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Sample records for acute brain injuries

  1. Autophagy in acute brain injury.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Blomgren, Klas; Kroemer, Guido

    2016-08-01

    Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID:27256553

  2. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    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

  3. Electrophysiologic monitoring in acute brain injury.

    PubMed

    Claassen, Jan; Vespa, Paul

    2014-12-01

    To determine the optimal use and indications of electroencephalography (EEG) in critical care management of acute brain injury (ABI). An electronic literature search was conducted for articles in English describing electrophysiological monitoring in ABI from January 1990 to August 2013. A total of 165 studies were included. EEG is a useful monitor for seizure and ischemia detection. There is a well-described role for EEG in convulsive status epilepticus and cardiac arrest (CA). Data suggest EEG should be considered in all patients with ABI and unexplained and persistent altered consciousness and in comatose intensive care unit (ICU) patients without an acute primary brain condition who have an unexplained impairment of mental status. There remain uncertainties about certain technical details, e.g., the minimum duration of EEG studies, the montage, and electrodes. Data obtained from both EEG and EP studies may help estimate prognosis in ABI patients, particularly following CA and traumatic brain injury. Data supporting these recommendations is sparse, and high quality studies are needed. EEG is used to monitor and detect seizures and ischemia in ICU patients and indications for EEG are clear for certain disease states, however, uncertainty remains on other applications. PMID:25208668

  4. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

    Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

    2015-01-01

    Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

  5. Acute blast injury reduces brain abeta in two rodent species.

    PubMed

    De Gasperi, Rita; Gama Sosa, Miguel A; Kim, Soong Ho; Steele, John W; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; Dekosky, Steven T; McCarron, Richard M; Nambiar, Madhusoodana P; Gandy, Sam; Ahlers, Stephen T; Elder, Gregory A

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer's disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain. PMID:23267342

  6. Pediatric traumatic brain injury: acute and rehabilitation costs.

    PubMed

    Jaffe, K M; Massagli, T L; Martin, K M; Rivara, J B; Fay, G C; Polissar, N L

    1993-07-01

    Pediatric traumatic brain injury constitutes an enormous public health problem, but little is known about the economic costs of such injury. Using charges as a proxy for cost, we prospectively collected data on initial hospital charges and professional fees for emergency department services, acute inpatient care, and acute inpatient rehabilitation for 96 patients with mild, moderate, and severe traumatic brain injuries. We also examined the relationship between these costs and injury severity and etiology. Acute care and rehabilitation median costs were $5,233 per child, $11,478 for hospitalized children, and $230 for those only seen in the emergency department. Median costs for injuries due to motor vehicles, bicycles, and falls were $15,213, $6,311, and $792, respectively. Using Glasgow Coma Scale criteria, median cost of mild, moderate, and severe traumatic brain injuries were $598, $12,022, and $53,332, respectively. Injury etiology added modestly but significantly to the prediction of cost over and above that predicted by injury severity alone. Rehabilitation costs accounted for 37% of the total for all children, but 45% of those with the most severe injuries. PMID:8328886

  7. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    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.

  8. Anemia management after acute brain injury.

    PubMed

    Lelubre, Christophe; Bouzat, Pierre; Crippa, Ilaria Alice; Taccone, Fabio Silvio

    2016-01-01

    Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this "blood transfusion anemia paradox", the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients. PMID:27311626

  9. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    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

  10. Biomarkers and acute brain injuries: interest and limits

    PubMed Central

    2014-01-01

    For patients presenting with acute brain injury (such as traumatic brain injury, subarachnoid haemorrhage and stroke), the diagnosis and identification of intracerebral lesions and evaluation of the severity, prognosis and treatment efficacy can be challenging. The complexity and heterogeneity of lesions after brain injury are most probably responsible for this difficulty. Patients with apparently comparable brain lesions on imaging may have different neurological outcomes or responses to therapy. In recent years, plasmatic and cerebrospinal fluid biomarkers have emerged as possible tools to distinguish between the different pathophysiological processes. This review aims to summarise the plasmatic and cerebrospinal fluid biomarkers evaluated in subarachnoid haemorrhage, traumatic brain injury and stroke, and to clarify their related interests and limits for diagnosis and prognosis. For subarachnoid haemorrhage, particular interest has been focused on the biomarkers used to predict vasospasm and cerebral ischaemia. The efficacy of biomarkers in predicting the severity and outcome of traumatic brain injury has been stressed. The very early diagnostic performance of biomarkers and their ability to discriminate ischaemic from haemorrhagic stroke were studied. PMID:25029344

  11. Effort test performance in clinical acute brain injury, community brain injury, and epilepsy populations.

    PubMed

    Hampson, Natalie E; Kemp, Steven; Coughlan, Anthony K; Moulin, Chris J A; Bhakta, Bipin B

    2014-01-01

    Effort tests have become commonplace within medico-legal and forensic contexts and their use is rising within clinical settings. It is recognized that some patients may fail effort tests due to cognitive impairment and not because of poor effort. However, investigation of the base rate of failure among clinical populations other than dementia is limited. Forty-seven clinical participants were recruited and comprised three subgroups: acute brain injury (N = 11), community brain injury (N = 20), and intractable epilepsy (N = 16). Base rates of failure on the Word Memory Test (WMT; Green, 2003 ) and six other less well-validated measures were investigated. A significant minority of patients failed effort tests according to standard cutoff scores, particularly patients with severe traumatic brain injury and marked frontal-executive features. The WMT was able to identify failures associated with significant cognitive impairment through the application of profile analysis and/or lowered cutoff levels. Implications for clinical assessment, effort test interpretation, and future research are discussed. PMID:25084843

  12. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats

    PubMed Central

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F.; Hua, Ya

    2014-01-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron level in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 hours (lateral ventricle volume: 24.1±3.0 vs. 9.9±0.2 mm3 in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm3 in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI. PMID:24935175

  13. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-01-01

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity. PMID:27145814

  14. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    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

    2016-01-01

    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

  15. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    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

    2016-06-01

    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.

  16. Pharmacotherapy in rehabilitation of post-acute traumatic brain injury.

    PubMed

    Bhatnagar, Saurabha; Iaccarino, Mary Alexis; Zafonte, Ross

    2016-06-01

    There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper-arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26801831

  17. Psychiatric Disease and Post-Acute Traumatic Brain Injury.

    PubMed

    Zgaljardic, Dennis J; Seale, Gary S; Schaefer, Lynn A; Temple, Richard O; Foreman, Jack; Elliott, Timothy R

    2015-12-01

    Psychiatric disorders are common following traumatic brain injury (TBI) and can include depression, anxiety, and psychosis, as well as other maladaptive behaviors and personality changes. The epidemiologic data of psychiatric disorders post-TBI vary widely, although the incidence and prevalence rates typically are higher than in the general population. Although the experience of psychiatric symptoms may be temporary and may resolve in the acute period, many patients with TBI can experience psychopathology that is persistent or that develops in the post-acute period. Long-term psychiatric disorder, along with cognitive and physical sequelae and greater risk for substance use disorders, can pose a number of life-long challenges for patients and their caregivers, as they can interfere with participation in rehabilitation as well as limit functional independence in the community. The current review of the literature considers the common psychiatric problems affecting individuals with TBI in the post-acute period, including personality changes, psychosis, executive dysfunction, depression, anxiety, and substance misuse. Although treatment considerations (pharmacological and nonpharmacological) are referred to, an extensive description of such protocols is beyond the scope of the current review. The impact of persistent psychiatric symptoms on perceived caregiver burden and distress is also discussed. PMID:25629222

  18. Preventing Flow-Metabolism Uncoupling Acutely Reduces Axonal Injury after Traumatic Brain Injury

    PubMed Central

    Mironova, Yevgeniya A.; Chen, Szu-Fu; Richards, Hugh K.; Pickard, John D.

    2012-01-01

    Abstract We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of β-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3–24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons. PMID:22321027

  19. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  20. Traumatic brain injury in children: acute care management.

    PubMed

    Geyer, Kristen; Meller, Karen; Kulpan, Carol; Mowery, Bernice D

    2013-01-01

    The care of the pediatric patient with a severe traumatic brain injury (TBI) is an all-encompassing nursing challenge. Nursing vigilance is required to maintain a physiological balance that protects the injured brain. From the time a child and family first enter the hospital, they are met with the risk of potential death and an uncertain future. The family is subjected to an influx of complex medical and nursing terminology and interventions. Nurses need to understand the complexities of TBI and the modalities of treatment, as well as provide patients and families with support throughout all phases of care. PMID:24640314

  1. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  2. Nutritional treatment for acute and chronic traumatic brain injury patients.

    PubMed

    Curtis, L; Epstein, P

    2014-09-01

    Proper nutrition is critical for recovery from traumatic brain injury (TBI). Prompt enteral feeding of moderate to severe TBI patients has been associated with significantly lower mortality and rates of infection. Probiotic supplementation has been associated with significantly lower rates of infection in TBI and other trauma patients. Human studies have suggested that supplementation with omega 3 fats, vitamin D, N-Acetylcysteine, branched chain amino acids, and zinc may be helpful for recovery from TBI. Animal TBI models have suggested that alpha-lipoic acid, magnesium, taurine, coenzyme Q10, and many phytonutrients (such as resveratrol) are also helpful. Unfortunately, recent human clinical trials with citicoline in TBI and stroke patients have produced disappointing results. Much more research is needed on multifaceted nutritional strategies to treat TBI patients in both the immediate post-injury phase and throughout the patients lifespan. PMID:24844176

  3. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    PubMed

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  4. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time. PMID:22514794

  5. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury

    PubMed Central

    Szczupak, Mikhaylo; Kiderman, Alexander; Crawford, James; Murphy, Sara; Marshall, Kathryn; Pelusso, Constanza

    2016-01-01

    Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications. PMID:26727256

  6. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke

    PubMed Central

    Khanna, Savita; Heigel, Mallory; Weist, Jessica; Gnyawali, Surya; Teplitsky, Seth; Roy, Sashwati; Sen, Chandan K.; Rink, Cameron

    2015-01-01

    The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a “more is better” approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.—Khanna, S., Heigel,M., Weist, J., Gnyawali, S., Teplitsky, S., Roy, S., Sen, C. K., Rink, C. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke. PMID:25411436

  7. Intraoperative Targeted Temperature Management in Acute Brain and Spinal Cord Injury.

    PubMed

    Kraft, Jacqueline; Karpenko, Anna; Rincon, Fred

    2016-02-01

    Acute brain and spinal cord injuries affect hundreds of thousands of people worldwide. Though advances in pre-hospital and emergency and neurocritical care have improved the survival of some to these devastating diseases, very few clinical trials of potential neuro-protective strategies have produced promising results. Medical therapies such as targeted temperature management (TTM) have been trialed in traumatic brain injury (TBI), spinal cord injury (SCI), acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH), but in no study has a meaningful effect on outcome been demonstrated. To this end, patient selection for potential neuro-protective therapies such as TTM may be the most important factor to effectively demonstrate efficacy in clinical trials. The use of TTM as a strategy to treat and prevent secondary neuronal damage in the intraoperative setting is an area of ongoing investigation. In this review we will discuss recent and ongoing studies that address the role of TTM in combination with surgical approaches for different types of brain injury. PMID:26759319

  8. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  9. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  10. Acute decrease in alkaline phosphatase after brain injury: A potential mechanism for tauopathy.

    PubMed

    Arun, Peethambaran; Oguntayo, Samuel; Albert, Stephen Van; Gist, Irene; Wang, Ying; Nambiar, Madhusoodana P; Long, Joseph B

    2015-11-16

    Dephosphorylation of phosphorylated Tau (pTau) protein, which is essential for the preservation of neuronal microtubule assemblies and for protection against trauma-induced tauopathy and chronic traumatic encephalopathy (CTE), is primarily achieved in brain by tissue non-specific alkaline phosphatase (TNAP). Paired helical filaments (PHFs) and Tau isolated from Alzheimer's disease (AD) patients' brains have been shown to form microtubule assemblies with tubulin only after treatment with TNAP or protein phosphatase-2A, 2B and -1, suggesting that Tau protein in the PHFs of neurons in AD brain is hyperphosphorylated, which prevents microtubule assembly. Using blast or weight drop models of traumatic brain injury (TBI) in rats, we observed pTau accumulation in the brain as early as 6h post-injury and further accumulation which varied regionally by 24h post-injury. The pTau accumulation was accompanied by reduced TNAP expression and activity in these brain regions and a significantly decreased plasma total alkaline phosphatase activity after the weight drop. These results reveal that both blast- and impact acceleration-induced head injuries cause an acute decrease in the level/activity of TNAP in the brain, which potentially contributes to trauma-induced accumulation of pTau and the resultant tauopathy. The regional changes in the level/activity of TNAP or accumulation of pTau after these injuries did not correlate with the accumulation of amyloid precursor protein, suggesting that the basic mechanism underlying tauopathy in TBI might be distinct from that associated with AD. PMID:26483321

  11. A creative alternative for providing constant observation on an acute-brain-injury unit.

    PubMed

    Bailey, Marci; Amato, Shelly; Mouhlas, Christopher

    2009-01-01

    A performance improvement project to explore creative alternatives to improve the efficiency of constant observation was performed on an acute-brain-injury rehabilitation unit. The goals of the project were to increase opportunities for therapeutic cognitive stimulation among patients, increase nursing satisfaction regarding efficient use of resources to deliver rehabilitative care, decrease constant-observation salary costs, and maintain fall and restraint rates within 10% of baseline. Implementing the project involved developing a new job description (rehabilitation patient companion) and creating a day room where patients receiving constant observation could go between therapies to receive therapeutic cognitive stimulation. The program benefited patients, staff and the hospital. This project illustrates how a creative alternative to constant observation proves beneficial on many levels and improves the delivery of rehabilitative care to patients with traumatic brain injury. PMID:19160919

  12. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  13. Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury

    PubMed Central

    Bennett, Rachel E.

    2014-01-01

    Abstract The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion. Low-dose (1 mg/mL) valganciclovir was found to reduce the microglial population in the corpus callosum and external capsule by 35% after rcTBI in CD11b-TK mice. At both acute (7 days) and subacute (21 days) time points after rcTBI, reduction of the microglial population did not alter the extent of axon injury as visualized by silver staining. Further reduction of the microglial population by 56%, using an intermediate dose (10 mg/mL), also did not alter the extent of silver staining, amyloid precursor protein accumulation, neurofilament labeling, or axon injury evident by electron microscopy at 7 days postinjury. Longer treatment of CD11b-TK mice with intermediate dose and treatment for 14 days with high-dose (50 mg/mL) valganciclovir were both found to be toxic in this injury model. Altogether, these data are most consistent with the idea that microglia do not contribute to acute axon degeneration after multiple concussive injuries. The possibility of longer-term effects on axon structure or function cannot be ruled out. Nonetheless, alternative strategies directly targeting injury to axons may be a more beneficial approach to concussion treatment than targeting secondary processes of microglial-driven inflammation. PMID:24797413

  14. Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.

    PubMed

    Wiseman-Hakes, Catherine; Duclos, Catherine; Blais, Hélène; Dumont, Marie; Bernard, Francis; Desautels, Alex; Menon, David K; Gilbert, Danielle; Carrier, Julie; Gosselin, Nadia

    2016-09-01

    Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI. PMID:26704256

  15. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials.

    PubMed Central

    Alderson, P.; Roberts, I.

    1997-01-01

    OBJECTIVE: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. DESIGN: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury. Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study. SETTING: Randomised trials available by March 1996. SUBJECTS: The included trials with outcome data comprised 2073 randomised participants. RESULTS: The effect of corticosteroids on the risk of death was reported in 13 included trials. The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12). Pooled absolute risk reduction was 1.8% (-2.5% to 5.7%). For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11). For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52). With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity. CONCLUSIONS: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects. Neither moderate benefits nor moderate harmful effects can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting. PMID:9224126

  16. Induction of acute brain injury in mice by irradiation with high-LET charged particles

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Hong

    The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

  17. Acute Minocycline Treatment Mitigates the Symptoms of Mild Blast-Induced Traumatic Brain Injury

    PubMed Central

    Kovesdi, Erzsebet; Kamnaksh, Alaa; Wingo, Daniel; Ahmed, Farid; Grunberg, Neil E.; Long, Joseph B.; Kasper, Christine E.; Agoston, Denes V.

    2012-01-01

    Mild traumatic brain injury (mTBI) represents a significant challenge for the civilian and military health care systems due to its high prevalence and overall complexity. Our earlier works showed evidence of neuroinflammation, a late onset of neurobehavioral changes, and lasting memory impairment in a rat model of mild blast-induced TBI (mbTBI). The aim of our present study was to determine whether acute treatment with the non-steroidal anti-inflammatory drug minocycline (Minocin®) can mitigate the neurobehavioral abnormalities associated with mbTBI, Furthermore, we aimed to assess the effects of the treatment on select inflammatory, vascular, neuronal, and glial markers in sera and in brain regions associated with anxiety and memory (amygdala, prefrontal cortex, ventral, and dorsal hippocampus) following the termination (51 days post-injury) of the experiment. Four hours after a single exposure to mild blast overpressure or sham conditions, we treated animals with a daily dose of minocycline (50 mg/kg) or physiological saline (vehicle) for four consecutive days. At 8 and 45 days post-injury, we tested animals for locomotion, anxiety, and spatial memory. Injured animals exhibited significantly impaired memory and increased anxiety especially at the later testing time point. Conversely, injured and minocycline treated rats’ performance was practically identical to control (sham) animals in the open field, elevated plus maze, and Barnes maze. Protein analyses of sera and brain regions showed significantly elevated levels of all of the measured biomarkers (except VEGF) in injured and untreated rats. Importantly, minocycline treatment normalized serum and tissue levels of the majority of the selected inflammatory, vascular, neuronal, and glial markers. In summary, acute minocycline treatment appears to prevent the development of neurobehavioral abnormalities likely through mitigating the molecular pathologies of the injury in an experimental model of mb

  18. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  19. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

    PubMed

    Wagner, Amy K; McCullough, Emily H; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L; Dobos, Julie A; Brett, Christopher A; Santarsieri, Martina; Dixon, C Edward; Berga, Sarah L; Fabio, Anthony

    2011-06-01

    Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for

  20. Traumatic Brain Injury in Young Children: Post-Acute Effects on Cognitive and School Readiness Skills

    PubMed Central

    Taylor, H. Gerry; Swartwout, Maegan; Yeates, Keith O.; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

    2009-01-01

    Previous studies have documented weaknesses in cognitive ability and early academic readiness in young children with traumatic brain injury (TBI). However, few of these studies have rigorously controlled for demographic characteristics, examined the effects of TBI severity on a wide range of skills, or explored moderating influences of environmental factors on outcomes. To meet these objectives, each of three groups of children with TBI (20 with severe, 64 with moderate, and 15 with mild) were compared with a group of 117 children with orthopedic injuries (OI group). The children were hospitalized for their injuries between 3 and 6 years of age and were assessed an average of 1½ months post injury. Analysis revealed generalized weaknesses in cognitive and school readiness skills in the severe TBI group and suggested less pervasive effects of moderate and mild TBI. Indices of TBI severity predicted outcomes within the TBI sample and environmental factors moderated the effects of TBI on some measures. The findings document adverse effects of TBI in early childhood on post-acute cognitive and school readiness skills and indicate that residual deficits are related to both injury severity and the family environment. PMID:18764969

  1. Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Ma, Junpeng; Xu, Jianguo

    2015-01-01

    Objective To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). Methods PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. Results A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66). Conclusions Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI. PMID:26473361

  2. [The effect of neurotrophic treatment on the activation of reparative processes in patients with acute traumatic brain injury].

