, Yangzheng; Paul, Ian A; LeBlanc, Michael H
Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.
Feng, Yangzheng; Paul, Ian A.; LeBlanc, Michael H.
Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity. PMID:16533659
Lane, Amy K; Benoit, Dana
Individuals with brain injury often present with cognitive, physical and emotional impairments which impact their ability to resume independence in activities of daily living. Of those activities, the resumption of driving privileges is cited as one of the greatest concerns by survivors of brain injury. The integration of driving fundamentals within the hierarchical model proposed by Keskinen represents the complexity of skills and behaviors necessary for driving. This paper provides a brief review of specific considerations concerning the driver with TBI and highlights current vehicle technology which has been developed by the automotive industry and by manufacturers of adaptive driving equipment that may facilitate the driving task. Adaptive equipment technology allows for compensation of a variety of operational deficits, whereas technological advances within the automotive industry provide drivers with improved safety and information systems. However, research has not yet supported the use of such intelligent transportation systems or advanced driving systems for drivers with brain injury. Although technologies are intended to improve the safety of drivers within the general population, the potential of negative consequences for drivers with brain injury must be considered. Ultimately, a comprehensive driving evaluation and training by a driving rehabilitation specialist is recommended for individuals with brain injury. An understanding of the potential impact of TBI on driving-related skills and knowledge of current adaptive equipment and technology is imperative to determine whether return-to-driving is a realistic and achievable goal for the individual with TBI.
Mckee, Ann C; Daneshvar, Daniel H
Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at
Liu, Su; Shen, Guangyu; Deng, Shukun; Wang, Xiubin; Wu, Qinfeng; Guo, Aisong
Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney's free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats' spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was significantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly improves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is mediated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.
Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J
Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children.
Goldberg, Scott A; Rojanasarntikul, Dhanadol; Jagoda, Andrew
Traumatic brain injury (TBI) is an important cause of death and disability, particularly in younger populations. The prehospital evaluation and management of TBI is a vital link between insult and definitive care and can have dramatic implications for subsequent morbidity. Following a TBI the brain is at high risk for further ischemic injury, with prehospital interventions targeted at reducing this secondary injury while optimizing cerebral physiology. In the following chapter we discuss the prehospital assessment and management of the brain-injured patient. The initial evaluation and physical examination are discussed with a focus on interpretation of specific physical examination findings and interpretation of vital signs. We evaluate patient management strategies including indications for advanced airway management, oxygenation, ventilation, and fluid resuscitation, as well as prehospital strategies for the management of suspected or impending cerebral herniation including hyperventilation and brain-directed hyperosmolar therapy. Transport decisions including the role of triage models and trauma centers are discussed. Finally, future directions in the prehospital management of traumatic brain injury are explored.
AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation...Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain...as a method for treating pain and autonomic dysreflexia in patients with chronic spinal cord injury (SCI). It is collaboration between the
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Traumatic brain injury (TBI) remains a major cause of death and permanent disability worldwide, especially in children and young adults. A total of 1.5 million people experience head trauma each year in the United States, with an annual economic cost exceeding $56 billion. Unfortunately, almost all Phase III TBI clinical trials have yet to yield a safe and effective neuroprotective treatment, raising questions regarding the use of neuroprotective strategies as the primary therapy for acute brain injuries. Recent preclinical data suggest that neurorestorative strategies that promote angiogenesis (formation of new blood vessels from pre-existing endothelial cells), axonal remodeling (axonal sprouting and pruning), neurogenesis (generation of new neurons) and synaptogenesis (formation of new synapses) provide promising opportunities for the treatment of TBI. This review discusses select cell-based and pharmacological therapies that activate and amplify these endogenous restorative brain plasticity processes to promote both repair and regeneration of injured brain tissue and functional recovery after TBI. PMID:21122475
Max, Jeffrey E.
Synopsis Pediatric traumatic brain injury (TBI) is a major public health problem. Psychiatric disorders with onset before the injury appear to be more common than population base rates. Novel (postinjury onset) psychiatric disorders (NPD) are also common and complicate child function after injury. Novel disorders include personality change due to TBI, secondary attention-deficit/hyperactivity disorder (SADHD), as well as other disruptive behavior disorders, and internalizing disorders. This article reviews preinjury psychiatric disorders as well as biopsychosocial risk factors and treatments for NPD. PMID:24529428
Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.
Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177
Degen, Ryan M; Fink, Matthew E; Callahan, Lisa; Fibel, Kenton H; Ramsay, Jim; Kelly, Bryan T
Head injuries are relatively common in ice hockey, with the majority represented by concussions, a form of mild traumatic brain injury. More severe head injuries are rare since the implementation of mandatory helmet use in the 1960s. We present a case of a 27 year-old male who sustained a traumatic intraparenchymal hemorrhage with an associated subdural hematoma resulting after being struck by a puck shot at high velocity. The patient presented with expressive aphasia, with no other apparent neurologic deficits. Acutely, he was successfully treated with observation and serial neuroimaging studies ensuring an absence of hematoma expansion. After a stable clinical picture following 24 hours of observation, the patient was discharged and managed with outpatient speech therapy with full resolution of symptoms and return to play 3 months later. We will outline the patient presentation and pertinent points in the management of acute head injuries in athletes.
... 162672.html Better Sleep May Signal Recovery From Brain Injury New research suggests sleep-wake cycles are ... Dec. 21, 2016 (HealthDay News) -- Recovery from traumatic brain injury appears to go hand-in-hand with ...
Lin, Zhenlang; Hu, Yingying; Wang, Zhouguang; Pan, Shulin; Zhang, Hao; Ye, Libing; Zhang, Hongyu; Fang, Mingchu; Jiang, Huai; Ye, Junming; Xiao, Jian; Liu, Li
Brain injury secondary to birth asphyxia is the major cause of death and long-term disability in newborns. Intranasal drug administration enables agents to bypass the blood-brain barrier (BBB) and enter the brain directly. In this study, we determined whether intranasal basic fibroblast growth factor (bFGF) could exert neuroprotective effects in neonatal rats after hypoxic-ischaemic (HI) brain injury and assessed whether attenuation of endoplasmic reticulum (ER) stress was associated with these neuroprotective effects. Rats were subjected to HI brain injury via unilateral carotid artery ligation followed by 2.5 h of hypoxia and then treated with intranasal bFGF or vehicle immediately after HI injury. We found that the unfolded protein response (UPR) was strongly activated after HI injury and that bFGF significantly reduced the levels of the ER stress signalling proteins GRP78 and PDI. bFGF also decreased brain infarction volumes and conferred long-term neuroprotective effects against brain atrophy and neuron loss after HI brain injury. Taken together, our results suggest that intranasal bFGF provides neuroprotection function partly by inhibiting HI injury-induced ER stress. bFGF may have potential as a therapy for human neonates after birth asphyxia. PMID:28337259
Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei
Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618
Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei
Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP.
Meyers, Joseph D; Doane, Tennyson; Burda, Clemens; Basilion, James P
Brain cancer tumors cause disruption of the selective properties of vascular endothelia, even causing disruptions in the very selective blood–brain barrier, which are collectively referred to as the blood–brain–tumor barrier. Nanoparticles (NPs) have previously shown great promise in taking advantage of this increased vascular permeability in other cancers, which results in increased accumulation in these cancers over time due to the accompanying loss of an effective lymph system. NPs have therefore attracted increased attention for treating brain cancer. While this research is just beginning, there have been many successes demonstrated thus far in both the laboratory and clinical setting. This review serves to present the reader with an overview of NPs for treating brain cancer and to provide an outlook on what may come in the future. For NPs, just like the blood–brain–tumor barrier, the future is wide open. PMID:23256496
Knox, Renatta; Jiang, Xiangning
The Src Family kinases (SFKs) are nonreceptor protein tyrosine kinases that are implicated in many normal and pathological processes in the nervous system. The SFKs Fyn, Src, Yes, Lyn and Lck are expressed in the brain. This review will focus on Fyn, as Fyn mutant mice have striking phenotypes in the brain and Fyn has been shown to be involved in ischemic brain injury in adult rodents, and with our work, in neonatal animals. An understanding of Fyn’s role in neurodevelopment and disease will allow researchers to target pathological pathways while preserving protective ones. PMID:25720756
Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio
Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS less than 8) in the phase of neurological stability and 14 neurologically intact participants…
Adams, Elaine Parker; Adams, Albert A., Jr.
This article goes beyond the typical guidance on how to address the educational needs of students with traumatic brain injury (TBI). A survivor of TBI and his parent advocate describe real-life encounters in the education arena and offer ways to respond to the problems depicted in the situations. Their candor enhances educator awareness of the…
Mohr, J. Darrell; Bullock, Lyndal M.
This article reports the outcomes from 2 focus groups conducted to ascertain professional educators' perceptions regarding their (a) level of preparedness for working with students with traumatic brain injury (TBI), (b) ideas regarding ways to improve support to students and families, and (c) concerns about meeting the diverse needs of children…
Lucas, Matthew D.
The participation of a student with Traumatic Brain Injury (TBI) in general physical education can often be challenging and rewarding for the student and physical education teacher. This article addresses common characteristics of students with TBI and presents basic solutions to improve the education of students with TBI in the general physical…
Schwarzbold, Marcelo; Diaz, Alexandre; Martins, Evandro Tostes; Rufino, Armanda; Amante, Lúcia Nazareth; Thais, Maria Emília; Quevedo, João; Hohl, Alexandre; Linhares, Marcelo Neves; Walz, Roger
Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed. PMID:19043523
The acadmic placement of 87 children (ages 6 to 16 years) who had sustained brain injuries was determined within 1 year after initial psychological assessment. Forty-five children had returned full time to regular academic programs, 21 children received special education support for less than half of their classes, and 21 children were enrolled in…
Fowler, Marc; McCabe, Paul C.
Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in the United States for individuals below the age of 45. Current estimates from the Center for Disease Control (CDC) indicate that at least 1.4 million Americans sustain a TBI annually. TBI affects 475,000 children under age 14 each year in the United States alone.…
Corthell, David W., Ed.
Intended to serve as a resource guide on traumatic brain injury for rehabilitation practitioners, the book's 10 chapters are grouped into sections which provide an introduction and examine aspects of evaluation, treatment and placement planning, and unresolved issues. Chapters have the following titles and authors: "Scope of the Problem" (Marilyn…
Deidrick, Kathleen K. M.; Farmer, Janet E.
Successful school reentry following traumatic brain injury (TBI) is critical to recovery. Physical, cognitive, behavioral, academic, and social problems can affect a child's school performance after a TBI. However, early intervention has the potential to improve child academic outcomes and promote effective coping with any persistent changes in…
Markowitz, Joy; Linehan, Patrice
This brief paper summarizes information concerning use of the traumatic brain injury (TBI) disability classification by states and the nature of state-level activities related to the education of children and youth with TBI. It notes addition of the TBI disability category to the Individuals with Disabilities Education Act in 1990 and provides the…
New York State Education Dept., Albany. Office for Special Education Services.
This guidebook is designed to help New York school staff better understand the specialized needs of students with traumatic brain injury (TBI) and appropriately apply educational interventions to improve special and general education services for these students. It provides information on the following areas: (1) the causes, incidence, and…
Gennarelli, Thomas A
This paper reviews the potential future directions that are important for brain injury research, especially with regard to concussion. The avenues of proposed research are categorized according to current concepts of concussion, types of concussion, and a global schema for globally reducing the burden of concussion.
Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard
The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…
Bahraini, Nazanin H; Breshears, Ryan E; Hernández, Theresa D; Schneider, Alexandra L; Forster, Jeri E; Brenner, Lisa A
Given the upsurge of research in posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), much of which has focused on military samples who served in Iraq and Afghanistan, the purpose of this article is to review the literature published after September 11th, 2001 that addresses the epidemiology, pathophysiology, evaluation, and treatment of PTSD in the context of TBI.
Reid, Matthew W; Velez, Carmen S
Traumatic brain injury (TBI) occurs at higher rates among service members than civilians. Explosions from improvised explosive devices and mines are the leading cause of TBI in the military. As such, TBI is frequently accompanied by other injuries, which makes its diagnosis and treatment difficult. In addition to postconcussion symptoms, those who sustain a TBI commonly report chronic pain and posttraumatic stress symptoms. This combination of symptoms is so typical they have been referred to as the "polytrauma clinical triad" among injured service members. We explore whether these symptoms discriminate civilian occurrences of TBI from those of service members, as well as the possibility that repeated blast exposure contributes to the development of chronic traumatic encephalopathy (CTE). This article is part of a Special Issue entitled 'Traumatic Brain Injury'.
Blyth, Brian J.; Bazarian, Jeffrey J.
Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244
Nordlund, Marcia R.
There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…
Morgan, A. S.
Most physical injuries in this country are the result of motorized vehicle accidents. Head trauma accounts for one fourth of all trauma deaths, and the cost to treat patients with head trauma is $83 billion. The author discusses injury patterns, methods of resuscitating patients with head injuries, surgical management and monitoring, and the clinical course and prospects for rehabilitation. An interdisciplinary approach to the management of such patients is encouraged, and the medical and surgical interventions undertaken at one institution are reviewed. PMID:2695652
Thurman, David J
This report reviews recent research on the epidemiology of traumatic brain injuries among children and youth aged 0 to 20 years. Studies representing populations in North America, Europe, Australia, and New Zealand yield these median estimates of the annual incidence of childhood brain injuries: 691 per 100 000 population treated in emergency departments, 74 per 100 000 treated in hospital, and 9 per 100 000 resulting in death. Males have a higher risk of injury than females: 1.4 times higher among those aged less than 10 years and 2.2 times among those older than 10 years. The leading cause of injury among children aged less than 5 years is falls, whereas the leading cause of injury among youths aged 15 years and older is motor vehicle crashes. The prevalence of disability among all persons who have sustained traumatic brain injury in childhood is unknown, but among those who were hospitalized could approximate 20%.
Wintermark, M; Coombs, L; Druzgal, T J; Field, A S; Filippi, C G; Hicks, R; Horton, R; Lui, Y W; Law, M; Mukherjee, P; Norbash, A; Riedy, G; Sanelli, P C; Stone, J R; Sze, G; Tilkin, M; Whitlow, C T; Wilde, E A; York, G; Provenzale, J M
The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic
Shultz, Sandy R; Wright, David K; Zheng, Ping; Stuchbery, Ryan; Liu, Shi-Jie; Sashindranath, Maithili; Medcalf, Robert L; Johnston, Leigh A; Hovens, Christopher M; Jones, Nigel C; O'Brien, Terence J
, attenuated brain damage, and improved behavioural outcomes in rats given a fluid percussion injury. Notably, total tau levels were decreased in rats 12 weeks after fluid percussion injury, and several other factors, including the use of anaesthetic, the length of recovery time, and that some brain injury and behavioural dysfunction still occurred in rats treated with sodium selenate must be considered in the interpretation of this study. However, taken together these data suggest protein phosphatase 2A and hyperphosphorylated tau may be involved in the neurodegenerative cascade of traumatic brain injury, and support the potential use of sodium selenate as a novel traumatic brain injury therapy.
Katzenberger, Rebeccah J; Ganetzky, Barry; Wassarman, David A
Traumatic brain injury (TBI) is a complex disorder that affects millions of people worldwide. The complexity of TBI partly stems from the fact that injuries to the brain instigate non-neurological injuries to other organs such as the intestine. Additionally, genetic variation is thought to play a large role in determining the nature and severity of non-neurological injuries. We recently reported that TBI in flies, as in humans, increases permeability of the intestinal epithelial barrier resulting in hyperglycemia and a higher risk of death. Furthermore, we demonstrated that genetic variation in flies is also pertinent to the complexity of non-neurological injuries following TBI. The goals of this review are to place our findings in the context of what is known about TBI-induced intestinal permeability from studies of TBI patients and rodent TBI models and to draw attention to how studies of the fly TBI model can provide unique insights that may facilitate diagnosis and treatment of TBI. PMID:26291482
Award Number: W81XWH-08-2-0017 TITLE: " Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...TITLE AND SUBTITLE 5a. CONTRACT NUMBER “ Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...traumatic brain injury (bTBI) is largely undefined. Along with reducing mortality, in preliminary experiments Kevlar vests significantly protected
Chapman, Julie C; Diaz-Arrastia, Ramon
Military mild traumatic brain injury (mTBI) differs from civilian injury in important ways. Although mTBI sustained in both military and civilian settings are likely to be underreported, the combat theater presents additional obstacles to reporting and accessing care. The impact of blast forces on the nervous system may differ from nonblast mechanisms, mTBI although studies comparing the neurologic and cognitive sequelae in mTBI survivors have not provided such evidence. However, emotional distress appears to figure prominently in symptoms following military mTBI. This review evaluates the extant literature with an eye towards future research directions.
Neistadt, M E
Adults with acquired brain injury often demonstrate dysfunction in meal preparation due to deficits in component cognitive-perceptual skills. Although occupational therapy for these clients routinely includes meal preparation training, there are no protocols in the occupational therapy literature to help structure that activity to address clients' cognitive-perceptual deficits. This paper describes a meal preparation treatment protocol based on cognitive-perceptual information processing theory that has been pilot tested in a treatment outcome study with adult men with traumatic or anoxic acquired brain injury. In that study, the group of 23 subjects treated with this meal preparation protocol showed significant improvement in their meal preparation skill, as measured by the Rabideau Kitchen Evaluation-Revised (RKE-R), a test of meal preparation skill, and in their cognitive-perceptual skill, as measured by the WAIS-R Block Design Test. The treatment protocol includes descriptions of the structure, grading, and cuing methods for light meal preparation activities.
Engelman, William; Hammond, Flora M; Malec, James F
Pseudobulbar affect (PBA) is defined by episodes of involuntary crying and/or laughing as a result of brain injury or other neurological disease. Epidemiology studies show that 5.3%–48.2% of people with traumatic brain injury (TBI) may have symptoms consistent with (or suggestive of) PBA. Yet it is a difficult and often overlooked condition in individuals with TBI, and is easily confused with depression or other mood disorders. As a result, it may be undertreated and persist for longer than it should. This review presents the signs and symptoms of PBA in patients with existing TBI and outlines how to distinguish PBA from other similar conditions. It also compares and contrasts the different diagnostic criteria found in the literature and briefly mentions appropriate treatments. This review follows a composite case with respect to the clinical course and treatment for PBA and presents typical challenges posed to a provider when diagnosing PBA. PMID:25336956
Aggarwal, Neil Krishan; Ford, Elizabeth
Neuroethics and neurolaw are fields of study that involve the interface of neuroscience with clinical and legal decision-making. The past two decades have seen increasing attention being paid to both fields, in large part because of the advances in neuroimaging techniques and improved ability to visualize and measure brain structure and function. Traumatic brain injury (TBI), along with its acute and chronic sequelae, has emerged as a focus of neuroethical issues, such as informed consent for treatment and research, diagnostic and prognostic uncertainties, and the subjectivity of interpretation of data. The law has also more frequently considered TBI in criminal settings for exculpation, mitigation and sentencing purposes and in tort and administrative law for personal injury, disability and worker's compensation cases. This article provides an overview of these topics with an emphasis on the current challenges that the neuroscience of TBI faces in the medicolegal arena.
Katada, Ryuichi; Watanabe, Satoshi; Ishizaka, Atsushi; Mizuo, Keisuke; Okazaki, Shunichiro; Matsumoto, Hiroshi
Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.
significant but still remains to be studied. Literature has pointed to the role of q in the entropy computation for EEG studies . In our study it is... EEG in the form of reduction during the bad physiological function outcome. The reduction level and recovery rate of TE are also consistent with...USA Abstract- Nonextensive entropy measure, Tsallis Entropy (TE), was undertaken to monitor the brain injury after cardiac arrest. EEG of human and
Russo, Matthew V.; McGavern, Dorian B.
Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed. PMID:27540166
Kochanek, Patrick M.; Jackson, Travis C.; Ferguson, Nikki Miller; Carlson, Shaun W.; Simon, Dennis W.; Brockman, Erik C.; Ji, Jing; Bayir, Hülya; Poloyac, Samuel M.; Wagner, Amy K.; Kline, Anthony E.; Empey, Philip E.; Clark, Robert S.B.; Jackson, Edwin K.; Dixon, C. Edward
Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discuss TBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field. PMID:25714870
Ling, Geoffrey S. F.; Hawley, Jason; Grimes, Jamie; Macedonia, Christian; Hancock, James; Jaffee, Michael; Dombroski, Todd; Ecklund, James M.
Traumatic brain injury (TBI) is common and especially with military service. In Iraq and Afghanistan, explosive blast related TBI has become prominent and is mainly from improvised explosive devices (IED). Civilian standard of care clinical practice guidelines (CPG) were appropriate has been applied to the combat setting. When such CPGs do not exist or are not applicable, new practice standards for the military are created, as for TBI. Thus, CPGs for prehospital care of combat TBI CPG  and mild TBI/concussion  were introduced as was a DoD system-wide clinical care program, the first large scale system wide effort to address all severities of TBI in a comprehensive organized way. As TBI remains incompletely understood, substantial research is underway. For the DoD, leading this effort are The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. This program is a beginning, a work in progress ready to leverage advances made scientifically and always with the intent of providing the best care to its military beneficiaries.
Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping
Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury.
Hoane, Michael R; Kaplan, Shelby A; Ellis, Amy L
Nicotinamide has been shown to protect against many of the pathophysiological factors associated with both ischemic and traumatic brain injuries. The present study evaluated the neuroprotective effect of nicotinamide on the breakdown of the blood-brain barrier (BBB) and apoptosis expression following traumatic brain injury (TBI). Animals were prepared with a unilateral cortical contusion injury (CCI). Fifteen minutes following injury the animals received either nicotinamide (500 mg/kg, ip) or 0.9% saline. The animals were perfused at 5, 24, and 72 h post-injury. BBB integrity was assessed by endogenous rat IgG immunoreactivity. Recent studies have shown that IgG immunoreactivity is a reliable measure of BBB integrity. The results indicated that IgG immunoreactivity was greatest at 5 h and declined at 24 h after injury. Nicotinamide significantly reduced IgG expression at every time point following injury. Apoptosis was examined using the TUNEL method. The results indicated that TUNEL immunoreactivity peaked at 24 h. TUNEL(+) cells were classified morphologically as nonapoptotic (Type I) or apoptotic (Type II) to verify that the neuroprotective effects of nicotinamide occur by inhibiting apoptosis or necrosis. Administration of nicotinamide significantly reduced the expression of all TUNEL(+) cells in the tissue surrounding the lesion cavity. Specifically there was a significant reduction in the number of Type I, Type II, and Total TUNEL(+) cells in the nicotinamide-treated animals. In addition, nicotinamide reduced lesion cavity expansion 72 h following CCI. These findings suggest that nicotinamide reduces BBB breach and neuronal cell loss acutely following injury and that these reductions may account for the beneficial behavioral effects seen in previous studies.
This guide is an introduction to head injury and to educational resources in the field. An introductory section describes traumatic brain injury (TBI) as a federally recognized disability category and provides its federal and Idaho definitions. The following section introduces the unique characteristics of students with brain injuries. A section…
Boardman, J P; Dyet, L E
Survivors of preterm birth are at high risk of neurocognitive impairment in childhood, but the disturbances to brain growth and function that underlie impairment are not completely understood. Improvements in perinatal care have led to a reduction in the major destructive parenchymal brain lesions that are associated with motor impairment, such as cystic periventricular leucomalacia and haemorrhagic parenchymal infarction. However, with the application of advanced magnetic resonance (MR) imaging and processing techniques in the neonatal period, subtle alterations in brain development have become apparent. These changes occur with similar frequency to long-term neurocognitive impairment, and may therefore represent candidate neural substrates for this group of disorders. Here we review the range of lesions and associated outcomes that are seen in the current era of perinatal care, and discuss how state of the art MR imaging techniques have helped to define the neural systems affected by preterm birth, and have provided insights into understanding mechanisms of injury.
Browne, Kevin D.; Chen, Xiao-Han; Meaney, David F.
Abstract Until recently, mild traumatic brain injury (mTBI) or “concussion” was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness. PMID:21740133
Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang
Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue.
Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang
Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644
Fiegenbaum, Ed, Ed.; And Others
This manual for the Portland (Oregon) Public Schools presents basic information on providing educational services to children with traumatic brain injury (TBI). Individual sections cover the following topics: the brain, central nervous system and behavior; physical, psychological and emotional implication; traumatic brain injury in children versus…
McKee, Celia A.; Lukens, John R.
Traumatic brain injury (TBI) affects an ever-growing population of all ages with long-term consequences on health and cognition. Many of the issues that TBI patients face are thought to be mediated by the immune system. Primary brain damage that occurs at the time of injury can be exacerbated and prolonged for months or even years by chronic inflammatory processes, which can ultimately lead to secondary cell death, neurodegeneration, and long-lasting neurological impairment. Researchers have turned to rodent models of TBI in order to understand how inflammatory cells and immunological signaling regulate the post-injury response and recovery mechanisms. In addition, the development of numerous methods to manipulate genes involved in inflammation has recently expanded the possibilities of investigating the immune response in TBI models. As results from these studies accumulate, scientists have started to link cells and signaling pathways to pro- and anti-inflammatory processes that may contribute beneficial or detrimental effects to the injured brain. Moreover, emerging data suggest that targeting aspects of the immune response may offer promising strategies to treat TBI. This review will cover insights gained from studies that approach TBI research from an immunological perspective and will summarize our current understanding of the involvement of specific immune cell types and cytokines in TBI pathogenesis. PMID:27994591
Andrews, Allison M.; Lutton, Evan M.; Merkel, Steven F.; Razmpour, Roshanak; Ramirez, Servio H.
It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma
Munivenkatappa, Ashok; Agrawal, Amit
Degree of recovery after traumatic brain injury is highly variable that lasts for many weeks to months. The evidence of brain structures involved in recovery mechanisms is limited. This review highlights evidence of the brain structure particularly thalamus in neuroplasticity mechanism. Thalamus with its complex global networking has potential role in refining the cortical and other brain structures. Thalamic nuclei activation both naturally or by neurorehabilitation in injured brain can enhance and facilitate the improvement of posttraumatic symptoms. This review provides evidence from literature that thalamus plays a key role in recovery mechanism after injury. The study also emphasize that thalamus should be specifically targeted in neurorehabilitation following brain injury. PMID:28163509
Zitnay, George A; Zitnay, Kevin M; Povlishock, John T; Hall, Edward D; Marion, Donald W; Trudel, Tina; Zafonte, Ross D; Zasler, Nathan; Nidiffer, F Don; DaVanzo, John; Barth, Jeffrey T
In 2005, an international symposium was convened with over 100 neuroscientists from 13 countries and major research centers to review current research in traumatic brain injury (TBI) and develop a consensus document on research issues and priorities. Four levels of TBI research were the focus of the discussion: basic science, acute care, post-acute neurorehabilitation, and improving quality of life (QOL). Each working group or committee was charged with reviewing current research, discussion and prioritizing future research directions, identifying critical issues that impede research in brain injury, and establishing a research agenda that will drive research over the next five years, leading to significantly improved outcomes and QOL for individuals suffering brain injuries. This symposium was organized at the request of the Congressional Brain Injury Task Force, to follow up on the National Institutes of Health Consensus Conference on TBI as mandated by the TBI ACT of 1996. The goal was to review what progress had been made since the National Institutes of Health (NIH) Consensus Conference, and also to follow up on the 1990's Decade of the Brain Project. The major purpose of the symposium was to provide recommendations to the U.S. Congress on a priority basis for research, treatment, and training in TBI over the next five years.
Pollak, Thomas A; Mulvenna, Catherine M; Lythgoe, Mark F
The effect of brain injury and disease on the output of established artists is an object of much study and debate. The emergence of de novo artistic behaviour following such injury or disease, while very rare, has been recorded in cases of frontotemporal dementia, epilepsy, subarachnoid haemorrhage and Parkinson's disease. This may be an underdiagnosed phenomenon and may represent an opportunity to further understand the neural bases of creative thought and behaviour in man and those of cognitive change after brain injury. There is clearly an important role for hemispheric localization of pathology, which is usually within the temporal cortex, upon the medium of artistic expression, and a likely role for mild frontal cortical dysfunction in producing certain behavioural and cognitive characteristics that may be conducive to the production of art. Possible mechanisms of 'artistic drive' and 'creative idea generation' in these patients are also considered. The increased recognition and responsible nurturing of this behaviour in patients may serve as a source of great comfort to individuals and their families at an otherwise difficult time.
van Veluw, Susanne J; Greenberg, Steven M
Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592
Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping
Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201
Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M
Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury.
Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M
Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury. Images PMID:3746322
Silver, Jonathan M; McAllister, Thomas W; Arciniegas, David B
Traumatic brain injury (TBI) is a common occurrence with multiple possible neuropsychiatric sequelae, including problems with cognition, emotion, and behavior. While many individuals experience significant improvement over the first months following mild TBI, a nontrivial minority will develop persistent, functionally impairing post-TBI symptoms. Depression and cognitive impairment are among the most common such symptoms, and they may respond to a combination of rehabilitative and pharmacologic treatments. This article discusses the clinical approach to treating an individual with depression and cognitive complaints following mild TBI. Recommendations regarding the diagnosis, evaluation, and treatment of these problems are offered.
Kim, Hyunki; Cam-Etoz, Betul; Zhai, Guihua; Hubbard, William J.; Zinn, Kurt R.