    PubMed

    Selianina, N V; Karakulova, Iu V

    2012-01-01

    The complex study of cognitive and emotional status, levels of serum serotonin and brain-derived neurotrophic factor (BDNF) were performed in 72 patients with acute traumatic brain injury, with a special focus on middle brain injuries (MBI), treated with Cerebrolysin. The neurological and cognitive impairment, mild state anxiety and depression and increased levels of humoral serotonin, which depends on the severity of the injury, were identified in patients with MBI before treatment. After the treatment, there were the decrease in the severity of neurological symptoms and a significant positive dynamics on the FAB scale as well as the increase in blood BDNF and serotonin levels. It has been concluded that using cerebrolysin in complex treatment of acute MBI promotes activation of neurotrophic processes and improves outcomes of closed craniocerebral injury. PMID:22951781

  3. Nanobodies as modulators of inflammation: potential applications for acute brain injury

    PubMed Central

    Rissiek, Björn; Koch-Nolte, Friedrich; Magnus, Tim

    2014-01-01

    Nanobodies are single domain antibodies derived from llama heavy-chain only antibodies (HCAbs). They represent a new generation of biologicals with unique properties: nanobodies show excellent tissue distribution, high temperature and pH stability, are easy to produce recombinantly and can readily be converted into different formats such as Fc-fusion proteins or hetero-dimers. Moreover, nanobodies have the unique ability to bind molecular clefts, such as the active site of enzymes, thereby interfering with the function of the target protein. Over the last decade, numerous nanobodies have been developed against proteins involved in inflammation with the aim to modulate their immune functions. Here, we give an overview about recently developed nanobodies that target immunological pathways linked to neuroinflammation. Furthermore, we highlight strategies to modify nanobodies so that they can overcome the blood brain barrier and serve as highly specific therapeutics for acute inflammatory brain injury. PMID:25374510

  4. Gender Differences in Awareness and Outcomes During Acute Traumatic Brain Injury Recovery

    PubMed Central

    Perrin, Paul B.; Holcomb, Megan G.; Rolston, Cynthia D.; Artman, Laura K.; Lu, Juan; Nersessova, Karine S.

    2014-01-01

    Abstract Background: Recent literature on traumatic brain injury (TBI), though mixed when reporting outcomes, seems collectively to suggest possible gender advantage for women in postinjury recovery, especially in executive functions. Hormonal neuroprotection, through female reproductive hormones, is often proposed as an underlying factor in these results. We explored potential gender differences in an aspect of executive functions, self-awareness (SA), which is often impaired after TBI, limits patient effort in critical rehabilitation, and increases caregiver burden. Methods: Within a prospective survey, repeated-measures design, 121 patients with moderate or severe TBI undergoing acute rehabilitation in a Level 1 trauma center, a family member or caregiver informant, and a treating clinician were asked to complete the Patient Competency Rating Scale (PCRS) and the Frontal Systems Behavior Scale (FrSBe) at admission and discharge. Results: Although overall, women and men with TBI showed generally similar levels of SA, women had significantly better awareness of their injury-related deficits at acute rehabilitation discharge, even when controlling for age, education, and injury severity. Conclusions: Mixed findings in this study mirror the pattern of results that dominate the published literature on gender and TBI. Gender differences in executive dysfunction may not be as large or robust as some researchers argue. In addition, complex interplays of socialization, gender-role expectations, naturally occurring male and female ability differences, and differences in access to postinjury rehabilitation are understudied potential moderators. PMID:24932911

  5. Risk taking in hospitalized patients with acute and severe traumatic brain injury.

    PubMed

    Fecteau, Shirley; Levasseur-Moreau, Jean; García-Molina, Alberto; Kumru, Hatiche; Vergara, Raúl Pelayo; Bernabeu, Monste; Roig, Teresa; Pascual-Leone, Alvaro; Tormos, José Maria

    2013-01-01

    Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients' characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury. PMID:24386232

  6. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    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

  7. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  8. Acute clinical care and care coordination for traumatic brain injury within Department of Defense.

    PubMed

    Jaffee, Michael S; Helmick, Kathy M; Girard, Philip D; Meyer, Kim S; Dinegar, Kathy; George, Karyn

    2009-01-01

    The nature of current combat situations that U.S. military forces encounter and the use of unconventional weaponry have dramatically increased service personnel's risks of sustaining a traumatic brain injury (TBI). Although the true incidence and prevalence of combat-related TBI are unknown, service personnel returning from deployment have reported rates of concussion between 10% and 20%. The Department of Defense has recently released statistics on TBI dating back to before the wars in Iraq and Afghanistan to better elucidate the impact and burden of TBI on America's warriors and veterans. Patients with severe TBI move through a well-established trauma system of care, beginning with triage of initial injury by first-responders in the war zone to acute care to rehabilitation and then returning home and to the community. Mild and moderate TBIs may pose different clinical challenges, especially when initially undetected or if treatment is delayed because more serious injuries are present. To ensure identification and prompt treatment of mild and moderate TBI, the U.S. Congress has mandated that military and Department of Veterans Affairs hospitals screen all service personnel returning from combat. Military health professionals must evaluate them for concussion and then treat the physical, emotional, and cognitive problems that may surface. A new approach to health management and care coordination is needed that will allow medical transitions between networks of care to become more centralized and allow for optimal recovery at all severity levels. This article summarizes the care systems available for the acute management of TBI from point of injury to stateside military treatment facilities. We describe TBI assessment, treatment, and overall coordination of care, including innovative clinical initiatives now used. PMID:20104395

  9. Pediatric Traumatic Brain Injury.

    PubMed

    Schaller, Alexandra L; Lakhani, Saquib A; Hsu, Benson S

    2015-10-01

    The purpose of this article is to provide a better understanding of pediatric traumatic brain injury and its management. Within the pediatric age group, ages 1 to 19, injuries are the number one cause of death with traumatic brain injury being involved in almost 50 percent of these cases. This, along with the fact that the medical system spends over $1 billion annually on pediatric traumatic brain injury, makes this issue both timely and relevant to health care providers. Over the course of this article the epidemiology, physiology, pathophysiology, and treatment of pediatric traumatic brain injury will be explored. Emphasis will be placed on the role of the early responder and the immediate interventions that should be considered and/or performed. The management discussed in this article follows the most recent recommendations from the 2012 edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents. Despite the focus of this article, it is important not to lose sight of the fact that an ounce of prevention is worth a pound--or, to be more precise and use the average human's brain measurements, just above three pounds--of cure. PMID:26630835

  10. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

    PubMed

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork

  11. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury

    PubMed Central

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J.; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork

  12. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  13. Traumatic Brain Injury

    MedlinePlus

    ... Center PTACs Workspaces Log-in Search for: Traumatic Brain Injury A legacy resource from NICHCY Disability Fact ... in her. Back to top What is Traumatic Brain Injury? A traumatic brain injury (TBI) is an ...

  14. Traumatic Brain Injury

    MedlinePlus

    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 ...

  15. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3.

    PubMed

    Denes, Adam; Coutts, Graham; Lénárt, Nikolett; Cruickshank, Sheena M; Pelegrin, Pablo; Skinner, Joanne; Rothwell, Nancy; Allan, Stuart M; Brough, David

    2015-03-31

    Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain. PMID:25775556

  16. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

    PubMed Central

    Denes, Adam; Coutts, Graham; Lénárt, Nikolett; Cruickshank, Sheena M.; Pelegrin, Pablo; Skinner, Joanne; Rothwell, Nancy; Allan, Stuart M.; Brough, David

    2015-01-01

    Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain. PMID:25775556

  17. Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

    PubMed Central

    Bhalala, Utpal S.; Koehler, Raymond C.; Kannan, Sujatha

    2015-01-01

    Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia – the so-called “brain macrophages,” infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds. PMID:25642419

  18. Serum neurogranin measurement as a biomarker of acute traumatic brain injury

    PubMed Central

    Yang, Jun; Korley, Frederick K.; Dai, Min; Everett, Allen D.

    2015-01-01

    Objectives Neurogranin (NRGN) is a small neuronal protein that plays an important role in synaptic signaling by regulating calmodulin (CaM) availability. In this study, we developed an ELISA to measure NRGN quantitatively in serum samples from a cohort of acute traumatic brain injury (TBI) patients and a non-TBI control cohort, and explored the potential value of NRGN as a circulating biomarker for TBI. Design and methods Recombinant His-NRGN protein was used to develop mouse monoclonal capture and rabbit polyclonal detection antibodies, and they were used to develop a sandwich ELISA. After validation, we used this ELISA to measure serum samples from a cohort of typical adult acute TBI patients (N = 76 TBI cases) and non-TBI control patients (N = 150 controls). Results The NRGN ELISA lower limit of detection was 0.055 ng/mL, lower limit of quantification was 0.2 ng/mL, and interassay CVs were ≤ 10.7%. The average recovery was 99.9% (range from 97.2–102%). Serum NRGN concentrations in TBI cases were significantly higher than in controls (median values were 0.18 ng/mL vs. 0.02 ng/mL, p < 0.0001), but did not discriminate TBI cases with intracranial hemorrhage (p = 0.09). Conclusions We have developed a highly sensitive and reproducible ELISA for measuring circulating NRGN in blood samples. Serum NRGN concentrations in acute TBI patients were significantly higher than in controls, indicating that NRGN could have utility as a circulating biomarker for acute TBI. This report provides evidence to support larger and controlled TBI clinical studies for NRGN validation and prediction of outcomes. PMID:26025774

  19. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    PubMed Central

    Di Battista, Alex P.; Rizoli, Sandro B.; Lejnieks, Brandon; Min, Arimie; Shiu, Maria Y.; Peng, Henry T.; Baker, Andrew J.; Hutchison, Michael G.; Churchill, Nathan; Inaba, Kenji; Nascimento, Bartolomeu B.; de Oliveira Manoel, Airton Leonardo; Beckett, Andrew; Rhind, Shawn G.

    2016-01-01

    ABSTRACT Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI. PMID:27206278

  20. Forward and inverse electroencephalographic modeling in health and in acute traumatic brain injury

    PubMed Central

    Irimia, Andrei; Goh, S.Y. Matthew; Torgerson, Carinna M.; Chambers, Micah C.; Kikinis, Ron; Van Horn, John D.

    2013-01-01

    Objective EEG source localization is demonstrated in three cases of acute traumatic brain injury (TBI) with progressive lesion loads using anatomically faithful models of the head which account for pathology. Methods Multimodal magnetic resonance imaging (MRI) volumes were used to generate head models via the finite element method (FEM). A total of 25 tissue types—including 6 types accounting for pathology— were included. To determine the effects of TBI upon source localization accuracy, a minimum-norm operator was used to perform inverse localization and to determine the accuracy of the latter. Results The importance of using a more comprehensive number of tissue types is confirmed in both health and in TBI. Pathology omission is found to cause substantial inaccuracies in EEG forward matrix calculations, with lead field sensitivity being underestimated by as much as ~200% in (peri-) contusional regions when TBI-related changes are ignored. Failing to account for such conductivity changes is found to misestimate substantial localization error by up to 35 mm. Conclusions Changes in head conductivity profiles should be accounted for when performing EEG modeling in acute TBI. Significance Given the challenges of inverse localization in TBI, this framework can benefit neurotrauma patients by providing useful insights on pathophysiology. PMID:23746499

  1. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury: acute versus chronic disturbances?

    PubMed

    Metting, Zwany; Spikman, Jacoba M; Rödiger, Lars A; van der Naalt, Joukje

    2014-04-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully understood. As the admission computed tomography (CT) often is normal, perfusion CT imaging may be a useful indicator of brain dysfunction in the acute phase after injury in these patients. In the present study, directly after admission perfusion CT imaging was performed in mild TBI patients with follow-up neuropsychological assessment in those with complaints and a normal non-contrast CT. Neuropsychological tests comprised the 15 Words test Immediate Recall, Trailmaking test part B, Zoo Map test and the FEEST, which were dichotomized into normal and abnormal. Perfusion CT results of patients with normal neuropsychological test scores were compared to those with abnormal test scores. In total eighteen patients were included. Those with an abnormal score on the Zoo Map test had a significant lower CBV in the right frontal and the bilateral parieto-temporal white matter. Patients with an abnormal score on the FEEST had a significant higher MTT in the bilateral frontal white matter and a significant decreased CBF in the left parieto-temporal grey matter. No significant relation between the perfusion CT parameters and the 15 Words test and the Trailmaking test part B was present. In conclusion, impairments in executive functioning and emotion perception assessed with neuropsychological tests during follow up were related to differences in cerebral perfusion at admission in mild TBI. The pathophysiological concept of these findings is discussed. PMID:24556319

  2. Acute traumatic brain injury: is current management evidence based? An empirical analysis of systematic reviews.

    PubMed

    Lei, Jin; Gao, Guoyi; Jiang, Jiyao

    2013-04-01

    Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide with a high rate of death and long-term disability. Previous studies have summarized evidence from large-scale randomized trials, finding no intervention showing convincing efficacy for acute TBI management. The present empirical study set out to assess another crucial component of evidence base-systematic review, which contributes a lot to evidence-based health care, in terms of clinical issues, methodological aspects, and implication for practice and research. A total of 44 systematic reviews pertaining to therapeutic interventions for acute TBI were identified through electronic database searching, clinical guideline retrieval, and expert consultation, of which 21 were published in Cochrane Library and 23 in peer-reviewed journals. Their methodological quality was generally satisfactory, with the median Overview Quality Assessment Questionnaire score of 5.5 (interquartile range 2-7). Cochrane reviews are of better quality than regular journal reviews. Twenty-nine high-quality reviews provided no conclusive evidence for the investigated 22 interventions except for an adverse effect of corticosteroids. Less than one-third of the component trials were reported with adequate allocation concealment. Additionally other methodological flaws in design-for example, ignoring heterogeneity among the TBI population-also contributed to the failure of past clinical research. Based on the above findings, evidence from both systematic reviews and clinical trials does not fully support current management of acute TBI. Translating from laboratory success to clinical effect remains an unique challenge. Accordingly it may be the time to rethink the way in future practice and clinical research in TBI. PMID:23151044

  3. Acute Neuroimmune Modulation Attenuates the Development of Anxiety-Like Freezing Behavior in an Animal Model of Traumatic Brain Injury

    PubMed Central

    Rodgers, Krista M.; Bercum, Florencia M.; McCallum, Danielle L.; Rudy, Jerry W.; Frey, Lauren C.; Johnson, Kirk W.; Watkins, Linda R.

    2012-01-01

    Abstract Chronic anxiety is a common and debilitating result of traumatic brain injury (TBI) in humans. While little is known about the neural mechanisms of this disorder, inflammation resulting from activation of the brain's immune response to insult has been implicated in both human post-traumatic anxiety and in recently developed animal models. In this study, we used a lateral fluid percussion injury (LFPI) model of TBI in the rat and examined freezing behavior as a measure of post-traumatic anxiety. We found that LFPI produced anxiety-like freezing behavior accompanied by increased reactive gliosis (reflecting neuroimmune inflammatory responses) in key brain structures associated with anxiety: the amygdala, insula, and hippocampus. Acute peri-injury administration of ibudilast (MN166), a glial cell activation inhibitor, suppressed both reactive gliosis and freezing behavior, and continued neuroprotective effects were apparent several months post-injury. These results support the conclusion that inflammation produced by neuroimmune responses to TBI play a role in post-traumatic anxiety, and that acute suppression of injury-induced glial cell activation may have promise for the prevention of post-traumatic anxiety in humans. PMID:22435644

  4. Clinical and imaging assessment of acute combat mild traumatic brain injury in Afghanistan

    PubMed Central

    Mac Donald, Christine L.; Rivet, Dennis; Ritter, John; May, Todd; Barefield, Maria; Duckworth, Josh; LaBarge, Donald; Asher, Dean; Drinkwine, Benjamin; Woods, Yvette; Connor, Michael; Brody, David L.

    2015-01-01

    Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery. Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI. Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 ± 12.9 vs 3.6 ± 7.1, p < 0.001), PCLM (32 ± 13.2 vs 20.9 ± 7.1, p < 0.001), BDI (7.4 ± 6.8 vs 2.5 ± 4.9, p < 0.001), and BESS (18.2 ± 8.4 vs 15.1 ± 8.3, p = 0.01). The largest effect size in ANAM performance decline was in simple reaction time (mTBI 74.5 ± 148.4 vs control −11 ± 46.6 milliseconds, p < 0.001). Fractional anisotropy was significantly reduced in mTBI compared with controls in the right superior longitudinal fasciculus (0.393 ± 0.022 vs 0.405 ± 0.023, p < 0.001). No abnormalities were detected with conventional MRI. Time to return to duty correlated with RPCSQ (r = 0.53, p < 0.001), ANAM simple reaction time decline (r = 0.49, p < 0.0001), PCLM (r = 0.47, p < 0.0001), and BDI (r = 0.36 p = 0.0005). Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in

  5. Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice

    PubMed Central

    Fenn, Ashley M.; Skendelas, John P.; Moussa, Daniel N.; Muccigrosso, Megan M.; Popovich, Phillip G.; Lifshitz, Jonathan

    2015-01-01

    Abstract Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15–30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1β, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1β and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1–7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. PMID:25070744

  6. Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

    PubMed Central

    Teng, Sophie X.

    2014-01-01

    Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

  7. Amplitude of Low-Frequency Fluctuations in Multiple-Frequency Bands in Acute Mild Traumatic Brain Injury

    PubMed Central

    Zhan, Jie; Gao, Lei; Zhou, Fuqing; Bai, Lijun; Kuang, Hongmei; He, Laichang; Zeng, Xianjun; Gong, Honghan

    2016-01-01

    Functional disconnectivity during the resting state has been observed in mild traumatic brain injury (mTBI) patients during the acute stage. However, it remains largely unknown whether the abnormalities are related to specific frequency bands of the low-frequency oscillations (LFO). Here, we used the amplitude of low-frequency fluctuations (ALFF) to examine the amplitudes of LFO in different frequency bands (slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz; and typical: 0.01–0.08 Hz) in patients with acute mTBI. A total of 24 acute mTBI patients and 24 age-, sex-, and education-matched healthy controls participated in this study. In the typical band, acute mTBI patients showed lower standardized ALFF in the right middle frontal gyrus and higher standardized ALFF in the right lingual/fusiform gyrus and left middle occipital gyrus. Further analyses showed that the difference between groups was concentrated in a narrower (slow-4) frequency band. In the slow-5 band, mTBI patients only exhibited higher standardized ALFF in the occipital areas. No significant correlation between the mini-mental state examination score and the standardized ALFF value was found in any brain region in the three frequency bands. Finally, no significant interaction between frequency bands and groups was found in any brain region. We concluded that the abnormality of spontaneous brain activity in acute mTBI patients existed in the frontal lobe as well as in distributed brain regions associated with integrative, sensory, and emotional roles, and the abnormal spontaneous neuronal activity in different brain regions could be better detected by the slow-4 band. These findings might contribute to a better understanding of local neural psychopathology of acute mTBI. Future studies should take the frequency bands into account when measuring intrinsic brain activity of mTBI patients. PMID:26869907

  8. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  9. Traumatic brain injury and post-acute decline: what role does environmental enrichment play? A scoping review

    PubMed Central

    Frasca, Diana; Tomaszczyk, Jennifer; McFadyen, Bradford J.; Green, Robin E.

    2013-01-01

    Objectives: While a growing number of studies provide evidence of neural and cognitive decline in traumatic brain injury (TBI) survivors during the post-acute stages of injury, there is limited research as of yet on environmental factors that may influence this decline. The purposes of this paper, therefore, are to (1) examine evidence that environmental enrichment (EE) can influence long-term outcome following TBI, and (2) examine the nature of post-acute environments, whether they vary in degree of EE, and what impact these variations have on outcomes. Methods: We conducted a scoping review to identify studies on EE in animals and humans, and post-discharge experiences that relate to barriers to recovery. Results: One hundred and twenty-three articles that met inclusion criteria demonstrated the benefits of EE on brain and behavior in healthy and brain-injured animals and humans. Nineteen papers on post-discharge experiences revealed that variables such as insurance coverage, financial, and social support, home therapy, and transition from hospital to home, can have an impact on clinical outcomes. Conclusion: There is evidence to suggest that lack of EE, whether from lack of resources or limited ability to engage in such environments, may play a role in post-acute cognitive and neural decline. Maximizing EE in the post-acute stages of TBI may improve long-term outcomes for the individual, their family and society. PMID:23616755

  10. Acute neuro-endocrine profile and prediction of outcome after severe brain injury

    PubMed Central

    2013-01-01

    Object The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome. Methods Prospective study, including consecutive patients, 15–70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08–10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17–19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E. Results Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3

  11. Global lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of acute brain injury

    PubMed Central

    Ji, Jing; Kline, Anthony E; Amoscato, Andrew; Arias, Alejandro S; Sparvero, Louis J; Tyurin, Vladimir A; Tyurina, Yulia Y; Fink, Bruno; Manole, Mioara D; Puccio, Ava M; Okonkwo, David O; Cheng, Jeffrey P; Alexander, Henry; Clark, Robert SB; Kochanek, Patrick M; Wipf, Peter; Kagan, Valerian E; Bayýr, Hülya

    2013-01-01

    Brain contains a highly diversified complement of molecular species of a mitochondria-specific phospholipid, cardiolipin (CL), which - due to its polyunsaturation - can readily undergo oxygenation. Here, we used global lipidomics analysis in experimental traumatic brain injury (TBI) and showed that TBI was accompanied by oxidative consumption of polyunsaturated CL and accumulation of more than 150 new oxygenated molecular species in CL. RNAi-based manipulations of CL-synthase and CL levels conferred resistance of primary rat cortical neurons to mechanical stretch - an in vitro model of traumatic neuronal injury. By applying the novel brain permeable mitochondria-targeted electron-scavenger, we prevented CL oxygenation in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, and markedly reduced behavioral deficits and cortical lesion volume. We conclude that CL oxygenation generates neuronal death signals and that its prevention by mitochondria-targeted small molecule inhibitors represents a new target for neuro-drug discovery. PMID:22922784

  12. Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury

    PubMed Central

    Barton, Samantha K.; Moss, Timothy J. M.; Hooper, Stuart B.; Crossley, Kelly J.; Gill, Andrew W.; Kluckow, Martin; Zahra, Valerie; Wong, Flora Y.; Pichler, Gerhard; Galinsky, Robert; Miller, Suzanne L.

    2014-01-01

    Background The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Methods Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. Results LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Conclusions Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor

  13. Brain injury - discharge

    MedlinePlus

    ... Rehabilitation Nurses. Care of the patient with mild traumatic brain injury. Available at: www.aann.org/pubs/content/guidelines. ... Stroud, NL, Zafonte R. Rehabilitation of patients with traumatic brain injury. In: Winn HR, ed. Youman's Neurological Surgery . 6th ...

  14. Neuropathophysiology of Brain Injury.

    PubMed

    Quillinan, Nidia; Herson, Paco S; Traystman, Richard J

    2016-09-01

    Every year in the United States, millions of individuals incur ischemic brain injury from stroke, cardiac arrest, or traumatic brain injury. These acquired brain injuries can lead to death or long-term neurologic and neuropsychological impairments. The mechanisms of ischemic and traumatic brain injury that lead to these deficiencies result from a complex interplay of interdependent molecular pathways, including excitotoxicity, acidotoxicity, ionic imbalance, oxidative stress, inflammation, and apoptosis. This article reviews several mechanisms of brain injury and discusses recent developments. Although much is known from animal models of injury, it has been difficult to translate these effects to humans. PMID:27521191

  15. Decreased Regional Homogeneity in Patients With Acute Mild Traumatic Brain Injury: A Resting-State fMRI Study.

    PubMed

    Zhan, Jie; Gao, Lei; Zhou, Fuqing; Kuang, Hongmei; Zhao, Jing; Wang, Siyong; He, Laichang; Zeng, Xianjun; Gong, Honghan

    2015-10-01

    Mild traumatic brain injury (mTBI) is characterized by structural disconnection and large-scale neural network dysfunction in the resting state. However, little is known concerning the intrinsic changes in local spontaneous brain activity in patients with mTBI. The aim of the current study was to assess regional synchronization in acute mTBI patients. Fifteen acute mTBI patients and 15 sex-, age-, and education-matched healthy controls (HCs) were studied. We used the regional homogeneity (ReHo) method to map local connectivity across the whole brain and performed a two-sample t-test between the two groups. Compared with HCs, patients with acute mTBI showed significantly decreased ReHo in the left insula, left precentral/postcentral gyrus, and left supramarginal gyrus (p < 0.05, AlphaSim corrected). The ReHo index of the left insula showed a positive correlation with the Mini-Mental State Examination (MMSE) scores across all acute mTBI patients (p < 0.05, uncorrected). The ReHo method may provide an objective biomarker for evaluating the functional abnormity of mTBI in the acute setting. PMID:26348589

  16. Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

    NASA Astrophysics Data System (ADS)

    Volkov, Boris; Mathews, Marlon S.; Abookasis, David

    2015-03-01

    Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

  17. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    PubMed Central

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  18. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

    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

  19. The Natural History of Acute Recovery of Blast-Induced Mild Traumatic Brain Injury: A Case Series During War.

    PubMed

    Larres, David T; Carr, Walter; Gonzales, Elizandro G; Hawley, Jason S

    2016-05-01

    Traumatic brain injury (TBI) secondary to blast exposure is a common injury in the Global War on Terrorism, but little is known about the acute effects, recovery, pathophysiology, and neuropathology of blast-induced mild TBI (mTBI) in humans in a battlefield environment. Moreover, there is ongoing debate whether blast-induced mTBI is a different injury with a unique pathophysiology compared with mTBI from blunt trauma. In the case series reported here from Craig Joint Theater Hospital at Bagram Airfield, Afghanistan, 15 military service members with acute concussion/mTBI associated with blast exposure were evaluated within the first 24 hours after concussion and on days 2, 3, 5, and 7 with a Graded Symptom Checklist and a balance assessment, the Balance Error Scoring System. These data suggest that the recovery in blast-induced mTBI follows the pattern of recovery in sports-related concussion reported in The National Collegiate Athletic Association Concussion Study. In this retrospective case series, we provide the first description of the natural history of acute recovery in blast-induced mTBI, and we suspect, given our experience treating military service members, that further observations of the natural history of recovery in blast-induced mTBI will continue to mirror the natural history of recovery in sports concussion. PMID:27168549

  20. Clinical review: Prognostic value of magnetic resonance imaging in acute brain injury and coma

    PubMed Central

    Weiss, Nicolas; Galanaud, Damien; Carpentier, Alexandre; Naccache, Lionel; Puybasset, Louis

    2007-01-01

    Progress in management of critically ill neurological patients has led to improved survival rates. However, severe residual neurological impairment, such as persistent coma, occurs in some survivors. This raises concerns about whether it is ethically appropriate to apply aggressive care routinely, which is also associated with burdensome long-term management costs. Adapting the management approach based on long-term neurological prognosis represents a major challenge to intensive care. Magnetic resonance imaging (MRI) can show brain lesions that are not visible by computed tomography, including early cytotoxic oedema after ischaemic stroke, diffuse axonal injury after traumatic brain injury and cortical laminar necrosis after cardiac arrest. Thus, MRI increases the accuracy of neurological diagnosis in critically ill patients. In addition, there is some evidence that MRI may have potential in terms of predicting outcome. Following a brief description of the sequences used, this review focuses on the prognostic value of MRI in patients with traumatic brain injury, anoxic/hypoxic encephalopathy and stroke. Finally, the roles played by the main anatomical structures involved in arousal and awareness are discussed and avenues for future research suggested. PMID:17980050

  1. Acute high-altitude hypoxic brain injury: Identification of ten differential proteins.

    PubMed

    Li, Jianyu; Qi, Yuting; Liu, Hui; Cui, Ying; Zhang, Li; Gong, Haiying; Li, Yaxiao; Li, Lingzhi; Zhang, Yongliang

    2013-11-01

    Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mitochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mitochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These detected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, isovaleryl-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyl-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production. PMID:25206614

  2. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

    PubMed

    Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

    2014-09-01

    Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient. PMID:24760409

  3. [Mild brain injuries in emergency medicine].

    PubMed

    Liimatainen, Suvi; Niskakangas, Tero; Ohman, Juha

    2011-01-01

    Diagnostics and correct classification of mild brain injuries is challenging. Problems caused by insufficient documentation at the acute phase become more obvious in situations in which legal insurance issues are to be considered. A small proportion of patients with mild brain injury suffer from prolonged symptoms. Medical recording and classification of the brain injury at the initial phase should therefore be carried out in a structured manner. The review deals with the diagnostic problems of mild brain injuries and presents a treatment protocol for adult patients at the acute phase, aiming at avoiding prolonged problems. PMID:22238915

  4. Traumatic Brain Injury

    MedlinePlus

    ... a concussion may feel dazed and may lose vision or balance for a while after the injury A brain contusion is a bruise of the brain. This ... consciousness Headache Confusion Feeling dizzy or lightheaded Blurry vision ... or severe traumatic brain injury include all of the symptoms listed above ...

  5. Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI).

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Cooper, Janine M; Beare, Richard; Ditchfield, Michael; Coleman, Lee; Silk, Timothy; Crossley, Louise; Rogers, Kirrily; Beauchamp, Miriam H; Yeates, Keith O; Anderson, Vicki A

    2015-01-01

    Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI. PMID:25445779

  6. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  7. Acute kidney injury.

    PubMed

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  8. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    PubMed

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI. PMID:26064794

  9. Cerebral hemodynamic changes of mild traumatic brain injury at the acute stage.

    PubMed

    Doshi, Hardik; Wiseman, Natalie; Liu, Jun; Wang, Wentao; Welch, Robert D; O'Neil, Brian J; Zuk, Conor; Wang, Xiao; Mika, Valerie; Szaflarski, Jerzy P; Haacke, E Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation. PMID:25659079

  10. Cerebral Hemodynamic Changes of Mild Traumatic Brain Injury at the Acute Stage

    PubMed Central

    Doshi, Hardik; Wiseman, Natalie; Liu, Jun; Wang, Wentao; Welch, Robert D.; O’Neil, Brian J.; Zuk, Conor; Wang, Xiao; Mika, Valerie; Szaflarski, Jerzy P.; Haacke, E. Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation. PMID:25659079

  11. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    PubMed Central

    Pedata, Felicita; Pugliese, Anna Maria; Coppi, Elisabetta; Dettori, Ilaria; Maraula, Giovanna; Cellai, Lucrezia; Melani, Alessia

    2014-01-01

    The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke. PMID:25165414

  12. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    PubMed

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions. PMID:25859655

  13. The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial

    PubMed Central

    Saxena, Manoj K.; Taylor, Colman; Billot, Laurent; Bompoint, Severine; Gowardman, John; Roberts, Jason A.; Lipman, Jeffery; Myburgh, John

    2015-01-01

    Background Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. Methods A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Results Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17–18) in the paracetamol group and 18 (16–18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67–76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. Conclusion The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000444280 PMID:26678710

  14. Cerebrolysin Asian Pacific trial in acute brain injury and neurorecovery: design and methods.

    PubMed

    Poon, Wai; Vos, Pieter; Muresanu, Dafin; Vester, Johannes; von Wild, Klaus; Hömberg, Volker; Wang, Ernest; Lee, Tatia M C; Matula, Christian

    2015-04-15

    Traumatic brain injury (TBI) is one of the leading causes of injury-related death. In the United States alone, an estimated 1.7 million people sustain a TBI each year, and approximately 5.3 million people live with a TBI-related disability. The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $76.5 billion in the U.S. in the year 2000. Improving the limited treatment options for this condition remains challenging. However, recent reports from interdisciplinary working groups (consisting primarily of neurologists, neurosurgeons, neuropsychologists, and biostatisticians) have stated that to improve TBI treatment, important methodological lessons from the past must be taken into account in future clinical research. An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited understanding of the underlying biological concepts and methodological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy. Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors. Cerebrolysin has a favorable adverse effect profile, and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment. CAPTAIN is a randomized, double-blind, placebo-controlled, multi-center, multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales. The CAPTAIN trial will be the first TBI trial with a 'true' multidimensional approach based on full outcome scales, while avoiding prior weaknesses, such as loss of information through "dichotomization," or unrealistic assumptions such as "normal distribution." PMID:25222349

  15. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration

    PubMed Central

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-01-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients’ motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period. PMID:27512262

  16. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration.

    PubMed

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-07-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients' motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period. PMID:27512262

  17. Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting.

    PubMed

    Dahlin, Andreas P; Purins, Karlis; Clausen, Fredrik; Chu, Jiangtao; Sedigh, Amir; Lorant, Tomas; Enblad, Per; Lewén, Anders; Hillered, Lars

    2014-09-01

    There is growing interest in cerebral microdialysis (MD) for sampling of protein biomarkers in neurointensive care (NIC) patients. Published data point to inherent problems with this methodology including protein interaction and biofouling leading to unstable catheter performance. This study tested the in vivo performance of a refined MD method including catheter surface modification, for protein biomarker sampling in a clinically relevant porcine brain injury model. Seven pigs of both sexes (10-12 weeks old; 22.2-27.3 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure (ICP) and cerebral perfusion pressure was recorded during the stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 min) until brain death. One naïve MD catheter and one surface modified with Pluronic F-127 (10 mm membrane, 100 kDa molecular weight cutoff MD catheter) were inserted into the right frontal cortex and perfused with mock CSF with 3% Dextran 500 at a flow rate of 1.0 μL/min and 20 min sample collection. Naïve catheters showed unstable fluid recovery, sensitive to ICP changes, which was significantly stabilized by surface modification. Three of seven naïve catheters failed to deliver a stable fluid recovery. MD levels of glucose, lactate, pyruvate, glutamate, glycerol and urea measured enzymatically showed an expected gradual ischemic and cellular distress response to the intervention without differences between naïve and surface modified catheters. The 17 most common proteins quantified by iTRAQ and nanoflow LC-MS/MS were used as biomarker models. These proteins showed a significantly more homogeneous response to the ICP intervention in surface modified compared to naïve MD catheters with improved extraction efficiency for most of the proteins. The refined MD method appears to improve the accuracy and precision of protein biomarker sampling in the NIC setting. PMID:25075428

  18. Osteopontin Expression in Acute Immune Response Mediates Hippocampal Synaptogenesis and Adaptive Outcome Following Cortical Brain Injury

    PubMed Central

    Chan, Julie L.; Reeves, Thomas M.; Phillips, Linda L.

    2014-01-01

    Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1–2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived from MMP proteolysis were elevated at 1d, consistent with prior reports of UEC glial activation and enzyme production. Postinjury minocycline immunosuppression attenuated MMP-9 gelatinase activity, which was correlated with reduction of neutrophil gelatinase-associated lipocalin (LCN2) expression, and reduced OPN fragment generation. The antibiotic also attenuated removal of synapsin-1 positive axons from the deafferented zone. OPN KO mice subjected to UEC had similar reduction of hippocampal MMP-9 activity, as well as lower synapsin-1 breakdown over the deafferented zone. MAP1B and N-cadherin, surrogates of cytoarchitecture and synaptic adhesion, were not affected. OPN KO mice with UEC exhibited time dependent cognitive deficits during the synaptogenic phase of recovery. This study demonstrates that OPN can mediate immune response during TBI synaptic repair, positively influencing synapse reorganization and functional recovery. PMID:25151457

  19. Traumatic Brain Injury

    MedlinePlus

    ... disabilities include problems with cognition (thinking, memory, and reasoning), sensory processing (sight, hearing, touch, taste, and smell), ... barrier. NIH Patient Recruitment for Traumatic Brain Injury Clinical Trials At NIH Clinical Center Throughout the U.S. ...