Abstract Estrogen plays an important role as a neuroprotector in the central nervous system (CNS), directly interacting with neurons and regulating physiological properties of non-neuronal cells. Here we evaluated estrogen sulfate (E2-SO4) for traumatic brain injury (TBI) using a Sprague–Dawley rat model. TBI was induced via lateral fluid percussion (LFP) at 24 h after craniectomy. E2-SO4 (1 mg/kg BW in 1 mL/kg BW) or saline (served as control) was intravenously administered at 1 h after TBI (n=5/group). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and partial brain oxygen pressure (pbtO2) were measured for 2 h (from 23 to 25 h after E2-SO4 injection). Brain edema and diffuse axonal injury (DAI) were assessed by diffusion tensor imaging (DTI), and cerebral glycolysis was measured by 18F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging, at 1 and 7 days after E2-SO4 injection. E2-SO4 significantly decreased ICP, while increasing CPP and pbtO2 (p<0.05) as compared with vehicle-treated TBI rats. The edema size in the brains of the E2-SO4 treated group was also significantly smaller than that of vehicle-treated group at 1 day after E2-SO4 injection (p=0.04), and cerebral glycolysis of injured region was also increased significantly during the same time period (p=0.04). However, E2-SO4 treatment did not affect DAI (p>0.05). These findings demonstrated the potential benefits of E2-SO4 in TBI. PMID:25646701
Elder, Gregory A; Cristian, Adrian
Mild traumatic brain injury has been called the signature injury of the wars in Iraq and Afghanistan. In both theaters of operation, traumatic brain injury has been a significant cause of mortality and morbidity, with blast-related injury the most common cause. Improvised explosive devices have been the major cause of blast injuries. It is estimated that 10% to 20% of veterans returning from these operations have suffered a traumatic brain injury, and there is concern that blast-related injury may produce adverse long-term health affects and affect the resilience and in-theater performance of troops. Blast-related injury occurs through several mechanisms related to the nature of the blast overpressure wave itself as well as secondary and tertiary injuries. Animal studies clearly show that blast overpressure waves are transmitted to the brain and can cause changes that neuropathologically are most similar to diffuse axonal injury. One striking feature of the mild traumatic brain injury cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of mild traumatic brain injury with posttraumatic stress disorder. The overlap in symptoms between the disorders has made distinguishing them clinically challenging. The high rates of mild traumatic brain injury and posttraumatic stress disorder in the current operations are of significant concern for the long-term health of US veterans with associated economic implications.
Phillips, Shawn; Woessner, Derek
Concussions have garnered more attention in the medical literature, media, and social media. As such, in the nomenclature according to the Centers for Disease Control and Prevention, the term concussion has been supplanted by the term mild traumatic brain injury. Current numbers indicate that 1.7 million TBIs are documented annually, with estimates around 3 million annually (173,285 sports- and recreation-related TBIs among children and adolescents). The Sideline Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are commonly used sideline tools.
Lorenz, Laura; Katz, Gabrielle
Acquired brain injury (ABI) is a major public health problem in Massachusetts (Hackman et al, 2014) and includes traumatic brain injury (TBI), stroke, ABI-related infectious diseases, metabolic disorders affecting the central nervous system (brain and spinal cord), and brain tumor. Advances in emergency medical care and neurosurgery mean that more people are surviving severe traumatic brain injury (Trexler et al, 2014). Yet many patients with severe TBI in particular, are not receiving inpatient services after initial treatment (Hackman et al, 2014; CDC, 2014) or later that are known to be effective (Malec & Kean, 2015; Lewis & Horn, 2015; BI Commission, 2011; Kolakowsky-Hayner et al, 2000; Interviews). These services include post-acute rehabilitation, case management, and brain injury-specific community programming (CDC, 2014; BI Commission, 2011; Interviews). Governance and data for decision-making are also major gaps in the continuum of care for severe brain injury in MA (Interviews; NASHIA, 2005). The last two decades saw a surge in interest in the brain, with advances in neuroscience, diagnosis and measurement of brain injury, rehabilitation services, and brain theory (Boyle, 2001). Severe brain injury however is the new "hidden epidemic" in our society. For many, an injury to the brain is not a short-term event that can be "cured" but the beginning of a life-long disability (CDC, 2014; Langlois et al, 2006). Fortunately, even after a severe brain injury, when the right rehabilitation is provided at the right time, the "rest of life" journey can be a positive one for many (Marquez de la Plata, 2015; Langlois et al, 2006). Severe brain injury can lead to a "new normal" as patients regain skills, find new meaning and in life, and take on new family, volunteer, and work roles. Throughout this brief, the term "severe brain injury" refers to "severe acquired brain injury," or any injury to the brain that occurs after birth. This definition does not include
... Why Some Kids Take Longer to Recover From Brain Injury Scans reveal white-matter decline after some ... 15, 2017 WEDNESDAY, March 15, 2017 (HealthDay News) -- Brain scans may reveal which children will take longer ...
Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel
We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to
not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT...of function after brain damage using a neural prosthesis (Complete main body of manuscript is included in the appendix.) Authors: David J. Guggenmos...feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as
Kelso, Matthew L.; Gendelman, Howard E.
The pathophysiology of degenerative, infectious, inflammatory and traumatic diseases of the central nervous system includes a significant immune component. As to the latter, damage to the cerebral vasculature and neural cell bodies, caused by traumatic brain injury (TBI) activates innate immunity with concomitant infiltration of immunocytes into the damaged nervous system. This leads to pro-inflammatory cytokine and prostaglandin production and lost synaptic integrity and more generalized neurotoxicity. Engagement of adaptive immune responses follows including the production of antibodies and lymphocyte proliferation. These affect the tempo of disease along with tissue repair and as such provide a number of potential targets for pharmacological treatments for TBI. However, despite a large body of research, no such treatment intervention is currently available. In this review we will discuss the immune response initiated following brain injuries, drawing on knowledge gained from a broad array of experimental and clinical studies. Our discussion seeks to address potential therapeutic targets and propose ways in which the immune system can be controlled to promote neuroprotection. PMID:24025052
Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik
Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.
Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik
Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738
Perel, Pablo; Roberts, Ian; Shakur, Haleema; Thinkhamrop, Bandit; Phuenpathom, Nakornchai; Yutthakasemsunt, Surakrant
Background Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. Objectives To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. Search methods We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). Selection criteria We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Data collection and analysis Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. Main results We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial
Breunig, Joshua J; Guillot-Sestier, Marie-Victoire; Town, Terrence
With as many as 300,000 United States troops in Iraq and Afghanistan having suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered much recent attention. While the cause and severity of these injuries is variable, severe cases can lead to lifelong disability or even death. While aging is the greatest risk factor for Alzheimer's disease (AD), it is now becoming clear that a history of TBI predisposes the individual to AD later in life (Sivanandam and Thakur, 2012). In this review article, we begin by defining hallmark pathological features of AD and the various forms of TBI. Putative mechanisms underlying the risk relationship between these two neurological disorders are then critically considered. Such mechanisms include precipitation and 'spreading' of cerebral amyloid pathology and the role of neuroinflammation. The combined problems of TBI and AD represent significant burdens to public health. A thorough, mechanistic understanding of the precise relationship between TBI and AD is of utmost importance in order to illuminate new therapeutic targets. Mechanistic investigations and the development of preclinical therapeutics are reliant upon a clearer understanding of these human diseases and accurate modeling of pathological hallmarks in animal systems.
Howes, Hannah; Edwards, Stephen; Benton, David
The purpose of this study was to investigate body image concerns and psycho-emotional health in males with acquired brain injury (ABI). Using a between subjects study of 25 males with ABI and 25 matched controls, variables were analysed using correlations and 2 x 2 analyses of variance (ANOVAs) with head injury and injury type as independent variables. Body image and psycho-emotional health were evaluated using self-report questionnaires. Disability and cognitive impairment were measured using a mixture of self-report, cognitive testing and clinical notes. Results indicated that males with ABI had significantly lower self-esteem and body dissatisfaction on a number of items relating to physical and sexual functioning. There were significant differences in body image between stroke and TBI, but there was no corresponding relationship with psycho-emotional health. These body image differences might be explained by age. The finding that ABI has a negative effect on body image and that this relates to psycho-emotional health should be investigated further, perhaps being included in future rehabilitation strategies.
Breunig, Joshua J.; Guillot-Sestier, Marie-Victoire; Town, Terrence
With as many as 300,000 United States troops in Iraq and Afghanistan having suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered much recent attention. While the cause and severity of these injuries is variable, severe cases can lead to lifelong disability or even death. While aging is the greatest risk factor for Alzheimer's disease (AD), it is now becoming clear that a history of TBI predisposes the individual to AD later in life (Sivanandam and Thakur, 2012). In this review article, we begin by defining hallmark pathological features of AD and the various forms of TBI. Putative mechanisms underlying the risk relationship between these two neurological disorders are then critically considered. Such mechanisms include precipitation and ‘spreading’ of cerebral amyloid pathology and the role of neuroinflammation. The combined problems of TBI and AD represent significant burdens to public health. A thorough, mechanistic understanding of the precise relationship between TBI and AD is of utmost importance in order to illuminate new therapeutic targets. Mechanistic investigations and the development of preclinical therapeutics are reliant upon a clearer understanding of these human diseases and accurate modeling of pathological hallmarks in animal systems. PMID:23874297
Whitlock, R I H
During the past 10 years of civil unrest in Northern Ireland a wide variety of facial injuries have been treated at the Royal Victoria Hospital, Belfast. The causes and nature of these injuries are described and the experience gained in their management is reviewed. Imagesp-ap-aFig. 1Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:7247260
Gray, Shannon E.; Finch, Caroline F.
Purpose: The purpose of this study was to provide an epidemiological profile of injuries sustained by participants in fitness activities in Victoria, Australia, based on hospital admissions and emergency department (ED) presentations and to identify the most common types, causes, and sites of these injuries. Method: Hospital-treated fitness…
Kohta, Masaaki; Minami, Hiroaki; Tanaka, Kazuhiro; Kuwamura, Keiichi; Kondoh, Takeshi; Kohmura, Eiji
A 52-year-old man fell from standing and a computed tomography (CT) scan revealed traumatic intracerebral haematoma and subarachnoid haemorrhage in the temporal cortex. He was treated without surgery and discharged. On day 30 after the accident, he had no neurological deficit. On day 37 he complained of headache and urinary incontinence, and on day 39 he was hospitalized due to progressive neurological deterioration (reduced conciousness, dilated pupils, and left hemiplegia). A CT scan revealed a diffuse low-density in the right cerebral hemisphere with marked midline shift. Emergency decompressive craniectomy and right temporal lobectomy were performed. Angiography after surgery revealed moderate vasospasm in the right middle and anterior cerebral arteries. The patient remained severely disabled. Delayed onset neurological deterioration can be caused by brain oedema and vasospasm after traumatic brain injury, despite an intervening period of improvement.
Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.
Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…
Polito, Mary Zemyan; Thompson, James W G; DeFina, Philip A
"The International Conference on Behavioral Health and Traumatic Brain Injury" held at St. Joseph's Regional Medical Center in Paterson, NJ., from October 12 to 15, 2008, included a presentation on the novel assessment and treatment approach to mild traumatic brain injury (mTBI) by Philip A. DeFina, PhD, of the International Brain Research Foundation (IBRF). Because of the urgent need to treat a large number of our troops who are diagnosed with mTBI and post-traumatic stress disorder (PTSD), the conference was held to create a report for Congress titled "Recommendations to Improve the Care of Wounded Warriors NOW. March 12, 2009." This article summarizes and adds greater detail to Dr. DeFina's presentation on the current standard and novel ways to approach assessment and treatment of mTBI and PTSD. Pilot data derived from collaborative studies through the IBRF have led to the development of clinical and research protocols utilizing currently accepted, valid, and reliable neuroimaging technologies combined in novel ways to develop "neuromarkers." These neuromarkers are being evaluated in the context of an "Integrity-Deficit Matrix" model to demonstrate their ability to improve diagnostic accuracy, guide treatment programs, and possibly predict outcomes for patients suffering from traumatic brain injury.
Lash, Marilyn; Savage, Ron; DePompei, Roberta; Blosser, Jean
These eight brochures for parents provide practical information and suggestions regarding various aspects of managing a child with a brain injury. The brochures are: (1) "Back to School after a Mild Brain Injury or Concussion," which covers helping the student in the classroom and changes that occur in school and knowing when extra help is needed…
microglia as ’sensors’ of injury in the pineal gland of rats following a non-penetrative blast." Neurosci Res 27(4): 317-322. ...including blood brain barrier disruption, glia activation and neuronal alterations. 15. SUBJECT TERMS blast; brain injury; experimental models
Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.
Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…
Finally, cell 13 death following injury can result from “slow excitotoxicity” ( Albin 92), in which cells are rendered vulnerable to physiologic...Janigro D. Traumatic brain injury and its effects on synaptic plasticity. Brain Inj. 2003 Aug;17(8):653-63. Albin RL, Greenamyre JT
Hotz, Gillian A.; Helm-Estabrooks, Nancy; Nelson, Nickola Wolf; Plante, Elena
The Pediatric Test of Brain Injury (PTBI) is designed to assess neurocognitive, language, and literacy abilities that are relevant to the school curriculum of children and adolescents recovering from brain injury. The PTBI is intended to help clinicians establish baseline levels of cognitive-linguistic abilities in the acute stages of recovery,…
Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James
White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…
Waaland, Pamela K.; Cockrell, Janice L.
This brief report summarizes what is known about pediatric traumatic brain injury, including the following: risk factors (e.g., males especially those ages 5 to 25, youth with preexisting problems including previous head injury victims, and children receiving inadequate supervision); life after injury; physical and neurological consequences (e.g.,…
Skidmore, Elizabeth R.
One of the major foci of rehabilitation after traumatic brain injury is the design and implementation of interventions to train individuals to learn new knowledge and skills or new ways to access and execute previously acquired knowledge and skills. To optimize these interventions, rehabilitation professionals require a clear understanding of how traumatic brain injury impacts learning, and how specific approaches may enhance learning after traumatic brain injury. This brief conceptual review provides an overview of learning, the impact of traumatic brain injury on explicit and implicit learning, and the current state of the science examining selected training approaches designed to advance learning after traumatic brain injury. Potential directions for future scientific inquiry are discussed throughout the review. PMID:26217546
Jadhav, Vikram; Zhang, John H
Neurosurgical procedures can cause inevitable brain damage resulting from the procedure itself. Unavoidable cortical and parenchymal incisions, intraoperative hemorrhage, brain lobe retraction and thermal injuries from electrocautery can cause brain injuries attributable exclusively to the neurosurgical operations and collectively referred to as surgical brain injury (SBI). This particular brain damage cannot be demarcated from the underlying brain pathology and has not been studied previously. Recently, we developed rat and mouse models to study SBI and the underlying cellular mechanisms. The animal modeling mimics a neurosurgical operation and causes commonly encountered postoperative complications such as brain edema following blood brain barrier (BBB) disruption, and neuronal cell death. Furthermore, the SBI animal model allows screening of known experimental neuroprotective agents and therapeutic agents being tried in clinical trials as possible pretreatments before neurosurgical procedures. In the present review, we elaborate on SBI and its clinical impact, the SBI animal models and their clinical relevance, and the importance of blanket neuroprotection before neurosurgical procedures.
Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent development in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury. PMID:26981070
... Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data Access Request SUMMARY: Under the... Collection: Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data...
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being less competent (Sawchyn, Mateer, & Suffi eld, 2005 ). Mild TBI has also been associated with greater emotional distress ( Leininger , Kreutzer...brain injury . Brain Injury , 23 , 83 – 91 . Leininger , B.E. , Kreutzer , J.S. , & Hill , M.R . ( 1991 ). Comparison of minor and severe
Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P
Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160
Menon, D K; Ercole, A
Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials. However, observational studies have informed the development of authoritative international guidelines, and the use of multimodality monitoring may facilitate rational approaches to optimizing acute physiology, allowing clinicians to optimize the balance between benefit and risk from these interventions in individual patients. Such approaches, along with the emerging impact of advanced neuroimaging, genomics, and protein biomarkers, could lead to the development of precision medicine approaches to the intensive care management of TBI.
Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685
Gaddam, Samson Sujit Kumar; Buell, Thomas; Robertson, Claudia S
Traumatic brain injury (TBI) affects functioning of various organ systems in the absence of concomitant non-neurologic organ injury or systemic infection. The systemic manifestations of TBI can be mild or severe and can present in the acute phase or during the recovery phase. Non-neurologic organ dysfunction can manifest following mild TBI or severe TBI. The pathophysiology of systemic manifestations following TBI is multifactorial and involves an effect on the autonomic nervous system, involvement of the hypothalamic-pituitary axis, release of inflammatory mediators, and treatment modalities used for TBI. Endocrine dysfunction, electrolyte imbalance, and respiratory manifestations are common following TBI. The influence of TBI on systemic immune response, coagulation cascade, cardiovascular system, gastrointestinal system, and other systems is becoming more evident through animal studies and clinical trials. Systemic manifestations can independently act as risk factors for mortality and morbidity following TBI. Some conditions like neurogenic pulmonary edema and disseminated intravascular coagulation can adversely affect the outcome. Early recognition and treatment of systemic manifestations may improve the clinical outcome following TBI. Further studies are required especially in the field of neuroimmunology to establish the role of various biochemical cascades, not only in the pathophysiology of TBI but also in its systemic manifestations and outcome.
Durham, William J; Foreman, Jack P; Randolph, Kathleen M; Danesi, Christopher P; Spratt, Heidi; Masel, Brian D; Summons, Jennifer R; Singh, Charan K; Morrison, Melissa; Robles, Claudia; Wolfram, Cindy; Kreber, Lisa A; Urban, Randall J; Sheffield-Moore, Melinda; Masel, Brent E
Individuals with a history of traumatic brain injury (TBI) are at increased risk for a number of disorders, including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. However, mediators of the long-term morbidity are uncertain. We conducted a multi-site, prospective trial in chronic TBI patients (∼18 years post-TBI) living in long-term 24-h care environments and local controls without a history of head injury. Inability to give informed consent was exclusionary for participation. A total of 41 individuals (17 moderate-severe TBI, 24 controls) were studied before and after consumption of a standardized breakfast to determine if concentrations of amino acids, cytokines, C-reactive protein, and insulin are potential mediators of long-term TBI morbidity. Analyte concentrations were measured in serum drawn before (fasting) and 1 h after meal consumption. Mean ages were 44 ± 15 and 49 ± 11 years for controls and chronic TBI patients, respectively. Chronic TBI patients had significantly lower circulating concentrations of numerous individual amino acids, as well as essential amino acids (p = 0.03) and large neutral amino acids (p = 0.003) considered as groups, and displayed fundamentally altered cytokine-amino acid relationships. Many years after injury, TBI patients exhibit abnormal metabolic responses and altered relationships between circulating amino acids, cytokines, and hormones. This pattern is consistent with TBI, inducing a chronic disease state in patients. Understanding the mechanisms causing the chronic disease state could lead to new treatments for its prevention.
Chew, Li-Jin; Takanohashi, Asako; Bell, Michael
Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the…
dependence development using both precipitated and spontaneous withdrawal. Key findings to date: • There was no difference in baseline nociception ( pain ...analgesia studies demonstrate that moderate brain injury does not result in an altered pain state or diminished response to oxycodone analgesia, the... pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions
Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald
Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.
Gonzalez, Peter G; Walker, Matthew T
Mild traumatic brain injury is a significant public health issue that has been gaining considerable attention over the past few years. After injury, a large percentage of patients experience postconcussive symptoms that affect work and school performance and that carry significant medicolegal implications. Conventional imaging modalities (computed tomography and magnetic resonance imaging) are insensitive to microstructural changes and underestimate the degree of diffuse axonal injury and metabolic changes. Newer imaging techniques have attempted to better diagnose and characterize diffuse axonal injury and the metabolic and functional aspects of traumatic brain injury. The following review article summarizes the currently available imaging studies and describes the novel and more investigational techniques available for mild traumatic brain injury. A suggested algorithm is offered.
an important step in the process of developing implantable BMBIs for neural repair in clinical populations. Differential Mechanisms Underlying the...anesthetized and ambulatory rats. Further, in semi-chronic experiments in rats with traumatic brain injury (TBI) using this microdevice, an unprecedented...Task 1 (Electronics Testing/Microsystem Packaging) 1.1 Conduct in vivo experiments in brain-injured monkeys using a fully assembled microsystem
Esnault, Pierre; Cardinale, Mickaël; Boret, Henry; D'Aranda, Erwan; Montcriol, Ambroise; Bordes, Julien; Prunet, Bertrand; Joubert, Christophe; Dagain, Arnaud; Goutorbe, Philippe; Kaiser, Eric; Meaudre, Eric
OBJECTIVE Blunt cerebrovascular injuries (BCVIs) affect approximately 1% of patients with blunt trauma. An antithrombotic or anticoagulation therapy is recommended to prevent the occurrence or recurrence of neurovascular events. This treatment has to be carefully considered after severe traumatic brain injury (TBI), due to the risk of intracranial hemorrhage expansion. Thus, the physician in charge of the patient is confronted with a hemorrhagic and ischemic risk. The main objective of this study was to determine the incidence of BCVI after severe TBI. METHODS The authors conducted a prospective, observational, single-center study including all patients with severe TBI admitted in the trauma center. Diagnosis of BCVI was performed using a 64-channel multidetector CT. Characteristics of the patients, CT scan results, and outcomes were collected. A multivariate logistic regression model was developed to determine the risk factors of BCVI. Patients in whom BCVI was diagnosed were treated with systemic anticoagulation. RESULTS In total, 228 patients with severe TBI who were treated over a period of 7 years were included. The incidence of BCVI was 9.2%. The main risk factors were as follows: motorcycle crash (OR 8.2, 95% CI 1.9-34.8), fracture involving the carotid canal (OR 11.7, 95% CI 1.7-80.9), cervical spine injury (OR 13.5, 95% CI 3.1-59.4), thoracic trauma (OR 7.3, 95% CI 1.1-51.2), and hepatic lesion (OR 13.3, 95% CI 2.1-84.5). Among survivors, 82% of patients with BCVI received systemic anticoagulation therapy, beginning at a median of Day 1.5. The overall stroke rate was 19%. One patient had an intracranial hemorrhagic complication. CONCLUSIONS Blunt cerebrovascular injuries are frequent after severe TBI (incidence 9.2%). The main risk factors are high-velocity lesions and injuries near cervical arteries.
Creasey, Graham H; Lateva, Zoia C; Schüssler-Fiorenza Rose, Sophia Miryam; Rose, Jon
Patients with both a spinal cord injury (SCI) and traumatic brain injury (TBI) are often very difficult to manage and can strain the resources of clinical units specialized in treating either diagnosis. However, a wide range of estimates exists on the extent of this problem. The aim of this study was to describe the scope of the problem in a well-defined population attending a comprehensive SCI unit. Electronic medical records of all patients with SCI being followed by the SCI unit in a U.S. Veterans' hospital were searched to identify those with concurrent TBI. The data were analyzed for age, sex, cause of injury, level and completeness of SCI, cognitive impairment, relationship with Active Duty military, and date of injury. Of 409 Veterans with a traumatic SCI, 99 (24.2%) were identified as having had a concurrent TBI. The occurrence did not appear to be closely related to military conflict. Reports of TBI were much more common in the last 20 yr than in previous decades. Documentation of TBI in patients with SCI was inconsistent. Improved screening and documentation could identify all patients with this dual diagnosis and facilitate appropriate management.
Shah, Mahim; Vavilala, Monica S.; Feldman, Kenneth W.; Hallam, Daniel K.
Objective: Children involved in motor vehicle crash (MVC) events might experience angular accelerations similar to those experienced by children with inflicted traumatic brain injury (iTBI). This is a pilot study to determine whether the progression of signs and symptoms and radiographic findings of MVC brain injury (mvcTBI) in children of the age…
Borek, L L; Butler, R; Fleminger, S
Studies suggest that neuropsychiatric symptoms are more common in patients with injury to the right side of the brain. However, most studies have examined patients with penetrating injuries because these allow more accurate localization of brain damage. This study investigates whether a similar association would be found in patients with non-penetrating brain injuries presenting to a neuropsychiatric unit. Over a 2 year period, 98 referrals were examined. Damage was localized using routine operation notes, EEG and neuroimaging. In total, 34 patients (35%) had a predominately right-sided injury, 33 (34%) had a left-sided injury and 31 (32%) had a diffuse or bilateral injury. Right-sided injuries were associated with hallucinations (p = 0.05), and left-sided injuries were associated with confabulation (p = 0.05) and lack of insight (p = 0.07). These results are consistent with findings from patients with penetrating head injuries. They suggest that evidence of the laterality of injury may be useful for planning the rehabilitation of patients seen in neuropsychiatric brain injury units.
Smith, Colin J.; Xiong, Guoxiang; Elkind, Jaclynn A.; Putnam, Brendan; Cohen, Akiva S.
More than 2.5 million Americans suffer a traumatic brain injury (TBI) each year. Even mild to moderate TBI causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI), the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice, while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI. PMID:26617569
Macedonia, Christian; Zamisch, Monica; Judy, Jack; Ling, Geoffrey
The repair of traumatic injuries to the central nervous system remains among the most challenging and exciting frontiers in medicine. In both traumatic brain injury and spinal cord injuries, the ultimate goals are to minimize damage and foster recovery. Numerous DARPA initiatives are in progress to meet these goals. The PREventing Violent Explosive Neurologic Trauma program focuses on the characterization of non-penetrating brain injuries resulting from explosive blast, devising predictive models and test platforms, and creating strategies for mitigation and treatment. To this end, animal models of blast induced brain injury are being established, including swine and non-human primates. Assessment of brain injury in blast injured humans will provide invaluable information on brain injury associated motor and cognitive dysfunctions. The Blast Gauge effort provided a device to measure warfighter's blast exposures which will contribute to diagnosing the level of brain injury. The program Cavitation as a Damage Mechanism for Traumatic Brain Injury from Explosive Blast developed mathematical models that predict stresses, strains, and cavitation induced from blast exposures, and is devising mitigation technologies to eliminate injuries resulting from cavitation. The Revolutionizing Prosthetics program is developing an avant-garde prosthetic arm that responds to direct neural control and provides sensory feedback through electrical stimulation. The Reliable Neural-Interface Technology effort will devise technologies to optimally extract information from the nervous system to control next generation prosthetic devices with high fidelity. The emerging knowledge and technologies arising from these DARPA programs will significantly improve the treatment of brain and spinal cord injured patients.
Schober, Michelle Elena; Block, Benjamin; Requena, Daniela F; Hale, Merica A; Lane, Robert H
Pediatric traumatic brain injury (TBI) is a major cause of acquired cognitive dysfunction in children. Hippocampal Brain Derived Neurotrophic Factor (BDNF) is important for normal cognition. Little is known about the effects of TBI on BDNF levels in the developing hippocampus. We used controlled cortical impact (CCI) in the 17 day old rat pup to test the hypothesis that CCI would first increase rat hippocampal BDNF mRNA/protein levels relative to SHAM and Naïve rats by post injury day (PID) 2 and then decrease BDNF mRNA/protein by PID14. Relative to SHAM, CCI did not change BDNF mRNA/protein levels in the injured hippocampus in the first 2 days after injury but did decrease BDNF protein at PID14. Surprisingly, BDNF mRNA decreased at PID 1, 3, 7 and 14, and BDNF protein decreased at PID 2, in SHAM and CCI hippocampi relative to Naïve. In conclusion, TBI decreased BDNF protein in the injured rat pup hippocampus 14 days after injury. BDNF mRNA levels decreased in both CCI and SHAM hippocampi relative to Naïve, suggesting that certain aspects of the experimental paradigm (such as craniotomy, anesthesia, and/or maternal separation) may decrease the expression of BDNF in the developing hippocampus. While BDNF is important for normal cognition, no inferences can be made regarding the cognitive impact of any of these factors. Such findings, however, suggest that meticulous attention to the experimental paradigm, and possible inclusion of a Naïve group, is warranted in studies of BDNF expression in the developing brain after TBI.
Rowe, Rachel K.; Striz, Martin; Bachstetter, Adam D.; Van Eldik, Linda J.; Donohue, Kevin D.; O'Hara, Bruce F.; Lifshitz, Jonathan
Objective Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep. Methods Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry. Results Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury. Conclusion Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair. PMID:24416145
Jackson, R D; Mysiw, W J
Fever is a common complication of a traumatic brain injury, occurring during both the acute-care phase and the rehabilitation phase of recovery. The aetiology of fever in this population may remain obscure because of the presence of cognitive confusion associated with post-traumatic amnesia interfering with history taking and the difficult physical examination. We present a case where recovery from a traumatic brain injury was complicated by a fever of unknown origin that proved to be secondary to lateral sinus thrombophlebitis. This case emphasises the importance of a thorough knowledge of the differential diagnosis for fever that is unique to the traumatic brain injury population.
Fogelman, David; Zafonte, Ross
Vigorous exercise has long been associated with improved health in many domains. Results of clinical observation have suggested that neurocognitive performance also is improved by vigorous exercise. Data derived from animal model-based research have been emerging that show molecular and neuroanatomic mechanisms that may explain how exercise improves cognition, particularly after traumatic brain injury. This article will summarize the current state of the basic science and clinical literature regarding exercise as an intervention, both independently and in conjunction with other modalities, for brain injury rehabilitation. A key principle is the factor of timing of the initiation of exercise after mild traumatic brain injury, balancing potentially favorable and detrimental effects on recovery.
Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G
There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures.
Roe, W D; Mayhew, I G; Jolly, R D; Marshall, J; Chilvers, B L
Trauma is a common cause of death in neonatal New Zealand sea lion pups, and subadult male sea lions have been observed picking up and violently shaking some pups. In humans, axonal injury is a common result of traumatic brain injury, and can be due to direct trauma to axons or to ischaemic damage secondary to trauma. 'Shaken baby syndrome', which has been described in human infants, is characterised by retinal and intracranial subdural haemorrhages, and has been associated with axonal injury to the brain, spinal cord and optic nerve. This study identifies mechanisms of traumatic brain injury in New Zealand sea lion pups, including impact injuries and shaking-type injuries, and identifies gross lesions of head trauma in 22/36 sea lion pups found dead at a breeding site in the Auckland Islands. Despite the high frequency of such gross lesions, only three of the pups had died of traumatic brain injury. Observational studies confirmed that shaking of pups occurred, but none were shown to die as a direct result of these shaking events. Axonal injury was evaluated in all 36 pup brains using β-amyloid precursor protein immunohistochemistry. Immunoreactive axons were present in the brains of all pups examined including seven with vascular axonal injury and two with diffuse axonal injury, but the severity and pattern of injury was not reliably associated with death due to traumatic brain injury. No dead pups had the typical combination of gross lesions and immunohistochemical findings that would conform to descriptions of 'shaken baby syndrome'. Axonal injury was present in the optic nerves of most pups, irrespective of cause of death, but was associated with ischaemia rather than trauma.
Ohguri, Takayuki . E-mail: email@example.com; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori
Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit.
Calvert, Sophie; Miller, Helen E.; Curran, Andrew; Hameed, Biju; McCarter, Renee; Edwards, Richard J.; Hunt, Linda; Sharples, Peta Mary
The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The…
Gopez, Jonas J.; Yue, Hongfei; Vasudevan, Ram; Malik, Amir S.; Fogelsanger, Lester N.; Lewis, Shawn; Panikashvili, David; Shohami, Esther; Jansen, Susan A.; Narayan, Raj K.; Strauss, Kenneth I.