  20. How Healthcare Provider Talk with Parents of Children Following Severe Traumatic Brain Injury is Perceived in Early Acute Care

    PubMed Central

    Savage, Teresa A.; Grant, Gerald; Philipsen, Gerry

    2013-01-01

    Healthcare provider talk with parents in early acute care following children’s severe traumatic brain injury (TBI) affects parents’ orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers’ and researchers’ views that these locales are generally neutral or supportive to parents’ subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005 – 2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers’ talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. PMID:23746606

  1. Acute Alcohol Intoxication and Long-Term Outcome in Patients with Traumatic Brain Injury

    PubMed Central

    Skrifvars, Markus B.; Kivisaari, Riku; Hernesniemi, Juha; Lappalainen, Jaakko; Siironen, Jari

    2015-01-01

    Abstract The effect of blood alcohol concentration (BAC) on outcome after traumatic brain injury (TBI) is controversial. We sought to assess the independent effect of positive BAC on long-term outcome in patients with TBI treated in the intensive care unit (ICU). We performed a retrospective analysis of 405 patients with TBI, admitted to the ICU of a large urban Level 1 trauma center between January 2009 and December 2012. Outcome was six-month mortality and unfavorable neurological outcome (defined as a Glasgow Outcome Scale score of 1 [death], 2, [vegetative state], or 3 [severe disability]). Patients were categorized by admission BAC into: no BAC (0.0‰; n=99), low BAC (<2.3‰; n=140) and high BAC (≥2.3‰; n=166). Logistic regression analysis, adjusting for baseline risk and severity of illness, was used to assess the independent effect of BAC on outcome (using the no BAC group as the reference). Overall six-month mortality was 25% and unfavorable outcome was 46%. Multivariate analysis showed low BAC to independently reduce risk of six-month mortality compared with no BAC (low BAC adjusted odds ratio [AOR] 0.41, 95% confidence interval [CI] 0.19–0.88, p=0.021) and high BAC (AOR 0.58, 95% CI 0.29–1.15, p=0.120). Furthermore, a trend towards reduced risk of six-month unfavorable neurological outcome for patients with positive BAC, compared to patients with negative BAC, was noted, although this did not reach statistical significance (low BAC AOR 0.65, 95% CI 0.34–1.22, p=0.178, and high BAC AOR 0.59, 95% CI 0.32–1.09, p=0.089). In conclusion, low admission BAC (<2.3‰) was found to independently reduce risk of six-month mortality for patients with TBI, and a trend towards improved long-term neurological outcome was found for BAC-positive patients. The role of alcohol as a neuroprotective agent warrants further studies. PMID:25010885

  2. Brain injury in sports.

    PubMed

    Lloyd, John; Conidi, Frank

    2016-03-01

    OBJECT Helmets are used for sports, military, and transportation to protect against impact forces and associated injuries. The common belief among end users is that the helmet protects the whole head, including the brain. However, current consensus among biomechanists and sports neurologists indicates that helmets do not provide significant protection against concussion and brain injuries. In this paper the authors present existing scientific evidence on the mechanisms underlying traumatic head and brain injuries, along with a biomechanical evaluation of 21 current and retired football helmets. METHODS The National Operating Committee on Standards for Athletic Equipment (NOCSAE) standard test apparatus was modified and validated for impact testing of protective headwear to include the measurement of both linear and angular kinematics. From a drop height of 2.0 m onto a flat steel anvil, each football helmet was impacted 5 times in the occipital area. RESULTS Skull fracture risk was determined for each of the current varsity football helmets by calculating the percentage reduction in linear acceleration relative to a 140-g skull fracture threshold. Risk of subdural hematoma was determined by calculating the percentage reduction in angular acceleration relative to the bridging vein failure threshold, computed as a function of impact duration. Ranking the helmets according to their performance under these criteria, the authors determined that the Schutt Vengeance performed the best overall. CONCLUSIONS The study findings demonstrated that not all football helmets provide equal or adequate protection against either focal head injuries or traumatic brain injuries. In fact, some of the most popular helmets on the field ranked among the worst. While protection is improving, none of the current or retired varsity football helmets can provide absolute protection against brain injuries, including concussions and subdural hematomas. To maximize protection against head and

  3. Comparison of non-sedated brain MRI and CT for the detection of acute traumatic injury in children 6 years of age or less.

    PubMed

    Young, Joseph Yeen; Duhaime, Ann-Christine; Caruso, Paul Albert; Rincon, Sandra Patricia

    2016-08-01

    CT is considered the first-line study for acute intracranial injury in children because of its availability, detection of acute hemorrhage, and lack of sedation. An MRI study with rapidly acquired sequences can obviate the need for sedation and radiation. We compared the detection rate of rapid non-sedated brain MRI to CT for traumatic head injury in young children. We reviewed a series of children 6 years of age or less who presented to our ED during a 5-year period with head trauma and received a non-sedated brain MRI and CT within 24 h of injury. Most MRI studies were limited to triplane T2 and susceptibility sequences. Two neuroradiologists reviewed the MRIs and CTs and assessed the following findings: fracture, epidural hematoma (EDH)/subdural hematoma (SDH), subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), and parenchymal injury. Thirty of 33 patients had radiologically identified traumatic injuries. There was an overall agreement of 82 % between the two modalities. Skull fracture was the only injury subtype which had a statistically significant difference in detection between CT and MRI (p = 0.0001), with MRI missing 14 of 21 fractures detected on CT. While not statistically significant, MRI had a higher detection rate of EDH/SDH (p = 0.34), SAH (p = 0.07), and parenchymal injuries (p = 0.50). Non-sedated MRI has similar detection rates to CT for intracranial injury in young children presenting with acute head trauma and may be an alternative to CT in select patients. PMID:27166965

  4. Increased Risk of Post-Trauma Stroke after Traumatic Brain Injury-Induced Acute Respiratory Distress Syndrome.

    PubMed

    Chen, Gunng-Shinng; Liao, Kuo-Hsing; Bien, Mauo-Ying; Peng, Giia-Sheun; Wang, Jia-Yi

    2016-07-01

    This study determines whether acute respiratory distress syndrome (ARDS) is an independent risk factor for an increased risk of post-traumatic brain injury (TBI) stroke during 3-month, 1-year, and 5-year follow-ups, respectively, after adjusting for other covariates. Clinical data for the analysis were from the National Health Insurance Database 2000, which covered a total of 2121 TBI patients and 101 patients with a diagnosis of TBI complicated with ARDS (TBI-ARDS) hospitalized between January 1, 2001 and December 31, 2005. Each patient was tracked for 5 years to record stroke occurrences after discharge from the hospital. The prognostic value of TBI-ARDS was evaluated using a multivariate Cox proportional hazard model. The main outcome found that stroke occurred in nearly 40% of patients with TBI-ARDS, and the hazard ratio for post-TBI stroke increased fourfold during the 5-year follow-up period after adjusting for other covariates. The increased risk of hemorrhagic stroke in the ARDS group was considerably higher than in the TBI-only cohort. This is the first study to report that post-traumatic ARDS yielded an approximate fourfold increased risk of stroke in TBI-only patients. We suggest intensive and appropriate medical management and intensive follow-up of TBI-ARDS patients during the beginning of the hospital discharge. PMID:26426583

  5. Radiation Injury to the Brain

    MedlinePlus

    ... 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. ...

  6. TRAUMATIC BRAIN INJURY (TBI) DATABASE

    EPA Science Inventory

    The Traumatic Brain Injury National Data Center (TBINDC) at Kessler Medical Rehabilitation Research and Education Center is the coordinating center for the research and dissemination efforts of the Traumatic Brain Injury Model Systems (TBIMS) program funded by the National Instit...

  7. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

    Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

    2016-01-01

    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. PMID:26048614

  8. Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study.

    PubMed

    Wang, Kevin K W; Yang, Zhihui; Yue, John K; Zhang, Zhiqun; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Lingsma, Hester F; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Manley, Geoffrey T; Cooper, Shelly R; Dams-O'Connor, Kristen; Hricik, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Sinha, Tuhin K; Vassar, Mary J

    2016-07-01

    We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI. PMID:26560343

  9. Acute Traumatic Brain Injury Does Not Exacerbate Amyotrophic Lateral Sclerosis in the SOD1 (G93A) Rat Model(1,2,3).

    PubMed

    Thomsen, Gretchen M; Vit, Jean-Philippe; Lamb, Alexander; Gowing, Genevieve; Shelest, Oksana; Alkaslasi, Mor; Ley, Eric J; Svendsen, Clive N

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which upper and lower motor neurons degenerate, leading to muscle atrophy, paralysis, and death within 3 to 5 years of onset. While a small percentage of ALS cases are genetically linked, the majority are sporadic with unknown origin. Currently, etiological links are associated with disease onset without mechanistic understanding. Of all the putative risk factors, however, head trauma has emerged as a consistent candidate for initiating the molecular cascades of ALS. Here, we test the hypothesis that traumatic brain injury (TBI) in the SOD1 (G93A) transgenic rat model of ALS leads to early disease onset and shortened lifespan. We demonstrate, however, that a one-time acute focal injury caused by controlled cortical impact does not affect disease onset or survival. Establishing the negligible involvement of a single acute focal brain injury in an ALS rat model increases the current understanding of the disease. Critically, untangling a single focal TBI from multiple mild injuries provides a rationale for scientists and physicians to increase focus on repeat injuries to hopefully pinpoint a contributing cause of ALS. PMID:26464984

  10. Traumatic Brain Injury (TBI)

    MedlinePlus

    ... A. (2008). Mild traumatic brain injury in U.S. soldiers returning from Iraq. New England Journal of Medicine, 358, 453–463. ... and Spotlights U.S. hospitals miss followup for suspected child abuse Q&A with NICHD Acting Director Catherine ...

  11. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    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…

  12. Brain Injury Association of America

    MedlinePlus

    ... Only) 1-800-444-6443 Welcome to the Brain Injury Association of America (BIAA) Brain injury is not an event or an outcome. ... misunderstood, under-funded neurological disease. People who sustain brain injuries must have timely access to expert trauma ...

  13. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  14. Boussignac CPAP system for brain death confirmation with apneic test in case of acute lung injury/adult respiratory distress syndrome – series of cases

    PubMed Central

    Wieczorek, Andrzej; Gaszynski, Tomasz

    2015-01-01

    Introduction There are some patients with severe respiratory disturbances like adult respiratory distress syndrome (ARDS) and suspicion of brain death, for whom typical performance of the apneic test is difficult to complete because of quick desaturation and rapid deterioration without effective ventilation. To avoid failure of brain death confirmation and possible loss of organ donation another approach to apneic test is needed. We present two cases of patients with clinical symptoms of brain death, with lung pathology (acute lung injury, ARDS, lung embolism and lung infection), in whom apneic tests for recognizing brain death were difficult to perform. During typical performance of apneic test involving the use of oxygen catheter for apneic oxygenation we observed severe desaturation with growing hypotension and hemodynamic destabilization. But with the use of Boussignac CPAP system all necessary tests were successfully completed, confirming the patient’s brain death, which gave us the opportunity to perform procedures for organ donation. The main reason of apneic test difficulties was severe gas exchange disturbances secondary to ARDS. Thus lack of positive end expiratory pressure during classical performance of apneic test leads to quick desaturation and rapid hemodynamic deterioration, limiting the observation period below dedicated at least 10-minute interval. Conclusion The Boussignac CPAP system may be an effective tool for performing transparent apneic test in case of serious respiratory disturbances, especially in the form of acute lung injury or ARDS. PMID:26124664

  15. Effects of Acute Restraint-Induced Stress on Glucocorticoid Receptors and BDNF after Mild Traumatic Brain Injury

    PubMed Central

    Griesbach, Grace S.; Vincelli, Jennifer; Tio, Delia L.; Hovda, David A.

    2012-01-01

    We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either a FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30-min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7 and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain derived neutrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors were determined by western blot analysis. Results indicated injury dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14, These findings suggest that the increased sensitivity to stressful events during the first post injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. PMID:22445725

  16. Astrocytes and oligodendrocytes can be generated from NG2+ progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice.

    PubMed

    Zhao, Jing-Wei; Raha-Chowdhury, Ruma; Fawcett, James W; Watts, Colin

    2009-05-01

    Brain injury induces gliosis and scar formation; its principal cell types are mainly astrocytes and some oligodendrocytes. The origin of the astrocytes and oligodendrocytes in the scar remains unclear together with the underlying mechanism of their fate choice. We examined the response of oligodendrocyte transcription factor (Olig)2(+) glial progenitors to acute brain injury. Both focal cortical (mechanical or excitotoxic) and systemic (kainic acid-induced seizure or lipopolysaccharide-induced inflammation) injury caused cytoplasmic translocation of Olig2 (Olig2(TL)) exclusively in affected brain regions as early as 2 h after injury in two-thirds of Olig2(+) cells. Many of the proliferating Olig2(+) cells reacting to injury co-expressed chondroitin sulphate proteoglycan neuron/glia antigen 2 (NG2). Using 5-bromodeoxyuridine (BrdU) tracing protocols, proliferating Olig2(TL)GFAP(+)BrdU(+) cells were observed from 2 days post-lesion (dpl). Immature oligodendrocytes were also seen from 2 dpl and all of them retained Olig2 in the nucleus (Olig2(Nuc)). From 5 dpl Olig2(TL)NG2(+)GFAP(+) cells were observed in the wound and some of them were proliferative. From 5 dpl NG2(+)RIP(+) cells were also seen, all of which were Olig2(Nuc) and some of which were also BrdU(+). Our results suggest that, in response to brain injury, NG2(+) progenitors may generate a subpopulation of astrocytes in addition to oligodendrocytes and their fate choice was associated with Olig2(TL) or Olig2(Nuc). However, the NG2(+)GFAP(+) phenotype was only seen within a limited time window (5-8 dpl) when up to 20% of glial fibrillary acidic protein (GFAP) cells co-expressed NG2. We also observed Olig2(TL)GFAP(+) cells that appeared after injury and before the NG2(+)GFAP(+) phenotype. This suggests that not all astrocytes are derived from an NG2(+) population. PMID:19473238

  17. Acute Kidney Injury.

    PubMed

    Zuk, Anna; Bonventre, Joseph V

    2016-01-01

    Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243

  18. Acute lung injury review.

    PubMed

    Tsushima, Kenji; King, Landon S; Aggarwal, Neil R; De Gorordo, Antonio; D'Alessio, Franco R; Kubo, Keishi

    2009-01-01

    The first report of acute respiratory distress syndrome (ARDS) was published in 1967, and even now acute lung injury (ALI) and ARDS are severe forms of diffuse lung disease that impose a substantial health burden all over the world. Recent estimates indicate approximately 190,000 cases per year of ALI in the United States each year, with an associated 74,500 deaths per year. Common causes of ALI/ARDS are sepsis, pneumonia, trauma, aspiration pneumonia, pancreatitis, and so on. Several pathologic stages of ALI/ARDS have been described: acute inflammation with neutrophil infiltration, fibroproliferative phase with hyaline membranes, with varying degrees of interstitial fibrosis, and resolution phase. There has been intense investigation into the pathophysiologic events relevant to each stage of ALI/ARDS, and much has been learned in the alveolar epithelial, endobronchial homeostasis, and alveolar cell immune responses, especially neutrophils and alveolar macrophages in an animal model. However, these effective results in the animal models are not equally adoptive to those in randomized, controlled trials. The clinical course of ALI/ARDS is variable with the likely pathophysiologic complexity of human ALI/ARDS. In 1994, the definition was recommended by the American-European Consensus Conference Committee, which facilitated easy nomination of patients with ALI/ARDS for a randomized, clinical trial. Here, we review the recent randomized, clinical trials of ALI/ARDS. PMID:19420806

  19. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  20. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

    PubMed

    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. PMID:26896832

  1. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

    PubMed Central

    Lloyd, Eric; Somera-Molina, Kathleen; Van Eldik, Linda J; Watterson, D Martin; Wainwright, Mark S

    2008-01-01

    Background Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. Methods We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. Results Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated

  2. A prospective study of the influence of acute alcohol intoxication versus chronic alcohol consumption on outcome following traumatic brain injury.

    PubMed

    Lange, Rael T; Shewchuk, Jason R; Rauscher, Alexander; Jarrett, Michael; Heran, Manraj K S; Brubacher, Jeffrey R; Iverson, Grant L

    2014-08-01

    The purpose of the study was to disentangle the relative contributions of day-of-injury alcohol intoxication and pre-injury alcohol misuse on outcome from TBI. Participants were 142 patients enrolled from a Level 1 Trauma Center (in Vancouver, Canada) following a traumatic brain injury (TBI; 43 uncomplicated mild TBI and 63 complicated mild-severe TBI) or orthopedic injury [36 trauma controls (TC)]. At 6-8 weeks post-injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Phillips 3T scanner. Participants also completed neuropsychological testing, an evaluation of lifetime alcohol consumption (LAC), and had blood alcohol levels (BALs) taken at the time of injury. Participants in the uncomplicated mild TBI and complicated mild-severe TBI groups had higher scores on measures of depression and postconcussion symptoms (d = 0.45-0.83), but not anxiety, compared with the TC group. The complicated mild-severe TBI group had more areas of abnormal white matter on DTI measures (all p < .05; d = 0.54-0.61) than the TC group. There were no difference between groups on all neurocognitive measures. Using hierarchical regression analyses and generalized linear modeling, LAC and BAL did provide a unique contribution toward the prediction of attention and executive functioning abilities; however, the variance accounted for was small. LAC and BAL did not provide a unique and meaningful contribution toward the prediction of self-reported symptoms, DTI measures, or the majority of neurocognitive measures. In this study, BAL and LAC were not predictive of mental health symptoms, postconcussion symptoms, cognition, or white-matter changes at 6-8 weeks following TBI. PMID:24964748

  3. Altered spontaneous brain activity patterns in patients with unilateral acute open globe injury using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study

    PubMed Central

    Tan, Gang; Huang, Xin; Ye, Lei; Wu, An-Hua; He, Li-Xian; Zhong, Yu-Lin; Jiang, Nan; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to evaluate altered spontaneous brain activities in patients with unilateral acute open globe injury (OGI) using amplitude of low-frequency fluctuation (ALFF) method and its relationship with their clinical manifestations. Patients and methods A total of 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs, 16 males and two females) closely matched in age, sex, and education were recruited in this study. The ALFF method was used to evaluate the altered spontaneous brain activities. The relationships between the mean ALFF signal values of different brain regions and the clinical features were evaluated by correlation analysis. Acute OGI patients were distinguished from HCs by receiver operating characteristic curve. Results Compared with HCs, acute OGI patients had significantly higher ALFF values in the left cuneus, left middle cingulum cortex, and bilateral precuneus. Furthermore, the age of OGI patients showed a negative correlation with the ALFF signal value of the left middle cingulum cortex (r=−0.557, P=0.016) and a negative correlation with the mean ALFF signal value of the bilateral precuneus (r=−0.746, P<0.001). The ALFF signal value of the bilateral precuneus was negatively correlated with the duration of OGI (r=−0.493, P=0.038) and positively correlated with the vision acuity of the injured eye (r=0.583, P=0.011). Conclusion Acute OGI mainly induces dysfunction in the left cuneus, left middle cingulum cortex, and bilateral precuneus, which may reflect the underlying pathologic mechanisms of abnormal brain activities in OGI patients. PMID:27570455

  4. Histone Deacetylases Exert Class-Specific Roles in Conditioning the Brain and Heart Against Acute Ischemic Injury

    PubMed Central

    Aune, Sverre E.; Herr, Daniel J.; Kutz, Craig J.; Menick, Donald R.

    2015-01-01

    Ischemia-reperfusion (IR) injury comprises a significant portion of morbidity and mortality from heart and brain diseases worldwide. This enduring clinical problem has inspired myriad reports in the scientific literature of experimental interventions seeking to elucidate the pathology of IR injury. Elective cardiac surgery presents perhaps the most viable scenario for protecting the heart and brain from IR injury due to the opportunity to condition the organs prior to insult. The physiological parameters for the preconditioning of vital organs prior to insult through mechanical and pharmacological maneuvers have been heavily examined. These investigations have revealed new insights into how preconditioning alters cellular responses to IR injury. However, the promise of preconditioning remains unfulfilled at the clinical level, and research seeking to implicate cell signals essential to this protection continues. Recent discoveries in molecular biology have revealed that gene expression can be controlled through posttranslational modifications, without altering the chemical structure of the genetic code. In this scenario, gene expression is repressed by enzymes that cause chromatin compaction through catalytic removal of acetyl moieties from lysine residues on histones. These enzymes, called histone deacetylases (HDACs), can be inhibited pharmacologically, leading to the de-repression of protective genes. The discovery that HDACs can also alter the function of non-histone proteins through posttranslational deacetylation has expanded the potential impact of HDAC inhibitors for the treatment of human disease. HDAC inhibitors have been applied in a very small number of experimental models of IR. However, the scientific literature contains an increasing number of reports demonstrating that HDACs converge on preconditioning signals in the cell. This review will describe the influence of HDACs on major preconditioning signaling pathways in the heart and brain. PMID

  5. Neurobiological consequences of traumatic brain injury

    PubMed Central

    McAllister, Thomas W.

    2011-01-01

    Traumatic brain injury (TBI) is a worldwide public health problem typically caused by contact and inertial forces acting on the brain. Recent attention has also focused on the mechanisms of injury associated with exposure to blast events or explosions. Advances in the understanding of the neuropathophysiology of TBI suggest that these forces initiate an elaborate and complex array of cellular and subcellular events related to alterations in Ca++ homeostasis and signaling. Furthermore, there is a fairly predictable profile of brain regions that are impacted by neurotrauma and the related events. This profile of brain damage accurately predicts the acute and chronic sequelae that TBI survivors suffer from, although there is enough variation to suggest that individual differences such as genetic polymorphisms and factors governing resiliency play a role in modulating outcome. This paper reviews our current understanding of the neuropathophysiology of TBI and how this relates to the common clinical presentation of neurobehavioral difficulties seen after an injury. PMID:22033563

  6. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  7. Acute kidney injury.

    PubMed

    Patschan, Daniel; Müller, Gerhard Anton

    2015-01-01

    Acute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives. PMID:25618438

  8. Acute kidney injury

    PubMed Central

    Müller, Gerhard Anton

    2015-01-01

    Abstract: Acute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives. PMID:25618438

  9. Traumatic brain injury

    PubMed Central

    Risdall, Jane E.; Menon, David K.

    2011-01-01

    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

  10. [Differential approach to the application of hyperventilation in acute period of severe brain injury in relation to cerebral circulation].

    PubMed

    Oshorov, A V; Kozlova, E A; Moldotashova, A K; Amcheslavskiĭ, V G; Potapov, A A

    2004-01-01

    Seventeen patients with severe brain injury (Glasgow-8 Coma Scale 3-8 scores) complicated by traumatic subarachnoidal hemorrhage and severe cerebral hemodynamic disorders (hyperemia, vasospasm) were examined. Hyperventilation was performed in different phases of cerebral circulation under multiparametrical monitoring (intracranial pressure, cerebral perfusion pressure, jugular oximetry, Doppler study using the carotid compression test). The use of hyperventilation to eliminate intracranial hypertension in victims with brain hyperemia was shown to make cerebral circulation consistent with brain tissue oxygen demands and to improve the autoregulatory reserve of cerebral vessels. The application of hyperventilation to eliminate intracranial hypertension in vasospasm leads to a temporary reduction in intracranial pressure, but simultaneously causes cerebral circulatory changes that do not correspond to cerebral oxygen demands, as well as lowered cerebral perfusion pressure, which increases a risk for ischemic brain tissue lesion. This requires a strict rationale for the use of hyperventilation and for multiparametrical monitoring of cerebral functions, which includes jugular oximetry, Doppler transcranial study, and measurement of intracranial pressure throughout the hyperventilation period in order to prevent secondary brain lesion. PMID:15326763

  11. A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury.

    PubMed

    Hausmann, R; Kaiser, A; Lang, C; Bohnert, M; Betz, P

    1999-01-01

    The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively. PMID:10433032

  12. Acute vertebrobasilar ischemic stroke due to electric injury.

    PubMed

    Singh Jain, Rajendra; Kumar, Sunil; Suresh, Desai Tushar; Agarwal, Rakesh

    2015-07-01

    Electrical injuries are most commonly due to household accidents.Various factors determine the severity of electric injury, including type of current, amperage, voltage, tissue resistance, pathway of current,and duration of contact with the body. Various types of neurologic damage due to electrical injury have been described in literature. It may manifest as peripheral nerve injury, spinal cord damage, seizures, cerebellarataxia, hypoxic encephalopathy, and intracerebral hemorrhage. Acute ischemic stroke is an infrequent complication of electrical injury. Herein,we report a case of middle-aged man, who accidentally sustained high voltage electrical injury followed by acute vertebrobasilar ischemic stroke. Magnetic resonance imaging of the brain showed acute infarctin bilateral cerebellar and medial occipital regions. Computed tomographic angiogram of the brain and neck vessels was normal. Possibly,in our patient, the mechanism could be related to direct vascular injury due to electric current. PMID:25684743

  13. Acute kidney injury in children.

    PubMed

    Merouani, A; Flechelles, O; Jouvet, P

    2012-04-01

    Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI. PMID:22495187

  14. Evaluation after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Trudel, Tina M.; Halper, James; Pines, Hayley; Cancro, Lorraine

    2010-01-01

    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…

  15. The Pediatric Test of Brain Injury: Development and Interpretation

    ERIC Educational Resources Information Center

    Hotz, Gillian A.; Helm-Estabrooks, Nancy; Nelson, Nickola Wolf; Plante, Elena

    2009-01-01

    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,…

  16. Clinical Outcomes after Traumatic Brain Injury.

    PubMed

    Sandsmark, Danielle K

    2016-06-01

    Traumatic brain injury (TBI) is a major cause of death and disability that often affects young people. After injury, the degree of recovery can be highly variable, with some people regaining near complete function while others remain severely disabled. Understanding what factors influence recovery is important for counseling patients and families in the acute period after injury and can help guide therapeutic decisions in the acute period following injury. In this review, prognostic algorithms useful for clinicians are discussed. Tools for grading patient outcomes, their role in clinical care and research studies, and their limitations are reviewed. Ongoing work focusing on the development of biomarkers to track TBI recovery and the refinement of clinical outcome metrics is summarized. PMID:27072952

  17. Brain Injury: A Manual For Educators.

    ERIC Educational Resources Information Center

    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…

  18. Controversies in preterm brain injury.

    PubMed

    Penn, Anna A; Gressens, Pierre; Fleiss, Bobbi; Back, Stephen A; Gallo, Vittorio

    2016-08-01

    In this review, we highlight critical unresolved questions in the etiology and mechanisms causing preterm brain injury. Involvement of neurons, glia, endogenous factors and exogenous exposures is considered. The structural and functional correlates of interrupted development and injury in the premature brain are under active investigation, with the hope that the cellular and molecular mechanisms underlying developmental abnormalities in the human preterm brain can be understood, prevented or repaired. PMID:26477300

  19. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

    Depending on severity, traumatic brain injury (TBI) induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1) the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2) how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3) how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury. PMID:23964217

  20. Molecular Mechanisms of Neonatal Brain Injury

    PubMed Central

    Thornton, Claire; Rousset, Catherine I.; Kichev, Anton; Miyakuni, Yasuka; Vontell, Regina; Baburamani, Ana A.; Fleiss, Bobbi; Gressens, Pierre; Hagberg, Henrik

    2012-01-01

    Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult. PMID:22363841

  1. Acute injuries in Taekwondo.

    PubMed

    Schlüter-Brust, K; Leistenschneider, P; Dargel, J; Springorum, H P; Eysel, P; Michael, J W-P

    2011-08-01

    Although Taekwondo is becoming an increasingly popular sport, there is a lack of reliable epidemiologic data on Taekwondo injuries. To perform an epidemiologic study on the variety of types of injury in professional and amateur Taekwondo athletes and to find a relation between Taekwondo style, skill level, weight-class and warm-up routine and the occurrence of injuries, we analysed the injury data using a 7-page questionnaire from a total of 356 Taekwondo athletes who were randomly selected. Overall, we registered a total of 2,164 injuries in 356 athletes. Most traumas were contusions and sprains in the lower extremities. Professional Taekwondo athletes have an increased risk of injury in comparison to recreational athletes. Taekwondo style, weight class and tournament frequency have an influence on the athlete's injury profile. Warm-up routines were found to have a positive effect on injury rates. Overall, Taekwondo may be considered a rather benign activity, if injuries during Taekwondo tournaments can be avoided. If not, Taekwondo can result in serious musculoskeletal problems. PMID:21563037

  2. Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain

    PubMed Central

    Semple, Bridgette D; Trivedi, Alpa; Gimlin, Kayleen; Noble-Haeusslein, Linda J

    2014-01-01

    While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12 h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further

  3. Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain.

    PubMed

    Semple, Bridgette D; Trivedi, Alpa; Gimlin, Kayleen; Noble-Haeusslein, Linda J

    2015-02-01

    While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further

  4. Subacute to chronic mild traumatic brain injury.

    PubMed

    Mott, Timothy F; McConnon, Michael L; Rieger, Brian P

    2012-12-01

    Although a universally accepted definition is lacking, mild traumatic brain injury and concussion are classified by transient loss of consciousness, amnesia, altered mental status, a Glasgow Coma Score of 13 to 15, and focal neurologic deficits following an acute closed head injury. Most patients recover quickly, with a predictable clinical course of recovery within the first one to two weeks following traumatic brain injury. Persistent physical, cognitive, or behavioral postconcussive symptoms may be noted in 5 to 20 percent of persons who have mild traumatic brain injury. Physical symptoms include headaches, dizziness, and nausea, and changes in coordination, balance, appetite, sleep, vision, and hearing. Cognitive and behavioral symptoms include fatigue, anxiety, depression, and irritability, and problems with memory, concentration and decision making. Women, older adults, less educated persons, and those with a previous mental health diagnosis are more likely to have persistent symptoms. The diagnostic workup for subacute to chronic mild traumatic brain injury focuses on the history and physical examination, with continuing observation for the development of red flags such as the progression of physical, cognitive, and behavioral symptoms, seizure, progressive vomiting, and altered mental status. Early patient and family education should include information on diagnosis and prognosis, symptoms, and further injury prevention. Symptom-specific treatment, gradual return to activity, and multidisciplinary coordination of care lead to the best outcomes. Psychiatric and medical comorbidities, psychosocial issues, and legal or compensatory incentives should be explored in patients resistant to treatment. PMID:23198672

  5. Combining Biochemical and Imaging Markers to Improve Diagnosis and Characterization of Mild Traumatic Brain Injury in the Acute Setting: Results from a Pilot Study

    PubMed Central

    Kou, Zhifeng; Gattu, Ramtilak; Kobeissy, Firas; Welch, Robert D.; O’Neil, Brian J.; Woodard, John L.; Ayaz, Syed Imran; Kulek, Andrew; Kas-Shamoun, Robert; Mika, Valerie; Zuk, Conor; Tomasello, Francesco; Mondello, Stefania

    2013-01-01

    Background Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury). Methods Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9±6.91 hours after injury. Patients’ neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument. Results The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients’ SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients’ DTI data nor SAC score. Conclusions Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury

  6. Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Kochanek, Patrick M; Bramlett, Helen M; Dixon, C Edward; Shear, Deborah A; Dietrich, W Dalton; Schmid, Kara E; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C

    2016-03-15

    Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan wars and the magnitude of its importance in the civilian setting is finally being recognized. Given the scope of the problem, new therapies are needed across the continuum of care. Few therapies have been shown to be successful. In severe TBI, current guidelines-based acute therapies are focused on the reduction of intracranial hypertension and optimization of cerebral perfusion. One factor considered important to the failure of drug development and translation in TBI relates to the recognition that TBI is extremely heterogeneous and presents with multiple phenotypes even within the category of severe injury. To address this possibility and attempt to bring the most promising therapies to clinical trials, we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug screening consortium for acute therapies in severe TBI. OBTT was developed to include a spectrum of established TBI models at experienced centers and assess the effect of promising therapies on both conventional outcomes and serum biomarker levels. In this review, we outline the approach to TBI modeling, evaluation of therapies, drug selection, and biomarker assessments for OBTT, and provide a framework for reports in this issue on the first five therapies evaluated by the consortium. PMID:26439468

  7. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  8. Sleep in traumatic brain injury.

    PubMed

    Vermaelen, James; Greiffenstein, Patrick; deBoisblanc, Bennett P

    2015-07-01

    More than one-half million patients are hospitalized annually for traumatic brain injury (TBI). One-quarter demonstrate sleep-disordered breathing, up to 50% experience insomnia, and half have hypersomnia. Sleep disturbances after TBI may result from injury to sleep-regulating brain tissue, nonspecific neurohormonal responses to systemic injury, ICU environmental interference, and medication side effects. A diagnosis of sleep disturbances requires a high index of suspicion and appropriate testing. Treatment starts with a focus on making the ICU environment conducive to normal sleep. Treating sleep-disordered breathing likely has outcome benefits in TBI. The use of sleep promoting sedative-hypnotics and anxiolytics should be judicious. PMID:26118920

  9. Traumatic Brain Injury Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen

    2010-01-01

    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…

  10. Evaluation of Autophagy Using Mouse Models of Brain Injury

    PubMed Central

    Au, Alicia K.; Bayir, Hülya; Kochanek, Patrick M.; Clark, Robert S. B.

    2009-01-01

    SUMMARY Autophagy is a homeostatic, carefully regulated, and dynamic process for intracellular recycling of bulk proteins, aging organelles, and lipids. Autophagy occurs in all tissues and cell types, including the brain and neurons. Alteration in the dynamics of autophagy has been observed in many diseases of the central nervous system. Disruption of autophagy for an extended period of time results in accumulation of unwanted proteins and neurodegeneration. However, the role of enhanced autophagy after acute brain injury remains undefined. Established mouse models of brain injury will be valuable in clarifying the role of autophagy after brain injury, and are the topic of discussion in this review. PMID:19879944

  11. Acute Shoulder Injuries in Adults.

    PubMed

    Monica, James; Vredenburgh, Zachary; Korsh, Jeremy; Gatt, Charles

    2016-07-15

    Acute shoulder injuries in adults are often initially managed by family physicians. Common acute shoulder injuries include acromioclavicular joint injuries, clavicle fractures, glenohumeral dislocations, proximal humerus fractures, and rotator cuff tears. Acromioclavicular joint injuries and clavicle fractures mostly occur in young adults as the result of a sports injury or direct trauma. Most nondisplaced or minimally displaced injuries can be treated conservatively. Treatment includes pain management, short-term use of a sling for comfort, and physical therapy as needed. Glenohumeral dislocations can result from contact sports, falls, bicycle accidents, and similar high-impact trauma. Patients will usually hold the affected arm in their contralateral hand and have pain with motion and decreased motion at the shoulder. Physical findings may include a palpable humeral head in the axilla or a dimple inferior to the acromion laterally. Reduction maneuvers usually require intra-articular lidocaine or intravenous analgesia. Proximal humerus fractures often occur in older patients after a low-energy fall. Radiography of the shoulder should include a true anteroposterior view of the glenoid, scapular Y view, and axillary view. Most of these fractures can be managed nonoperatively, using a sling, early range-of-motion exercises, and strength training. Rotator cuff tears can cause difficulty with overhead activities or pain that awakens the patient from sleep. On physical examination, patients may be unable to hold the affected arm in an elevated position. It is important to recognize the sometimes subtle signs and symptoms of acute shoulder injuries to ensure proper management and timely referral if necessary. PMID:27419328

  12. NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

    PubMed Central

    Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Bernabeu, Montserrat; Tormos, Jose M.; Pascual-Leone, Alvaro

    2012-01-01

    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

  13. Acute Kidney Injury in Cirrhosis.

    PubMed

    Karvellas, Constantine J; Durand, Francois; Nadim, Mitra K

    2015-10-01

    Acute kidney injury (AKI) is a frequent complication of end-stage liver disease, especially in those with acute-on-chronic liver failure, occurring in up to 50% of hospitalized patients with cirrhosis. There is no specific blood or urine biomarker that can reliably identify the cause of AKI in cirrhotic patients. This review examines studies used to assess renal dysfunction in cirrhotic patients including new diagnostic criteria and potential novel biomarkers. Although biomarker development to differentiate the cause of AKI in cirrhosis has promise, the utility of biomarkers to determine irreversible renal dysfunction with liver transplant remains lacking, warranting further investigation. PMID:26410141

  14. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    SciTech Connect

    Zgoda-Pols, Joanna R.; Chowdhury, Swapan; Wirth, Mark; Milburn, Michael V.; Alexander, Danny C.; Alton, Kevin B.

    2011-08-15

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research Highlights: > Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. > MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. > 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than creatinine

  15. Traumatic brain injury-induced sleep disorders.

    PubMed

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    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

  16. Traumatic brain injury-induced sleep disorders

    PubMed Central

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    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

  17. Antifibrinolytic drugs for acute traumatic injury.

    PubMed

    McCaul, Michael; Kredo, Tamara

    2016-08-01

    In South Africa, trauma is a major concern, with violence and road traffic accidents being the fifth and seventh leading causes of death, respectively. Antifibrinolytic agents have been used in trauma and major surgery to prevent fibrinolysis and reduce blood loss. We highlight an updated Cochrane review investigating the effect of antifibrinolytic drugs in patients with acute traumatic injury. The review authorsconducted comprehensive literature searches in January 2015 with regard to all randomised controlled trials comparing antifibrinolytic agents after acute traumatic injury. Three randomised controlled trials, of which two (n=20 451) assessed the effect of tranexamic acid (TXA), were included. The authors concluded that TXA safely reduces mortality in trauma with bleeding without increasing the risk ofadverse events. TXA should be administered as early as possible, and within 3 hours of injury. There is still uncertainty with regard to the effect of TXA on patients with traumatic brain injury; however, ongoing randomised controlled trials should shed more light on this. PMID:27499400

  18. Traumatic Brain Injury

    MedlinePlus

    ... a wide range of changes affecting thinking, sensation, language, or emotions. TBI can be associated with post-traumatic stress disorder. People with severe injuries usually need rehabilitation. NIH: National Institute of Neurological Disorders and Stroke

  19. Epigenetics in acute kidney injury

    PubMed Central

    Tang, Jinhua; Zhuang, Shougang

    2015-01-01

    Purpose of review Recent advances in epigenetics indicate the involvement of several epigenetic modifications in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to summarize our understanding of recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and microRNA expression in the pathological processes of AKI. Recent findings Enhancement of protein acetylation by pharmacological inhibition of histone deacetylases (HDACs) leads to more severe tubular injury and impairment of renal structural and functional recovery. The changes in promoter DNA methylation occur in the kidney with ischemia/reperfusion. microRNA expression is associated with regulation of both renal injury and regeneration after AKI. Summary Recent studies on epigenetic regulation indicate that acetylation, methylation, and microRNA expression are critically implicated in the pathogenesis of AKI. Strategies targeting epigenetic processes may hold a therapeutic potential for patients with AKI. PMID:26050122

  20. Bullet injuries of the brain

    PubMed Central

    Crockard, H Alan

    1974-01-01

    Experience gained with a wide variety of missile injuries of the brain is presented. Clinical signs and intracranial pressure (ICP) studied in the early post-injury period have been correlated with survival and treatment. Stress is laid on fluid requirements and the importance of controlled ventilation in the management of the labile clinical condition of such patients. Coughing and struggling caused extrusion of blood and brain from the wound, and this was reduced considerably with endotracheal intubation and mechanical ventilation. Post-operatively high ICP could be controlled in potential survivors with continued ventilation. ImagesFig. 1Fig. 2Fig. 5Fig. 7 PMID:4608115

  1. Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans.