OBJECTIVE Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3–immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3–immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuro-protective endocannabinoid, in the injured brain. CONCLUSION These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials. PMID:15730585
Dilmen, Özlem Korkmaz; Akçıl, Eren Fatma; Tunalı, Yusuf
Head injury remains a serious public problem, especially in the young population. The understanding of the mechanism of secondary injury and the development of appropriate monitoring and critical care treatment strategies reduced the mortality of head injury. The pathophysiology, monitoring and treatment principles of head injury are summarised in this article. PMID:27366456
Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery Mariko Nishibe,1,2 Scott Barbay,2,3 David ...J.S., Matthews, M.A., Davidson, J.F., Tabor , S.L., and Carey, M.E. (1996). Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in
Hawley, C; Ward, A; Magnay, A; Mychalkiw, W
Aims: To examine return to school and classroom performance following traumatic brain injury (TBI). Methods: This cross-sectional study set in the community comprised a group of 67 school-age children with TBI (35 mild, 13 moderate, 19 severe) and 14 uninjured matched controls. Parents and children were interviewed and children assessed at a mean of 2 years post injury. Teachers reported on academic performance and educational needs. The main measures used were classroom performance, the Children's Memory Scale (CMS), the Wechsler Intelligence Scale for Children–third edition UK (WISC-III) and the Weschler Objective Reading Dimensions (WORD). Results: One third of teachers were unaware of the TBI. On return to school, special arrangements were made for 18 children (27%). Special educational needs were identified for 16 (24%), but only six children (9%) received specialist help. Two thirds of children with TBI had difficulties with school work, half had attention/concentration problems and 26 (39%) had memory problems. Compared to other pupils in the class, one third of children with TBI were performing below average. On the CMS, one third of the severe group were impaired/borderline for immediate and delayed recall of verbal material, and over one quarter were impaired/borderline for general memory. Children in the severe group had a mean full-scale IQ significantly lower than controls. Half the TBI group had a reading age ⩾1 year below their chronological age, one third were reading ⩾2 years below their chronological age. Conclusions: Schools rely on parents to inform them about a TBI, and rarely receive information on possible long-term sequelae. At hospital discharge, health professionals should provide schools with information about TBI and possible long-term impairments, so that children returning to school receive appropriate support. PMID:14736628
Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas
Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship
Duerden, Emma G; Taylor, Margot J; Miller, Steven P
Infants born very preterm are high risk for acquired brain injury and disturbances in brain maturation. Although survival rates for preterm infants have increased in the last decades owing to improved neonatal intensive care, motor disabilities including cerebral palsy persist, and impairments in cognitive, language, social, and executive functions have not decreased. Evidence from neuroimaging studies exploring brain structure, function, and metabolism has indicated abnormalities in the brain development trajectory of very preterm-born infants that persist through to adulthood. In this chapter, we review neuroimaging approaches for the identification of brain injury in the preterm neonate. Advances in medical imaging and availability of specialized equipment necessary to scan infants have facilitated the feasibility of conducting longitudinal studies to provide greater understanding of early brain injury and atypical brain development and their effects on neurodevelopmental outcome. Improved understanding of the risk factors for acquired brain injury and associated factors that affect brain development in this population is setting the stage for improving the brain health of children born preterm.
ZHANG, CHENGCHENG; CHEN, JIANQIANG; LU, HONG
Aquaporin 4 (AQP4) is a widely distributed membrane protein, which is found in glial cells, ependymocytes and capillary endothelial cells in the brain, and particularly in the choroid plexus. AQP4 is a key regulator of water metabolism, and changes in its expression following brain injury are associated with pathological changes in the damaged side of the brain; however, the effects of brain injury on AQP4 and injury-induced pathological changes in the contralateral non-damaged side of the brain remain to be fully elucidated. In the present study, male Sprague-Dawley rats were subjected to traumatic brain injury (TBI) and changes in brain water content, the expression of AQP4 expression and pathological characteristics in the damaged and contralateral non-damaged sides of the brain were examined. In the damaged side of the brain, vasogenic edema appeared first, followed by cellular edema. The aggravated cellular edema in the damaged side of the brain resulted in two periods of peak edema severity. Pathological changes in the contralateral non-damaged side of the brain occurred later than those in the damaged side; cellular edema appeared first, followed by vasogenic edema, which was alleviated earlier than the cellular edema. AQP4 was downregulated during vasogenic edema, and upregulated during cellular edema. Taken together, these results suggested that the downregulation of AQP4 was a result of vasogenic edema and that the upregulation of AQP4 may have induced cellular edema. PMID:26459070
Ghayoumi, Zahra; Yadegari, Fariba; Mahmoodi-Bakhtiari, Behrooz; Fakharian, Esmaeil; Rahgozar, Mehdi; Rasouli, Maryam
Background: Considering the cognitive and linguistic complexity of discourse production, it is expected that individuals with traumatic brain injury (TBI) should face difficulties in this task. Therefore, clinical examination of discourse has become a useful tool for studying and assessment of communication skills of people suffering from TBI. Among different genres of discourse, persuasive discourse is considered as a more cognitively demanding task. However, little is known about persuasive discourse in individuals suffering from TBI. Objectives: The purpose of this study was to evaluate the performance of adults with TBI on a task of spoken persuasive discourse to determine the impaired linguistic measures. Patients and Methods: Thirteen TBI nonaphasic Persian speaking individuals, ranged between 19 to 40 years (Mean = 25.64 years; SD = 6.10) and 59 healthy adults matched by age, were asked to perform the persuasive discourse task. The task included asking the participants to express their opinion on a topic, and after the analysis of the produced discourse, the two groups were compared on the basis of their language productivity, sentential complexity, maze ratio and cohesion ratio. Results: The TBI group produced discourses with less productivity, sentential complexity, cohesion ratio and more maze ratio compared the control group. Conclusions: As it is important to consider acquired communication disorders particularly discourse impairment of brain injured patients along with their other clinical impairments and regarding the fact that persuasive discourse is crucial in academic and social situations, the persuasive discourse task presented in this study could be a useful tool for speech therapists, intending to evaluate communication disorders in patients with TBI. PMID:25798418
Fife, Terry D; Kalra, Deepak
Vertigo, dizziness, and disequilibrium are common symptoms following concussion or mild traumatic brain injury (mTBI). Dizziness and vertigo may be the result of trauma to the peripheral vestibular system or the central nervous system, or, in some cases, may be due to anxiety, depression, or posttraumatic stress disorder; these mechanisms are not mutually exclusive. While most peripheral vestibular disorders can be identified by testing and examination, those without inner-ear causes that have persisting complaints of dizziness and motion sickness are more difficult to understand and to manage. Some of these patients exhibit features compatible with vestibular migraine and may be treated successfully with migraine-preventative medications. This paper reviews the nonotogenic causes of persisting dizziness, the possible mechanisms, and the pathophysiology, as a framework for patient management and for future research.
Larpthaveesarp, Amara; Ferriero, Donna M; Gonzalez, Fernando F
In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans.
Sanchez, Erin J; Gabler, Lee F; McGhee, James S; Olszko, Ardyn V; Chancey, Valeta Carol; Crandall, Jeff; Panzer, Matthew B
Risk assessment models are developed to estimate the probability of brain injury during head impact using mechanical response variables such as head kinematics and brain tissue deformation. Existing injury risk functions have been developed using different datasets based on human volunteer and scaled animal injury responses to impact. However, many of these functions have not been independently evaluated with respect to laboratory-controlled human response data. In this study, the specificity of fourteen existing brain injury risk functions was assessed by evaluating their ability to correctly predict non-injurious response using previously conducted sled tests with well-instrumented human research volunteers. Six degree-of-freedom head kinematics data were obtained for 335 sled tests involving subjects in frontal, lateral, and oblique sled conditions up to 16 Gs peak sled acceleration. A review of the medical reports associated with each individual test indicated no clinical diagnosis of mild or moderate brain injury in any of the cases evaluated. Kinematic-based head and brain injury risk probabilities were calculated directly from the kinematic data, while strain-based risks were determined through finite element model simulation of the 335 tests. Several injury risk functions sub¬stanti¬ally over pre¬dict the likelihood of concussion and diffuse axonal injury; proposed maximum principal strain (MPS)-based injury risk functions predicted nearly 80 concussions and 14 cases of severe diffuse axonal injury out of the 335 non-injurious cases. This work is an important first step in assessing the efficacy of existing brain risk functions and highlights the need for more predictive injury assessment models.
Gropman, Andrea L.
Many inborn errors of metabolism (IEMs) are associated with irreversible brain injury. For many, it is unclear how metabolite intoxication or substrate depletion accounts for the specific neurologic findings observed. IEM-associated brain injury patterns are characterized by whether the process involves gray matter, white matter, or both, and beyond that, whether subcortical or cortical gray matter nuclei are involved. Despite global insults, IEMs may result in selective injury to deep gray matter nuclei or white matter. This manuscript reviews the neuro-imaging patterns of neural injury in selected disorders of metabolism involving small molecule and macromolecular disorders (ie, Phenylketonuria, urea cycle disorders, and maple syrup urine disease) and discusses the contribution of diet and nutrition to the prevention or exacerbation of injury in selected inborn metabolic disorders. Where known, a review of the roles of individual differences in blood–brain permeability and transport mechanisms in the etiology of these disorders will be discussed. PMID:23245553
Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed. PMID:28265255
Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed.
rats induces structural changes in brain regions associated with reward/risk circuitry including the nucleus accumbens, amygdala, hippocampus , and...to injury, animals underwent surgical implantation of a chronic indwelling venous catheter under isoflurane anesthesia with morphine pretreatment. A
... Information Clinical Trials Resources and Publications How do health care providers diagnose traumatic brain injury (TBI)? Skip sharing ... links Share this: Page Content To diagnose TBI, health care providers may use one or more tests that ...
Pal, Ranabir; Munivenkatappa, Ashok; Agrawal, Amit; Menon, Geetha R.; Galwankar, Sagar; Mohan, P. Rama; Kumar, S. Satish; Subrahmanyam, B. V.
Background: A reliable prediction of outcome for the victims of traumatic brain injury (TBI) on admission is possible from concurrent data analysis from any systematic real-time registry. Objective: To determine the clinical relevance of the findings from our TBI registry to develop prognostic futuristic models with readily available traditional and novel predictors. Materials and Methods: Prospectively collected data using predesigned pro forma were analyzed from the first phase of a trauma registry from a South Indian Trauma Centre, compatible with computerized management system at electronic data entry and web data entry interface on demographics, clinical, management, and discharge status. Statistical Analysis: On univariate analysis, the variables with P < 0.15 were chosen for binary logistic model. On regression model, variables were selected with test of coefficient 0.001 and with Nagelkerke R2 with alpha error of 5%. Results: From 337 cases, predominantly males from rural areas in their productive age, road traffic injuries accounted for two-thirds cases, one-fourths occurred during postmonsoon while two-wheeler was the most common prerequisite. Fifty percent of patients had moderate to severe brain injury; the most common finding was unconsciousness followed by vomiting, ear bleed, seizures, and traumatic amnesia. Fifteen percent required intracranial surgery. Patients with severe Glasgow coma scale score were 4.5 times likely to have the fatal outcome (P = 0.003). Other important clinical variables accountable for fatal outcomes were oral bleeds and cervical spine injury while imperative socio-demographic risk correlates were age and seasons. Conclusion: TBI registry helped us finding predictors of clinical relevance for the outcomes in victims of TBI in search of prognostic futuristic models in TBI victims. PMID:27722114
Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio
Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS<8) in the phase of neurological stability and 14 neurologically intact participants were recruited for the experiment. Their cognitive, linguistic and narrative skills were thoroughly assessed. The group of non-aphasic individuals with TBI had normal lexical and grammatical skills. However, they produced narratives with increased errors of cohesion and coherence due to the frequent interruption of ongoing utterances, derailments and extraneous utterances that made their discourse vague and ambiguous. They produced a normal amount of thematic units (i.e. concepts) in their narratives. However, this information was not correctly organized at micro- and macrolinguistic levels of processing. A Principal Component Analysis showed that a single factor accounted for the production of global coherence errors, and the reduction of both propositional density at the utterance level and proportion of words that conveyed information. It is hypothesized that the linguistic deficits observed in the participants with TBI may reflect a deficit at the interface between cognitive and linguistic processing rather than a specific linguistic disturbance.
Tanguay, Annick N.; Davidson, Patrick S. R.; Guerrero Nuñez, Karla V.; Ferland, Mark B.
Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik and Bialystok, 2006) as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task. Patients also completed the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003) and prepared actual meals that were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on) relative to controls. Surprisingly, however, patients' Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency. PMID:25228863
Edlow, Brian L.; Wu, Ona
Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483
Ponce, Lucido L.; Navarro, Jovany Cruz; Ahmed, Osama; Robertson, Claudia S.
Numerous experimental studies in recent years have suggested that erythropoietin (EPO) is an endogenous mediator of neuroprotection in various central nervous system disorders, including TBI. Many characteristics of EPO neuroprotection that have been defined in TBI experimental models suggest that it is an attractive candidate for a new treatment of TBI. EPO targets multiple mechanisms known to cause secondary injury after TBI, including anti-excitotoxic, antioxidant, anti-edematous, and anti-inflammatory mechanisms. EPO crosses the blood brain barrier. EPO has a known dose response and time window for neuroprotection and neurorestoration that would be practical in the clinical setting. However, EPO also stimulates erythropoiesis, which can result in thromboembolic complications. Derivatives of EPO which do not bind to the classical EPO receptor (carbamylated EPO) or that have such a brief half-life in the circulation that they do not stimulate erythropoiesis (asialo EPO and neuro EPO) have the neuroprotective activities of EPO without these potential thromboembolic adverse effects associated with EPO administration. Likewise, a peptide based on the structure of the Helix B segment of the EPO molecule that does not bind to the EPO receptor (pyruglutamate Helix B surface peptide) has promise as another alternative to EPO that may provide neuroprotection without stimulating erythropoiesis. PMID:22421507
Antonopoulos, Constantine N; Kadoglou, Nikolaos P E
Traumatic brain injury (TBI) has been recognized among the leading causes of mortality and morbidity in young adults. Traditionally, the diagnosis of TBI has been based on neuroimaging. However, a significant portion of insulted patients appear to be apparently asymptomatic. As a result, more elaborate indices of silent TBI are required in order to immediately detect focal and diffuse asymptomatic TBI. Such valid indices will potentially increase the efficacy of therapeutic strategies in TBI patients. In this review of the literature, we present novel circulating biomolecules, as potential biomarkers of silent TBI, like neurofilaments, Cleaved-Tau (C-Tau), Microtubule-Associated Protein 2 (MAP2), Neuron-Specific Enolase, S100B and ferritin. In addition to this, assessment of white matter abnormalities and white matter integrity by diffusion tensor imaging (DTI) have emerged as promising sensitive neuroimaging methods of silent TBI. An integrated research is needed to fully understand the interplay between all the aforementioned indices and DTI. The potential diagnostic, therapeutic and prognostic values of the all aforementioned indices will be analyzed in the proposed review.
Goffus, Andrea M; Anderson, Gail D; Hoane, Michael
Previously, we have demonstrated that nicotinamide (NAM), a neuroprotective soluble B-group vitamin, improves recovery of function following traumatic brain injury (TBI). However, no prior studies have examined whether NAM is beneficial following continuous infusions over 7 days post-TBI. The purpose of this study was to investigate the preclinical efficacy of NAM treatment as it might be delivered clinically; over several days by slow infusion. Rats were prepared with either unilateral controlled cortical impact (CCI) injuries or sham procedures and divided into three groups: CCI-NAM, CCI-vehicle, and sham. Thirty minutes following CCI, Alzet osmotic mini-pumps were implanted subcutaneously. NAM was delivered at a rate of 50 mg/kg/day for 7 days immediately post-CCI. On day 7 following injury, the pumps were removed and blood draws were collected for serum NAM and nicotinamide adenine dinucleotide (NAD+) analyses. Starting on day 2 post-CCI, animals were tested on a battery of sensorimotor tests (bilateral tactile adhesive removal, locomotor placing, and limb-use asymmetry). Continuous infusion of NAM resulted in a significant serum elevation in NAM, but not NAD+. Statistical analyses of the tactile removal and locomotor placing data revealed that continuous administration of NAM significantly reduced the initial magnitude of the injury deficit and improved overall recovery compared to the vehicle-treated animals. NAM treatment also significantly decreased limb-use asymmetries compared to vehicle-treated animals. The overall extent of the cortical damage was also reduced by NAM treatment. No detrimental effects were seen following continuous infusion. The present results suggest that NAM delivered via a clinically relevant therapeutic regimen may truncate behavioral damage following TBI. Thus our results offer strong support for translation into the clinical population.
Goffus, Andrea M; Anderson, Gail D
Previously, we have demonstrated that nicotinamide (NAM), a neuroprotective soluble B-group vitamin, improves recovery of function following traumatic brain injury (TBI). However, no prior studies have examined whether NAM is beneficial following continuous infusions over 7 days post-TBI. The purpose of this study was to investigate the preclinical efficacy of NAM treatment as it might be delivered clinically; over several days by slow infusion. Rats were prepared with either unilateral controlled cortical impact (CCI) injuries or sham procedures and divided into three groups: CCI-NAM, CCI-vehicle and sham. Thirty minutes following CCI, Alzet osmotic mini-pumps were implanted subcutaneously. NAM was delivered at a rate of 50 mg/kg/day for 7 days immediately post-CCI. On day 7 following injury, the pumps were removed and blood draws were collected for serum NAM and nicotinamide adenine dinucleotide (NAD+) analyses. Starting on day 2 post-CCI, animals were tested on a battery of sensorimotor tests (bilateral tactile adhesive removal, locomotor placing and limb-use asymmetry). Continuous infusion of NAM resulted in a significant serum elevation in NAM, but not NAD+. Statistical analyses of the tactile removal and locomotor placing data revealed that continuous administration of NAM significantly reduced the initial magnitude of the injury deficit and improved overall recovery compared to the vehicle-treated animals. NAM treatment also significantly decreased limb-use asymmetries compared to vehicle-treated animals. The overall extent of the cortical damage was also reduced by NAM treatment. No detrimental effects were seen following continuous infusion. The present results suggest that NAM delivered via a clinically relevant therapeutic regimen may truncate behavioral damage following TBI. Thus our results offer strong support for translation into the clinical population. PMID:20716938
Juul, Sandra E; Beyer, Richard P; Bammler, Theo K; McPherson, Ronald J; Wilkerson, Jasmine; Farin, Federico M
Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of brain injury. Proposed mechanisms of neuroprotection include activation of gene pathways that decrease oxidative injury, inflammation, and apoptosis, while increasing vasculogenesis and neurogenesis. To determine the effects of rEpo on gene expression in 10-d-old BALB-c mice with unilateral brain injury, we compared microarrays from the hippocampi of brain-injured pups treated with saline or rEpo to similarly treated sham animals. Total RNA was extracted 24 h after brain injury and analyzed using Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. We identified sex-specific differences in hippocampal gene expression after brain injury and after high-dose rEpo treatment using single-gene and gene set analysis. Although high-dose rEpo had minimal effects on hippocampal gene expression in shams, at 24-h post brain injury, high-dose rEpo treatment significantly decreased the proinflammatory and antiapoptotic response noted in saline-treated brain-injured comparison animals.
Mammi, P; Zaccaria, B; Dazzi, F; Saccavini, M
Percutaneous endoscopic gastrostomy (PEG) has recently become a usual procedure for patients with prolonged disorders of consciousness after brain injuries. Despite a high rate of success and a very low procedure-related mortality, morbidity associated to PEG placement reaches 9.4% in a recent large meta-analysis. This case report describes an uncommon complication of PEG placement in a patient with vegetative state after traumatic brain injury: the development of prolonged duodenal paralysis. This patient was treated by placement of a transient jejunostomy until recovery of duodenal functional activity, to permit adequate nutrition. This procedure-related complication is previously unreported in scientific literature.
Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.
Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.
Raad, M; Nohra, E; Chams, N; Itani, M; Talih, F; Mondello, S; Kobeissy, F
Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. Of interest, is the occurrence of autoantibodies which are produced following CNS trauma-induced disruption of the blood-brain barrier (BBB) and released into peripheral circulation mounted against self-brain-specific proteins acting as autoantigens. Recently, autoantibodies have been proposed as the new generation class of biomarkers due to their long-term presence in serum compared to their counterpart antigens. The diagnostic and prognostic value of several existing autoantibodies is currently being actively studied. Furthermore, the degree of direct and latent contribution of autoantibodies to CNS insult is still not fully characterized. It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.
Alvis-Miranda, Hernando Raphael; Castellar-Leones, Sandra Milena; Moscote-Salazar, Luis Rafael
The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various supportive therapeutic strategies in the pre-hospital and pre-operative stages is essential for optimal care. The immediate rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure is now the standard treatment of patients with combined traumatic brain injury (TBI) and hemorrhagic shock (HS). The fluid in patients with brain trauma and especially in patients with brain injur y is a critical issue. In this context we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regarding the use of fluid therapy in traumatic brain injury and decompressive craniectomy. PMID:27162857
Ettel, Deborah; Glang, Ann E.; Todis, Bonnie; Davies, Susan C.
Each year approximately 700,000 U.S. children aged 0-19 years sustain a traumatic brain injury (TBI) placing them at risk for academic, cognitive, and behavioural challenges. Although TBI has been a special education disability category for 25 years, prevalence studies show that of the 145,000 students each year who sustain long-term injury from…
Following a traumatic brain injury, including a mild concussion, most students will have some degree of memory impairment. It can take 1-3 years for a child's memory to improve to its maximum capability following injury. Children cannot wait that long before returning to school. Teachers need to know how to diversify their instruction in order to…
Grove, Michael J.
Traumatic Brain Injury (TBI) rehabilitation interventions are very heterogeneous due to injury characteristics and pathology, patient demographics, healthcare settings, caregiver variability, and individualized, multi-discipline treatment plans. Consequently, comparing and generalizing the effectiveness of interventions is limited largely due to…
Carroll, Emma; Coetzer, Rudi
The objective of this study was to investigate perceived identity change in adults with traumatic brain injury (TBI) and explore associations between identity change, grief, depression, self-esteem and self-awareness. The participants were 29 adults with TBI who were being followed up by a community brain injury rehabilitation service. Participants were longer post-injury than those more commonly studied. Time since injury ranged from 2.25 to 40 years (mean = 11.17 years, SD = 11.4 years). Participants completed a battery of questionnaires. Significant others and clinicians completed a parallel version of one of these measures. Questionnaires included the Head Injury Semantic Differential Scale (HISDS-III), Brain Injury Grief Inventory (BIGI), Hospital Anxiety and Depression Scale - Depression, Rosenberg Self-Esteem Scale (RSES) and the Awareness Questionnaire (Self/Significant other/Clinician versions). The main findings were that participants reported significant changes in self-concept with current self being viewed negatively in comparison to pre-injury self. Perceived identity change was positively associated with depression and grief and negatively associated with self-esteem and awareness. Awareness was negatively associated with self-esteem and positively associated with depression. These findings were consistent with previous research, revealing changes in identity following TBI. Further research is needed to increase our understanding of the psychological factors involved in emotional adjustment after TBI and to inform brain injury rehabilitation interventions, including psychotherapy approaches.
Wang, Yida; Fang, Wei; Wu, Liang; Yao, Xueya; Wu, Suzhen; Wang, Jie; Xu, Zhen; Tian, Fubo; He, Zhenzhou; Dong, Bin
Various types of brain injury which led to the damage of brain tissue structure and neurological dysfunction continues to be the major causes of disability and mortality. Picroside II (PII) possesses a wide range of pharmacological effects and has been proved to ameliorate ischemia and reperfusion injury of kidney and brain. However, critical questions remain about other brain injuries. We investigated the protective effect of PII in four well-characterized murine models of brain injury. Models showed a subsequent regional inflammatory response and oxidative stress in common, which might be improved by the administration of PII (20 mg/kg). Meanwhile, a series of morphological and histological analyses for reinforcement was performed. In traumatic, ischemic and infectious induced injuries, it was observed that the survival rate, apoptosis related proteins, Caspase-3, and the expression of acute inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly alleviated after PII injection, but PII treatment alone showed no effect on them as well. The western blot results indicated that TLR4 and NF-κB were clearly downregulated with PII administration. In conclusion, our results suggested that PII with a recommended concentration of 20 mg/kg could provide neuroprotective effects against multi-cerebral injuries in mice by suppressing the over-reactive inflammatory responses and oxidative stress and attenuating the damage of brain tissue for further neurological recovery.
Wang, Yida; Fang, Wei; Wu, Liang; Yao, Xueya; Wu, Suzhen; Wang, Jie; Xu, Zhen; Tian, Fubo; He, Zhenzhou; Dong, Bin
Various types of brain injury which led to the damage of brain tissue structure and neurological dysfunction continues to be the major causes of disability and mortality. Picroside II (PII) possesses a wide range of pharmacological effects and has been proved to ameliorate ischemia and reperfusion injury of kidney and brain. However, critical questions remain about other brain injuries. We investigated the protective effect of PII in four well-characterized murine models of brain injury. Models showed a subsequent regional inflammatory response and oxidative stress in common, which might be improved by the administration of PII (20 mg/kg). Meanwhile, a series of morphological and histological analyses for reinforcement was performed. In traumatic, ischemic and infectious induced injuries, it was observed that the survival rate, apoptosis related proteins, Caspase-3, and the expression of acute inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly alleviated after PII injection, but PII treatment alone showed no effect on them as well. The western blot results indicated that TLR4 and NF-κB were clearly downregulated with PII administration. In conclusion, our results suggested that PII with a recommended concentration of 20 mg/kg could provide neuroprotective effects against multi-cerebral injuries in mice by suppressing the over-reactive inflammatory responses and oxidative stress and attenuating the damage of brain tissue for further neurological recovery. PMID:28078024
Burke, D; Alexander, K; Baxter, M; Baker, F; Connell, K; Diggles, S; Feldman, K; Horny, A; Kokinos, M; Moloney, D; Withers, J
A case study report of a long and intensive rehabilitation programme for a young woman after she sustained a severe diffuse axonal injury in a motor vehicle accident is described in detail. The purpose of this paper is to encourage specialist brain injury rehabilitation services to offer extended rehabilitation programmes to patients, even with very severe injuries. Significant functional improvements and enhanced quality of life frequently reward the high cost and hard work involved.
Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo
Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711
Lanska, Douglas J
As a result of the wartime urgency to understand, prevent, and treat patients with traumatic brain injury (TBI) during World War II (WWII), clinicians and basic scientists in Great Britain collaborated on research projects that included accident investigations, epidemiologic studies, and development of animal and physical models. Very quickly, investigators from different disciplines shared information and ideas that not only led to new insights into the mechanisms of TBI but also provided very practical approaches for preventing or ameliorating at least some forms of TBI. Neurosurgeon Hugh Cairns (1896-1952) conducted a series of influential studies on the prevention and treatment of head injuries that led to recognition of a high rate of fatal TBI among motorcycle riders and subsequently to demonstrations of the utility of helmets in lowering head injury incidence and case fatality. Neurologists Derek Denny-Brown (1901-1981) and (William) Ritchie Russell (1903-1980) developed an animal model of TBI that demonstrated the fundamental importance of sudden acceleration (i.e., jerking) of the head in causing concussion and forced a distinction between head injury associated with sudden acceleration/deceleration and that associated with crush or compression. Physicist A.H.S. Holbourn (1907-1962) used theoretical arguments and simple physical models to illustrate the importance of shear stress in TBI. The work of these British neurological clinicians and scientists during WWII had a strong influence on subsequent clinical and experimental studies of TBI and also eventually resulted in effective (albeit controversial) public health campaigns and legislation in several countries to prevent head injuries among motorcycle riders and others through the use of protective helmets. Collectively, these studies accelerated our understanding of TBI and had subsequent important implications for both military and civilian populations. As a result of the wartime urgency to understand
Marcus, Steven C.; Wan, George J.; Zhang, Huabin F.; Olfson, Mark
Objective: To assess risk factors for injury among children and adolescents treated with stimulants for ADHD. Method: An analysis was performed of pharmacy and service claims data from 2000-2003 California Medicaid (Medi-Cal) focusing on children and adolescents ages 6 to 17 years who initiated stimulant therapy for ADHD. Bivariate and…
CHEN, AI; XIONG, LI-JING; TONG, YU; MAO, MENG
Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury. PMID:24648914
Nakanishi, Keiko; Sato, Yoshiaki; Mizutani, Yuka; Ito, Miharu; Hirakawa, Akihiro; Higashi, Yujiro
Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells. PMID:28281676
Shenton, ME; Hamoda, HM; Schneiderman, JS; Bouix, S; Pasternak, O; Rathi, Y; M-A, Vu; Purohit, MP; Helmer, K; Koerte, I; Lin, AP; C-F, Westin; Kikinis, R; Kubicki, M; Stern, RA; Zafonte, R
is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI. PMID:22438191
Ling, Helen; Hardy, John; Zetterberg, Henrik
Traumatic brain injury (TBI) is common in boxing and other contact sports. The long term irreversible and progressive aftermath of TBI in boxers depicted as punch drunk syndrome was described almost a century ago and is now widely referred as chronic traumatic encephalopathy (CTE). The short term sequelae of acute brain injury including subdural haematoma and catastrophic brain injury may lead to death, whereas mild TBI, or concussion, causes functional disturbance and axonal injury rather than gross structural brain damage. Following concussion, symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend to develop acutely but usually resolve within a week or two. Severe concussion can also lead to loss of consciousness. Despite the transient nature of the clinical symptoms, functional neuroimaging, electrophysiological, neuropsychological and neurochemical assessments indicate that the disturbance of concussion takes over a month to return to baseline and neuropathological evaluation shows that concussion-induced axonopathy may persist for years. The developing brains in children and adolescents are more susceptible to concussion than adult brain. The mechanism by which acute TBI may lead to the neurodegenerative process of CTE associated with tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) remains speculative. Focal tau-positive NFTs and neurites in close proximity to focal axonal injury and foci of microhaemorrhage and the predilection of CTE-tau pathology for perivascular and subcortical regions suggest that acute TBI-related axonal injury, loss of microvascular integrity, breach of the blood brain barrier, resulting inflammatory cascade and microglia and astrocyte activation are likely to be the basis of the mechanistic link of TBI and CTE. This article provides an overview of the acute and long-term neurological consequences of TBI in sports. Clinical, neuropathological and the possible pathophysiological
Ehsaei, Mohamadreza; Khajavi, Mehdi; Arjmand, Mohammad Hassan; Abuee, Mohammad Ali; Ghayour-Mobarhan, Majid; Hamidi Alamdari, Daryoush
Brain trauma is an important cause of mortality and disability among young people worldwide. One of the mechanisms of post-traumatic secondary brain damage is related to free radical release and oxidative stress (OS). OS is the consequence of an imbalance between pro-oxidants and antioxidants in favor of pro-oxidants. This imbalance may lead to macromolecule damage including lipid peroxidation, protein crosslinking, DNA damage and changes in growth and function of cells in brain. Free radical release and subsequent lipid peroxidation are early events following neural tissues injury and are associated with hypo-perfusion, edema, and disruption of axonal guidance. In this study, we determined the prooxidant-antioxidant balance (PAB) in patients with brain injury, and its correlation with number of demographic and clinical parameters. Sera from 98 patients with traumatic brain and 100 healthy subjects were collected. The serum PAB was measured. Age, sex, GCS (Glasgow coma scale), mechanism of injury, brain lesions found on CT scan and lesions in other parts of the body, caused by trauma, were determined. A significantly higher PAB value was observed in the patient group (138.97 ± 15.9 HK unit) compared to the controls (60.82 ± 12.6 HK) (P = 0.001). In the patient group, there was no significant correlation of PAB with GCS, brain lesion characteristic, mechanism of injury, other accompanying traumatic injury, age and gender. When patients were classified into three groups according to GCS: group 1 (GCS>13, n = 28, PAB serum value = 138.51 ± 62.66 HK), group 2 (GCS between 8 and 12, n = 29, PAB serum value = 162.7 ± 50.6 HK) and group 3 (GCS <8, n = 41, PAB serum value = 155.56 ± 58.21 HK); there was no significant difference between groups. The serum PAB values were higher in patients with traumatic brain injury, although this was not associated with the extent of injury.