    PubMed

    Johnson, Victoria E; Stewart, William; Trojanowski, John Q; Smith, Douglas H

    2011-12-01

    The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer's disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43) and phosphorylation-independent TDP-43 (pi-TDP-43), we examined acute (n = 23: Survival < 2 weeks) and long-term (n = 39; 1-47 years survival) survivors of a single TBI versus age-matched controls (n = 47). Multiple regions were examined including the hippocampus, medial temporal lobe, cingulate gyrus, superior frontal gyrus and brainstem. No association was found between a history of single TBI and abnormally phosphorylated TDP-43 (p-TDP-43) inclusions. Specifically, just 3 of 62 TBI cases displayed p-TDP-43 pathology versus 2 of 47 control cases. However, while aggregates of p-TDP-43 were not increased acutely or long-term following TBI, immunoreactivity to phosphorylation-independent TDP-43 was commonly increased in the cytoplasm following TBI with both acute and long-term survival. Moreover, while single TBI can induce multiple long-term neurodegenerative changes, the absence of TDP-43 proteinopathy may indicate a fundamental difference in the processes induced following single TBI from those of repetitive TBI. PMID:22101322

  2. A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury.

    PubMed

    Bragge, Peter; Synnot, Anneliese; Maas, Andrew I; Menon, David K; Cooper, D James; Rosenfeld, Jeffrey V; Gruen, Russell L

    2016-08-15

    Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n > 100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative

  3. Neurological consequences of traumatic brain injuries in sports.

    PubMed

    Ling, Helen; Hardy, John; Zetterberg, Henrik

    2015-05-01

    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

  4. Inflammatory neuroprotection following traumatic brain injury.

    PubMed

    Russo, Matthew V; McGavern, Dorian B

    2016-08-19

    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

  5. Traumatic Brain Injury: FDA Research and Actions

    MedlinePlus

    ... For Consumers Home For Consumers Consumer Updates Traumatic Brain Injury: FDA Research and Actions Share Tweet Linkedin ... top What to Do if You Suspect Traumatic Brain Injury Anyone with signs of moderate or severe ...

  6. Inductive and Deductive Approaches to Acute Cell Injury

    PubMed Central

    DeGracia, Donald J.; Tri Anggraini, Fika; Taha, Doaa Taha Metwally; Huang, Zhi-Feng

    2014-01-01

    Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems. PMID:27437490

  7. Pathophysiology of Acute Kidney Injury

    PubMed Central

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  8. Transcranial amelioration of inflammation and cell death after brain injury

    NASA Astrophysics Data System (ADS)

    Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

    2014-01-01

    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.

  9. Pathology of traumatic brain injury.

    PubMed

    Finnie, John W

    2014-12-01

    Although traumatic brain injury (TBI) is frequently encountered in veterinary practice in companion animals, livestock and horses, inflicted head injury is a common method of euthanasia in domestic livestock, and malicious head trauma can lead to forensic investigation, the pathology of TBI has generally received little attention in the veterinary literature. This review highlights the pathology and pathogenesis of cerebral lesions produced by blunt, non-missile and penetrating, missile head injuries as an aid to the more accurate diagnosis of neurotrauma cases. If more cases of TBI in animals that result in fatality or euthanasia are subjected to rigorous neuropathological examination, this will lead to a better understanding of the nature and development of brain lesions in these species, rather than extrapolating data from human studies. PMID:25178417

  10. Knowledge of Traumatic Brain Injury among Educators

    ERIC Educational Resources Information Center

    Ernst, William J.; Gallo, Adrienne B.; Sellers, Amanda L.; Mulrine, Jessica; MacNamara, Luciana; Abrahamson, Allison; Kneavel, Meredith

    2016-01-01

    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…

  11. Assessment of Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Chesire, David J.; Buckley, Valerie A.; Canto, Angela I.

    2011-01-01

    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…

  12. Biomarkers of Acute Kidney Injury

    PubMed Central

    Vaidya, Vishal S.; Ferguson, Michael A.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside. PMID:17937594

  13. Exenatide induced acute kidney injury.

    PubMed

    Aijazi, Ishma; Abdulla, Fadhil M; Zuberi, Beyla J; Elhassan, Ahmed

    2014-01-01

    Exenatide is an incretin mimetic. It was approved by the federal drug authority in 2005 for the treatment of type-2 diabetes. Since it is a relatively new medicine clinicians have limited experience with regards to its side effects and safety profile. We report a 47 year old lady who presented with exenatide associated acute kidney injury. She had type-2 diabetes for 10 years with mild micro albuminuria and normal renal functions. She was also taking a stable dose of metformin, gliclazide, angiotensin converting enzyme inhibitor and diuretic for over a year and there was no history of any recent use of non-steroid anti-inflammatory medications. One week after starting exenatide, she developed severe vomiting, followed by hypotension. She presented with acute renal insufficiency and severe lactic acidosis and had to be dialyzed on emergency basis. To our knowledge this is probably the first case reported in the local United Arab Emirate (U.A.E) population. PMID:25672206

  14. Preconditioning for traumatic brain injury

    PubMed Central

    Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    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

  15. Management of penetrating brain injury

    PubMed Central

    Kazim, Syed Faraz; Shamim, Muhammad Shahzad; Tahir, Muhammad Zubair; Enam, Syed Ather; Waheed, Shahan

    2011-01-01

    Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI patients. Cerebral angiography is recommended in patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI patients. PMID:21887033

  16. Neurostimulation for traumatic brain injury.

    PubMed

    Shin, Samuel S; Dixon, C Edward; Okonkwo, David O; Richardson, R Mark

    2014-11-01

    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. PMID:25170668

  17. Imaging assessment of traumatic brain injury.

    PubMed

    Currie, Stuart; Saleem, Nayyar; Straiton, John A; Macmullen-Price, Jeremy; Warren, Daniel J; Craven, Ian J

    2016-01-01

    Traumatic brain injury (TBI) constitutes injury that occurs to the brain as a result of trauma. It should be appreciated as a heterogeneous, dynamic pathophysiological process that starts from the moment of impact and continues over time with sequelae potentially seen many years after the initial event. Primary traumatic brain lesions that may occur at the moment of impact include contusions, haematomas, parenchymal fractures and diffuse axonal injury. The presence of extra-axial intracranial lesions such as epidural and subdural haematomas and subarachnoid haemorrhage must be anticipated as they may contribute greatly to secondary brain insult by provoking brain herniation syndromes, cranial nerve deficits, oedema and ischaemia and infarction. Imaging is fundamental to the management of patients with TBI. CT remains the imaging modality of choice for initial assessment due to its ease of access, rapid acquisition and for its sensitivity for detection of acute haemorrhagic lesions for surgical intervention. MRI is typically reserved for the detection of lesions that may explain clinical symptoms that remain unresolved despite initial CT. This is especially apparent in the setting of diffuse axonal injury, which is poorly discerned on CT. Use of particular MRI sequences may increase the sensitivity of detecting such lesions: diffusion-weighted imaging defining acute infarction, susceptibility-weighted imaging affording exquisite data on microhaemorrhage. Additional advanced MRI techniques such as diffusion tensor imaging and functional MRI may provide important information regarding coexistent structural and functional brain damage. Gaining robust prognostic information for patients following TBI remains a challenge. Advanced MRI sequences are showing potential for biomarkers of disease, but this largely remains at the research level. Various global collaborative research groups have been established in an effort to combine imaging data with clinical and

  18. Acute Kidney Injury is More Common in Acute Haemorrhagic Stroke in Mymensingh Medical College Hospital.

    PubMed

    Ray, N C; Chowdhury, M A; Sarkar, S R

    2016-01-01

    Acute kidney injury (AKI) is a common complication after acute stroke and is an independent predictor of both early and long-term mortality after acute stroke. Acute kidney injury is associated with increased mortality in haemorrhagic stroke patients. This cross sectional observational study was conducted in Nephrology, Neuromedicine and Medicine department of Mymensingh Medical College & Hospital, Mymensingh from July 2012 to June 2014. A total of 240 patients with newly detected acute stroke confirmed by CT scan of brain were included in this study. According to this study, 15.42% of acute stroke patients developed AKI. Among the patients with haemorrhagic stroke 21.87% developed AKI while only 13.07% patients with ischaemic stroke developed AKI. So, early diagnosis and management of AKI in patients with acute stroke especially in haemorrhagic stroke is very important to reduce the morbidity and mortality of these patients. PMID:26931240

  19. [Acute kidney injury in children].

    PubMed

    Amira-Peco-Antić; Paripović, Dusan

    2014-01-01

    Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients. PMID:25033598

  20. Midline (Central) Fluid Percussion Model of Traumatic Brain Injury.

    PubMed

    Rowe, Rachel K; Griffiths, Daniel R; Lifshitz, Jonathan

    2016-01-01

    Research models of traumatic brain injury (TBI) hold significant validity towards the human condition, with each model replicating a subset of clinical features and symptoms. After 30 years of characterization and implementation, fluid percussion injury (FPI) is firmly recognized as a clinically relevant model of TBI, encompassing concussion through severe injury. The midline variation of FPI may best represent mild and diffuse clinical brain injury, because of the acute behavioral deficits, the late onset of subtle behavioral morbidities, and the absence of gross histopathology. This chapter outlines the procedures for midline (diffuse) FPI in adult male rats and mice. With these procedures, it becomes possible to generate brain-injured laboratory animals for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented. PMID:27604721

  1. The cell cycle and acute kidney injury

    PubMed Central

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute kidney injury. PMID:19536080

  2. Effects of Neuroglobin Overexpression on Acute Brain Injury and Long-Term Outcomes After Focal Cerebral Ischemia

    PubMed Central

    Wang, Xiaoying; Liu, Jianxiang; Zhu, Haihao; Tejima, Emiri; Tsuji, Kiyoshi; Murata, Yoshihiro; Atochin, Dmitriy N.; Huang, Paul L.; Zhang, Chenggang; Lo, Eng H.

    2009-01-01

    Background and Purpose Emerging data suggest that neuroglobin (Ngb) may protect against hypoxic/ischemic neuronal insults. However, the underlying mechanisms in vivo and implications for long-term outcomes are still not well understood. Methods Using our newly created Ngb overexpressing transgenic (Ngb-Tg) mice, we measured brain infarction on day 1 and day 14 after transient focal cerebral ischemia and performed neurobehavioral assessments in sensorimotor deficits on days 1, 3, 7, and 14. To test the hypothesis that Ngb may play a role in reducing oxidative stress after stroke, intracellular malondialdehyde levels were measured and compared in Ngb-Tg and wild-type mice. Results Increased Ngb mRNA and protein levels were identified in Ngb-Tg brains. Malondialdehyde levels in ischemic hemispheres of Ngb-Tg were significantly reduced compared with wild-type controls at 8 hours and 22 hours after transient focal cerebral ischemia. Compared with wild-type controls, brain infarction volumes 1 day and 14 days after transient focal cerebral ischemia were significantly reduced in Ngb-Tg mice. However, there were no significant improvements in sensorimotor deficits for up to 14 days after stroke in Ngb-Tg mice compared with wild-type controls. Conclusions Ngb reduces tissue infarction and markers of oxidative stress after stroke. Tissue protection by overexpressing Ngb can be sustained for up to 2 weeks. PMID:18403737

  3. MG53 permeates through blood-brain barrier to protect ischemic brain injury

    PubMed Central

    Li, Haichang; Han, Yu; Chen, Ken; Wang, Zhen; Zeng, Jing; Liu, Yukai; Wang, Xinquan; Li, Yu; He, Duofen; Lin, Peihui; Zhou, Xinyu; Park, Ki Ho; Bian, Zehua; Chen, Zhishui; Gong, Nianqiao; Tan, Tao; Zhou, Jingsong; Zhang, Meng; Ma, Jianjie; Zeng, Chunyu

    2016-01-01

    Ischemic injury to neurons represents the underlying cause of stroke to the brain. Our previous studies identified MG53 as an essential component of the cell membrane repair machinery. Here we show that the recombinant human (rh)MG53 protein facilitates repair of ischemia-reperfusion (IR) injury to the brain. MG53 rapidly moves to acute injury sites on neuronal cells to form a membrane repair patch. IR-induced brain injury increases permeability of the blood-brain-barrier, providing access of MG53 from blood circulation to target the injured brain tissues. Exogenous rhMG53 protein can protect cultured neurons against hypoxia/reoxygenation-induced damages. Transgenic mice with increased levels of MG53 in the bloodstream are resistant to IR-induced brain injury. Intravenous administration of rhMG53, either prior to or after ischemia, can effectively alleviate brain injuries in rats. rhMG53-mediated neuroprotection involves suppression of apoptotic neuronal cell death, as well as activation of the pro-survival RISK signaling pathway. Our data indicate a physiological function for MG53 in the brain and suggest that targeting membrane repair or RISK signaling may be an effective means to treat ischemic brain injury. PMID:26967557

  4. Rock Climbing Injuries: Acute and Chronic Repetitive Trauma.

    PubMed

    Chang, Connie Y; Torriani, Martin; Huang, Ambrose J

    2016-01-01

    Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis. PMID:26360057

  5. TRAUMATIC BRAIN INJURY SURVEILLANCE SYSTEM (TBISS)

    EPA Science Inventory

    The National Center for Injury Prevention and Control (NCIPC), Centers for Disease Control and Prevention (CDC) had developed and maintains a surveillance system to understand the magnitude and characteristics of hospitalized and fatal traumatic brain injuries in the United State...

  6. Traumatic brain injury among Indiana state prisoners.

    PubMed

    Ray, Bradley; Sapp, Dona; Kincaid, Ashley

    2014-09-01

    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. PMID:24588316

  7. Nephrology Update: Acute Kidney Injury.

    PubMed

    Sarabu, Nagaraju; Rahman, Mahboob

    2016-05-01

    Acute kidney injury (AKI) refers to any acute decrease in glomerular filtration rate, regardless of etiology. Staging of AKI has been recommended to stratify AKI patients according to severity of the condition, based on serum creatinine level and urine output. Classification of AKI into prerenal, intrinsic renal, and postrenal etiologies is helpful in differential diagnosis and management. AKI in hospitalized patients typically occurs due to decreased renal perfusion. Drug-induced, contrast-associated, postoperative, and sepsis-associated AKI also can occur. Clinical assessment of a patient with AKI involves a medical record review, thorough history and physical examination, urinary and blood tests, renal imaging, and, in some instances, renal biopsy. Contrast-induced nephropathy is a common iatrogenic etiology of AKI associated with administration of intravenous iodinated contrast media. Measures to prevent AKI should be taken before administration of intravenous iodinated contrast. AKI can result in many short- and long-term complications, including chronic kidney disease and end-stage renal disease. Appropriate treatment of AKI patients involves management of the underlying etiology, when possible, and use of nondialytic and dialytic therapies. PMID:27163760

  8. How woodpecker avoids brain injury?

    NASA Astrophysics Data System (ADS)

    Wu, C. W.; Zhu, Z. D.; Zhang, W.

    2015-07-01

    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.

  9. Traumatic Brain Injury by a Closed Head Injury Device Induces Cerebral Blood Flow Changes and Microhemorrhages

    PubMed Central

    Kallakuri, Srinivasu; Bandaru, Sharath; Zakaria, Nisrine; Shen, Yimin; Kou, Zhifeng; Zhang, Liying; Haacke, Ewart Mark; Cavanaugh, John M

    2015-01-01

    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

  10. Targeting Iron Homeostasis in Acute Kidney Injury.

    PubMed

    Walker, Vyvyca J; Agarwal, Anupam

    2016-01-01

    Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron's ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

  11. Quality of Life Following Brain Injury: Perspectives from Brain Injury Association of America State Affiliates

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Tucker, Mark

    2012-01-01

    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:…

  12. Immediate neurological recovery following perispinal etanercept years after brain injury.

    PubMed

    Tobinick, Edward; Rodriguez-Romanacce, Helen; Levine, Arthur; Ignatowski, Tracey A; Spengler, Robert N

    2014-05-01

    Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this pathology through its modulation of microglial activation, role in synaptic dysfunction, and induction of depressive symptoms and neuropathic pain. Etanercept is a recombinant TNF receptor fusion protein and potent TNF inhibitor that has been found to reduce microglial activation and neuropathic pain in multiple experimental models. We report that a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury. These results indicate that acute brain injury-induced pathologic levels of TNF may provide a therapeutic target that can be addressed years after injury. Perispinal administration of etanercept is capable of producing immediate relief from brain injury-mediated neurological dysfunction. PMID:24647830

  13. Toll-Like Receptors and Ischemic Brain Injury

    PubMed Central

    Gesuete, Raffaella; Kohama, Steven G.; Stenzel-Poore, Mary

    2014-01-01

    Toll-like receptors (TLRs) are master regulators of innate immunity and play an integral role in the activation of the inflammatory response during infections. In addition, TLRs influence the body’s response to numerous forms of injury. Recent data have shown that TLRs play a modulating role in ischemic brain damage after stroke. Interestingly, their stimulation prior to ischemia induces a tolerant state that is neuroprotective. This phenomenon, referred to as TLR preconditioning, is the result of reprogramming of the TLR response to ischemic injury. This review addresses the role of TLRs in brain ischemia and the activation of endogenous neuroprotective pathways in the setting of preconditioning. We highlight the protective role of the interferon-related response and the potential site of action for TLR preconditioning involving the blood-brain-barrier. Pharmacological modulation of TLR activation to promote protection against stroke is a promising approach for the development of prophylactic and acute therapies targeting ischemic brain injury. PMID:24709682

  14. Neurorestoration after traumatic brain injury through angiotensin II receptor blockage.

    PubMed

    Villapol, Sonia; Balarezo, María G; Affram, Kwame; Saavedra, Juan M; Symes, Aviva J

    2015-11-01

    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

  15. Brain Imaging and Behavioral Outcome in Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Bigler, Erin D.

    1996-01-01

    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…

  16. ANTIOXIDANT THERAPIES FOR TRAUMATIC BRAIN INJURY

    PubMed Central

    Hall, Edward D.; Vaishnav, Radhika A.; Mustafa, Ayman G.