Papadimitriou, Konstantinos I.; Wang, Chu; Rogers, Michelle L.; Gowers, Sally A. N.; Leong, Chi L.; Boutelle, Martyn G.; Drakakis, Emmanuel M.
Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30–40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation. PMID:27242477
Jullienne, Amandine; Badaut, Jérôme
The revised ‘expanded’ neurovascular unit (eNVU) is a physiological and functional unit encompassing endothelial cells, pericytes, smooth muscle cells, astrocytes and neurons. Ischemic stroke and traumatic brain injury are acute brain injuries directly affecting the eNVU with secondary damage, such as blood–brain barrier (BBB) disruption, edema formation and hypoperfusion. BBB dysfunctions are observed at an early postinjury time point, and are associated with eNVU activation of proteases, such as tissue plasminogen activator and matrix metalloproteinases. BBB opening is accompanied by edema formation using astrocytic AQP4 as a key protein regulating water movement. Finally, nitric oxide dysfunction plays a dual role in association with BBB injury and dysregulation of cerebral blood flow. These mechanisms are discussed including all targets of eNVU encompassing endothelium, glial cells and neurons, as well as larger blood vessels with smooth muscle. In fact, the feeding blood vessels should also be considered to treat stroke and traumatic brain injury. This review underlines the importance of the eNVU in drug development aimed at improving clinical outcome after stroke and traumatic brain injury. PMID:24489483
Wang, Bo; Kang, Mitchell; Marchese, Michelle; Rodriguez, Esther; Lu, Wei; Li, Xintong; Maeda, Yasuhiro; Dowling, Peter
There is currently no effective medical treatment for traumatic brain injury (TBI). Beyond the immediate physical damage caused by the initial impact, additional damage evolves due to the inflammatory response that follows brain injury. Here we show that therapy with JM4, a low molecular weight 19-amino acid nonhematopoietic erythropoietin (EPO) peptidyl fragment, containing amino acids 28-46 derived from the first loop of EPO, markedly reduces acute brain injury. Mice underwent controlled cortical injury and received either whole molecule EPO, JM4, or sham-treatment with phosphate-buffered saline. Animals treated with JM4 peptide exhibited a large decrease in number of dead neural cells and a marked reduction in lesion size at both 3 and 8 days postinjury. Therapy with JM4 also led to improved functional recovery and we observed a treatment window for JM4 peptide that remained open for at least 9 h postinjury. The full-length EPO molecule was divided into a series of 6 contiguous peptide segments; the JM4-containing segment and the adjoining downstream region contained the bulk of the death attenuating effects seen with intact EPO molecule following TBI. These findings indicate that the JM4 molecule substantially blocks cell death and brain injury following acute brain trauma and, as such, presents an excellent opportunity to explore the therapeutic potential of a small-peptide EPO derivative in the medical treatment of TBI.
Bailes, Julian E; Dashnaw, Matthew L; Petraglia, Anthony L; Turner, Ryan C
The majority of traumatic brain injuries (TBI) in the USA are mild in severity. Sports, particularly American football, and military experience are especially associated with repetitive, mild TBI (mTBI). The consequences of repetitive brain injury have garnered increasing scientific and public attention following reports of altered mood and behavior, as well as progressive neurological dysfunction many years after injury. This report provides an up-to-date review of the clinical, pathological, and pathophysiological changes associated with repetitive mTBI, and their potential for cumulative effects in certain individuals.
Slifer, Keith J.; Amari, Adrianna
Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have…
Levine, Susan C.; Kraus, Ruth; Alexander, Erin; Suriyakham, Linda Whealton; Huttenlocher, Peter R.
We examine whether children with early unilateral brain injury show an IQ decline over the course of development. Fifteen brain injured children were administered an IQ test once before age 7 and again several years later. Post-7 IQ scores were significantly lower than pre-7 IQ scores. In addition, pre-7 IQ scores were lower for children with…
Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen
Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI. PMID:27602324
Orhan, Nurcan; Ugur Yilmaz, Canan; Ekizoglu, Oguzhan; Ahishali, Bulent; Kucuk, Mutlu; Arican, Nadir; Elmas, Imdat; Gürses, Candan; Kaya, Mehmet
This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-κB) were performed, and Glut-1 and NF-κB activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-κB protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-κB expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals.
Harrison-Felix, Cynthia L.; Menon, David; Adelson, P. David; Balkin, Tom; Bullock, Ross; Engel, Doortje C.; Gordon, Wayne; Langlois-Orman, Jean; Lew, Henry L.; Robertson, Claudia; Temkin, Nancy; Valadka, Alex; Verfaellie, Mieke; Wainwright, Mark; Wright, David W.; Schwab, Karen
Abstract Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we “speak the same language.” Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies. Randomized controlled trials can never address the many uncertainties concerning treatment approaches in TBI. Pooling data from different clinical studies and high-quality observational studies combined with comparative effectiveness research may provide excellent alternatives in a cost-efficient way. Standardization of data collection and coding is essential to this end. Common data elements (CDEs) are presented for demographics and clinical variables applicable across the broad spectrum of TBI. Most recommendations represent a consensus derived from clinical practice. Some recommendations concern novel approaches, for example assessment of the intensity of therapy in severely injured patients. Up to three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail attained in the advanced version. More detailed codings can be collapsed into the basic version. Templates were produced to summarize coding formats, explanation of choices, and recommendations for procedures. Endorsement of the recommendations has been obtained from many authoritative organizations. The development of CDEs for TBI should be viewed as a continuing process; as more experience is gained, refinement and amendments will be required. This proposed process of standardization will facilitate comparative effectiveness research and encourage high-quality meta-analysis of individual patient data. PMID:21162610
Arciniegas, David B.; Held, Kerri; Wagner, Peter
Cognitive impairments due to traumatic brain injury (TBI) are substantial sources of morbidity for affected individuals, their family members, and society. Disturbances of attention, memory, and executive functioning are the most common neurocognitive consequences of TBI at all levels of severity. Disturbances of attention and memory are particularly problematic, as disruption of these relatively basic cognitive functions may cause or exacerbate additional disturbances in executive function, communication, and other relatively more complex cognitive functions. Because of the high rate of other physical, neurologic, and psychiatric syndromes following TBI, a thorough neuropsychiatric assessment of the patient is a prerequisite to the prescription of any treatment for impaired cognition. Psychostimulants and other dopaminergically active agents (eg, methylphenidate, dextroamphetamine, amantadine, levodopa/carbidopa, bromocriptine) may modestly improve arousal and speed of information processing, reduce distractibility, and improve some aspects of executive function. Cautious dosing (start-low and go-slow), frequent standardized assessment of effects and side effects, and monitoring for drug-drug interactions are recommended. Cognitive rehabilitation is useful for the treatment of memory impairments following TBI. Cognitive rehabilitation may also be useful for the treatment of impaired attention, interpersonal communication skills, and executive function following TBI. This form of treatment is most useful for patients with mild to moderate cognitive impairments, and may be particularly useful for those who are still relatively functionally independent and motivated to engage in and rehearse these strategies. Psychotherapy (eg, supportive, individual, cognitive-behavioral, group, and family) is an important component of treatment. For patients with medication- and rehabilitation-refractory cognitive impairments, psychotherapy may be needed to assist both patients and
Curnow, W J
An examination is made of a meta-analysis by Attewell, Glase and McFadden which concludes that bicycle helmets prevent serious injury, to the brain in particular, and that there is mounting scientific evidence of this. The Australian Transport Safety Bureau (ATSB) initiated and directed the meta-analysis of 16 observational studies dated 1987-1998. This examination concentrates on injury to the brain and shows that the meta-analysis and its included studies take no account of scientific knowledge of its mechanisms. Consequently, the choice of studies for the meta-analysis and the collection, treatment and interpretation of their data lack the guidance needed to distinguish injuries caused through fracture of the skull and by angular acceleration. It is shown that the design of helmets reflects a discredited theory of brain injury. The conclusions are that the meta-analysis does not provide scientific evidence that such helmets reduce serious injury to the brain, and the Australian policy of compulsory wearing lacks a basis of verified efficacy against brain injury.
Salehi, Arjang; Zhang, John H; Obenaus, Andre
The critical role of the vasculature and its repair in neurological disease states is beginning to emerge particularly for stroke, dementia, epilepsy, Parkinson's disease, tumors and others. However, little attention has been focused on how the cerebral vasculature responds following traumatic brain injury (TBI). TBI often results in significant injury to the vasculature in the brain with subsequent cerebral hypoperfusion, ischemia, hypoxia, hemorrhage, blood-brain barrier disruption and edema. The sequalae that follow TBI result in neurological dysfunction across a host of physiological and psychological domains. Given the importance of restoring vascular function after injury, emerging research has focused on understanding the vascular response after TBI and the key cellular and molecular components of vascular repair. A more complete understanding of vascular repair mechanisms are needed and could lead to development of new vasculogenic therapies, not only for TBI but potentially vascular-related brain injuries. In this review, we delineate the vascular effects of TBI, its temporal response to injury and putative biomarkers for arterial and venous repair in TBI. We highlight several molecular pathways that may play a significant role in vascular repair after brain injury.
Zhu, Qiliang; Prange, Michael; Margulies, Susan
The objective of this study was to utilize tissue deformation thresholds associated with acute axonal injury in the immature brain to predict the duration of unconsciousness. Ten anesthetized 3- to 5-day-old piglets were subjected to nonimpact axial rotations (110-260 rad/s) producing graded injury, with periods of unconsciousness from 0 to 80 min. Coronal sections of the perfusion-fixed brain were immunostained with neurofilament antibody (NF-68) and examined microscopically to identify regions of swollen axons and terminal retraction balls. Each experiment was simulated with a finite element computational model of the piglet brain and the recorded head velocity traces to estimate the local tissue deformation (strain), the strain rate and their product. Using thresholds associated with 50, 80 and 90% probability of axonal injury, white matter regions experiencing suprathreshold responses were determined and expressed as a fraction of the total white matter volume. These volume fractions were then correlated with the duration of unconsciousness, assuming a linear relationship. The thresholds for 80 and 90% probability of predicting injury were found to correlate better with injury severity than those for 50%, and the product of strain and strain rate was the best predictor of injury severity (p=0.02). Predictive capacity of the linear relationship was confirmed with additional (n=13) animal experiments. We conclude that the suprathreshold injured volume can provide a satisfactory prediction of injury severity in the immature brain.
Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio
There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.
Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P
Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.
Shen, Qiang; Watts, Lora Tally; Li, Wei; Duong, Timothy Q
Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. Common causes of TBI include falls, violence, injuries from wars, and vehicular and sporting accidents. The initial direct mechanical damage in TBI is followed by progressive secondary injuries such as brain swelling, perturbed cerebral blood flow (CBF), abnormal cerebrovascular reactivity (CR), metabolic dysfunction, blood-brain-barrier disruption, inflammation, oxidative stress, and excitotoxicity, among others. Magnetic resonance imaging (MRI) offers the means to noninvasively probe many of these secondary injuries. MRI has been used to image anatomical, physiological, and functional changes associated with TBI in a longitudinal manner. This chapter describes controlled cortical impact (CCI) TBI surgical procedures, a few common MRI protocols used in TBI imaging, and, finally, image analysis pertaining to experimental TBI imaging in rats.
Titova, E; Ostrowski, R P; Zhang, J H; Tang, J
Recent studies have shown that amantadine, an uncompetitive N-methyl-d-aspartate receptor antagonist and dopamine agonist, is effective for the treatment of various cerebral disorders and causes relatively mild side effects. In this study, we investigated whether administration of amantadine will provide a neuroprotective effect in the intracerebral hemorrhage (ICH) rat model. A total of 15 male Sprague Dawley rats (300-380 g) were divided into sham, ICH-untreated, and ICH-treated with amantadine sulphate groups. ICH was induced by collagenase injection. Total dose 6 mg/kg of amantadine sulphate was divided into 3 injections and administered intraperitoneally at 1, 8, and 16 h after ICH. Brain injury was evaluated by investigating neurological function and brain edema at 24 h after ICH. Our data demonstrates that ICH caused significant neurological deficit associated with marked brain edema. Amantadine did not reduce brain injury after ICH; neurological function and brain edema in the treated group were not different from those of the untreated group. We conclude that amantadine sulphate does not offer neuroprotection in acute stage of experimental ICH-induced brain injury.
Gennai, S; Monsel, A; Hao, Q; Liu, J; Gudapati, V; Barbier, E L; Lee, J W
Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.
Ikeda, Y; Mochizuki, Y; Matsumoto, H; Nakamura, Y; Dohi, K; Jimbo, H; Shimazu, M; Hayashi, M; Matsumoto, K
Oxygen free radicals have been implicated in the genesis of traumatic brain injury and brain edema (BE). Recent studies have suggested that hydroxyl radical can initiate lipid peroxidation, thus producing lipid-free radicals that may become important sources of singlet oxygen. L-histidine, a singlet oxygen scavenger, potentially can be used to treat BE. In this study we investigated the effects of L-histidine and D-histidine on BE following cryogenic injury in rats. Male Wistar rats were anaesthetized with chloral hydrate. Vasogenic BE was produced by a cortical freezing lesion. Generation of singlet oxygen from photoactivation of rose bengal was studied by electron spin resonance (ESR). Animals were separated into four groups: sham rats (n = 5), saline-treated rats (n = 10), L-histidine treated rats (n = 6) and D-histidine treated rats (n = 7). Each agent (100 mg/kg) was administered intravenously at 30 minutes before lesion production. Animals were sacrificed at 24 hours after lesion production and the brain water content was determined by the dry-wet weight method. L-histidine had no effect on rectal and brain temperature. Election Spin Resonance studies demonstrated that L-histidine is a singlet oxygen scavenger. L-histidine but not D-histidine significantly attenuated BE following cryogenic injury (p < 0.05). In conclusion, L-histidine is useful in the treatment of traumatic BE.
Introduction Traumatic brain injury is a form of acquired brain injury that results from sudden trauma to the head. Specifically, mild traumatic brain injury is a clinical diagnosis that can have significant effects on an individual's life, yet is difficult to identify through traditional imaging techniques. Case presentation This is the case of a 68-year-old previously healthy African American woman who was involved in a motor vehicle accident that resulted in significant head trauma. After the accident, she experienced symptoms indicative of mild traumatic brain injury and sought a neurological consultation when her symptoms did not subside. She was initially evaluated with a neurological examination, psychological evaluation, acute concussion evaluation and a third-party memory test using software from CNS Vital Signs for neurocognitive function. A diagnosis of post-concussion syndrome was suggested. Diffusion tensor imaging revealed decreased fractional anisotropy in the region immediately adjacent to both lateral ventricles, which was used to confirm the diagnosis. Fractional anisotropy is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. These results are indicative of post-traumatic gliosis and are undetectable by magnetic resonance imaging. Our patient was treated with cognitive therapy. Conclusion Minor traumatic brain injury is a common injury with variable clinical presentation. The system of diagnosis used in this case found a significant relationship between the clinical assessment and imaging results. This would not have been possible using traditional imaging techniques and highlights the benefits of using diffusion tensor imaging in the sub-acute assessment of minor traumatic brain injury. PMID:22339800
Schiff, Nicholas D.
Recovery of consciousness following severe brain injuries may occur over long time intervals. Importantly, evolving cognitive recovery can be strongly dissociated from motor recovery in some individuals, resulting in underestimation of cognitive capacities. Common mechanisms of cerebral dysfunction that arise at the neuronal population level may explain slow functional recoveries from severe brain injuries. This review proposes a “mesocircuit” model that predicts specific roles for different structural and dynamic changes that may occur gradually during recovery. Recent functional neuroimaging studies that operationally identify varying levels of awareness, memory and other higher brain functions in patients with no behavioral evidence of these cognitive capacities are discussed. Measuring evolving changes in underlying brain function and dynamics post-injury and post-treatment frames future investigative work. PMID:19954851
Smith, Craig M.; Chen, Yaming; Sullivan, Mara L.; Kochanek, Patrick M.; Clark, Robert S. B.
In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell’s autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury, and are the subject of this review. PMID:20883784
Cuestas, Eduardo; Caceres, Alfredo; Palacio, Santiago
Animal models of injury and repair in developing brain. Brain injury is a major contributor to neonatal morbidity and mortality, a considerable group of these children will develop long term neurological sequels. Despite the great clinical and social significance and the advances in neonatal medicine, no therapy yet does exist that prevent or decrease detrimental effects in cases of neonatal brain injury. Our objective was to review recent research in relation to the hypothesis for repair mechanism in the developing brain, based in animal models that show developmental compensatory mechanisms that promote neural and functional plasticity. A better understanding of these adaptive mechanisms will help clinicians to apply knowledge derived from animals to human clinical situations.
Nakagawa, A.; Ohtani, K.; Arafune, T.; Washio, T.; Iwasaki, M.; Endo, T.; Ogawa, Y.; Kumabe, T.; Takayama, K.; Tominaga, T.
1. Investigation of shock wave-induced phenomenon: blast-induced traumatic brain injury Blast wave (BW) is generated by explosion and is comprised of lead shock wave (SE) followed by subsequent supersonic flow.
Xie, J.; Qian, Z.; Yang, T.; Li, W.; Hu, G.
The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (μs') and BWC. By recording μs' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.
cations compared to other mechanisms of injury such as acceleration -deceleration impact has become an im- portant question in the care of our service...injury. The above concepts lead to a frame of reference debate in relation to blast induced concussion or mTBI sug- gesting that lethal injury would...results in a 3D complex flow field that is altered by ambient conditions and envi- ronmental boundaries. This may result in multiple wave reflections and
Blaya, Meghan O; Bramlett, Helen M; Naidoo, Jacinth; Pieper, Andrew A; Dietrich, W Dalton
Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. Sprague-Dawley rats subjected to moderate fluid percussion brain injury were evaluated for quantitative immunohistochemical and behavioral changes after trauma. P7C3-A20 (10 mg/kg) or vehicle was initiated intraperitoneally 30 min postsurgery and twice per day every day thereafter for 7 days. Administration of P7C3-A20 significantly reduced overall contusion volume, preserved vulnerable anti-neuronal nuclei (NeuN)-positive pericontusional cortical neurons, and improved sensorimotor function 1 week after trauma. P7C3-A20 treatment also significantly increased both bromodeoxyuridine (BrdU)- and doublecortin (DCX)-positive cells within the subgranular zone of the ipsilateral dentate gyrus 1 week after TBI. Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI.
Blaya, Meghan O.; Bramlett, Helen M.; Naidoo, Jacinth
Abstract Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. Sprague-Dawley rats subjected to moderate fluid percussion brain injury were evaluated for quantitative immunohistochemical and behavioral changes after trauma. P7C3-A20 (10 mg/kg) or vehicle was initiated intraperitoneally 30 min postsurgery and twice per day every day thereafter for 7 days. Administration of P7C3-A20 significantly reduced overall contusion volume, preserved vulnerable anti-neuronal nuclei (NeuN)-positive pericontusional cortical neurons, and improved sensorimotor function 1 week after trauma. P7C3-A20 treatment also significantly increased both bromodeoxyuridine (BrdU)- and doublecortin (DCX)-positive cells within the subgranular zone of the ipsilateral dentate gyrus 1 week after TBI. Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI. PMID:24070637
Shankaran, Seetha; Barnes, Patrick D; Hintz, Susan R; Laptook, Abbott R; Zaterka-Baxter, Kristin M; McDonald, Scott A; Ehrenkranz, Richard A; Walsh, Michele C; Tyson, Jon E; Donovan, Edward F; Goldberg, Ronald N; Bara, Rebecca; Das, Abhik; Finer, Neil N; Sanchez, Pablo J; Poindexter, Brenda B; Van Meurs, Krisa P; Carlo, Waldemar A; Stoll, Barbara J; Duara, Shahnaz; Guillet, Ronnie; Higgins, Rosemary D
Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy. PMID:23080477
Kallakuri, Srinivasu; Bandaru, Sharath; Zakaria, Nisrine; Shen, Yimin; Kou, Zhifeng; Zhang, Liying; Haacke, Ewart Mark; Cavanaugh, John M
Objectives: Traumatic brain injury is a poly-pathology characterized by changes in the cerebral blood flow, inflammation, diffuse axonal, cellular, and vascular injuries. However, studies related to understanding the temporal changes in the cerebral blood flow following traumatic brain injury extending to sub-acute periods are limited. In addition, knowledge related to microhemorrhages, such as their detection, localization, and temporal progression, is important in the evaluation of traumatic brain injury. Materials and Methods: Cerebral blood flow changes and microhemorrhages in male Sprague Dawley rats at 4 h, 24 h, 3 days, and 7 days were assessed following a closed head injury induced by the Marmarou impact acceleration device (2 m height, 450 g brass weight). Cerebral blood flow was measured by arterial spin labeling. Microhemorrhages were assessed by susceptibility-weighted imaging and Prussian blue histology. Results: Traumatic brain injury rats showed reduced regional and global cerebral blood flow at 4 h and 7 days post-injury. Injured rats showed hemorrhagic lesions in the cortex, corpus callosum, hippocampus, and brainstem in susceptibility-weighted imaging. Injured rats also showed Prussian blue reaction products in both the white and gray matter regions up to 7 days after the injury. These lesions were observed in various areas of the cortex, corpus callosum, hippocampus, thalamus, and midbrain. Conclusions: These results suggest that changes in cerebral blood flow and hemorrhagic lesions can persist for sub-acute periods after the initial traumatic insult in an animal model. In addition, microhemorrhages otherwise not seen by susceptibility-weighted imaging are present in diverse regions of the brain. The combination of altered cerebral blood flow and microhemorrhages can potentially be a source of secondary injury changes following traumatic brain injury and may need to be taken into consideration in the long-term care of these cases. PMID:26605126
Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.
Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478
Alabbasi, Thamer; Nathens, Avery B.; Tien, Col Homer
Background The initial nonoperative management (NOM) of blunt splenic injuries in hemodynamically stable patients is common. In soldiers who experience blunt splenic injuries with concomitant severe brain injury while on deployment, however, NOM may put the injured soldier at risk for secondary brain injury from prolonged hypotension. Methods We conducted a decision analysis using a Markov process to evaluate 2 strategies for managing hemodynamically stable patients with blunt splenic injuries and severe brain injury — immediate splenectomy and NOM — in the setting of a field hospital with surgical capability but no angiography capabilities. We considered the base case of a 40-year-old man with a life expectancy of 78 years who experienced blunt trauma resulting in a severe traumatic brain injury and an isolated splenic injury with an estimated failure rate of NOM of 19.6%. The primary outcome measured was life expectancy. We assumed that failure of NOM would occur in the setting of a prolonged casualty evacuation, where surgical capability was not present. Results Immediate splenectomy was the slightly more effective strategy, resulting in a very modest increase in overall survival compared with NOM. Immediate splenectomy yielded a survival benefit of only 0.4 years over NOM. Conclusion In terms of overall survival, we would not recommend splenectomy unless the estimated failure rate of NOM exceeded 20%, which corresponds to an American Association for the Surgery of Trauma grade III splenic injury. For military patients for whom angiography may not be available at the field hospital and who require prolonged evacuation, immediate splenectomy should be considered for grade III–V injuries in the presence of severe brain injury. PMID:26100770
Anderson, Vicki; Beauchamp, Miriam Helen; Yeates, Keith Owen; Crossley, Louise; Ryan, Nicholas Peter; Hearps, Stephen J C; Catroppa, Cathy
Children with traumatic brain injury (TBI) are at risk of social impairment, but research is yet to document the trajectory of these skills post-injury and factors that may predict social problems. The study addressed these gaps in knowledge, reporting on findings from a prospective, longitudinal follow-up study which investigated social outcomes post injury and explored factors contributing to these outcomes at 2 years post-injury. The sample included 113 children, 74 with TBI and 39 typically developing (TD) controls. TBI participants were recruited on presentation to hospital. Parents rated pre-injury function at that time and all children underwent magnetic resonance imaging (MRI) scan. Participants were followed up at 2 years post-injury. Outcomes were social adjustment, social participation, social relationships, and social cognition. Predictors of social outcomes examined included brain lesion characteristics, child cognition (6 months post-TBI) and behavior and environmental factors (pre-injury and 2 years). Reduced social adjustment (p=.011) and social participation (p<.001) were evident in children with TBI compared to TD controls. Poor social adjustment was predicted by externalizing behaviour problems and younger age at injury. Reduced social participation was linked to internalizing behavior problems. Greater lesion volume, lower socioeconomic status and family burden contributed to poorer social relationships, while age at injury predicted social cognition. Within the TBI group, 23% of children exhibited social impairment: younger age at injury, greater pre-injury and current behavior problems and family dysfunction, poorer IQ, processing speed, and empathy were linked to impairment. Further follow-up is required to track social recovery and the influences of cognition, brain, and environment over time.
Geffen, Saul J
Evaluation of patients for rehabilitation after musculoskeletal injury involves identifying, grading and assessing the injury and its impact on the patient's normal activities. Management is guided by a multidisciplinary team, comprising the patient, doctor and physical therapist, with other health professionals recruited as required. Parallel interventions involving the various team members are specified in a customised management plan. The key component of the plan is active mobilisation utilising strengthening, flexibility and endurance exercise programs. Passive physical treatments (heat, ice, and manual therapy), as well as drug therapy and psychological interventions, are used as adjunctive therapy. Biomechanical devices or techniques (eg, orthotic devices) may also be helpful. Coexisting conditions such as depression and drug dependence are treated at the same time as the injury. Effective team communication, simulated environmental testing and, for those employed, contact with the employer facilitate a staged return to normal living, sports and occupational activities.
Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed
Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific
Corbett, Sandra L.; Ross-Thomson, Betty
This resource and planning guide provides a framework for practitioners to create an effective educational program for students with traumatic brain injuries. Chapters 1 and 2 provide an overview of brain injuries including information on brain physiology, types of brain injuries, and differences by age. Chapter 3 discusses returning to school,…
Shin, Tae Kyeong; Kang, Mi Sun; Lee, Ho Youn; Seo, Moo Sang; Kim, Si Geun; Kim, Chi Dae; Lee, Won Suk
This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1alpha proteins expression, thereby providing a benefit in therapy of cerebral ischemia.
Astur, Diego Costa; Santos, Bruno; de Moraes, Eduardo Ramalho; Arliani, Gustavo Gonçalves; dos Santos, Paulo Roberto Dias; Pochini, Alberto de Castro
ABSTRACT Objective: To evaluate the low energy extracorporeal shock waves therapy (ESWT) associated with physical therapy in the treatment of chronic muscle injuries classified as grades 2 and 3 in the lower limbs of amateur athletes. Methods: Eight athletes presenting with lower limb muscle injury for more than three weeks were treated with physiotherapy and ESWT. We evaluated the following parameters during treatment: palpable gap, muscle strength, pain, and Tegner score, as well as ultrasound image features and the ability to return to sports practice. Results: The average time of the first evaluation of the injury was 8.75 weeks. All patients presented muscle strength grade V after eight weeks. The pain score evolved from 5.75 to 0.5 points of the visual analogue scale (VAS), at the end of the treatment. The Tegner score after treatment was six points on average. Patients returned to sports practice after 8.14 weeks. Conclusion: ESWT associated with physical therapy proved to be effective to treat long-term muscle injury, with good performance and the ability to return to sport practice for all patients. Level of Evidence IV, Case Series, Prospective Study. PMID:26981031
Adeleye, A.; Biegon, A.; Adeleye, A.; Shohami, E.; Nachman, D.; Alexandrovich, A.; Trembovler, V.; Yaka, R.; Shoshan, Y.; Dhawan, J.; Biegon, A.
It has been long thought that hyperactivation of N-methyl-D-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor antagonists failed. Since NMDA receptors are down-regulated from 4 h to 2 weeks after brain injury, activation at 24 h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice. Here, we tested the therapeutic window, dose regimen and mechanism of action of the NMDA receptor partial agonist d-cycloserine (DCS) in traumatic brain injury. Male mice were subjected to trauma using a weight-drop model, and administered 10 mg/kg (i.p.) DCS or vehicle once (8, 16, 24, or 72 h) twice (24 and 48 h) or three times (24, 48 and 72 h). Functional recovery was assessed for up to 60 days, using a Neurological Severity Score that measures neurobehavioral parameters. In all groups in which treatment was begun at 24 or 72 h neurobehavioral function was significantly better than in the vehicle-treated groups. Additional doses, on days 2 and 3 did not further improve recovery. Mice treated at 8 h or 16 h post injury did not differ from the vehicle-treated controls. Co-administration of the NMDA receptor antagonist MK-801 completely blocked the protective effect of DCS given at 24 h. Infarct volume measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h or by cresyl violet at 28 days was not affected by DCS treatment. Since DCS is used clinically for other indications, the present study offers a novel approach for treating human traumatic brain injury with a therapeutic window of at least 24 h.