    2010-01-01

    Free radical-induced oxidative damage reactions, and membrane lipid peroxidation (LP) in particular, are one of the best validated secondary injury mechanisms in preclinical traumatic brain injury models. In addition to the disruption of the membrane phospholipid architecture, LP results in the formation of cytotoxic aldehyde-containing products that bind to cellular proteins and impair their normal functions. This article reviews the progress over the past three decades in regards to the preclinical discovery and attempted clinical development of antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic consequences via different mechanisms including the O2•- scavenger superoxide dismutase (SOD) and the lipid peroxidation inhibitor tirilazad. In addition, various other antioxidant agents that have been shown to have efficacy in preclinical TBI models are briefly presented such as the LP inhibitors U83836E, resveratrol, curcumin, OPC-14177 and lipoic acid; the iron chelator deferoxamine and the nitroxide-containing antioxidants such as α-phenyl-tert-butyl nitrone and tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed at the scavenging of aldehydic LP by-products that are highly neurotoxic with “carbonyl scavenging” compounds. Finally, it is proposed that the most effective approach to interrupt posttraumatic oxidative brain damage after TBI might involve the combined treatment with mechanistically-complementary antioxidants that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation and lastly remove neurotoxic LP byproducts. PMID:20129497

  17. Pathophysiology and Management of Moderate and Severe Traumatic Brain Injury in Children.

    PubMed

    Guilliams, Kristin; Wainwright, Mark S

    2016-01-01

    Traumatic brain injury remains a leading cause of morbidity and mortality in children. Key pathophysiologic processes of traumatic brain injury are initiated by mechanical forces at the time of trauma, followed by complex excitotoxic cascades associated with compromised cerebral autoregulation and progressive edema. Acute care focuses on avoiding secondary insults, including hypoxia, hypotension, and hyperthermia. Children with moderate or severe traumatic brain injury often require intensive monitoring and treatment of multiple parameters, including intracranial pressure, blood pressure, metabolism, and seizures, to minimize secondary brain injury. Child neurologists can play an important role in acute and long-term care. Acutely, as members of a multidisciplinary team in the intensive care unit, child neurologists monitor for early signs of neurological change, guide neuroprotective therapies, and transition patients to long-term recovery. In the longer term, neurologists are uniquely positioned to treat complications of moderate and severe traumatic brain injury, including epilepsy and cognitive and behavioral issues. PMID:25512361

  18. Behavioral Considerations Associated with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Mayfield, Joan; Homack, Susan

    2005-01-01

    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…

  19. Traumatic Brain Injury. Fact Sheet Number 18.

    ERIC Educational Resources Information Center

    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,…

  20. Resource Guide on Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Monfore, Dorothea

    2005-01-01

    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…

  1. Traumatic Brain Injury: A Challenge for Educators

    ERIC Educational Resources Information Center

    Bullock, Lyndal M.; Gable, Robert A.; Mohr, J. Darrell

    2005-01-01

    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…

  2. Support Network Responses to Acquired Brain Injury

    ERIC Educational Resources Information Center

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  3. Traumatic Brain Injury Models in Animals.

    PubMed

    Rostami, Elham

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults in industrialized nations and in the developing world the WHO considers TBI a silent epidemic caused by an increasing number of traffic accidents. Despite the major improvement of TBI outcome in the acute setting in the past 20 years, the assessment, therapeutic interventions, and prevention of long-term complications remain a challenge. In order to get a deeper insight into the pathology of TBI and advancement of medical understanding and clinical progress experimental animal models are an essential requirement. This chapter provides an overview of most commonly used experimental animal TBI models and the pathobiological findings based on current data. In addition, limitations and advantages of each TBI model are mentioned. This will hopefully give an insight into the possibilities of each model and be of value in choosing one when designing a study. PMID:27604712

  4. [Perioperative acute kidney injury and failure].

    PubMed

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance. PMID:24656890

  5. Management of acute spinal cord injury.

    PubMed

    Wagner, F C

    1977-06-01

    Based on the experience with 58 patients with acute spinal cord injuries, a system for rapidly evaluating such patients has been developed. With the knowledge that has been acquired clinically and experimentally of spinal cord injury and with the information provided by laminography and by either air or Pantopaque myelography, a reasonably certain diagnosis of the type of spinal cord injury may be made. Treatment designed to restore neurological function may then be instituted promptly. PMID:882906

  6. Radiation-induced brain injury: A review

    PubMed Central

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  7. Cyclosporine Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Dixon, C Edward; Bramlett, Helen M; Dietrich, W Dalton; Shear, Deborah A; Yan, Hong Q; Deng-Bryant, Ying; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Empey, Philip E; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Operation Brain Trauma Therapy (OBTT) is a consortium of investigators using multiple pre-clinical models of traumatic brain injury (TBI) to bring acute therapies to clinical trials. To screen therapies, we used three rat models (parasagittal fluid percussion injury [FPI], controlled cortical impact [CCI], and penetrating ballistic-like brain injury [PBBI]). We report results of the third therapy (cyclosporin-A; cyclosporine; [CsA]) tested by OBTT. At each site, rats were randomized to treatment with an identical regimen (TBI + vehicle, TBI + CsA [10 mg/kg], or TBI + CsA [20 mg/kg] given intravenously at 15 min and 24 h after injury, and sham). We assessed motor and Morris water maze (MWM) tasks over 3 weeks after TBI and lesion volume and hemispheric tissue loss at 21 days. In FPI, CsA (10 mg/kg) produced histological protection, but 20 mg/kg worsened working memory. In CCI, CsA (20 mg/kg) impaired MWM performance; surprisingly, neither dose showed benefit on any outcome. After PBBI, neither dose produced benefit on any outcome, and mortality was increased (20 mg/kg) partly caused by the solvent vehicle. In OBTT, CsA produced complex effects with histological protection at the lowest dose in the least severe model (FPI), but only deleterious effects as model severity increased (CCI and PBBI). Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No positive treatment effects were seen on biomarker levels in any of the models, whereas significant increases in 24 h UCH-L1 levels were seen with CsA (20 mg/kg) after CCI and 24 h GFAP levels in both CsA treated groups in the PBBI model. Lack of behavioral protection in any model, indicators of toxicity, and a narrow therapeutic index reduce enthusiasm for clinical translation. PMID:26671075

  8. Rehabilitation outcome after traumatic brain injury.

    PubMed

    Irdesel, J; Aydiner, S B; Akgoz, S

    2007-02-01

    Rehabilitation goals after traumatic brain injury are improving function, increasing the level of independence as high as possible, preventing complications and providing an acceptable environment to the patient. Several complications can be encountered during the rehabilitation period which lead to physical, cognitive and neurobehavioral impairments that cause major delay in functional improvement. This prospective study was designed in order to investigate the complications and their relations with functional recovery in patients that were included in the acute phase of a rehabilitation program. Thirty traumatic brain injured patients admitted to the Intensive Care Units of Uludag University School of Medicine were included in the study. Rehabilitation program consisted in appropriate positioning, range of motion exercises, postural drainage and respiratory exercises. Complications that were encountered during intensive care rehabilitation program were recorded. All patients were evaluated by Functional Independence Measure, Disability Rating Scale and Ranchos Los Amigos Levels of Cognitive Function Scale at admission and discharge. Improvement was observed in patients in terms of functional outcome and disability levels. Pneumonia, athelectasis, anemia and meningitis were the most frequent complications. Deterioration in functional outcome and disability levels was noted as the number of these complications increased. In conclusion, rehabilitation has an important role in the management of traumatic brain injured patients. Reduction of frequency of complications and improvement in functional outcome and disability levels can be achieved through rehabilitation programs. Long-term controlled studies with large number of patients are needed in order to obtain accurate data on factors associated with rehabilitation outcomes. PMID:17393041

  9. Robust whole-brain segmentation: application to traumatic brain injury.

    PubMed

    Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel

    2015-04-01

    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

  10. Brain contusion with aphasia following an ice hockey injury.

    PubMed

    Degen, Ryan M; Fink, Matthew E; Callahan, Lisa; Fibel, Kenton H; Ramsay, Jim; Kelly, Bryan T

    2016-09-01

    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. PMID:27074595

  11. Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

    PubMed

    Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

    2016-04-01

    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 adaptorSarm1(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 toSarm1(+/+)mice. Furthermore, mice lackingSarm1had 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 inSarm1(-/-)animals. Finally, usingin vivoproton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism inSarm1(-/-)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. PMID:26912636

  12. Acute forefoot and midfoot injuries.

    PubMed

    Laird, R Clinton

    2015-04-01

    Forefoot and midfoot injuries in the athlete are common. Injuries of the digits include subungual hematomas and fractures. Metatarsal fractures occur frequently in sports, and their treatments range greatly. Hyperflexion and extension injuries about the first metatarsophalangeal joint can be very debilitating. Midfoot sprains and fractures require a high index of suspicion for diagnosis. PMID:25804712

  13. Components of Traumatic Brain Injury Severity Indices

    PubMed Central

    Corrigan, John D.; Kreider, Scott; Cuthbert, Jeffrey; Whyte, John; Dams-O’Connor, Kristen; Faul, Mark; Harrison-Felix, Cynthia; Whiteneck, Gale; Pretz, Christopher R.

    2015-01-01

    The purpose of this study was to determine whether there are underlying dimensions common among traditional traumatic brain injury (TBI) severity indices and, if so, the extent to which they are interchangeable when predicting short-term outcomes. This study had an observational design, and took place in United States trauma centers reporting to the National Trauma Data Bank (NTDB). The sample consisted of 77,470 unweighted adult cases reported to the NTDB from 2007 to 2010, with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) TBI codes. There were no interventions. Severity indices used were the Emergency Department Glasgow Coma Scale (GCS) Total score and each of the subscales for eye opening (four levels), verbal response (five levels), and motor response (six levels); the worst Abbreviated Injury Scale (AIS) severity score for the head (six levels); and the worst Barell index type (three categories). Prediction models were computed for acute care length of stay (days), intensive care unit length of stay (days), hospital discharge status (alive or dead), and, if alive, discharge disposition (home versus institutional). Multiple correspondence analysis (MCA) indicated a two dimensional relationship among items of severity indexes. The primary dimension reflected overall injury severity. The second dimension seemed to capture volitional behavior without the capability for cogent responding. Together, they defined two vectors around which most of the items clustered. A scale that took advantage of the order of items along these vectors proved to be the most consistent index for predicting short-term health outcomes. MCA provided useful insight into the relationships among components of traditional TBI severity indices. The two vector pattern may reflect the impact of injury on different cortical and subcortical networks. Results are discussed in terms of score substitution and the ability to impute missing values. PMID

  14. Defining sleep disturbance after brain injury.

    PubMed

    Clinchot, D M; Bogner, J; Mysiw, W J; Fugate, L; Corrigan, J

    1998-01-01

    Sleep disorders are a relatively common occurrence after brain injury. Sleep disturbances often result in a poor daytime performance and a poor individual sense of well-being. Unfortunately, there has been minimal attention paid to this common and often disabling sequela of brain injury. This study attempts to define and to correlate the incidence and type of sleep disturbances that occur after brain injury. Consecutive admissions to a rehabilitation unit were used to create a longitudinal database designed to predict long-term outcomes for individuals who suffered a brain injury. Fifty percent of subjects had difficulty sleeping. Sixty-four percent described waking up too early, 25% described sleeping more than usual, and 45% described problems falling asleep. Eighty percent of subjects reporting sleep problems also reported problems with fatigue. Logistic regression analysis revealed the following: the more severe the brain injury the less likely the subject would be to have a sleep disturbance; subjects who had sleep disturbances were more likely to have problems with fatigue; females were more likely to have trouble with sleep. This study demonstrates the substantial prevalence of sleep disturbances after brain injury. It underscores the relationship between sleep disorders and perception of fatigue. It also underscores the need for clinicians to strive for interventional studies to look at the treatment of sleep and fatigue problems after brain injury. PMID:9715917

  15. Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

    PubMed Central

    Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

    2016-01-01

    Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID

  16. Animal models of acute lung injury

    PubMed Central

    Matute-Bello, Gustavo; Frevert, Charles W.; Martin, Thomas R.

    2008-01-01

    Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury. PMID:18621912

  17. Diabetes Insipidus after Traumatic Brain Injury

    PubMed Central

    Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki

    2015-01-01

    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

  18. Clinimetric measurement in traumatic brain injuries

    PubMed Central

    Opara, N; Małecka, I; Szczygiel, M

    2014-01-01

    Abstract Traumatic brain injury is a leading cause of death and disability worldwide. Every year, about 1.5 million affected people die and several millions receive emergency treatment. Most of the burden (90%) is in low and middle-income countries. The costs of care depend on the level of disability. The burden of care after traumatic brain injury is caused by disability as well as by psychosocial and emotional sequelae of injury. The final consequence of brain injury is the reduction of quality of life. It is very difficult to predict the outcome after traumatic brain injury. The basic clinical model included four predictors: age, score in Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. These are the neuroradiological markers of recovery after TBI (CT, MRI and PET) and biomarkers: genetic markers of ApoE Gene, ectoenzyme CD 38 (cluster of differentiation 38), serum S100B, myelin basic protein (MBP), neuron specific endolase (NSE), and glial fibrillary acidic protein (GPAP). These are many clinimetric scales which are helpful in prognosing after head injury. In this review paper, the most commonly used scales evaluating the level of consciousness after traumatic brain injury have been presented. PMID:25408714

  19. Mitochondrial specific therapeutic targets following brain injury.

    PubMed

    Yonutas, H M; Vekaria, H J; Sullivan, P G

    2016-06-01

    Traumatic brain injury is a complicated disease to treat due to the complex multi-factorial secondary injury cascade that is initiated following the initial impact. This secondary injury cascade causes nonmechanical tissue damage, which is where therapeutic interventions may be efficacious for intervention. One therapeutic target that has shown much promise following brain injury are mitochondria. Mitochondria are complex organelles found within the cell. At a superficial level, mitochondria are known to produce the energy substrate used within the cell called ATP. However, their importance to overall cellular homeostasis is even larger than their production of ATP. These organelles are necessary for calcium cycling, ROS production and play a role in the initiation of cell death pathways. When mitochondria become dysfunctional, they can become dysregulated leading to a loss of cellular homeostasis and eventual cell death. Within this review there will be a deep discussion into mitochondrial bioenergetics followed by a brief discussion into traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. The review will conclude with a discussion pertaining to the therapeutic approaches currently being studied to ameliorate mitochondrial dysfunction following brain injury. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26872596

  20. Staff-reported antecedents to aggression in a post-acute brain injury treatment programme: what are they and what implications do they have for treatment?

    PubMed

    Giles, Gordon Muir; Scott, Karen; Manchester, David

    2013-01-01

    Research in psychiatric settings has found that staff attribute the majority of in-patient aggression to immediate environmental stressors. We sought to determine if staff working with persons with brain injury-related severe and chronic impairment make similar causal attributions. If immediate environmental stressors precipitate the majority of aggressive incidents in this client group, it is possible an increased focus on the management of factors that initiate client aggression may be helpful. The research was conducted in a low-demand treatment programme for individuals with chronic cognitive impairment due to acquired brain injury. Over a six-week period, 63 staff and a research assistant reported on 508 aggressive incidents. Staff views as to the causes of client aggression were elicited within 72 hours of observing an aggressive incident. Staff descriptions of causes were categorised using qualitative methods and analysed both qualitatively and quantitatively. Aggression towards staff was predominantly preceded by (a) actions that interrupted or redirected a client behaviour, (b) an activity demand, or (c) a physical intrusion. The majority of aggressive incidents appeared hostile/angry in nature and were not considered by staff to be pre-meditated. Common treatment approaches can be usefully augmented by a renewed focus on interventions aimed at reducing antecedents that provoke aggression. Possible approaches for achieving this are considered. PMID:23782342

  1. Staff-reported antecedents to aggression in a post-acute brain injury treatment programme: What are they and what implications do they have for treatment?

    PubMed Central

    Giles, Gordon Muir; Scott, Karen; Manchester, David

    2013-01-01

    Research in psychiatric settings has found that staff attribute the majority of inpatient aggression to immediate environmental stressors. We sought to determine if staff working with persons with brain injury-related severe and chronic impairment make similar causal attributions. If immediate environmental stressors precipitate the majority of aggressive incidents in this client group, it is possible an increased focus on the management of factors that initiate client aggression may be helpful. The research was conducted in a low-demand treatment programme for individuals with chronic cognitive impairment due to acquired brain injury. Over a six-week period, 63 staff and a research assistant reported on 508 aggressive incidents. Staff views as to the causes of client aggression were elicited within 72 hours of observing an aggressive incident. Staff descriptions of causes were categorised using qualitative methods and analysed both qualitatively and quantitatively. Aggression towards staff was predominantly preceded by (a) actions that interrupted or redirected a client behaviour, (b) an activity demand, or (c) a physical intrusion. The majority of aggressive incidents appeared hostile/angry in nature and were not considered by staff to be pre-meditated. Common treatment approaches can be usefully augmented by a renewed focus on interventions aimed at reducing antecedents that provoke aggression. Possible approaches for achieving this are considered. PMID:23782342

  2. Alterations in brain protein kinase C after experimental brain injury.

    PubMed

    Padmaperuma, B; Mark, R; Dhillon, H S; Mattson, M P; Prasad, M R

    1996-04-01

    Regional activities and levels of protein kinase C were measured after lateral fluid percussion brain injury in rats. At 5 min and 20 min after injury, neither cofactor-dependent nor -independent PKC activities in the cytosol and membrane fractions changed in the injured and contralateral cortices or in the ipsilateral hippocampus. Western blot analysis revealed decreases in the levels of cytosolic PKC alpha and PKC beta in the injured cortex after brain injury. In the same site, a significant increase in the levels of membrane PKC alpha and PKC beta was observed after injury. Although the level of PKC alpha did not change and that of PKC beta decreased in the cytosol of the ipsilateral hippocampus, these levels did not increase in the membrane fraction after injury. The levels of PKC gamma were generally unchanged in the cytosol and the membrane, except for its decrease in the cytosol of the hippocampus. There were no changes in the levels of any PKC isoform in either the cytosol or the membrane of the contralateral cortex after injury. The present results suggest a translocation of PKC alpha and PKC beta from the cytosol to the membrane in the injured cortex after brain injury. The observation that such a translocation occurs only in the brain regions that undergo substantial neuronal loss suggests that membrane PKC may play a role in neuronal damage after brain injury. PMID:8861605

  3. [Treatment of delayed brain injury after pituitary irradiation].