Hughes, Bryan G; Schulz, Richard
Matrix metalloproteinase (MMPs) are long understood to be involved in remodeling of the extracellular matrix. However, over the past decade, it has become clear that one of the most ubiquitous MMPs, MMP-2, has numerous intracellular targets in cardiac myocytes. Notably, MMP-2 proteolyzes components of the sarcomere, and its intracellular activity contributes to ischemia-reperfusion injury of the heart. Together with the well documented role played by MMPs in the myocardial remodeling that occurs following myocardial infarction, this has led to great interest in targeting MMPs to treat cardiac ischemic injury. In this review we will describe the expanding understanding of intracellular MMP-2 biology, and how this knowledge may lead to improved treatments for ischemic heart injury. We also critically review the numerous preclinical studies investigating the effects of MMP inhibition in animal models of myocardial infarction and ischemia-reperfusion injury, as well as the recent clinical trials that are part of the effort to translate these results into clinical practice. Acknowledging the disappointing results of past clinical trials of MMP inhibitors for other diseases, we discuss the need for carefully designed preclinical and clinical studies to avoid mistakes that have been previously made. We conclude that inhibition of MMPs, and in particular MMP-2, shows promise as a therapy to prevent the progression from ischemic injury to heart failure. However, it is critical that the full breadth of MMP-2 biology be taken into account as such therapies are developed.
Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M.; Vannucci, Susan J.; Levison, Steven W.; Vexler, Zinaida S.; Gressens, Pierre
Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals. PMID:25686754
Karelina, Kate; Gaier, Kristopher R; Prabhu, Maya; Wenger, Vanessa; Corrigan, Timothy E D; Weil, Zachary M
Traumatic brain injuries (TBI) are a major public health problem with enormous costs in terms of health care dollars, lost productivity, and reduced quality of life. Alcohol is bidirectionally linked to TBI as many TBI patients are intoxicated at the time of their injury and we recently reported that, in accordance with human epidemiological data, animals injured during juvenile development self-administered significantly more alcohol as adults than did sham injured mice. There are also clinical data that drinking after TBI significantly reduces the efficacy of rehabilitation and leads to poorer long-term outcomes. In order to determine whether juvenile traumatic brain injury also increased the vulnerability of the brain to the toxic effects of high dose alcohol, mice were injured at 21days of age and then seven weeks later treated daily with binge-like levels of alcohol 5g/kg (by oral gavage) for ten days. Binge-like alcohol produced a greater degree of neuronal damage and neuroinflammation in mice that sustained a TBI. Further, mice that sustained a juvenile TBI exhibited mild learning and memory impairments in adulthood following binge alcohol and express a significant increase in hippocampal ectopic localization of newborn neurons. Taken together, these data provide strong evidence that a mild brain injury occurring early in life renders the brain highly vulnerable to the consequences of binge-like alcohol consumption.
Yang, Tuo; Sun, Yang; Zhang, Feng
Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury. PMID:28217295
O'Connell, Karen M; Littleton-Kearney, Marguerite T
Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.
Kaczorowski, S L; Schiding, J K; Toth, C A; Kochanek, P M
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 pre-treated 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 0.2712 +/- 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.
Chalkias, Athanasios; Xanthos, Theodoros
Cardiac arrest is a leading cause of death that affects more than a million individuals worldwide every year. Despite the recent advancement in the field of cardiac arrest and resuscitation, the management and prognosis of post-cardiac arrest brain injury remain suboptimal. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Considering that a potentially broad therapeutic window for neuroprotective drug therapy is offered in most successfully resuscitated patient after cardiac arrest, the need for further research is imperative. The aim of this article is to present the major pathophysiological disturbances leading to post-cardiac arrest brain injury, as well as to review the available pharmacological therapies.
Patients with acute brain injury (ABI) frequently require diagnostic and therapeutic procedures in the areas located outside of the intensive care unit. Transports can be risky for critically ill patients with ABI. Secondary brain injury can occur during the transport from causes such as ischemia, hypotension, hypoxia, hypercapnia, and cerebral edema. Preparation and implementation of preventive procedures including pretransport assessment, monitoring during transport, and posttransport examination and documentation for transports of patients with ABI deem to be necessary. The purpose of this article is to review the typical risks associated with the transports of the patients with ABI out of the intensive care unit and to propose the strategies that can be used to minimize the risks of secondary brain injury.
... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...
Zagorchev, Lyubomir; Meyer, Carsten; Stehle, Thomas; Wenzel, Fabian; Young, Stewart; Peters, Jochen; Weese, Juergen; Paulsen, Keith; Garlinghouse, Matthew; Ford, James; Roth, Robert; Flashman, Laura; McAllister, Thomas
Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.
Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M
Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.
Tian, Runfa; Hou, Zonggang; Hao, Shuyu; Wu, Weichuan; Mao, Xiang; Tao, Xiaogang; Lu, Te; Liu, Baiyun
Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.
Ross, David E; Castelvecchi, Cody; Ochs, Alfred L
This letter to the editor describes the case of a 42 year old man with mild traumatic brain injury and multiple neuropsychiatric symptoms which persisted for a few years after the injury. Initial CT scans and MRI scans of the brain showed no signs of atrophy. Brain volume was measured using NeuroQuant®, an FDA-approved, commercially available software method. Volumetric cross-sectional (one point in time) analysis also showed no atrophy. However, volumetric longitudinal (two points in time) analysis showed progressive atrophy in several brain regions. This case illustrated in a single patient the principle discovered in multiple previous group studies, namely that the longitudinal design is more powerful than the cross-sectional design for finding atrophy in patients with traumatic brain injury.
Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003
Cao, Fang; Wu, Yue; Zhong, Jianjun; Liu, Jieshi; Qin, Xinghu; Chen, Ligang; Vitek, Michael P.; Li, Fengqiao; Xu, Lu
Abstract The degree of post-traumatic brain edema and dysfunction of the blood–brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury. PMID:26192010
Dobrota, Dusan; Fedorova, Tatiana; Stvolinsky, Sergey; Babusikova, Eva; Likavcanova, Katarina; Drgova, Anna; Strapkova, Adriana; Boldyrev, Alexander
Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.
Li, Jingang; McDonald, Courtney A.; Fahey, Michael C.; Jenkin, Graham; Miller, Suzanne L.
Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia–ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia–ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications. PMID:25346720
Kalinich, John F; Kasper, Christine E
Metal translocation to the brain is strictly controlled and often prevented by the blood-brain barrier. For the most part, only those metals required to maintain normal function are transported into the brain where they are under tight metabolic control. From the literature, there are reports that traumatic brain injury disrupts the blood-brain barrier. This could allow the influx of metals that would normally have been excluded from the brain. We also have preliminary data showing that metal pellets, surgically-implanted into the leg muscle of a rat to simulate a shrapnel wound, solubilize and the metals comprising the pellet can enter the brain. Surprisingly, rats implanted with a military-grade tungsten alloy composed of tungsten, nickel, and cobalt also showed significantly elevated uranium levels in their brains as early as 1 month after pellet implantation. The only source of uranium was low levels that are naturally found in food and water. Conversely, rats implanted with depleted uranium pellets demonstrated elevated uranium levels in brain resulting from degradation of the implanted pellets. However, when cobalt levels were measured, there were no significant increases in the brain until the rats had reached old age. The only source of cobalt for these rats was the low levels found in their food and water. These data suggest that some metals or metal mixtures (i.e., tungsten alloy), when embedded into muscle, can enhance the translocation of other, endogenous metals (e.g., uranium) across the blood-brain barrier. For other embedded metals (i.e., depleted uranium), this effect is not observed until the animal is of advanced age. This raises the possibility that metal body-burdens can affect blood-brain barrier permeability in a metal-specific and age-dependent manner. This possibility is disconcerting when traumatic brain injury is considered. Traumatic brain injury has been called the "signature" wound of the conflicts in Iraq and Afghanistan, often, an
Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S
The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.
Kemp, A; Stoodley, N; Cobley, C; Coles, L; Kemp, K; Geddes, J
Aims: (1) To identify whether infants and young children admitted to hospital with subdural haematomas (SDH) secondary to non-accidental head injury (NAHI), suffer from apnoea leading to radiological evidence of hypoxic ischaemic brain damage, and whether this is related to a poor prognosis; and (2) to determine what degree of trauma is associated with NAHI. Methods: Retrospective case series (1992–98) with case control analysis of 65 children under 2 years old, with an SDH secondary to NAHI. Outcome measures were presenting symptoms, associated injuries and apnoea at presentation, brain swelling or hypoxic ischaemic changes on neuroimaging, and clinical outcome (KOSCHI). Results: Twenty two children had a history of apnoea at presentation to hospital. Apnoea was significantly associated with hypoxic ischaemic brain damage. Severe symptoms at presentation, apnoea, and diffuse brain swelling/hypoxic ischaemic damage were significantly associated with a poor prognosis. Eighty five per cent of cases had associated injuries consistent with a diagnosis of non-accidental injury. Conclusions: Coma at presentation, apnoea, and diffuse brain swelling or hypoxic ischaemia all predict a poor outcome in an infant who has suffered from SDH after NAHI. There is evidence of associated violence in the majority of infants with NAHI. At this point in time we do not know the minimum forces necessary to cause NAHI. It is clear however that it is never acceptable to shake a baby. PMID:12765909
Rapp, Paul E.; Keyser, David O.; Albano, Alfonso; Hernandez, Rene; Gibson, Douglas B.; Zambon, Robert A.; Hairston, W. David; Hughes, John D.; Krystal, Andrew; Nichols, Andrew S.
Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3) The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in q
Burns, Alexis; Adeli, Hojjat; Buford, John A
Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders.
Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng
Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.
TBI, November 18, 2011, Detroit, Prof. Haacke Wayne State University, TBI Workshop, Mild TBI, November 18, 2011, Detroit, Prof. Kou. Henry Ford...Del Campo -Perez V, Alvarez-Garcıa E, Vara-Perez C, Andrade-Olivie MA. 2011. Model predicting survival/exitus after traumatic brain injury: biomarker...visualize blood products and improve tumor contrast in the study of brain masses. J Magn Reson Imaging 2006;24: 41–51. 4. Kohler R, Vargas MI, Masterson K
Zhou, Xiaogang; Zhou, Jian; Li, Xilei; Guo, Chang'an; Fang, Taolin; Chen, Zhengrong
Previous studies have shown that GSK-3β inhibitor could reduce infarct volume after ischemia brain injury. However, the underlying mechanisms of GSK-3β inhibitor involving neuroprotection remain poorly understood. In the present study, we demonstrated that GSK-3β inhibitor suppressed insult-induced neuroinflammation in rat cortex by increasing autophagy activation in ischemic injury. Male rats were subjected to pMCAO (permanent middle cerebral artery occlusion) followed by treating with SB216763, a GSK-3β inhibitor. We found that insult-induced inflammatory response was significantly decreased by intraperitoneal infusion of SB216763 in rat cortex. A higher level of autophagy was also detected after SB216763 treatment. In the cultured primary microglia, SB216763 activated autophagy and suppressed inflammatory response. Importantly, inhibition of autophagy by Beclin1-siRNA increased inflammatory response in the SB216763-treated microglia. These data suggest that GSK-3β inhibitor suppressed neuroinflammation by activating autophagy after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.
Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A.
Abstract Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6–24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6–24 h), then increased by ∼50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6–72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24–72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally
Lisembee, Amanda M.
Disruption and consequent reorganization of central nervous system circuits following traumatic brain injury may manifest as functional deficits and behavioral morbidities. We previously reported axotomy and neuronal atrophy in the ventral basal (VB) complex of the thalamus, without gross degeneration after experimental diffuse brain injury in adult rats. Pathology in VB coincided with the development of late-onset aberrant behavioral responses to whisker stimulation, which lead to the current hypothesis that neurodegeneration after experimental diffuse brain injury includes the primary somatosensory barrel cortex (S1BF), which receives projection of VB neurons and mediates whisker somatosensation. Over 28 days after midline fluid percussion brain injury, argyrophilic reaction product within superficial layers and layer IV barrels at 1 day progresses into the cortex to subcortical white matter by 7 days, and selective inter-barrel septa and subcortical white matter labeling at 28 days. Cellular consequences were determined by stereological estimates of neuronal nuclear volumes and number. In all cortical layers, neuronal nuclear volumes significantly atrophied by 42–49% at 7 days compared to sham, which marginally attenuated by 28 days. Concomitantly, the number of healthy neurons was reduced by 34–45% at 7 days compared to sham, returning to control levels by 28 days. Progressive neurodegeneration, including argyrophilic reaction product and neuronal nuclear atrophy, indicates injury-induced damage and reorganization of the reciprocal thalamocortical projections that mediate whisker somatosensation. The rodent whisker barrel circuit may serve as a discrete model to evaluate the causes and consequences of circuit reorganization after diffuse brain injury. PMID:21597967
Hazeldine, Jon; Lord, Janet M.; Belli, Antonio
Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay, and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post-TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarizing our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post-TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis, include the CNS-driven emergence into the circulation of myeloid-derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues, such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalized TBI patient. PMID:26594196
Hazeldine, Jon; Lord, Janet M; Belli, Antonio
Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay, and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post-TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarizing our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post-TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis, include the CNS-driven emergence into the circulation of myeloid-derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues, such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalized TBI patient.
Cardozo, Luis Carlos Maia; da Silva, Redson Ruy
Objective Patients with traumatic brain injury are particularly susceptible to sepsis, which may exacerbate the systemic inflammatory response and lead to organ dysfunction. The influence of clinical variables on the mortality of intensive care unit patients with traumatic brain injury and sepsis was investigated. Methods The present investigation was a retrospective study involving 175 patients with traumatic brain injury who were treated in a period of 1 year at a reference hospital for trauma and who had sepsis, severe sepsis, or septic shock. Demographic and clinical data were obtained, and the SOFA score was calculated at the time sepsis was found and after 72 hours. Results There was a predominance of young men with severe traumatic brain injury, multiple head injuries, sepsis with a pulmonary focus, prolonged hospital stay, and high mortality (37.7%). Circulatory and respiratory failure had a high incidence, but renal and coagulation failure were less frequent, and liver failure was not observed. After logistic regression, the presence of septic shock and respiratory failure 72 hours after the sepsis diagnosis was associated with higher mortality, with an odds ratio of 7.56 (95%CI=2.04-27.31, p=0.0024) and 6.62 (95%CI=1.93-22.78, p=0.0027), respectively. In addition, there was a higher mortality among patients who had no organ failure on D1 but who developed the condition after 72 hours of sepsis and in those patients who already had organ failure at the time sepsis was diagnosed and remained in this condition after 72 hours. Conclusion Septic shock and progressive organ (particularly respiratory) dysfunction increases the mortality of patients with traumatic brain injury and sepsis. PMID:25028949
as Biomarkers for Traumatic Brain Injury (TBI) and Alzheimer Disease (AD) PRINCIPAL INVESTIGATOR: Michael Sierks CONTRACTING...Oligomeric Neuronal Protein Aggregates as Biomarkers for Traumatic Brain Injury (TBI) and Alzheimer Disease (AD) 5b. GRANT NUMBER 12109023 5c
to Traumatic Brain Injury and Alzheimer Disease ”, 5-th International Annual Symposium of the Brain Mapping and Intraoperative Surgical Planning... Alzheimer Disease , Proc Intl Soc Mag Reson Med 15: 343, 2007. 9. Singh M and Jeong J-W, “ICA based multi-fiber tractography” Proceedings, 17-th
Han, Xiaodi; Tong, Jing; Zhang, Jun; Farahvar, Arash; Wang, Ernest; Yang, Jiankai; Samadani, Uzma; Smith, Douglas H; Huang, Jason H
Previous animal and human studies have demonstrated that chronic treatment with several different antidepressants can stimulate neurogenesis, neural remodeling, and synaptic plasticity in the normal hippocampus. Imipramine is a commonly used tricyclic antidepressant (TCA). We employed a controlled cortical impact (CCI) mouse model of traumatic brain injury (TBI) to assess the effect of imipramine on neurogenesis and cognitive and motor function recovery after TBI. Mice were given daily imipramine injections for either 2 or 4 weeks after injury. Bromodeoxyuridine (BrdU) was administered 3-7 days post-brain injury to label the cells that proliferated as a result of the injury. We assessed the effects of imipramine on post-traumatic motor function using a beam-walk test and an assessment of cognitive function: the novel object recognition test (NOR). Histological analyses were performed at 2 and 4 weeks after CCI. Brain-injured mice treated with imipramine showed significantly improved cognitive function compared to a saline-treated group (p<0.001). However, there was no significant difference in motor function recovery between imipramine-treated and saline-treated mice. Histological examination revealed increased preservation of proliferation of Ki-67- and BrdU-positive cells in the hippocampal dentate gyrus (DG) at 2 and 4 weeks after TBI. Immunofluorescence double-labeling with BrdU and neuron-specific markers at 4 weeks after injury showed that most progenitors became neurons in the DG and astrocytes in the hilus. Notably, treatment with imipramine increased preservation of the total number of newly-generated neurons. Our findings provide direct evidence that imipramine treatment contributes to cognitive improvement after TBI, perhaps by enhanced hippocampal neurogenesis.
Kukreti, Vinay; Mohseni-Bod, Hadi; Drake, James
Increased intracranial pressure (ICP) is associated with worse outcome after traumatic brain injury (TBI). The current guidelines and management strategies are aimed at maintaining adequate cerebral perfusion pressure and treating elevated ICP. Despite controversies, ICP monitoring is important particularly after severe TBI to guide treatment and in developed countries is accepted as a standard of care. We provide a narrative review of the recent evidence for the use of ICP monitoring and management of ICP in pediatric TBI. PMID:25624921
Le Prieult, Florie; Thal, Serge C; Engelhard, Kristin; Imbrosci, Barbara; Mittmann, Thomas
Focal neocortical brain injuries lead to functional alterations, which can spread beyond lesion-neighboring brain areas. The undamaged hemisphere and its associated disturbances after a unilateral lesion, so-called transhemispheric diaschisis, have been progressively disclosed over the last decades; they are strongly involved in the pathophysiology and, potentially, recovery of brain injuries. Understanding the temporal dynamics of these transhemispheric functional changes is crucial to decipher the role of the undamaged cortex in the processes of functional reorganization at different stages post-lesion. In this regard, little is known about the acute-subacute processes after 24-48 h in the brain hemisphere contralateral to injury. In the present study, we performed a controlled cortical impact to produce a unilateral traumatic brain injury (TBI) in the motor and somatosensory cortex of mice. In vitro extracellular multi-unit recordings from large neuronal populations, together with single-cell patch-clamp recordings in the cortical network contralateral to the lesion, revealed a strong, but transient, neuronal hyperactivity as early as 24-48 h post-TBI. This abnormal excitable state in the intact hemisphere was not accompanied by alterations in neuronal intrinsic properties, but it was associated with an impairment of the phasic gamma aminobutyric acid (GABA)ergic transmission and an increased expression of GABAA receptor subunits related to tonic inhibition exclusively in the contralateral hemisphere. These data unravel a series of early transhemispheric functional alterations after diffuse unilateral cortical injury, which may compensate and stabilize the disrupted brain functions. Therefore, our findings support the hypothesis that the undamaged hemisphere could play a significant role in early functional reorganization processes after a TBI.
Kesikburun, Serdar; Alaca, Rıdvan; Aras, Berke; Tuğcu, Ilknur; Tan, Arif Kenan
Bruxism is involuntary grinding of the teeth and can occur as a complication of brain injury. If untreated, bruxism can lead to severe occlusal trauma. Herein, we present a patient with traumatic brain injury and nocturnal bruxism that was treated with botulinum toxin injection. A 21 yr old male patient with traumatic brain injury from a car accident was admitted to our inpatient rehabilitation unit. He had a history of coma for 2 wk in the intensive care unit. The initial cranial computed tomography scan indicated a superior thalamic hemorrhage. On admission to our department 3 mo postinjury, his mental status was good and he was able to walk without assistance, but he had mild ataxia. He complained about severe teeth grinding at night, which began 2 mo postinjury. Botulinum toxin-A was injected into the masseter muscles (20 U in each muscle) and temporalis muscles (15 U in each muscle) bilaterally. A decrease in bruxism was reported within 3 d. Clinical improvement persisted at assessment 4 mo posttreatment. Botulinum toxin injection can be used as an effective treatment for bruxism associated with brain injury.
Flanagan, Steven R; Cantor, Joshua B; Ashman, Teresa A
Traumatic brain injury (TBI) is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine. PMID:19183780
Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H
Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury.
Schurman, Lesley D; Lichtman, Aron H
The endogenous cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG). Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms. Traumatic brain injury (TBI) pathology remains mostly refractory to currently available drugs, perhaps due to its heterogeneous nature in etiology, clinical presentation, and severity. Here, we review pre-clinical studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system to ameliorate TBI pathology. Specifically, manipulations of endocannabinoid degradative enzymes (e.g., fatty acid amide hydrolase, monoacylglycerol lipase, and α/β-hydrolase domain-6), CB1 and CB2 receptors, and their endogenous ligands have shown promise in modulating cellular and molecular hallmarks of TBI pathology such as; cell death, excitotoxicity, neuroinflammation, cerebrovascular breakdown, and cell structure and remodeling. TBI-induced behavioral deficits, such as learning and memory, neurological motor impairments, post-traumatic convulsions or seizures, and anxiety also respond to manipulations of the endocannabinoid system. As such, the endocannabinoid system possesses potential drugable receptor and enzyme targets for the treatment of diverse TBI pathology. Yet, full characterization of TBI-induced changes in endocannabinoid ligands, enzymes, and receptor populations will be important to understand that role this system plays in TBI pathology. Promising classes of compounds, such as the plant-derived phytocannabinoids, synthetic cannabinoids, and endocannabinoids, as well as their non-cannabinoid receptor
Schurman, Lesley D.; Lichtman, Aron H.
The endogenous cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG). Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms. Traumatic brain injury (TBI) pathology remains mostly refractory to currently available drugs, perhaps due to its heterogeneous nature in etiology, clinical presentation, and severity. Here, we review pre-clinical studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system to ameliorate TBI pathology. Specifically, manipulations of endocannabinoid degradative enzymes (e.g., fatty acid amide hydrolase, monoacylglycerol lipase, and α/β-hydrolase domain-6), CB1 and CB2 receptors, and their endogenous ligands have shown promise in modulating cellular and molecular hallmarks of TBI pathology such as; cell death, excitotoxicity, neuroinflammation, cerebrovascular breakdown, and cell structure and remodeling. TBI-induced behavioral deficits, such as learning and memory, neurological motor impairments, post-traumatic convulsions or seizures, and anxiety also respond to manipulations of the endocannabinoid system. As such, the endocannabinoid system possesses potential drugable receptor and enzyme targets for the treatment of diverse TBI pathology. Yet, full characterization of TBI-induced changes in endocannabinoid ligands, enzymes, and receptor populations will be important to understand that role this system plays in TBI pathology. Promising classes of compounds, such as the plant-derived phytocannabinoids, synthetic cannabinoids, and endocannabinoids, as well as their non-cannabinoid receptor
Ivancevic, Vladimir G.; Reid, Darryn J.
Recently, the first author has proposed a new coupled loading-rate hypothesis as a unique cause of both brain and spinal injuries, which states that they are both caused by a Euclidean jolt, an impulsive loading that strikes head and spine (or, any other part of the human body)- in several coupled degrees-of-freedom simultaneously. Injury never happens in a single direction only, nor is it ever caused by a static force. It is always an impulsive translational plus rotational force. The Euclidean jolt causes two basic forms of brain, spine and other musculo-skeletal injuries: (i) localized translational dislocations; and (ii) localized rotational disclinations. In the present Chapter, we first review this unique mechanics of a general human mechanical injury, and then describe how it can be predicted and controlled by a crash simulator toolbox. This rigorous Matlab toolbox has been developed using an existing thirdparty toolbox DiffMan, for accurately solving differential equations on smooth manifolds and mechanical Lie groups. The present crash simulator toolbox performs prediction/control of brain and spinal injuries within the framework of the Euclidean group SE(3) of rigid motions in our natural 3-dimensional space.
Garcia, Jane Mertz; Sellers, Debra M.; Hilgendorf, Amy E.; Burnett, Debra L.
Objective: Our aim was to evaluate a health education programme (TBIoptions: Promoting Knowledge) designed to increase public awareness and understanding about traumatic brain injury (TBI) through in-person (classroom) and computer-based (electronic) learning environments. Design: We used a pre-post survey design with randomization of participants…
Ornstein, Tisha J.; Levin, Harvey S.; Chen, Shirley; Hanten, Gerri; Ewing-Cobbs, Linda; Dennis, Maureen; Barnes, Marcia; Max, Jeffrey E.; Logan, Gordon D.; Schachar, Russell
Background: Executive control deficits are common sequelae of childhood traumatic brain injury (TBI). The goal of the current study was to assess a specific executive control function, performance monitoring, in children following TBI. Methods: Thirty-one children with mild-moderate TBI, 18 with severe TBI, and 37 control children without TBI, of…
Aldrich, Erin M.; Obrzut, John E.
Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…
Angeleri, R.; Bosco, F. M.; Zettin, M.; Sacco, K.; Colle, L.; Bara, B. G.
The aim of the present study was to examine the communicative abilities of traumatic brain injury patients (TBI). We wish to provide a complete assessment of their communicative ability/disability using a new experimental protocol, the "Assessment Battery of Communication," ("ABaCo") comprising five scales--linguistic, extralinguistic,…
Arroyos-Jurado, Elsa; Savage, Todd A.
As school-age children are at the highest risk for sustaining a traumatic brain injury (TBI), educational professionals working in school settings will encounter students dealing with the after-effects of a TBI. These effects can influence students' ability to navigate the behavioral, social, and academic demands of the classroom. This article…
Nair, Syam; Hagberg, Henrik; Krishnamurthy, Rajanikant; Thornton, Claire; Mallard, Carina
Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk) family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1 potentiates NMDA receptor-mediated excitotoxicity through interaction with the NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels are particularly highly expressed in the developing brain and thus, we hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to reviewing current knowledge, we present new aspects of the molecular structure of DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk-regulation in NMDA-induced cerebral injury and novel approaches to blocking the injurious effects of DAPk1. PMID:23880846
Nair, Syam; Hagberg, Henrik; Krishnamurthy, Rajanikant; Thornton, Claire; Mallard, Carina
Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk) family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1 potentiates NMDA receptor-mediated excitotoxicity through interaction with the NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels are particularly highly expressed in the developing brain and thus, we hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to reviewing current knowledge, we present new aspects of the molecular structure of DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk-regulation in NMDA-induced cerebral injury and novel approaches to blocking the injurious effects of DAPk1.
Ludwigsen, John S.; Ford, Corey C.
Objective Many troops deployed in Iraq and Afghanistan have sustained blast-related, closed-head injuries from being within non-lethal distance of detonated explosive devices. Little is known, however, about the mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI). This study attempts to identify the precise conditions of focused stress wave energy within the brain, resulting from blast exposure, which will correlate with a threshold for persistent brain injury. Methods This study developed and validated a set of modelling tools to simulate blast loading to the human head. Using these tools, the blast-induced, early-time intracranial wave motions that lead to focal brain damage were simulated. Results The simulations predict the deposition of three distinct wave energy components, two of which can be related to injury-inducing mechanisms, namely cavitation and shear. Furthermore, the results suggest that the spatial distributions of these damaging energy components are independent of blast direction. Conclusions The predictions reported herein will simplify efforts to correlate simulation predictions with clinical measures of TBI and aid in the development of protective headwear. PMID:24766453
Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F
Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy.
... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Traumatic brain injury. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD...
Davies, Susan C.
Traumatic brain injuries (TBIs), including concussions, can result in a constellation of physical, cognitive, emotional, and behavioral symptoms that affect students' well-being and performance at school. Despite these effects, school personnel remain underprepared identify, educate, and assist this population of students. This article describes a…
development of cerebral edema ...... 15 3.2 Overview of Hemostasis...and development of cerebral edema The development of cerebral edema is another important type of secondary brain injury. It is clear that the...formation of cerebral edema is a major factor leading to the high morbidity and mortality in patients with TBI.25 No new treatments have been developed in
Brew, Nadine; Walker, David; Wong, Flora Y
Cerebrovascular lesions, mainly germinal matrix hemorrhage and ischemic injury to the periventricular white matter, are major causes of adverse neurodevelopmental outcome in preterm infants. Cerebrovascular lesions and neuromorbidity increase with decreasing gestational age, with the white matter predominantly affected. Developmental immaturity in the cerebral circulation, including ongoing angiogenesis and vasoregulatory immaturity, plays a major role in the severity and pattern of preterm brain injury. Prevention of this injury requires insight into pathogenesis. Cerebral blood flow (CBF) is low in the preterm white matter, which also has blunted vasoreactivity compared with other brain regions. Vasoreactivity in the preterm brain to cerebral perfusion pressure, oxygen, carbon dioxide, and neuronal metabolism is also immature. This could be related to immaturity of both the vasculature and vasoactive signaling. Other pathologies arising from preterm birth and the neonatal intensive care environment itself may contribute to impaired vasoreactivity and ineffective CBF regulation, resulting in the marked variations in cerebral hemodynamics reported both within and between infants depending on their clinical condition. Many gaps exist in our understanding of how neonatal treatment procedures and medications have an impact on cerebral hemodynamics and preterm brain injury. Future research directions for neuroprotective strategies include establishing cotside, real-time clinical reference values for cerebral hemodynamics and vasoregulatory capacity and to demonstrate that these thresholds improve long-term outcomes for the preterm infant. In addition, stimulation of vascular development and repair with growth factor and cell-based therapies also hold promise.
Alvis-Miranda, Hernando; Castellar-Leones, Sandra Milena; Moscote-Salazar, Luis Rafael
Intracranial hypertension is the largest cause of death in young patients with severe traumatic brain injury. Decompressive craniectomy is part of the second level measures for the management of increased intracranial pressure refractory to medical management as moderate hypothermia and barbiturate coma. The literature lack of concepts is their indications. We present a review on the state of the art. PMID:27162826
Czirják, Sándor; Rácz, Károly; Góth, Miklós
Posttraumatic hypopituitarism is of major public health importance because it is more prevalent than previously thought. The prevalence of hypopituitarism in children with traumatic brain injury is unknown. Most cases of posttraumatic hypopituitarism remain undiagnosed and untreated in the clinical practice, and it may contribute to the severe morbidity seen in patients with traumatic brain injury. In the acute phase of brain injury, the diagnosis of adrenal insufficiency should not be missed. Determination of morning serum cortisol concentration is mandatory, because adrenal insufficiency can be life threatening. Morning serum cortisol lower than 200 nmol/L strongly suggests adrenal insufficiency. A complete hormonal investigation should be performed after one year of the trauma. Isolated growth hormone deficiency is the most common deficiency after traumatic brain injury. Sports-related chronic repetitive head trauma (because of boxing, kickboxing, football and ice hockey) may also result in hypopituitarism. Close co-operation between neurosurgeons, endocrinologists, rehabilitation physicians and representatives of other disciplines is important to provide better care for these patients.
Intended for use by the classroom teacher, this guide presents teaching suggestions as well as suggested resources for teaching children with traumatic brain injuries (TBI). Emphasis is placed on working with the injured family and the importance of planning for transition and re-entry into the classroom through a continuum of settings. Teachers…
Bowen, Julie M.
Students who have sustained a traumatic brain injury (TBI) return to the school setting with a range of cognitive, psychosocial, and physical deficits that can significantly affect their academic functioning. Successful educational reintegration for students with TBI requires careful assessment of each child's unique needs and abilities and the…
Rosenthal, Stacy B.
Over one million people suffer a traumatic brain injury every year, many of whom are students between the ages of 5 and 18. Using a qualitative case study approach, I wanted to discover the specific factors that both impede and help the school re-entry process for students in grades kindergarten through twelve so that these students can return to…
Stevens, Alice M.
This resource guide of annotated references on traumatic brain injury (TBI) was created to help educators locate information from such disciplines as neurology, neuropsychology, rehabilitation, and pediatric medicine. Twenty-four resources published from 1990 to 1994 are listed, with annotations. The resources include research reports/reviews,…
Johnson, Abigail R.; DeMatt, Ellen; Salorio, Cynthia F.
Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources,…
haemorrhage, and 6 with subarach- noid hemorrhage from ruptured aneurysm . There were 4 cases of cerebral contusions and a single case of traumatic...B. Goldstein, 2003: Significance of Intracranial Pressure Pulse Morphology in Pediatric Traumatic Brain Injury. IEEE, 2491-2494. Anile, C., H. D
DeRuyter, Frank; Donoghue, Kathleen A.
A case study of a difficult to manage nonspeaking young man with brain injury is presented. Assessment and intervention indicated severe cognitive-linguistic deficits, severe physical involvement of all extremities, extensive surgical management, visual perceptual and acuity deficits, and behavioral problems. (Author/DB)
Zirkel, Perry A.
This article provides a comprehensive and current synthesis of the legislation, regulations, policy interpretations, and case law concerning students with traumatic and nontraumatic brain injury from pre-K to grade 12. The primary focus is the Individuals with Disabilities Education Act, but the scope extends to other applicable legal bases. The…
Donders, Jacobus; Nesbit-Greene, Kelly
The influence of neurological and demographic variables on neuropsychological test performance was examined in 100 9- to 16-year-old children with traumatic brain injury (TBI). Regression analyses were conducted to determine the relative contributions of coma, neuroimaging findings, ethnicity, socioeconomic status, and gender to variance in…
Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…
Lowenthal, Barbara; Lowenthal, Barbara
Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)
Pavlovskaya, Marina; Groswasser, Zeev; Keren, Ofer; Mordvinov, Eugene; Hochstein, Shaul
We find a spatially asymmetric allocation of attention in patients with traumatic brain injury (TBI) despite the lack of obvious asymmetry in neurological indicators. Identification performance was measured for simple spatial patterns presented briefly to a locus 5 degrees into the left or right hemifield, after precuing attention to the same…
Bennett, Sheila; Good, Dawn; Zinga, Dawn; Kumpf, John
The leading cause of death and injuries in school age children is acquired brain injury (Savage & Wolcott, 1994). Each year approximately 1 in 450 school age children and 1 in 200 adolescents/young adults suffer an injury as a result of some form of acquired brain injury. Approximately 27,000 students in the Ontario school system have acquired…
Hawryluk, Gregory W J; Bullock, M Ross
Traumatic brain injury (TBI) is the greatest cause of death and severe disability in young adults; its incidence is increasing in the elderly and in the developing world. Outcome from severe TBI has improved dramatically as a result of advancements in trauma systems and supportive critical care, however we remain without a therapeutic which acts directly to attenuate brain injury. Recognition of secondary injury and its molecular mediators has raised hopes for such targeted treatments. Unfortunately, over 30 late-phase clinical trials investigating promising agents have failed to translate a therapeutic for clinical use. Numerous explanations for this failure have been postulated and are reviewed here. With this historical context we review ongoing research and anticipated future trends which are armed with lessons from past trials, new scientific advances, as well as improved research infrastructure and funding. There is great hope that these new efforts will finally lead to an effective therapeutic for TBI as well as better clinical management strategies.
Park, C L; Moor, P; Birch, K; Shirley, P J
The primary brain insult that occurs at the time of head injury, is determined by the degree of neuronal damage or death and so cannot be influenced by further treatment. The focus of immediate and ongoing care from the point of wounding to intensive care management at Role 4 should be to reduce or prevent any secondary brain injury. The interventions and triage decisions must be reassessed at every stage of the process, but should focus on appropriate airway management, maintenance of oxygenation and carbon dioxide levels and maintenance of adequate cerebral perfusion pressure. Early identification of raised intracranial pressure and appropriate surgical intervention are imperative. Concurrent injuries must also be managed appropriately. Attention to detail at every stage of the evacuation chain should allow the head-injured patient the best chance of recovery.
Vos, Pieter E
Traumatic brain injury (TBI) is a pathologically heterogeneous disease affecting people of all ages. The highest incidence of TBI occurs in young people and the average age is 30 to 40 years. Injury grading may range from mild with a low frequency (1 per 100) of life-threatening intracranial hematoma that needs immediate neurosurgical operation and very low mortality (1 per 1,000) to severe with a high likelihood of life-threatening intracranial hematoma (up to 1 per 3), a 40% case fatality rate and a high disability rate (2 per 3) in survivors. Estimation of the prognosis in severe TBI is currently based on demographic and clinical predictors, including age, Glasgow Coma Scale, pupillary reactions, extracranial injury (hypotension and hypoxia) and computed tomography indices (brain swelling, focal mass lesions, subarachnoid hemorrhage). Biomarkers reflecting damage to neurons and astrocytes may add important complementary information to clinical predictors of outcome and provide insight into the pathophysiology of TBI.
... HUMAN SERVICES Health Resources and Services Administration Current Traumatic Brain Injury State...-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State Implementation Partnership... by the Traumatic Brain Injury Act of 1996 (Pub. L. 104-166) and was most recently reauthorized by...
... Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers AGENCY: Office... Brain Injury Model Systems Centers. CFDA Number: 84.133A-5. SUMMARY: The Assistant Secretary for Special... Projects (DRRPs) to serve as Traumatic Brain Injury Model Systems (TBIMS) Centers. The Assistant...
Wolcott, Gary; And Others
This resource guide offers strategies for working with children having mild to severe brain injuries. Chapter 1 corrects common misunderstandings about brain injuries and gives suggestions and illustrative case examples. Chapter 2 discusses 12 common changes in students with brain injuries such as tiredness, irritability, passivity, depression,…
Word finding in relation to brain injury is discussed for children and adolescents with unilateral congenital malformations of the brain, early hydrocephalus, childhood-acquired left hemisphere stroke, and acquired traumatic head injury. Studies examining the recovery of word-finding deficits after brain injury are discussed, along with…
In the long term after traumatic brain injury, the most disabling problems are generally related to neuropsychiatric sequelae, including personality change and cognitive impairment, rather than neurophysical sequelae. Cognitive impairment after severe injury is likely to include impaired speed of information processing, poor memory and executive problems. Personality change may include poor motivation, and a tendency to be self-centred and less aware of the needs of others. Patients may be described as lazy and thoughtless. Some become disinhibited and rude. Agitation and aggression can be very difficult to manage. Anxiety and depression symptoms are quite frequent and play a role in the development of persistent post-concussion syndrome after milder injury. Depression may be associated with a deterioration in disability over time after injury. Psychosis is not unusual though it has been difficult to confirm that traumatic brain injury is a cause of schizophrenia. Head injury may, many years later, increase the risk of Alzheimer's disease. Good rehabilitation probably minimizes the risk of psychiatric sequelae, but specific psychological and pharmacological treatments may be needed.
Kim, Ho Jeong
Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury. PMID:28070456
Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo
Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986
Ratnasingam, Denesh; Lovick, Darren S.; Weber, Dennis M.; Buonocore, Richard V.; Williams, William V.
extremely serious leading to bleeding, loss of consciousness, and can affect verbal responses, muscles movement in motor responses, and responses with eye movement. Traumatic brain injuries require medical care to assess the severity and treat the injury. In this case report, we discuss a patient's very severe closed head injury while rollerblading without a helmet from which he was not expected to make a full recovery, but did so following intensive medical treatment, rehabilitation, and intercessory prayer to Saint Don Guanella to combat the initial injury and subsequent issues. PMID:25698843
Bandak, F A; Ling, G; Bandak, A; De Lanerolle, N C
Explosive blast shock waves and blunt impact to the head are two types of loading shown to result in mild traumatic brain injury (mTBI). While mTBI from these two causes shares some common features behaviorally, there are distinct differences in the pathophysiology of the underlying injury mechanisms. Various elucidations have been offered in the literature to explain the organic damage associated with mTBI resulting from both types of loading. The current state of understanding in this field is somewhat limited by the degree of appreciation of the physics and biomechanics governing the effects of explosive blast shock waves and blunt impact on the head, which has resulted in the various approaches to the investigation of the operative brain injury "wounding mechanisms". In this chapter we provide a simplified description of terminology associated with forces on the head from explosive blast shock waves and blunt impact, to assist readers in the field in evaluating interpretations of brain injury "wounding" processes. Remarkably, mTBI from either loading is shown generally to result in only a small loss of neurons, with hippocampal neurons appearing to be particularly vulnerable to explosive blast shock waves. Explosive blast studies in large animal models show a unique pattern of periventricular injury, which is different from the classic diffuse axonal injury. Both astrocyte and microglial activation are also seen in explosive blast as well as impact trauma, but this may be a general secondary brain injury response, nonspecific to explosive blast or blunt trauma. Additionally, while moderate to severe impact closed head injuries sometimes result in petechial hemorrhages or hematomas, they do not appear to be associated with explosive blast mTBI even with repeated exposure to blasts.
Ali, Ahmer; Konakondla, Sanjay; Zwagerman, Nathan T; Peng, Changya; Schafer, Steven; Ding, Jamie Y; Dornbos, David; Sikharam, Chaitanya; Geng, Xiaokun; Guthikonda, Murali; Kreipke, Christian W; Rafols, José A; Ding, Yuchuan
Traumatic brain injury (TBI) induces brain edema via water and glycerol transport channels, called aquaporins (AQPs). The passage of glycerol across brain cellular compartments has been shown during edema. Using a modified impact/head acceleration rodent model of diffuse TBI, we assessed the role of hypoxia inducible factor (HIF)-1alpha in regulating AQP9 expression and glycerol accumulation during the edema formation. Adult (400-425 g) male Sprague-Dawley rats received a closed head injury with a weight drop (450 g, 2-m height) and were allowed to survive up to 48 hours. Some rat groups were administered 2-methoxyestradiol (2ME2, a HIF-1alpha inhibitor) 30 minutes after injury and were euthanized at 4 and 24 hours after injury. Brain edema was measured directly by water content, and glycerol concentration was determined by the Cayman Glycerol Assay. HIF-1alpha and AQP9 protein levels were assessed by Western immunoblotting. This study demonstrated a significant (P<0·05) increase in brain water content at 4-48 hours following impact. Cerebral glycerol was significantly (P<0.05) up-regulated at as early as 1 hour and remained at high levels for up to 48 hours. Similarly, significant (P<0.05) increases in HIF-1alpha and AQP9 protein levels were found at 1 hour and up to 48 hours after injury. Compared to untreated but injured rats, inhibition of HIF-1alpha by 2ME2 significantly (P<0.05) reduced the TBI-induced AQP9 up-regulation. This reduction was temporally associated with significant (P<0.05) decreases in both edema and glycerol accumulation. The data suggested an associated induction of HIF-1alpha, AQP9, and extracellular glycerol accumulation in edema formation following diffuse TBI. The implication of HIF-1alpha and AQP9 underlying TBI-induced edema formation offers possibilities for novel TBI therapies.
Kolb, Bryan; Mychasiuk, Richelle; Williams, Preston; Gibb, Robbin
Neocortical development represents more than a simple unfolding of a genetic blueprint: rather, it represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Most cortical regions are sensitive to a wide range of experiential factors during development and later in life, but the injured cortex appears to be unusually sensitive to perinatal experiences. This paper reviews the factors that influence how normal and injured brains (both focal and ischemic injuries) develop and adapt into adulthood. Such factors include prenatal experiences in utero as well as postnatal experiences throughout life. Examples include the effects of sensory and motor stimulation, psychoactive drugs (including illicit and prescription drugs), maternal and postnatal stress, neurotrophic factors, and pre- and postnatal diet. All these factors influence cerebral development and influence recovery from brain injury during development.
Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.
Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872
Hart, Tessa; Schomer, Katherine G.
Abstract The aim of this systematic review was to critically evaluate the evidence on interventions for depression following traumatic brain injury (TBI) and provide recommendations for clinical practice and future research. We reviewed pharmacological, other biological, psychotherapeutic, and rehabilitation interventions for depression following TBI from the following data sources: PubMed, CINAHL, PsycINFO, ProQuest, Web of Science, and Google Scholar. We included studies written in English published since 1980 investigating depression and depressive symptomatology in adults with TBI; 658 articles were identified. After reviewing the abstracts, 57 articles met the inclusion criteria. In addition to studies describing interventions designed to treat depression, we included intervention studies in which depressive symptoms were reported as a secondary outcome. At the end of a full review in which two independent reviewers extracted data, 26 articles met the final criteria that included reporting data on participants with TBI, and using validated depression diagnostic or severity measures pre- and post-treatment. Three external reviewers also examined the study methods and evidence tables, adding 1 article, for a total of 27 studies. Evidence was classified based on American Academy of Neurology criteria. The largest pharmacological study enrolled 54 patients, and none of the psychotherapeutic/rehabilitation interventions prospectively targeted depression. This systematic review documents that there is a paucity of randomized controlled trials for depression following TBI. Serotonergic antidepressants and cognitive behavioral interventions appear to have the best preliminary evidence for treating depression following TBI. More research is needed to provide evidence-based treatment recommendations for depression following TBI. PMID:19698070
Nudo, Randolph J.
Substantial data have accumulated over the past decade indicating that the adult brain is capable of substantial structural and functional reorganization after stroke. While some limited recovery is known to occur spontaneously, especially within the first month post-stroke, there is currently significant optimism that new interventions based on…
Menzel, Lutz; Kleber, Lisa; Friedrich, Carina; Hummel, Regina; Dangel, Larissa; Winter, Jennifer; Schmitz, Katja; Tegeder, Irmgard; Schäfer, Michael K E
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI. Grn(-/-) mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was elevated in Grn(-/-) mice as reflected by increased transcription of pro-inflammatory cytokines TNFα, IL-1β, IL-6, and decreased transcription of the anti-inflammatory cytokine IL-10. However, numbers of Iba1(+) microglia/macrophages and immigrated CD45(+) leukocytes were similar at perilesional sites while determination of IgG extravasation suggested stronger impairment of blood brain barrier integrity in Grn(-/-) compared to wild-type mice. Most strikingly, Grn(-/-) mice displayed exaggerated astrogliosis 5 days after TBI as demonstrated by anti-GFAP immunohistochemistry and immunoblot. GFAP(+) astrocytes at perilesional sites were immunolabelled for iNOS and TNFα suggesting that pro-inflammatory activation of astrocytes was attenuated by PGRN. Accordingly, recombinant PGRN (rPGRN) attenuated LPS- and cytokine-evoked iNOS and TNFα mRNA expression in cultured astrocytes. Moreover, intracerebroventricular administration of rPGRN immediately before trauma reduced brain damage and neurological deficits, and restored normal levels of cytokine transcription, axonal injury and astrogliosis 5 days after TBI in Grn(-/-) mice. Our results show that endogenous and recombinant PGRN limit axonal injury and astrogliosis and suggest therapeutic potential of PGRN in TBI. GLIA 2017;65:278-292.
Scafidi, Susanna; Racz, Jennifer; Hazelton, Julie; McKenna, Mary C; Fiskum, Gary
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-L-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21-22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3-7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was significantly
Scafidi, Susanna; Racz, Jennifer; Hazelton, Julie; McKenna, Mary C.; Fiskum, Gary
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-l-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21–22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3–7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was
Rakhunde, Purushottam B.; Saher, Sana; Ali, Syed Ayaz
Objectives: Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. Materials and Methods: We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. Results: The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). Conclusion: These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation. PMID:25538333
Background Blast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Results Rats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions. Conclusions These lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted. PMID:24252601
Lithium, a well-known drug for the treatment of bipolar disorder, may also have the ability to reduce neurodegeneration and stimulate cell proliferation. Systemic injection of mitochondrial toxin 3-nitropropionic acid (3NPA) is known to induce a relatively selective, Huntington disease-like brain injury. The aim of this study was to determine the effect of lithium chloride (LiCl) on brain injury caused by 3NPA. Female adult Wistar rats were pre-treated with LiCl (127 mg/kg) 1 day before the first injection of 3NPA (28 mg/kg), and then for 8 days with the same treatment but receiving LiCl 1 hour before 3NPA. Control groups were pre-treated accordingly, with LiCl or with normal saline, but were not treated with 3NPA. Staining for cytochrome c oxidase activity and in situ hybridization autoradiography of synaptotagmin-4 and -7 mRNAs were used to evaluate brain injury caused by 3NPA. There was a significant reduction of body weight in the 3NPA+LiCl group (79%) compared to the 3NPA group (90%, p = 0.031) and both control groups (100%, p = 0.000). Densitometric evaluation of cytochrome c oxidase staining and in situ hybridization autoradiograms revealed that the pre-treatment with LiCl caused an increase in striatal lesion for about 40% (p = 0.049). Moreover, the lesion was observed also in the hippocampus of three animals from the 3NPA+LiCl group and in two animals from the 3NPA group. However, there were no differences between the LiCl and saline group in any of the measured parameters. We concluded that the pre-treatment with a relatively nontoxic dose of LiCl could aggravate brain injury caused by 3NPA. PMID:27289244
Meng, X E; Zhang, Y; Li, N; Fan, D F; Yang, C; Li, H; Guo, D Z; Pan, S Y
We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P < 0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P < 0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P < 0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.
Moretti, Raffaella; Chhor, Vibol; Bettati, Donatella; Banino, Elena; De Lucia, Silvana; Le Charpentier, Tifenn; Lebon, Sophie; Schwendimann, Leslie; Pansiot, Julien; Rasika, Sowmyalakshmi; Degos, Vincent; Titomanlio, Luigi; Gressens, Pierre; Fleiss, Bobbi
The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than injuries to the adult brain. Understanding this developmental sensitivity is critical because children under 4 years of age of sustain TBI more frequently than any other age group. One of the first events after TBI is the infiltration and degranulation of mast cells (MCs) in the brain, releasing a range of immunomodulatory substances; inhibition of these cells is neuroprotective in other types of neonatal brain injury. This study investigates for the first time the role of MCs in mediating injury in a P7 mouse model of pediatric contusion-induced TBI. We show that various neural cell types express histamine receptors and that histamine exacerbates excitotoxic cell death in primary cultured neurons. Cromoglycate, an inhibitor of MC degranulation, altered the inflammatory phenotype of microglia activated by TBI, reversing several changes but accentuating others, when administered before TBI. However, without regard to the time of cromoglycate administration, inhibiting MC degranulation did not affect cell loss, as evaluated by ventricular dilatation or cleaved caspase-3 labeling, or the density of activated microglia, neurons, or myelin. In double-heterozygous cKit mutant mice lacking MCs, this overall lack of effect was confirmed. These results suggest that the role of MCs in this model of pediatric TBI is restricted to subtle effects and that they are unlikely to be viable neurotherapeutic targets. © 2016 Wiley Periodicals, Inc.
Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai
Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221
Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando
Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…
Davidsson, Johan; Risling, Mårten
Severe impacts to the head commonly lead to localized brain damage. Such impacts may also give rise to temporary pressure changes that produce secondary injuries in brain volumes distal to the impact site. Monitoring pressure changes in a clinical setting is difficult; detailed studies into the effect of pressure changes in the brain call for the development and use of animal models. The aim of this study is to characterize the pressure distribution in an animal model of penetrating traumatic brain injuries (pTBI). This data may be used to validate mathematical models of the animal model and to facilitate correlation studies between pressure changes and pathology. Pressure changes were measured in rat brains while subjected to pTBI for a variety of different probe velocities and shapes; pointy, blunt, and flat. Experiments on ballistic gel samples were carried out to study the formation of any temporary cavities. In addition, pressure recordings from the gel experiments were compared to values recorded in the animal experiments. The pTBI generated short lasting pressure changes in the brain tissue; the pressure in the contralateral ventricle (CLV) increased to 8 bar followed by a drop to 0.4 bar when applying flat probes. The pressure changes in the periphery of the probe, in the Cisterna Magna, and the spinal canal, were significantly less than those recorded in the CLV or the vicinity of the skull base. High-speed videos of the gel samples revealed the formation of spherically shaped cavities when flat and spherical probes were applied. Pressure changes in the gel were similar to those recorded in the animals, although amplitudes were lower in the gel samples. We concluded cavity expansion rate rather than cavity size correlated with pressure changes in the gel or brain secondary to probe impact. The new data can serve as validation data for finite element models of the trauma model and the animal and to correlate physical measurements with secondary injuries
Wang, Yu; Wang, Shengqing; Cui, Wenhui; He, Jiujun; Wang, Zhenfu; Yang, Xiaolu
Olive leaves have an antioxidant capacity, and olive leaf extract can protect the blood, spleen and hippocampus in lead-poisoned mice. However, little is known about the effects of olive leaf extract on lead-induced brain injury. This study was designed to determine whether olive leaf extract can inhibit lead-induced brain injury, and whether this effect is associated with antioxidant capacity. First, we established a mouse model of lead poisoning by continuous intragastric administration of lead acetate for 30 days. Two hours after successful model establishment, lead-poisoned mice were given olive leaf extract at doses of 250, 500 or 1 000 mg/kg daily by intragastric administration for 50 days. Under the transmission electron microscope, olive leaf extract attenuated neuronal and capillary injury and reduced damage to organelles and the matrix around the capillaries in the frontal lobe of the cerebral cortex in the lead-poisoned mice. Olive leaf extract at a dose of 1 000 mg/kg had the greatest protective effect. Spectrophotometry showed that olive leaf extract significantly increased the activities of superoxide dismutase, catalase, alkaline phosphatase and acid phosphatase, while it reduced malondialdehyde content, in a dose-dependent manner. Furthermore, immunohistochemical staining revealed that olive leaf extract dose-dependently decreased Bax protein expression in the cerebral cortex of lead-poisoned mice. Our findings indicate that olive leaf extract can inhibit lead-induced brain injury by increasing antioxidant capacity and reducing apoptosis. PMID:25206510
Hetherington, H; Bandak, A; Ling, G; Bandak, F A
In the past, direct physical evidence of mild traumatic brain injury (mTBI) from explosive blast has been difficult to obtain through conventional imaging modalities such as T1- and T2-weighted magnetic resonance imaging (MRI) and computed tomography (CT). Here, we review current progress in detecting evidence of brain injury from explosive blast using advanced imaging, including diffusion tensor imaging (DTI), functional MRI (fMRI), and the metabolic imaging methods such as positron emission tomography (PET) and magnetic resonance spectroscopic imaging (MRSI), where each targets different aspects of the pathology involved in mTBI. DTI provides a highly sensitive measure to detect primary changes in the microstructure of white matter tracts. fMRI enables the measurement of changes in brain activity in response to different stimuli or tasks. Remarkably, all three of these paradigms have found significant success in conventional mTBI where conventional clinical imaging frequently fails to provide definitive differences. Additionally, although used less frequently for conventional mTBI, PET has the potential to characterize a variety of neurotransmitter systems using target agents and will undoubtedly play a larger role, once the basic mechanisms of injury are better understood and techniques to identify the injury are more common. Finally, our MRSI imaging studies, although acquired at much lower spatial resolution, have demonstrated selectivity to different metabolic and physiologic processes, uncovering some of the most profound differences on an individual by individual basis, suggesting the potential for utility in the management of individual patients.
Abstract Traumatic brain injuries (TBIs) are caused by a hit to the head or a sudden acceleration/deceleration movement of the head. Mild TBIs (mTBIs) and concussions are difficult to diagnose. Imaging techniques often fail to find alterations in the brain, and computed tomography exposes the patient to radiation. Brain-specific biomolecules that are released upon cellular damage serve as another means of diagnosing TBI and assessing the severity of injury. These biomarkers can be detected from samples of body fluids using laboratory tests. Dozens of TBI biomarkers have been studied, and research related to them is increasing. We reviewed the recent literature and selected 12 biomarkers relevant to rapid and accurate diagnostics of TBI for further evaluation. The objective was especially to get a view of the temporal profiles of the biomarkers’ rise and decline after a TBI event. Most biomarkers are rapidly elevated after injury, and they serve as diagnostics tools for some days. Some biomarkers are elevated for months after injury, although the literature on long-term biomarkers is scarce. Clinical utilization of TBI biomarkers is still at a very early phase despite years of active research. PMID:28032118
Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui
Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.
Grafman, Jordan; Salazar, Andres M
The purpose of this chapter is to summarize some key topics discussed in this volume and describe trends suggesting the direction of future traumatic brain injury (TBI) research. Interest in, and funding for, TBI has ebbed and flowed with the public awareness of injury risk from combat, sports, or everyday life. Advances in acute resuscitation, emergency response systems, and early management have had a major impact on survival after TBI, while recent research has emphasized underlying genetic substrates and the molecular mechanisms of brain injury, repair, and neuroplasticity. This in turn impacts not only on primary and secondary neuroprotection strategies for minimizing injury, but also on the other critical remaining challenge, that of identification and validation of optimal strategies for physical and cognitive TBI rehabilitation. New information also highlights long-term degenerative conditions associated with earlier TBI and mediated by a signature cascade of abnormal molecular processes. Thus, TBI has emerged as a recognized significant public health risk with both immediate and lifelong repercussions. The linkage of a TBI to late-life neurodegenerative diseases, the observation of persistent pathologic processes including neuroinflammation and accumulation of tau protein, as well as individual differences in the genetic predisposition for brain repair and plasticity should lead to meaningful translational research with a significant impact on the efficacy and cost-efficiency of acute and chronic treatment for TBI survivors.
Fuentes, Daniel; Rzezak, Patricia; Pereira, Fabricio R; Malloy-Diniz, Leandro F; Santos, Luciana C; Duran, Fábio L S; Barreiros, Maria A; Castro, Cláudio C; Busatto, Geraldo F; Tavares, Hermano; Gorenstein, Clarice
Several magnetic resonance imaging (MRI) studies to date have investigated brain abnormalities in association with the diagnosis of pathological gambling (PG), but very few of these have specifically searched for brain volume differences between PG patients and healthy volunteers (HV). To investigate brain volume differences between PG patients and HV, 30 male never-treated PG patients (DSM-IV-TR criteria) and 30 closely matched HV without history of psychiatric disorders in the past 2 years underwent structural magnetic resonance imaging with a 1.5-T instrument. Using Freesurfer software, we performed an exploratory whole-brain voxelwise volume comparison between the PG group and the HV group, with false-discovery rate correction for multiple comparisons (p < 0.05). Using a more flexible statistical threshold (p < 0.01, uncorrected for multiple comparisons), we also measured absolute and regional volumes of several brain structures separately. The voxelwise analysis showed no clusters of significant regional differences between the PG and HV groups. The additional analyses of absolute and regional brain volumes showed increased absolute global gray matter volumes in PG patients relative to the HV group, as well as relatively decreased volumes specifically in the left putamen, right thalamus and right hippocampus (corrected for total gray matter). Our findings indicate that structural brain abnormalities may contribute to the functional changes associated with the symptoms of PG, and they highlight the relevance of the brain reward system to the pathophysiology of this disorder.
Xuan, Weijun; Agrawal, Tanupriya; Huang, Liyi; Gupta, Gaurav K; Hamblin, Michael R
Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2). Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF) was significantly upregulated by laser treatment in the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ) but not in the perilesional cortex (lesion) at day 7 but not at day 28. Synapsin-1 (a marker for synaptogenesis, the formation of new connections between existing neurons) was significantly upregulated in lesion and SVZ but not DG, at 28 days but not 7 days. The data suggest that the benefit of LLLT to the brain is partly mediated by stimulation of BDNF production, which may in turn encourage synaptogenesis. Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have wider applications to neurodegenerative and psychiatric disorders. Neurological Severity Score (NSS) for TBI mice.
Peng, Ying; Lu, Kui; Li, Zichen; Zhao, Yaodong; Wang, Yiping; Hu, Bin; Xu, Pengfei; Shi, Xiaolei; Zhou, Bin; Pennington, Michael; Chandy, K. George; Tang, Yamei
Background Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)–170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury. Methods Mice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique. Results Radiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor–α by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells. Conclusions The therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells. PMID:24305723
McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P; Juul, Sandra E
ultrastructural white matter abnormalities, characterized by perinuclear vacuolation and axonal dilation, in 3 of 4 animals. Immunolabeling of Nogo-A, a negative regulator of neuronal growth, was not increased in the injured brains compared to 2 control animals. Using GC × GC-TOFMS, we identified metabolites previously recognized as potential biomarkers of perinatal asphyxia. The basal ganglia-thalamus-brain stem injury produced by UCO is consistent with the deep nuclear/brainstem injury pattern seen in human neonates after severe, abrupt hypoxic-ischemic insults. The UCO model permits timely detection of biomarkers associated with specific patterns of neonatal brain injury, and it may ultimately be useful for validating therapeutic strategies to treat neonatal HIE.
Barnes, Clifford L; Sierra, Michelle; Delay, Eugene R
We developed a series of hands-on laboratory exercises on "Brain Injury" designed around several pedagogical goals that included the development of: 1) knowledge of the scientific method, 2) student problem solving skills by testing cause and effect relationships, 3) student analytical and critical thinking skills by evaluating and interpreting data, identifying alternative explanations for data, and identifying confounding variables, and 4) student writing skills by reporting their findings in manuscript form. Students, facilitated by the instructor, developed a testable hypothesis on short-term effects of brain injury by analyzing lesion size and astrocytic activity. Four sequential laboratory exercises were used to present and practice ablation techniques, histological processing, microscopic visualization and image-capture, and computer aided image analysis. This exercise culminated in a laboratory report that mimicked a research article. The effectiveness of the laboratory sequence was assessed by measuring the acquisition of 1) content on anatomical, physiological, and cellular responses of the brain to traumatic brain injury, and 2) laboratory skills and methods of data-collection and analysis using surgical procedures, histology, microscopy, and image analysis. Post-course test scores, significantly greater than pre-course test scores and greater than scores from a similar but unstructured laboratory class, indicated that this hands-on approach to teaching an undergraduate research laboratory was successful. Potential variations in the integrated laboratory exercise, including multidisciplinary collaborations, are also noted.
Atkins, Coleen M
There are more than 3.17 million people coping with long-term disabilities due to traumatic brain injury (TBI) in the United States. The majority of TBI research is focused on developing acute neuroprotective treatments to prevent or minimize these long-term disabilities. Therefore, chronic TBI survivors represent a large, underserved population that could significantly benefit from a therapy that capitalizes on the endogenous recovery mechanisms occurring during the weeks to months following brain trauma. Previous studies have found that the hippocampus is highly vulnerable to brain injury, in both experimental models of TBI and during human TBI. Although often not directly mechanically injured by the head injury, in the weeks to months following TBI, the hippocampus undergoes atrophy and exhibits deficits in long-term potentiation (LTP), a persistent increase in synaptic strength that is considered to be a model of learning and memory. Decoding the chronic hippocampal LTP and cell signaling deficits after brain trauma will provide new insights into the molecular mechanisms of hippocampal-dependent learning impairments caused by TBI and facilitate the development of effective therapeutic strategies to improve hippocampal-dependent learning for chronic survivors of TBI.
Kawata, Keisuke; Liu, Charles Y.; Merkel, Steven F.; Ramirez, Servio H.; Tierney, Ryan T.; Langford, Dianne
Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID:27181909
Franco Rodríguez, N E; Dueñas Jiménez, J M; De la Torre Valdovinos, B; López Ruiz, J R; Hernández Hernández, L; Dueñas Jiménez, S H
A penetrating brain injury produces a glial scar formed by astrocytes, oligodendrocytes, microglia and NG2 cells. Glial scar is a barrier preventing the extent of damage but it has deleterious effects in the regeneration of the axons. Estradiol and tamoxifen reduce gliosis and have neuroprotective effects in the hippocampus and the spinal cord. We evaluated the proliferation of glia and the electrocorticogram in the sensorial cortex in a brain injury model. At seven days post-injury, estradiol, tamoxifen and estradiol plus tamoxifen reduced the number of resident and proliferative NG2 and reactive astrocyte vimentin+ cells. Estradiol and tamoxifen effects on NG2 cells could be produced by the classical oestrogen receptors found in these cells. The glial scar was also reduced by tamoxifen. At thirty days post-injury, the amount of resident and proliferative astrocytes increased significantly, except in the estradiol plus tamoxifen group, whilst the oligodendrocytes proliferation in the glial scar was reduced in treated animals. Tamoxifen promotes the survival of FOX-3+ neurons in the injured area and a recovery in the amplitude of electrocorticogram waves. At thirty days, estradiol did not favour the survival of neurons but produced a greater number of reactive astrocytes. In contrast, the number of oligodendrocytes was reduced. Tamoxifen could favour brain repair promoting neuron survival and adjusting glial cell number. It seems to recover adequate neural communication.
Pérez-Arredondo, Adán; Cázares-Ramírez, Eduardo; Carrillo-Mora, Paul; Martínez-Vargas, Marina; Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Alemón-Medina, Radamés; Sampieri, Aristides; Navarro, Luz; Carmona-Aparicio, Liliana
Abstract Traumatic brain injury (TBI) is an alteration in brain function, caused by an external force, which may be a hit on the skull, rapid acceleration or deceleration, penetration of an object, or shock waves from an explosion. Traumatic brain injury is a major cause of morbidity and mortality worldwide, with a high prevalence rate in pediatric patients, in which treatment options are still limited, not available at present neuroprotective drugs. Although the therapeutic management of these patients is varied and dependent on the severity of the injury, general techniques of drug types are handled, as well as physical and surgical. Baclofen is a muscle relaxant used to treat spasticity and improve mobility in patients with spinal cord injuries, relieving pain and muscle stiffness. Pharmacological support with baclofen is contradictory, because disruption of its oral administration may cause increased muscle tone syndrome and muscle spasm, prolonged seizures, hyperthermia, dysesthesia, hallucinations, or even multisystem organ failure. Combined treatments must consider the pathophysiology of broader alterations than only excitation/inhibition context, allowing the patient's reintegration with the greatest functionality. PMID:27563745
Pérez-Arredondo, Adán; Cázares-Ramírez, Eduardo; Carrillo-Mora, Paul; Martínez-Vargas, Marina; Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Alemón-Medina, Radamés; Sampieri, Aristides; Navarro, Luz; Carmona-Aparicio, Liliana
Traumatic brain injury (TBI) is an alteration in brain function, caused by an external force, which may be a hit on the skull, rapid acceleration or deceleration, penetration of an object, or shock waves from an explosion. Traumatic brain injury is a major cause of morbidity and mortality worldwide, with a high prevalence rate in pediatric patients, in which treatment options are still limited, not available at present neuroprotective drugs. Although the therapeutic management of these patients is varied and dependent on the severity of the injury, general techniques of drug types are handled, as well as physical and surgical. Baclofen is a muscle relaxant used to treat spasticity and improve mobility in patients with spinal cord injuries, relieving pain and muscle stiffness. Pharmacological support with baclofen is contradictory, because disruption of its oral administration may cause increased muscle tone syndrome and muscle spasm, prolonged seizures, hyperthermia, dysesthesia, hallucinations, or even multisystem organ failure. Combined treatments must consider the pathophysiology of broader alterations than only excitation/inhibition context, allowing the patient's reintegration with the greatest functionality.
Lu, Dunyue; Mahmood, Asim; Qu, Changsheng; Goussev, Anton; Schallert, Timothy; Chopp, Michael
Erythropoietin (EPO) is neuroprotective in models of stroke and traumatic brain injury (TBI) when administered prior to or within the first few hours after injury. We seek to demonstrate that EPO also has neurorestorative effects when administered late (i.e., 1 day) after TBI in the rat. Twelve rats were subjected to TBI. Six rats were treated with EPO daily for 14 days starting 1 day after injury, and an additional six rats were treated with saline. Bromodeoxyuridine (BrdU) was administered daily for 14 days. Memory tests using a Morris Water Maze were performed prior to and after injury and treatment. Animals were sacrificed at 15 days after TBI, and their brains were prepared for histological analysis of damage to the dentate gyrus (DG) and for evaluation of newly formed neurons using double labeling of BrdU and MAP-2. The data revealed a significant improvement in spatial memory and significant increase in the number of newly formed neurons with EPO treatment compared with control animals. These data suggest that EPO treatment initiated 1 day after TBI is neurorestorative by enhancing neurogenesis, as well as neuroprotective.
Shannon, Richard J; van der Heide, Susan; Carter, Eleanor L; Jalloh, Ibrahim; Menon, David K; Hutchinson, Peter J; Carpenter, Keri L H
N-acetylaspartate (NAA) is an amino acid derivative primarily located in the neurons of the adult brain. The function of NAA is incompletely understood. Decrease in brain tissue NAA is presently considered symptomatic and a potential biomarker of acute and chronic neuropathological conditions. The aim of this study was to use microdialysis to investigate the behavior of extracellular NAA (eNAA) levels after traumatic brain injury (TBI). Sampling for this study was performed using cerebral microdialysis catheters (M Dialysis 71) perfused at 0.3 μL/min. Extracellular NAA was measured in microdialysates by high-performance liquid chromatography in 30 patients with severe TBI and for comparison, in radiographically "normal" areas of brain in six non-TBI neurosurgical patients. We established a detailed temporal eNAA profile in eight of the severe TBI patients. Microdialysate concentrations of glucose, lactate, pyruvate, glutamate, and glycerol were measured on an ISCUS clinical microdialysis analyzer. Here, we show that the temporal profile of microdialysate eNAA was characterized by highest levels in the earliest time-points post-injury, followed by a steady decline; beyond 70 h post-injury, average levels were 40% lower than those measured in non-TBI patients. There was a significant inverse correlation between concentrations of eNAA and pyruvate; eNAA showed significant positive correlations with glycerol and the lactate/pyruvate (L/P) ratio measured in microdialysates. The results of this on-going study suggest that changes in eNAA after TBI relate to the release of intracellular components, possibly due to neuronal death or injury, as well as to adverse brain energy metabolism.
Chen, Anthony J.-W.; Novakovic-Agopian, Tatjana; Gratton, Caterina; Nomura, Emi M.; D'Esposito, Mark
Objective: We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury. Methods: Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions. We examined the relationship of baseline modularity with pre- to posttraining changes in neuropsychological measures of attention and executive control. Results: The modularity of brain network organization at baseline predicted improvement in attention and executive function after cognitive training, but not after the comparison intervention. Individuals with higher baseline modularity exhibited greater improvements with cognitive training, suggesting that a more modular baseline network state may contribute to greater adaptation in response to cognitive training. Conclusions: Brain network properties such as modularity provide valuable information for understanding mechanisms that influence rehabilitation of cognitive function after brain injury, and may contribute to the discovery of clinically relevant biomarkers that could guide rehabilitation efforts. PMID:25788557
Park, Katya J; Park, Eugene; Liu, Elaine; Baker, Andrew J
White matter sparing after traumatic brain injury (TBI) is an important predictor of survival and outcome. Blood vessels and axons are intimately associated anatomically and developmentally. Neural input is required for appropriate vascular patterning, and vascular signaling is important for neuron development and axon growth. Owing to this codependence between endothelial cells and axons during development and the contribution of endothelial progenitor cells (EPCs) in ischemic injury, we hypothesized that EPCs are important in axonal survival after TBI. We examined the effects of allogenic-cultured EPCs on white matter protection and microvascular maintenance after midline fluid percussion injury in adult Sprague-Dawley rats. We used two in vitro models of injury, mechanical stretch and oxygen-glucose deprivation (OGD), to examine the effects of EPCs on the mechanical and ischemic components of brain trauma, respectively. Our results indicate that EPCs improve the white matter integrity and decrease capillary breakdown after injury. Cultured cortical neurons exposed to OGD had less axon degeneration when treated with EPC-conditioned media, whereas no effect was seen in axons injured by mechanical stretch. The results indicate that EPCs are important for the protection of the white matter after trauma and represent a potential avenue for therapy.
Very little research has been done on the effect of dancing on the rehabilitation of patients having a severe brain injury. In addition to motor problems, the symptom picture of the sequelae of severe brain injuries often involves strong fatigability, reduced physiological arousal, disturbances of coordination of attention, difficulties of emotional control and impairment of memory. This review deals with the neural foundation of dancing and the possibilities of dancing in the rehabilitation of severe brain injuries.
McBride, Devin W; Szu, Jenny I; Hale, Chris; Hsu, Mike S; Rodgers, Victor G J; Binder, Devin K
Traumatic brain injury (TBI) is significant, from a public health standpoint, because it is a major cause of the morbidity and mortality of young people. Cerebral edema after a TBI, if untreated, can lead to devastating damage of the remaining tissue. The current therapies of severe TBI (sTBI), as outlined by the Brain Trauma Foundation, are often ineffective, thus a new method for the treatment of sTBI is necessary. Herein, the reduction of cerebral edema, after TBI, using an osmotic transport device (OTD) was evaluated. Controlled cortical impact (CCI) was performed on adult female CD-1 mice, and cerebral edema was allowed to form for 3 h, followed by 2 h of treatment. The treatment groups were craniectomy only, craniectomy with a hydrogel, OTD without bovine serum albumin (BSA), and OTD. After CCI, brain water content was significantly higher for animals treated with a craniectomy only, craniectomy with a hydrogel, and OTD without BSA, compared to that of control animals. However, when TBI animals were treated with an OTD, brain water content was not significantly higher than that of controls. Further, brain water content of TBI animals treated with an OTD was significantly reduced, compared to that of untreated TBI animals, TBI animals treated with a craniectomy and a hydrogel, and TBI animals treated with an OTD without BSA. Here, we demonstrate the successful reduction of cerebral edema, as determined by brain water content, after TBI using an OTD. These results demonstrate proof of principle for direct water extraction from edematous brain tissue by direct osmotherapy using an OTD.
Kenardy, Justin; Le Brocque, Robyne; Hendrikz, Joan; Iselin, Greg; Anderson, Vicki; McKinlay, Lynne
The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a…
Arroyos-Jurado, Elsa; Paulsen, Jane S.; Ehly, Stewart; Max, Jeffrey E.
This study was conducted to examine the impact of childhood traumatic brain injury (TBI) on intellectual and academic outcomes postinjury. A comprehensive assessment of cognition, achievement, learning, and memory was administered to 27 children and adolescents 6 to 8 years post-TBI. Findings revealed that parent ratings of premorbid achievement…
Shear, Deborah A.; Tortella, Frank C.
Studies in animals show that many compounds and therapeutics have the potential to greatly reduce the morbidity and post-injury clinical sequela for soldiers experiencing TBI. However, to date there are no FDA approved drugs for the treatment of TBI. In fact, expert opinion suggests that combination therapies will be necessary to treat any stage of TBI recovery. Our approach to this research effort is to conduct comprehensive pre-clinical neuroprotection studies in military-relevant animal models of TBI using the most promising neuroprotective agents. In addition, emerging efforts incorporating novel treatment strategies such as stem cell based therapies and alternative therapeutic approaches will be discussed. The development of a non-surgical, non-invasive brain injury therapeutic clearly addresses a major, unresolved medical problem for the Combat Casualty Care Research Program. Since drug discovery is too expensive to be pursued by DOD in the TBI arena, this effort capitalizes on partnerships with the Private Sector (Pharmaceutical Companies) and academic collaborations (Operation Brain Trauma Therapy Consortium) to study therapies already under advanced development. Candidate therapies selected for research include drugs that are aimed at reducing the acute and delayed effects of the traumatic incident, stem cell therapies aimed at brain repair, and selective brain cooling to stabilize cerebral metabolism. Each of these efforts can also focus on combination therapies targeting multiple mechanisms of neuronal injury. PMID:23781213
Maas, A I
Changes in CSF enzyme activity were studied after brain trauma for their prognostic value. Raised values of CPK and HBDH were demonstrated in the CSF of patients with severe brain injuries. Standardised cold lesions of the brain were induced in cats. The activities of the enzymes CPK, HBDH, LDH, GOT, GPT, and pseudocholinesterase were studied at half hour intervals in the cerebrospinal fluid and at hourly intervals in the serum. A statistically highly significant increase of all enzymes studied developed in the CSF. The greatest changes occurred within four hours of freezing. Large increases could occur in half an hour. Isoenzyme studies demonstrated that CPK and LDH were of cerebral origin. No consistently significant changes could be shown in the serum enzyme activity. It is concluded that after brain injuries, enzymes are released into the extracellular fluid of the brain and transported to the CSF. The limited value of a single enzyme estimation is emphasised. The results described seem to provide indirect evidence for transependymal flow of extracellular fluid in brain oedema. Images PMID:915509
Masel, Brent E; Bell, Randy S; Brossart, Shawn; Grill, Raymond J; Hayes, Ronald L; Levin, Harvey S; Rasband, Matthew N; Ritzel, David V; Wade, Charles E; DeWitt, Douglas S
Blast injury is the most prevalent source of mortality and morbidity among combatants in Operations Iraqi and Enduring Freedom. Blast-induced neurotrauma (BINT) is a common cause of mortality, and even mild BINT may be associated with chronic cognitive and emotional deficits. In addition to military personnel, the increasing use of explosives by terrorists has resulted in growing numbers of blast injuries in civilian populations. Since the medical and rehabilitative communities are likely to be faced with increasing numbers of patients suffering from blast injury, the 2010 Galveston Brain Injury Conference focused on topics related to the diagnosis, treatment, and mechanisms of BINT. Although past military actions have resulted in large numbers of blast casualties, BINT is considered the signature injury of the conflicts in Iraq and Afghanistan. The attention focused on BINT has led to increased financial support for research on blast effects, contributing to the development of better experimental models of blast injury and a clearer understanding of the mechanisms of BINT. This more thorough understanding of blast injury mechanisms will result in novel and more effective therapeutic and rehabilitative strategies designed to reduce injury and facilitate recovery, thereby improving long-term outcomes in patients suffering from the devastating and often lasting effects of BINT. The following is a summary of the 2010 Galveston Brain Injury Conference, that included presentations related to the diagnosis and treatment of acute BINT, the evaluation of the long-term neuropsychological effects of BINT, summaries of current experimental models of BINT, and a debate about the relative importance of primary blast effects on the acute and long-term consequences of blast exposure.
Dietrich, W. Dalton
Abstract Traumatic brain injury (TBI) is a significant clinical problem with few therapeutic interventions successfully translated to the clinic. Increased importance on the progressive, long-term consequences of TBI have been emphasized, both in the experimental and clinical literature. Thus, there is a need for a better understanding of the chronic consequences of TBI, with the ultimate goal of developing novel therapeutic interventions to treat the devastating consequences of brain injury. In models of mild, moderate, and severe TBI, histopathological and behavioral studies have emphasized the progressive nature of the initial traumatic insult and the involvement of multiple pathophysiological mechanisms, including sustained injury cascades leading to prolonged motor and cognitive deficits. Recently, the increased incidence in age-dependent neurodegenerative diseases in this patient population has also been emphasized. Pathomechanisms felt to be active in the acute and long-term consequences of TBI include excitotoxicity, apoptosis, inflammatory events, seizures, demyelination, white matter pathology, as well as decreased neurogenesis. The current article will review many of these pathophysiological mechanisms that may be important targets for limiting the chronic consequences of TBI. PMID:25158206
Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Stovell, Matthew G; van der Heide, Susan; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri Lh
Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients). Metabolites 2,3-(13)C2 malate and 2,3-(13)C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-(13)C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD(+) by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-(13)C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and (13)C-labelling patterns in metabolites.
Award Number: W81XWH-08-2-0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain...of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER PT075168 5c. PROGRAM ELEMENT...expressed as affective lability, will decrease significantly in TBI subjects treated with divalproex sodium , a mood stabilizing medication, as
Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.
Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247
Duncan, Connie C; Summers, Angela C; Perla, Elizabeth J; Coburn, Kerry L; Mirsky, Allan F
The focus of this review is an analysis of the use of event-related brain potential (ERP) abnormalities as indices of functional pathophysiology in survivors of traumatic brain injury (TBI). TBI may be the most prevalent but least understood neurological disorder in both civilian and military populations. In the military, thousands of new brain injuries occur yearly; this lends considerable urgency to the use of highly sensitive ERP tools to illuminate brain changes and to address remediation issues. We review the processes thought to be indexed by the cognitive components of the ERP and outline the rationale for applying ERPs to evaluate deficits after TBI. Studies in which ERPs were used to clarify the nature of cognitive complaints of TBI survivors are reviewed, emphasizing impairment in attention, information processing, and cognitive control. Also highlighted is research on the application of ERPs to predict emergence from coma and eventual outcome. We describe primary blast injury, the leading cause of TBI for active duty military personnel in present day warfare. The review concludes with a description of an ongoing investigation of mild TBI, aimed at using indices of brain structure and function to predict the course of posttraumatic stress disorder. An additional goal of this ongoing investigation is to characterize the structural and functional sequelae of blast injury.
Jereb, B; Korenjak, R; Krzisnik, C; Petric-Grabnar, G; Zadravec-Zaletel, L; Anzic, J; Stare, J
Forty-two survivors treated at an age of 2-16 years for brain tumors or leukemia were, 4-21 years after treatment, subjected to an extensive follow-up investigation, including physical examination and interview; 35 of them also had endocrinological and 33 psychological evaluation. Hormonal deficiencies were found in about two-thirds of patients and were most common in those treated for brain tumors. The great majority had verbal intelligence quotient (VIQ) within normal range. Also, the performance intelligence quotients (PIQ) were normal in most patients. However, the results suggested that the primary intellectual capacity in children treated for cancer was not being fully utilized, their PIQ being on the average higher than their VIQ; this tendency was especially pronounced in the leukemia patients.
Lane, Kristy S; St Pierre, Maria E; Lauterbach, Margo D; Koliatsos, Vassilis E
Traumatic brain injury (TBI) can lead to significant post-traumatic disturbances in mood and behavior, with the frontal lobes playing a key role in emotional and behavioral regulation. Injury to the frontal lobe can result in disinhibition and aggression which can result in police intervention and/or incarceration. We highlight four adult cases with a history of severe TBI with frontal lobe injuries and the presence of post-TBI criminal behaviors. There is evidence to support an anatomical basis for aggressive behaviors, yet there are other risk factors to be considered. Behaviors must be investigated thoroughly by obtaining adequate pre- and post-TBI psychiatric and psychosocial histories. By having a comprehensive understanding of aggression while appreciating the complex relationship between TBI, aggression, and premorbid risk factors, clinicians can more adequately treat patients with TBI, with the aim of potentially preventing criminal behaviors and recidivism.
Steventon, D M; John, P R
Following neonatal ischaemic brain injury, irregular vessels increase in size owing to luxury perfusion. These may be demonstrated by conventional colour flow Doppler (CFD) imaging at the periphery of the infarcted area. We present a case in which power Doppler imaging (PDI) was performed in addition to CFD in a neonate with unexplained seizures and which proved more sensitive than CFD in demonstrating luxury perfusion. Ultrasound appearances were compared with those seen on cranial CT. PDI can be a useful adjunct to conventional CFD examination of the neonatal brain in cerebral infarction.
from collagen sponges using the dish test method (Figure 16B). The advantage of the dish test over the diffusion cells test is that samples can be...composite mat with collagen fibers and some chitosan fibers as well as globules but were not able to test for cell response to these matrices...dimensional collagen scaffold. MSCs cultured in monolayer and on a three- dimensional collagen sponge were treated with retinoic acid (RA) for up to
speed `y Judgment `y Executive control `y Depression `y Anxiety `y Agitation `y Irritability `y Impulsivity `y Aggression 11 Step four: determine if...energy drinks) `– Sleep patterns and sleep hygiene `– Co-existing illnesses Step Three: evaluate and Treat Co-occurring disorders Comorbid psychiatric...pharmacologic interventions. Comorbid psychiatric problems may include, but are not limited to: `y Major depressive episode `y Anxiety disorders
Cox, Charles S; Hetz, Robert A; Liao, George P; Aertker, Benjamin M; Ewing-Cobbs, Linda; Juranek, Jenifer; Savitz, Sean I; Jackson, Margaret L; Romanowska-Pawliczek, Anna M; Triolo, Fabio; Dash, Pramod K; Pedroza, Claudia; Lee, Dean A; Worth, Laura; Aisiku, Imoigele P; Choi, Huimahn A; Holcomb, John B; Kitagawa, Ryan S
Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×10(6) cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest
of BDNF and its receptor, trkB in response to injury. This study demonstrated that regions of the brain that are resistant to cell damage have...increased gene expression for BDNF and its high affinity receptor, tyrosine kinase B ( trkB ) during the acute periods after injury. Study 2 examined whether...the alterations in mRNA levels following FP injury resulted in subsequent alterations in protein levels of BDNF and trkB and activation of the ERK/MAP
Blennow, Kaj; Hardy, John; Zetterberg, Henrik
The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE.
Chiou, Kathy S; Carlson, Richard A; Arnett, Peter A; Cosentino, Stephanie A; Hillary, Frank G
The ability to engage in self-reflective processes is a capacity that may be disrupted after neurological compromise; research to date has demonstrated that patients with traumatic brain injury (TBI) show reduced awareness of their deficits and functional ability compared to caretaker or clinician reports. Assessment of awareness of deficit, however, has been limited by the use of subjective measures (without comparison to actual performance) that are susceptible to report bias. This study used concurrent measurements from cognitive testing and confidence judgments about performance to investigate in-the-moment metacognitive experiences after moderate and severe traumatic brain injury. Deficits in metacognitive accuracy were found in adults with TBI for some but not all indices, suggesting that metacognition may not be a unitary construct. Findings also revealed that not all indices of executive functioning reliably predict metacognitive ability.
Dong, Hui; Ma, Yunfu; Ren, Zengxi; Xu, Bin; Zhang, Yunhe; Chen, Jing; Yang, Bo
Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future.
Kernie, Steven G; Parent, Jack M
Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent neurogenesis, the subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus, are stimulated by brain insults such as stroke or trauma. Here we focus on the effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke, and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI). Stroke potently stimulates forebrain SVZ cell proliferation and neurogenesis. SVZ neuroblasts are induced to migrate to the injured striatum, and to a lesser extent to the peri-infarct cortex. Controversy exists as to the types of neurons that are generated in the injured striatum, and whether adult-born neurons contribute to functional restoration remains uncertain. Advances in understanding the regulation of SVZ neurogenesis in general, and stroke-induced neurogenesis in particular, may lead to improved integration and survival of adult-born neurons at sites of injury. Dentate gyrus cell proliferation and neurogenesis similarly increase after experimental TBI. However, pre-existing neuroblasts in the dentate gyrus are vulnerable to traumatic insults, which appear to stimulate neural stem cells in the SGZ to proliferate and replace them, leading to increased numbers of new granule cells. Interventions that stimulate hippocampal neurogenesis appear to improve cognitive recovery after experimental TBI. Transgenic methods to conditionally label or ablate neural stem cells are beginning to further address critical questions regarding underlying mechanisms and functional significance of neurogenesis after stroke or TBI. Future therapies should be aimed at directing appropriate neuronal replacement after ischemic or traumatic injury while suppressing aberrant integration that may contribute to co-morbidities such as epilepsy or
Roughton, Karolina; Andreasson, Ulf; Blomgren, Klas; Kalm, Marie
Radiotherapy is an effective treatment strategy in the treatment of brain tumors, but it is also a major cause of long-term complications, especially in survivors of pediatric brain tumors. Cognitive decline caused by cranial radiotherapy is thought, at least partly, to depend on injury to stem and progenitor cells in the dentate gyrus of the hippocampus. This study investigated the effects of lipopolysaccharide (LPS)-induced inflammation at the time of irradiation (IR) in the growing mouse brain. A single injection of LPS (0.3 mg/kg) was administered 24 h prior to cranial IR of 14-day-old male mice. LPS pretreatment increased the levels of the chemokine CCL2 and the cytokine IL-1β in the brain by 440 and 560%, respectively, compared to IR alone. IR disrupted hippocampal neurogenesis and the growth of the dentate gyrus, and the mice pretreated with LPS displayed an even more pronounced lack of growth than the vehicle-treated group 2 months after IR. The density of microglia was not affected, but LPS-pretreated mice displayed 48% fewer bromodeoxyuridine-positive cells and 43% fewer doublecortin-positive cells in the granule cell layer 2 months after IR compared with the vehicle-treated group. In conclusion, an ongoing inflammation in the brain at the time of IR further enhanced the IR-induced loss of neurogenesis, and may aggravate future cognitive deficits in patients treated with cranial radiotherapy.
Gill, Raminder; Chang, Philip K-Y; Prenosil, George A; Deane, Emily C; McKinney, Rebecca A
Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin-related kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury-induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB-Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two-fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB-Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury-induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post-traumatic epilepsy. Therefore, our data suggest that blocking the BDNF-TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post-traumatic epilepsy.
Archives of Clinical Neuropsychology , 11(2), 139-145. Since no empirical evidence existed at the time for treatment concerning PSC...severity levels. Moser, R.S., and Schatz, P. 2002. Enduring effects of concussion in youth athletes. Archives of Clinical Neuropsychology , 17, 91...Melnyk, A., and Nagy, J. 2002. Patient complaints within 1 month of mild traumatic brain injury: A controlled study. Archives of Clinical Neuropsychology ,
refine goal directed therapy for traumatic brain injury. 2. Evaluate the Novel Screening tool and identifying cognitive impairment for mild...neuropsychological performance/cognitive impairment in real time, such as in the military field. Our study will compare these two novel methods of...portable and may prove to be useful in assessing cognitive impairment in real time, in the military field. Although, diagnosing mTBI is one of the biggest
of having no clinical history of brain or ocular abnormalities, while 12 failed the criteria for normality. Of these, 8 individuals had residual ...proportion of variance accounted for is of the the order of 0.995, indicating that the residual variance both across saccades and between the model...neurological loss are numerous and include stroke, motor vehicle accidents, falls, sports injury, assaults, and gunshot wounds. The recent utilization of
accompany any repeated cognitive exam. Providers should be mindful of other factors affecting the MACE cognitive score such as sleep deprivation ...G. DeMunck June 2015 Thesis Advisor: Lee Sciarini Second Reader: Joseph Sullivan This thesis was performed at the MOVES Institute...ENVIRONMENT TRAUMATIC BRAIN INJURY SCREEN (VETS) 5. FUNDING NUMBERS 6. AUTHOR(S) Casey G. DeMunck 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES
patients with chronic migraine, fibromyalgia , post-traumatic pain post mTBI, asymptomatic individuals post mTBI, and normal controls. Resting state...disorders. The specific study groups to be compared for this work include patients with chronic migraine, fibromyalgia , post-traumatic pain post...following mild traumatic brain injury (mTBI), those with fibromyalgia , chronic migraine without aura, asymptomatic individuals after mTBI, and in
Funk, J. R.; Duma, S. M.; Manoogian, S. J.; Rowson, S.
The objective of this study was to characterize the risk of mild traumatic brain injury (MTBI) in living humans based on a large set of head impact data taken from American football players at the collegiate level. Real-time head accelerations were recorded from helmet-mounted accelerometers designed to stay in contact with the player’s head. Over 27,000 head impacts were recorded, including four impacts resulting in MTBI. Parametric risk curves were developed by normalizing MTBI incidence data by head impact exposure data. An important finding of this research is that living humans, at least in the setting of collegiate football, sustain much more significant head impacts without apparent injury than previously thought. The following preliminary nominal injury assessment reference values associated with a 10% risk of MTBI are proposed: a peak linear head acceleration of 165 g, a HIC of 400, and a peak angular head acceleration of 9000 rad/s2. PMID:18184501
Kasper, Christine E
Traumatic brain injury (TBI) in all of its forms--blast, concussive, and penetrating--has been an unfortunate sequela of warfare since ancient times. The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to blast-related TBI whose long-term effects on behavior and cognition are not yet known. Advances in medical care have greatly increased survival from these types of injuries. Therefore, an understanding of the potential health effects of TBI is essential. This review focuses on specific aspects of military-related TBI. There exists a large body of literature reporting the environmental conditions, forces, and staging of injury. Many of these studies are focused on the neuropathology of TBI, due to blast overpressure waves, and the emergence of large numbers of mild blast-related TBI cases.
Tsaousides, Theodore; Gordon, Wayne A
Cognitive rehabilitation refers to a set of interventions that aim to improve a person's ability to perform cognitive tasks by retraining previously learned skills and teaching compensatory strategies. Cognitive rehabilitation begins with a thorough neuropsychological assessment to identify cognitive strengths and weaknesses and the degree of change in cognitive ability following a brain injury. The conclusions of the assessment are used to formulate appropriate treatment plans. Common interventions for improvements in attention, memory, and executive function, as well as the nature of comprehensive programs, which combine treatment modalities, are reviewed. Cognitive rehabilitation is effective for mild-to-severe injuries and beneficial at any time post-injury. Sufficient evidence exists supporting the efficacy and effectiveness of cognitive rehabilitation, which has become the treatment of choice for cognitive impairments and leads to improvements in cognitive and psychosocial functioning.
Zhang, Zhi; Saraswati, Manda; Koehler, Raymond C.; Robertson, Courtney
Abstract Traumatic brain injury (TBI) is a common cause of disability in childhood, resulting in numerous physical, behavioral, and cognitive sequelae, which can influence development through the lifespan. The mechanisms by which TBI influences normal development and maturation remain largely unknown. Pediatric rodent models of TBI often do not demonstrate the spectrum of motor and cognitive deficits seen in patients. To address this problem, we developed a New Zealand white rabbit model of pediatric TBI that better mimics the neurological injury seen after TBI in children. On postnatal Day 5-7 (P5-7), rabbits were injured by a controlled cortical impact (6-mm impactor tip; 5.5 m/sec, 2-mm depth, 50-msec duration). Rabbits from the same litter served as naïve (no injury) and sham (craniotomy alone) controls. Functional abilities and activity levels were measured 1 and 5 d after injury. Maturation level was monitored daily. We performed cognitive tests during P14-24 and sacrificed the animals at 1, 3, 7, and 21 d after injury to evaluate lesion volume and microglia. TBI kits exhibited delayed achievement of normal developmental milestones. They also demonstrated significant cognitive deficits, with lower percentage of correct alternation rate in the T-maze (n=9-15/group; p<0.001) and less discrimination between novel and old objects (p<0.001). Lesion volume increased from 16% at Day 3 to 30% at Day 7 after injury, indicating ongoing secondary injury. Activated microglia were noted at the injury site and also in white matter regions of the ipsilateral and contralateral hemispheres. The neurologic and histologic changes in this model are comparable to those reported clinically. Thus, this rabbit model provides a novel platform for evaluating neuroprotective therapies in pediatric TBI. PMID:25758339
Max, Jeffrey E.; Levin, Harvey S.; Landis, Julie; Schachar, Russell; Saunders, Ann; Ewing-Cobbs, Linda; Chapman, Sandra B.; Dennis, Maureen
Objective: To assess the phenomenology and predictive factors of personality change due to traumatic brain injury. Method: Children (N = 177), aged 5 to 14 years with traumatic brain injury from consecutive admissions to five trauma centers, were followed prospectively at baseline and 6 months with semistructured psychiatric interviews. Injury…
Babaee, Abdolreza; Eftekhar-Vaghefi, Seyed Hassan; Asadi-shekaari, Majid; Shahrokhi, Nader; Soltani, Samereh Dehghani; Malekpour-Afshar, Reza; Basiri, Mohsen
Objective(s): Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis) in several models of brain injury. Secondary injury following the primary traumatic brain injury (TBI) results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis), as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline) and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg). All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP) marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P<0.05) in melatonin- treated groups (no dose dependent) compared to the vehicle group. Furthermore, based on TUNEL results, melatonin treatment considerably reduced the number of apoptotic cells (P<0.05). Conclusion: In total, the present findings suggest that melatonin treatment following TBI diminishes astrocyte reactivity and neuronal cells apoptosis in brain cortex in the rat model. PMID:26523219
Taylor, Douglas D; Gercel-Taylor, Cicek
We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression.
Kabadi, Shruti V.; Hilton, Genell D.; Stoica, Bogdan A.; Zapple, David N.; Faden, Alan I.
Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 45–50 min. PMID:20725070
Chandel, Shammy; Gupta, Sunil Kumar; Medhi, Bikash
Traumatic brain injury (TBI) is a complex neurotrauma in civilian life and the battlefield with a broad spectrum of symptoms, long-term neuropsychological disability, as well as mortality worldwide. Posttraumatic epilepsy (PTE) is a common outcome of TBI with unknown mechanisms, followed by posttraumatic epileptogenesis. There are numerous rodent models of TBI available with varying pathomechanisms of head injury similar to human TBI, but there is no evidence for an adequate TBI model that can properly mimic all aspects of clinical TBI and the first successive spontaneous focal seizures follow a single episode of neurotrauma with respect to epileptogenesis. This review aims to provide current information regarding the various experimental animal models of TBI relevant to clinical TBI. Mossy fiber sprouting, loss of dentate hilar neurons along with recurrent seizures, and epileptic discharge similar to human PTE have been studied in fluid percussion injury, weight-drop injury, and cortical impact models, but further refinement of animal models and functional test is warranted to better understand the underlying pathophysiology of posttraumatic epileptogenesis. A multifaceted research approach in TBI model may lead to exploration of the potential treatment measures, which are a major challenge to the research community and drug developers. With respect to clinical setting, proper patient data collection, improved clinical trials with advancement in drug delivery strategies, blood-brain barrier permeability, and proper monitoring of level and effects of target drug are also important.
Walcott, Brian P; Nahed, Brian V; Sheth, Sameer A; Yanamadala, Vijay; Caracci, James R; Asaad, Wael F
Traumatic brain injury is a heterogeneous entity that encompasses both surgical and non-surgical conditions. Surgery may be indicated with traumatic lesions such as hemorrhage, fractures, or malignant cerebral edema. However, the neurological exam may be clouded by the effects of medications administered in the field, systemic injuries, and inaccuracies in hyperacute prognostication. Typically, neurological injury is considered irreversible if diffuse loss of grey/white matter differentiation or if brainstem hemorrhage (Duret hemorrhage) exists. We aim to characterize a cohort of patients undergoing bilateral hemicraniectomy for severe traumatic brain injury. A retrospective consecutive cohort of adult patients undergoing craniectomy for trauma was established between the dates of January 2008 and November 2011. The primary outcome of the study was in-hospital mortality. Secondary outcomes were ICU length of stay, surgical complications, and Glasgow Outcome Score at most recent follow-up. During the study period, 210 patients undergoing craniectomy for traumatic mass-occupying lesion (epidural hematoma, subdural hematoma, or parenchymal contusion) were analyzed. Of those, 9 met study criteria. In-hospital mortality was 67% (6 of 9 patients). The average ICU length of stay was 12 days. The GOS score was 3 in surviving patients. Bilateral hemicraniectomy is a heroic intervention for patients with severe TBI, but can be a life-saving procedure.
Dams-O’Connor, Kristen; Cantor, Joshua B.; Brown, Margaret; Dijkers, Marcel P.; Spielman, Lisa A.; Gordon, Wayne A.
Objective To provide an overview of a series of projects that used a structured self-report screening tool in diverse settings and samples to screen for lifetime history of traumatic brain injury (TBI). Setting Diverse community settings. Participants Homeless persons (n = 111), individuals with HIV seeking vocational rehabilitation (n = 173), youth in the juvenile justice system (n = 271), public schoolchildren (n = 174), substance users (n = 845), intercollegiate athletes (n = 90), and other community-based samples (n = 396). Design Cross-sectional. Main Measure Brain Injury Screening Questionnaire. Results Screening using the Brain Injury Screening Questionnaire finds that 27% to 54% of those in high-risk populations report a history of TBI with chronic symptoms. Associations between TBI and social, academic, or other problems are evident in several studies. In non–high-risk community samples, 9% to 12% of individuals report TBI with chronic symptoms. Conclusion Systematic TBI screening can be implemented efficiently and inexpensively in a variety of settings. Lifetime TBI history data gathered using a structured self-report instrument can augment existing estimates of the prevalence of TBI, both as an acute event and as a chronic condition. Identification of individuals with TBI can facilitate primary prevention efforts, such as reducing risk for reinjury in high-risk groups, and provide access to appropriate interventions that can reduce the personal and societal costs of TBI (tertiary prevention). PMID:25370440
Juengst, Shannon B; Arenth, Patricia M; Raina, Ketki D; McCue, Michael; Skidmore, Elizabeth R
Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. In addition, they have focused on frequency of participation in various activities, failing to address an individual's subjective satisfaction with participation. The purpose of this study was to examine how affective state contributes to frequency of participation and satisfaction with participation after traumatic brain injury among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild-to-severe traumatic brain injury participated in this cross-sectional cohort study. High positive affect contributed significantly to frequency of participation (β = 0.401, P = 0.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess the direction of these relationships may better inform effective targets for intervention. These findings highlight the importance of assessing affective state after traumatic brain injury and incorporating a subjective measure of participation when considering community integration outcomes.
Keller, M; Hiltbrunner, B; Dill, C; Kesselring, J
OBJECTIVES—To determine the influence of motivation on performance in a divided attention test of patients after mild traumatic brain injury (MBI). METHODS—Comparison of the performance of 12 patients with MBI with 10 patients with severe brain injury (SBI) and 11 healthy controls in a computer supported divided attention task before (T1) and after (T2) verbal motivation. RESULTS—At T1, the MBI group performed the same as the SBI group but significantly worse than the controls in all variables. At T2, the MBI group performed worse than the controls at T2 but the results were equal to the results of the controls at T1 and significantly better than the SBI group at T1 or T2. At T2 the MBI group performed at the level of published norms for the rest. CONCLUSION—Before verbal motivation the MBI group's results in the divided attention task were comparable with those from patients with severe brain injury. They failed to exploit their performance potential when it depended on self motivation but were able to perform at the level of the control group when external motivation was applied. PMID:10811701
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities. PMID:28250732
Zheng, Weimin; Chen, Qian; Chen, Xin; Wan, Lu; Qin, Wen; Qi, Zhigang; Li, Kuncheng
It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) (p < 0.01, TFCE corrected). No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD) of left AG and total motor scores (uncorrected p < 0.05). Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future. PMID:28255458
Agrawal, Shruti; Branco, Ricardo Garcia
Traumatic brain injury (TBI) is a major cause of death and disability in children. Severe TBI is a leading cause of death and often leads to life changing disabilities in survivors. The modern management of severe TBI in children on intensive care unit focuses on preventing secondary brain injury to improve outcome. Standard neuroprotective measures are based on management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) to optimize the cerebral blood flow and oxygenation, with the intention to avoid and minimise secondary brain injury. In this article, we review the current trends in management of severe TBI in children, detailing the general and specific measures followed to achieve the desired ICP and CPP goals. We discuss the often limited evidence for these therapeutic interventions in children, extrapolation of data from adults, and current recommendation from paediatric guidelines. We also review the recent advances in understanding the intracranial physiology and neuroprotective therapies, the current research focus on advanced and multi-modal neuromonitoring, and potential new therapeutic and prognostic targets. PMID:26855892
A case study of late onset psychopathology following brain injury is presented to illustrate the effects of cognitive and perceptual loss on personality functions. Based on Hughling Jackson's (1884/1958) notion of the duality of the symptom, we proposed a model of the development and process of psychopathology following brain injury, which views the development of the psychopathological behavior as a product of acquired cognitive and perceptual defects and ensuing compensatory strategies. For the present case study of paranoia, this involved defects in long-term memory, conceptual ability, and compensatory strategies of confabulation and self-referential orientation. Neuropsychological testing established defects in concept formation tasks including the Raven Progressive Matrices, the Leiter International Performance Scale, and the Wisconsin Card Sorting test, as well as long-term memory defects where cognitive reorganization was needed. The paranoid process was understood as a product of disordered conceptual ability in interpersonal situations, and a self-referential conceptual classification system, which took time, and changed social relations, to emerge. The implications of this model for psychotherapy with brain injury is elaborated in our case study, in which psychotherapeutic intervention included training on interpersonal hypothesis formation.
Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan
Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559
Gardner, Raquel C; Yaffe, Kristine
Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. The role of MTBI in risk of PD or ALS is less well established. Repetitive MTBI and repetitive sub-concussive head trauma have been linked to increased risk for a variety of neurodegenerative diseases including chronic traumatic encephalopathy (CTE). CTE is a unique neurodegenerative tauopathy first described in boxers but more recently described in a variety of contact sport athletes, military veterans, and civilians exposed to repetitive MTBI. Studies of repetitive MTBI and CTE have been limited by referral bias, lack of consensus clinical criteria for CTE, challenges of quantifying MTBI exposure, and potential for confounding. The prevalence of CTE is unknown and the amount of MTBI or sub-concussive trauma exposure necessary to produce CTE is unclear. This review will summarize the current literature regarding the epidemiology of MTBI, post-TBI dementia and Parkinson's disease, and CTE while highlighting methodological challenges and critical future directions of research in this field. This article is part of a Special Issue entitled SI:Traumatic Brain Injury.
Jordan, Barry D
Acute and chronic sports-related traumatic brain injuries (TBIs) are a substantial public health concern. Various types of acute TBI can occur in sport, but detection and management of cerebral concussion is of greatest importance as mismanagement of this syndrome can lead to persistent or chronic postconcussion syndrome (CPCS) or diffuse cerebral swelling. Chronic TBI encompasses a spectrum of disorders that are associated with long-term consequences of brain injury, including chronic traumatic encephalopathy (CTE), dementia pugilistica, post-traumatic parkinsonism, post-traumatic dementia and CPCS. CTE is the prototype of chronic TBI, but can only be definitively diagnosed at autopsy as no reliable biomarkers of this disorder are available. Whether CTE shares neuropathological features with CPCS is unknown. Evidence suggests that participation in contact-collision sports may increase the risk of neurodegenerative disorders such as Alzheimer disease, but the data are conflicting. In this Review, the spectrum of acute and chronic sport-related TBI is discussed, highlighting how examination of athletes involved in high-impact sports has advanced our understanding of pathology of brain injury and enabled improvements in detection and diagnosis of sport-related TBI.
Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K
Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values
Woodcock, Thomas; Morganti-Kossmann, Maria Cristina
Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia, and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (Interleukin-1, Tumor Necrosis Factor, Interleukin-6), the anti-inflammatory cytokines (IL-4, Interleukin-10, and TGF-beta), and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following Traumatic brain injury (TBI), the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring, and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality, or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This
Robson, John A; Davenport, R John
Advances in neuroscience, engineering and computer technologies are creating opportunities to connect the brain directly to devices to treat a variety of disorders, both neurological and psychiatric. They are opening a new field of neuroscience called "neurotechnology." This article reviews efforts in this area that are ongoing at Brown University and the hospitals affiliated with Brown's Alpert Medical School. Two general approaches are being used. One uses advanced electrodes to "sense" the activity of many individual neurons in the cerebral cortex and then use that activity for therapeutic purposes. The other uses various types of devices to stimulate specific networks in the brain in order to restore normal function and alleviate symptoms.
Nelson, David V; Esty, Mary Lee
Previous report suggested the beneficial effects of an adaptation of the Flexyx Neurotherapy System (FNS) for the amelioration of mixed traumatic brain injury/post-traumatic stress symptoms in veterans of the Afghanistan and Iraq wars. As a novel variant of electroencephalograph biofeedback, FNS falls within the bioenergy domain of complementary and alternative medicine. Rather than learning voluntary control over the production/inhibition of brain wave patterns, FNS involves offsetting stimulation of brain wave activity by means of an external energy source, specifically, the conduction of electromagnetic energy stimulation via the connecting electroencephalograph cables. Essentially, these procedures subliminally induce strategic distortion of ongoing brain wave activity to presumably facilitate resetting of more adaptive patterns of activity. Reported herein are two cases of Vietnam veterans with mixed traumatic brain injury/post-traumatic stress symptoms, each treated with FNS for 25 sessions. Comparisons of pre- and post-treatment questionnaire assessments revealed notable decreases for all symptoms, suggesting improvements across the broad domains of cognition, pain, sleep, fatigue, and mood/emotion, including post-traumatic stress symptoms, as well as for overall activity levels. Findings suggest FNS treatment may be of potential benefit for the partial amelioration of symptoms, even in some individuals for whom symptoms have been present for decades.
Cozzarelli, Tara A
The Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE) and the Defense and Veterans Brain Injury Center (DVBIC) hosted a consensus conference to address persistent cognitive impairments following mild traumatic brain injury (mTBI) and the role of cognitive rehabilitation in this population. Fifty military and civilian subject matter experts developed clinical guidance for cognitive rehabilitation of Service members with cognitive symptoms persisting three or more months following injury. This article highlights the initial evaluation, comprehensive assessment and treatment recommendations contained within the guidance "Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury and Defense and Veterans Brain Injury Center Consensus Conference on Cognitive Rehabilitation for Mild Traumatic Brain Injury." The full clinical guidance is available at: (http://www.dcoe.health.mil/Resources.aspx).
Morrissey, Kirsten; Fairbrother, Hilary
More than 1.7 million traumatic brain injuries occur in adults and children each year in the United States, with approximately 30% occurring in children aged < 14 years. Traumatic brain injury is a significant cause of morbidity and mortality in pediatric trauma patients. Early identification and management of severe traumatic brain injury is crucial in decreasing the risk of secondary brain injury and optimizing outcome. The main focus for early management of severe traumatic brain injury is to mitigate and prevent secondary injury, specifically by avoiding hypotension and hypoxia, which have been associated with poorer outcomes. This issue discusses methods to maintain adequate oxygenation, maximize management of intracranial hypertension, and optimize blood pressure in the emergency department to improve neurologic outcomes following pediatric severe traumatic brain injury.
Ahmad, Akbar; Crupi, Rosalia; Impellizzeri, Daniela; Campolo, Michela; Marino, Angela; Esposito, Emanuela; Cuzzocrea, Salvatore
Traumatic brain injury (TBI) is a major cause of preventable death and morbidity in young adults. This complex condition is characterized by significant blood brain barrier leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Recovery of function after TBI is partly through neuronal plasticity. In order to test whether treatments that enhance plasticity might improve functional recovery, a controlled cortical impact (CCI) in adult mice, as a model of TBI, in which a controlled cortical impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex, was performed. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family that maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether PEA shows efficacy in a mice model of experimental TBI. PEA treatment is able to reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level further support the efficacy of PEA therapy. The PEA treatment blocked infiltration of astrocytes and restored CCI-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, CD11b and GFAP. PEA inhibited the TBI-mediated decrease in the expression of pJNK and NF-κB. PEA-treated injured animals improved neurobehavioral functions as evaluated by behavioral tests.
Wei, Guo; Lu, Xi-Chun M; Shear, Deborah A; Yang, Xiaofang; Tortella, Frank C
Induced hypothermia has been reported to provide neuroprotection against traumatic brain injury. We recently developed a novel method of selective brain cooling (SBC) and demonstrated its safety and neuroprotection efficacy in a rat model of ischemic brain injury. The primary focus of the current study was to evaluate the potential neuroprotective efficacy of SBC in a rat model of penetrating ballistic-like brain injury (PBBI) with a particular focus on the acute cerebral pathophysiology, neurofunction, and cognition. SBC (34°C) was induced immediately after PBBI, and maintained for 2 hours, followed by a spontaneous re-warming. Intracranial pressure (ICP) and regional cerebral blood flow were monitored continuously for 3 hours, and the ICP was measured again at 24 hours postinjury. Brain swelling, blood-brain barrier permeability, intracerebral hemorrhage, lesion size, and neurological status were assessed at 24 hours postinjury. Cognitive abilities were evaluated in a Morris water maze task at 12-16 days postinjury. Results showed that SBC significantly attenuated PBBI-induced elevation of ICP (PBBI = 33.2 ± 10.4; PBBI + SBC = 18.8 ± 6.7 mmHg) and reduced brain swelling, blood-brain barrier leakage, intracerebral hemorrhage, and lesion volume by 40%-45% for each matrix, and significantly improved neurologic function. However, these acute neuroprotective benefits of SBC did not translate into improved cognitive performance in the Morris water maze task. These results indicate that 34°C SBC is effective in protecting against acute brain damage and related neurological dysfunction. Further studies are required to establish the optimal treatment conditions (i.e., duration of cooling and/or combined therapeutic approaches) needed to achieve significant neurocognitive benefits.
Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki
Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915
Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki
Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.
van der Merwe, Yolandi
Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910
Gurley, Jessica R; Marcus, David K
Although neurological evidence is used with increasing frequency in criminal trials, there is limited research examining the effects that this evidence has on juror decision-making in insanity trials. Participants (396) were presented with a case summary and psychological testimony and asked to render either a verdict of guilty or not guilty by reason of insanity in a 2 (psychosis or psychopathy) x (presence or absence of an MRI indicating a brain lesion) x (presence or absence of testimony describing a car accident that caused injury to the brain) factorial design. Defendants diagnosed with a psychotic disorder, defendants who could demonstrate the existence of a brain lesion via MRI, and defendants who had a history of brain injury were more likely to be found not guilty by reason of insanity than those defendants who did not present any neurological testimony. Participants who reported they were more influenced by the psychological and neurological testimony were almost six times more likely to render a verdict of NGRI than those participants who reported that the psychological and neurological testimony and evidence did not influence their decision regarding verdict.
Gianakis, Anastasia; McNett, Molly; Belle, Josie; Moran, Cristina; Grimm, Dawn
Ventilator-associated pneumonia (VAP) rates remain highest among trauma and brain injured patients; yet, no research compares VAP risk factors between the 2 groups. This retrospective, case-controlled study identified risk factors for VAP among critically ill trauma patients with and without brain injury. Data were abstracted on trauma patients with (cases) and without (controls) brain injury. Data gathered on n = 157 subjects. Trauma patients with brain injury had more emergent and field intubations. Age was strongest predictor of VAP in cases, and ventilator days predicted VAP in controls. Trauma patients with brain injury may be at higher risk for VAP.
Traumatic brain injury (TBI) is usually combined with cervical spine (C-spine) injury. The possibility of C-spine injury is always considered when performing endotracheal intubation in these patients. Rapid sequence intubation is recommended with adequate sedative or analgesics and a muscle relaxant to prevent an increase in intracranial pressure during intubation in TBI patients. Normocapnia and mild hyperoxemia should be maintained to prevent secondary brain injury. The manual-in-line-stabilization (MILS) technique effectively lessens C-spine movement during intubation. However, the MILS technique can reduce mouth opening and lead to a poor laryngoscopic view. The newly introduced video laryngoscope can manage these problems. The AirWay Scope® (AWS) and AirTraq laryngoscope decreased the extension movement of C-spines at the occiput-C1 and C2-C4 levels, improving intubation conditions and shortening the time to complete tracheal intubation compared with a direct laryngoscope. The Glidescope® also decreased cervical movement in the C2-C5 levels during intubation and improved vocal cord visualization, but a longer duration was required to complete intubation compared with other devices. A lightwand also reduced cervical motion across all segments. A fiberoptic bronchoscope-guided nasal intubation is the best method to reduce cervical movement, but a skilled operator is required. In conclusion, a video laryngoscope assists airway management in TBI patients with C-spine injury. PMID:26045922
Jung, Jin Yong
Traumatic brain injury (TBI) is usually combined with cervical spine (C-spine) injury. The possibility of C-spine injury is always considered when performing endotracheal intubation in these patients. Rapid sequence intubation is recommended with adequate sedative or analgesics and a muscle relaxant to prevent an increase in intracranial pressure during intubation in TBI patients. Normocapnia and mild hyperoxemia should be maintained to prevent secondary brain injury. The manual-in-line-stabilization (MILS) technique effectively lessens C-spine movement during intubation. However, the MILS technique can reduce mouth opening and lead to a poor laryngoscopic view. The newly introduced video laryngoscope can manage these problems. The AirWay Scope® (AWS) and AirTraq laryngoscope decreased the extension movement of C-spines at the occiput-C1 and C2-C4 levels, improving intubation conditions and shortening the time to complete tracheal intubation compared with a direct laryngoscope. The Glidescope® also decreased cervical movement in the C2-C5 levels during intubation and improved vocal cord visualization, but a longer duration was required to complete intubation compared with other devices. A lightwand also reduced cervical motion across all segments. A fiberoptic bronchoscope-guided nasal intubation is the best method to reduce cervical movement, but a skilled operator is required. In conclusion, a video laryngoscope assists airway management in TBI patients with C-spine injury.
Fakharian, Esmaeil; Mohammadzadeh, Mahdi; Behdadmehr, Shirin; Sabri, Hamid Reza; Mirzadeh, Azadeh Sadat; Mohammadzadeh, Javad
Background Traumatic brain injury (TBI) is a worldwide problem, especially in countries with high incidence of road traffic accidents such as Iran. Patients with a single occurrence of TBI have been shown to be at increased risk to sustain future TBI. Objectives The aim of this study was to present the incidence and characteristics of repeated TBI (RTBI) in Iranian patients. Patients and Methods During one year, all admitted TBI patients with prior TBI history were enrolled into the study. In each patient, data such as age, gender, past medical history, injury cause, anatomic site of injury, TBI severity, clinical findings and CT scan findings were collected. Results RTBI comprised 2.5% of TBI cases (41 of 1629). The incidence of RTBI per 100,000 individuals per years was 9.7. The main cause of RTBI was road traffic accident (68.3%); 9.7 % of cases had preexisting seizure/epilepsy disorder; 36.6% of patients with RTBI had pervious ICU admission due to severe TBI. Ten patients had Glasgow coma scale (GCS) ≤ 13 (24.4%). Seizure was seen in seven patients (17.1%). Thirty-nine percent of patients with RTBI had associated injuries. Eleven patients had abnormal CT scan findings (26.9%). Conclusions Considering the high incidence of trauma in developing countries, RTBI may also be more common compared with that of developed countries. This mandates a newer approach to preventive strategies, particularly in those with a previous experience of head injury. PMID:28180123
Kreuzer, Peter Michael; Landgrebe, Michael; Frank, Elmar; Langguth, Berthold
Tinnitus is a frequent symptom of traumatic brain injury, which is difficult to treat. Repetitive transcranial magnetic stimulation has shown beneficial effects in some forms of tinnitus. However, traumatic brain injury in the past has been considered as a relative contraindication for repetitive transcranial magnetic stimulation because of the increased risk of seizures. Here we present the case of a 53-year-old male patient suffering from severe tinnitus after traumatic brain injury with comorbid depression and alcohol abuse, who received 5 treatment series of repetitive transcranial magnetic stimulation (1 Hz stimulation protocol over left primary auditory cortex, 10 sessions of 2000 stimuli each, stimulation intensity 110% resting motor threshold). Repetitive transcranial magnetic stimulation was tolerated without any side effects and tinnitus complaints (measured by a validated tinnitus questionnaire and numeric rating scales) were improved in a replicable way throughout 5 courses of transcranial magnetic stimulation up to now.
Attella, M J; Hoffman, S W; Stasio, M J; Stein, D G
Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed-spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury.
Kasili, P.M.; Mobley, J.; Norton, S.J.; Vo-Dinh, T.
In this work, we evaluate methods for detecting brain injury using ultrasound. We have used simulations of ultrasonic fields in the head to model the phase distortion of the skull. In addition we present experimental data from the crania of large animals. The experimental data help us understand and evaluate the performance of different transducers in acquiring the backscatter data from the brain through the skull. Both the simulations and acquired data illustrate the superiority of lower-frequency (<= 1 MHz) ultrasonic fields for transcranial acquisition of signals from inside the brain. Additionally, the experimental work shows that the higher-frequency (5 MHz) ultrasound can also be useful in acquiring clean nearfield data to help detect the position of the inner boundary of the skull.
Koskinen, L-O D; Olivecrona, M; Grände, P O
This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment.
Siegele, Rainer; Howell, Nicholas R.; Callaghan, Paul D.; Pastuovic, Zeljko
Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca+2 cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca+2 cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma.
Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity. PMID:27047695
Zhu, Huiping; Gao, Qi; Xia, Xin; Xiang, Joe; Yao, Hongli; Shao, Jianbo
This study investigated injury patterns and the use of computed tomography (CT) among Chinese children with mild traumatic brain injury (MTBI). We enrolled children with MTBI who were treated within 24 hours of head trauma in the emergency department of Wuhan Medical Care Center for Women and Children in Wuhan, China. Characteristics of MTBIs were analyzed by age and gender. Results of cranial CT scan and clinically-important brain injury (ciTBI) for children were obtained. The definition of ciTBI was: death from TBI, intubation for more than 24 h for TBI, neurosurgery, or hospital admission of 2 nights or more. Of 455 eligible patients with MTBI, ciTBI occurred in two, and no one underwent neurosurgical intervention. CT scans were performed for 441 TBI patients (96.9%), and abnormal findings were reported for 147 patients (33.3%, 95% CI 29.0-37.8). Falls were the leading cause of MTBI (61.5%), followed by blows (18.9%) and traffic collisions (14.1%) for children in the 0-2 group and 10-14 group. For children aged between 3 and 9, the top three causes of TBI were falls, traffic collisions and blows. Leisure activity was the most reported activity when injuries occurred for all age groups. Sleeping/resting and walking ranked in the second and third place for children between 0 and 2 years of age, and walking and riding for the other two groups. The places where the majority injuries occurred were the home for the 0-2 and 3-9 years of age groups, and school for the 10-14 years of age group. There was no statistical difference between boys and girls with regard to the activity that caused the MTBI. This study highlights the important roles that parents and school administrators in the development of preventive measures to reduce the risk of traumatic brain injury in children. Also, identifying children who had a head trauma at very low risk of clinically important TBI for whom CT might be unnecessary is a priority area of research in China.