    PubMed

    Fujii, T; Misumi, S; Shibasaki, T; Tamura, M; Kunimine, H; Hayakawa, K; Niibe, H; Miyazaki, M; Miyagi, O

    1988-03-01

    Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following: (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible "necrosis" occurs. (3) Steroids should be maintained for a long period over 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2453809

  4. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

    PubMed Central

    Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

    2015-01-01

    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

  5. Traumatic brain injury and forensic neuropsychology.

    PubMed

    Bigler, Erin D; Brooks, Michael

    2009-01-01

    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. PMID:19333063

  6. Acute kidney injury due to decompression illness.

    PubMed

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-08-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  7. Acute kidney injury due to decompression illness

    PubMed Central

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-01-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  8. Traumatic brain injury: pathophysiology for neurocritical care.

    PubMed

    Kinoshita, Kosaku

    2016-01-01

    Severe cases of traumatic brain injury (TBI) require neurocritical care, the goal being to stabilize hemodynamics and systemic oxygenation to prevent secondary brain injury. It is reported that approximately 45 % of dysoxygenation episodes during critical care have both extracranial and intracranial causes, such as intracranial hypertension and brain edema. For this reason, neurocritical care is incomplete if it only focuses on prevention of increased intracranial pressure (ICP) or decreased cerebral perfusion pressure (CPP). Arterial hypotension is a major risk factor for secondary brain injury, but hypertension with a loss of autoregulation response or excess hyperventilation to reduce ICP can also result in a critical condition in the brain and is associated with a poor outcome after TBI. Moreover, brain injury itself stimulates systemic inflammation, leading to increased permeability of the blood-brain barrier, exacerbated by secondary brain injury and resulting in increased ICP. Indeed, systemic inflammatory response syndrome after TBI reflects the extent of tissue damage at onset and predicts further tissue disruption, producing a worsening clinical condition and ultimately a poor outcome. Elevation of blood catecholamine levels after severe brain damage has been reported to contribute to the regulation of the cytokine network, but this phenomenon is a systemic protective response against systemic insults. Catecholamines are directly involved in the regulation of cytokines, and elevated levels appear to influence the immune system during stress. Medical complications are the leading cause of late morbidity and mortality in many types of brain damage. Neurocritical care after severe TBI has therefore been refined to focus not only on secondary brain injury but also on systemic organ damage after excitation of sympathetic nerves following a stress reaction. PMID:27123305

  9. PROGESTERONE EXERTS NEUROPROTECTIVE EFFECTS AFTER BRAIN INJURY

    PubMed Central

    Stein, Donald G.

    2009-01-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic brain injury and other neural disorders in humans. PMID:17826842

  10. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

    PubMed

    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

    2015-05-01

    Traumatic brain injury is a common and serious neurodegenerative condition that lacks a pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau is implicated in some of the consequences of traumatic brain injury and is a potential pharmacological target. Protein phosphatase 2A is a heterotrimeric protein that regulates key signalling pathways, and protein phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major tau phosphatase in the brain. Here we investigated whether traumatic brain injury in rats and humans would induce changes in protein phosphatase 2A and phosphorylated tau, and whether treatment with sodium selenate-a potent PR55 activator-would reduce phosphorylated tau and improve traumatic brain injury outcomes in rats. Ninety young adult male Long-Evans rats were administered either a fluid percussion injury or sham-injury. A proportion of rats were killed at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A and tau. Other rats were given either sodium selenate or saline-vehicle treatment that was continuously administered via subcutaneous osmotic pump for 12 weeks. Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12 weeks post-injury to assess evolving structural brain damage and axonal injury. Behavioural impairments were assessed at 12 weeks post-injury. The results showed that traumatic brain injury in rats acutely reduced PR55 expression and protein phosphatase 2A activity, and increased the expression of phosphorylated tau and the ratio of phosphorylated tau to total tau. Similar findings were seen in post-mortem brain samples from acute human traumatic brain injury patients, although many did not reach statistical significance. Continuous sodium selenate treatment for 12 weeks after sham or fluid percussion injury in rats increased protein phosphatase 2A activity and PR55 expression, and reduced the ratio of phosphorylated tau to total tau

  11. Microglia toxicity in preterm brain injury

    PubMed Central

    Baburamani, Ana A.; Supramaniam, Veena G.; Hagberg, Henrik; Mallard, Carina

    2014-01-01

    Microglia are the resident phagocytic cells of the central nervous system. During brain development they are also imperative for apoptosis of excessive neurons, synaptic pruning, phagocytosis of debris and maintaining brain homeostasis. Brain damage results in a fast and dynamic microglia reaction, which can influence the extent and distribution of subsequent neuronal dysfunction. As a consequence, microglia responses can promote tissue protection and repair following brain injury, or become detrimental for the tissue integrity and functionality. In this review, we will describe microglia responses in the human developing brain in association with injury, with particular focus on the preterm infant. We also explore microglia responses and mechanisms of microglia toxicity in animal models of preterm white matter injury and in vitro primary microglia cell culture experiments. PMID:24768662

  12. Weight Drop Models in Traumatic Brain Injury.

    PubMed

    Kalish, Brian T; Whalen, Michael J

    2016-01-01

    Weight drop models in rodents have been used for several decades to advance our understanding of the pathophysiology of traumatic brain injury. Weight drop models have been used to replicate focal cerebral contusion as well as diffuse brain injury characterized by axonal damage. More recently, closed head injury models with free head rotation have been developed to model sports concussions, which feature functional disturbances in the absence of overt brain damage assessed by conventional imaging techniques. Here, we describe the history of development of closed head injury models in the first part of the chapter. In the second part, we describe the development of our own weight drop closed head injury model that features impact plus rapid downward head rotation, no structural brain injury, and long-term cognitive deficits in the case of multiple injuries. This rodent model was developed to reproduce key aspects of sports concussion so that a mechanistic understanding of how long-term cognitive deficits might develop will eventually follow. Such knowledge is hoped to impact athletes and war fighters and others who suffer concussive head injuries by leading to targeted therapies aimed at preventing cognitive and other neurological sequelae in these high-risk groups. PMID:27604720

  13. Understanding Traumatic Brain Injury: An Introduction

    ERIC Educational Resources Information Center

    Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen

    2009-01-01

    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,…

  14. Traumatic Brain Injury: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

    Bartlett, Sue; Lorenz, Laura; Rankin, Theresa; Elias, Eileen; Weider, Katie

    2011-01-01

    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…

  15. Microglia in ischemic brain injury

    PubMed Central

    Weinstein, Jonathan R; Koerner, Ines P; Möller, Thomas

    2010-01-01

    Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity. PMID:20401171

  16. 'Hidden' Brain Injury a Challenge for Military Doctors

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_159316.html 'Hidden' Brain Injury a Challenge for Military Doctors Potentially fatal ... may suffer from a distinctive pattern of "hidden" brain injury, a small study finds. "Blast-related brain ...

  17. Blood-brain barrier in acute liver failure

    PubMed Central

    Nguyen, Justin H.

    2011-01-01

    Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF. PMID:22100566

  18. CAPing inflammation and acute kidney injury.

    PubMed

    Inoue, Tsuyoshi; Rosin, Diane L; Okusa, Mark D

    2016-09-01

    The cholinergic anti-inflammatory pathway has been shown to modulate inflammation in disease models such as rheumatoid arthritis and inflammatory bowel disease. A recent study demonstrated a protective effect of vagus nerve stimulation with activation of the cholinergic anti-inflammatory pathway in the ischemia reperfusion model of acute kidney injury. PMID:27521104

  19. Purines: forgotten mediators in traumatic brain injury.

    PubMed

    Jackson, Edwin K; Boison, Detlev; Schwarzschild, Michael A; Kochanek, Patrick M

    2016-04-01

    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. PMID:26809224

  20. Traumatic Brain Injury and Sleep Disorders

    PubMed Central

    Viola-Saltzman, Mari; Watson, Nathaniel F.

    2012-01-01

    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

  1. Mapping the Connectome Following Traumatic Brain Injury.

    PubMed

    Hannawi, Yousef; Stevens, Robert D

    2016-05-01

    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. PMID:27021773

  2. A SCUBA diver with acute kidney injury.

    PubMed

    Gleeson, Patrick James; Kelly, Yvelynne; Ni Sheaghdha, Eadaoin; Lappin, David

    2015-01-01

    An otherwise healthy young man was transferred to our hospital after a diving incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared well. No hypotensive episodes occurred during the transfer. He denied having arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory investigations revealed acutely elevated creatinine (170 µmol/L) and creatine kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism (AGE). We determined that our patient suffered acute kidney injury as a result of gas embolisation to his renal vasculature from an area of pulmonary barotrauma. Creatinine fell the following day in response to aggressive intravenous fluids. This is the first reported case of acute kidney injury secondary to AGE. Biochemical studies should be part of the routine assessment of patients involved in diving incidents. PMID:25948841

  3. Microglia: Dismantling and rebuilding circuits after acute neurological injury

    PubMed Central

    Ziebell, Jenna M.; Adelson, P. David; Lifshitz, Jonathan

    2014-01-01

    The brain is comprised of neurons and its support system including astrocytes, glial cells and microglia, thereby forming neurovascular units. Neurons require support from glial cells to establish and maintain functional circuits, but microglia are often overlooked. Microglia function as the immune cell of the central nervous system, acting to monitor the microenvironment for changes in signaling, pathogens and injury. More recently, other functional roles for microglia within the healthy brain have been identified, including regulating synapse formation, elimination and function. This review aims to highlight and discuss these alternate microglial roles in the healthy and in contrast, diseased brain with a focus on two acute neurological diseases, traumatic brain injury and epilepsy. In these conditions, microglial roles in synaptic stripping and stabilization as part of neuronal:glial interactions may position them as mediators of the transition between injury-induced circuit dismantling and subsequent reorganization. Increased understanding of microglia roles could identify therapeutic targets to mitigate the consequences of neurological disease. PMID:24733573

  4. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

    PubMed

    Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K

    2005-01-01

    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

  5. Low level laser therapy for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wu, Qiuhe; Huang, Ying-Ying; Dhital, Saphala; Sharma, Sulbha K.; Chen, Aaron C.-H.; Whalen, Michael J.; Hamblin, Michael R.

    2010-02-01

    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.

  6. Galveston Brain Injury Conference 2010: clinical and experimental aspects of blast injury.

    PubMed

    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

    2012-08-10

    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. PMID:22655746

  7. Adenosine Neuromodulation and Traumatic Brain Injury

    PubMed Central

    Lusardi, T.A

    2009-01-01

    Adenosine is a ubiquitous signaling molecule, with widespread activity across all organ systems. There is evidence that adenosine regulation is a significant factor in traumatic brain injury (TBI) onset, recovery, and outcome, and a growing body of experimental work examining the therapeutic potential of adenosine neuromodulation in the treatment of TBI. In the central nervous system (CNS), adenosine (dys)regulation has been demonstrated following TBI, and correlated to several TBI pathologies, including impaired cerebral hemodynamics, anaerobic metabolism, and inflammation. In addition to acute pathologies, adenosine function has been implicated in TBI comorbidities, such as cognitive deficits, psychiatric function, and post-traumatic epilepsy. This review presents studies in TBI as well as adenosine-related mechanisms in co-morbidities of and unfavorable outcomes resulting from TBI. While the exact role of the adenosine system following TBI remains unclear, there is increasing evidence that a thorough understanding of adenosine signaling will be critical to the development of diagnostic and therapeutic tools for the treatment of TBI. PMID:20190964

  8. Catecholamines and cognition after traumatic brain injury.

    PubMed

    Jenkins, Peter O; Mehta, Mitul A; Sharp, David J

    2016-09-01

    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

  9. Catecholamines and cognition after traumatic brain injury

    PubMed Central

    Jenkins, Peter O.; Mehta, Mitul A.

    2016-01-01

    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

  10. Driving, brain injury and assistive technology.

    PubMed

    Lane, Amy K; Benoit, Dana

    2011-01-01

    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. PMID:21558628

  11. Students with Traumatic Brain Injury: Making the Transition from Hospital to School.

    ERIC Educational Resources Information Center

    Mira, Mary P.; Tyler, Janet Siantz

    1991-01-01

    This paper uses a case study of a 16-year-old girl with traumatic brain injury (TBI) to present information on the demographics of head injury, neuropathology, recovery patterns, acute rehabilitation, educationally significant effects, behavioral sequelae, the school as a vehicle for rehabilitation, a transition model, school reentry, and…

  12. Acute kidney injury: current concepts and new insights

    PubMed Central

    Koza, Yavuzer

    2016-01-01

    Abstract: Background: Acute kidney injury, which was previously named as acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria and the acute kidney injury network (AKIN) criteria, which have previously been defined. However the clinical utility of these criteria is still uncertain. Several biomarkers such as Cystatin C and neutrophil gelatinase-associated lipocalin have been suggested for the diagnosis, severity classification and most importantly, the modification of outcome in acute kidney injury. Methods: Current literature on the definition, biomarkers, management and epidemiology of acute kidney injury was reviewed by searching keywords in Medline and PubMed databases. Results: The epidemiology, pathophysiology and diagnosis of acute kidney injury were discussed. The clinical implications of novel biomarkers and management of acute kidney injury were also discussed. Conclusions: The current definitions of acute kidney injury are based on the RIFLE, AKIN and KDIGO criteria. Although these criteria have been widely validated, some of limitations are still remain. Since acute kidney injury is common and harmful, all preventive measures should be taken to avoid its occurrence. Currently, there is no a definitive role for novel biomarkers. PMID:26804946

  13. Minocycline Attenuates Iron-Induced Brain Injury.

    PubMed

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism. PMID:26463975

  14. Stillbirth: Correlations Between Brain Injury and Placental Pathology.

    PubMed

    Ernst, Linda M; Bit-Ivan, Esther N; Miller, Emily S; Minturn, Lucy; Bigio, Eileen H; Weese-Mayer, Debra E

    2016-01-01

    Chronic placental pathologic processes such as fetal thrombotic vasculopathy have been linked to brain injury in neonates. We hypothesize that using stillbirth as a model, placental pathology can predict risk for hypoxic-ischemic brain injury. From a single institutional database of stillbirths ≥23 weeks' gestational age, we included cases with full autopsy and neuropathology examination. Bivariable analyses were performed to identify whether there was an association between placental pathologic findings and neuropathologic findings. Logistic regression was used to control for potential confounders. Among 97 potential cases, adequate tissue was analyzable from 79 cases (mean gestational age  =  33 weeks). Acute central nervous system hemorrhage and acute neuronal necrosis were the most common neuropathologic processes seen in this cohort (57% for each). Maternal vascular underperfusion was the most common placental pathology but was not significantly associated with a specific neuropathologic finding. High-grade chronic villitis (HGCV) and fetal thrombotic vasculopathy (FTV) were significantly associated with increased risk for pontosubicular necrosis (odds ratios, 15.73 and 3.79, respectively). These associations persisted after controlling for potential confounders. Chronic placental pathologies, specifically HGCV and FTV, were associated with pontosubicular necrosis, suggesting that placental pathology involving the fetal vasculature and altered fetoplacental blood flow carry the greatest likelihood of hypoxic/ischemic brain injury. PMID:26492345

  15. Acute Kidney Injury in the Surgical Patient.

    PubMed

    Hobson, Charles; Singhania, Girish; Bihorac, Azra

    2015-10-01

    Perioperative acute kidney injury (AKI) is a common, morbid, and costly surgical complication. Current efforts to understand and manage AKI in surgical patients focus on prevention, mitigation of further injury when AKI has occurred, treatment of associated conditions, and facilitation of renal recovery. Lesser severity AKI is now understood to be much more common, and more morbid, than was previously thought. The ability to detect AKI within hours of onset would be helpful in protecting the kidney and in preserving renal function, and several imaging and biomarker modalities are currently being evaluated. PMID:26410139

  16. Epidemiology of traumatic brain injuries: Indian scenario.

    PubMed

    Gururaj, G

    2002-01-01

    Traumatic brain injuries (TBIs) are a leading cause of morbidity, mortality, disability and socioeconomic losses in India and other developing countries. Specific topics addressed in this paper include magnitude of the problem, causes, context of injury occurrence, risk factors, severity, outcome and impact of TBIs on rapidly transforming societies. It is estimated that nearly 1.5 to 2 million persons are injured and 1 million succumb to death every year in India. Road traffic injuries are the leading cause (60%) of TBIs followed by falls (20%-25%) and violence (10%). Alcohol involvement is known to be present among 15%-20% of TBIs at the time of injury. The rehabilitation needs of brain injured persons are significantly high and increasing from year to year. India and other developing countries face the major challenges of prevention, pre-hospital care and rehabilitation in their rapidly changing environments to reduce the burden of TBIs. PMID:11783750

  17. Traumatic Brain Injury and Dystonia

    MedlinePlus

    ... various neurological symptoms, often including dystonia and other movement disorders. Symptoms • Symptoms of a TBI can be mild, ... following an injury. Symptoms of dystonia and other movement disorders may be delayed by several months or years ...

  18. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

    Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J

    2016-01-01

    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. PMID:27604726

  19. Managing traumatic brain injury secondary to explosions

    PubMed Central

    Burgess, Paula; E Sullivent, Ernest; M Sasser, Scott; M Wald, Marlena; Ossmann, Eric; Kapil, Vikas

    2010-01-01

    Explosions and bombings are the most common deliberate cause of disasters with large numbers of casualties. Despite this fact, disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks with biological, chemical, and nuclear agents. The following article is a clinical primer for physicians regarding traumatic brain injury (TBI) caused by explosions and bombings. The history, physics, and treatment of TBI are outlined. PMID:20606794

  20. Severe Traumatic Brain Injury: A Case Report

    PubMed Central

    Nelson, Clinton G.; Elta, Tara; Bannister, Jeanette; Dzandu, James; Mangram, Alicia; Zach, Victor

    2016-01-01

    Patient: Male, 28 Final Diagnosis: Closed head injury Symptoms: Bilateral mydriasis • coma Medication: — Clinical Procedure: Ventriculostomy and hemicraniectomy Specialty: Neurology Objective: Unusual clinical course Background: Traumatic brain injury remains a challenging and complicated disease process to care for, despite the advance of technology used to monitor and guide treatment. Currently, the mainstay of treatment is aimed at limiting secondary brain injury, with the help of multiple specialties in a critical care setting. Prognosis after TBI is often even more challenging than the treatment itself, although there are various exam and imaging findings that are associated with poor outcome. These findings are important because they can be used to guide families and loved ones when making decisions about goals of care. Case Report: In this case report, we demonstrate the unanticipated recovery of a 28-year-old male patient who presented with a severe traumatic brain injury after being in a motorcycle accident without wearing a helmet. He presented with several exam and imaging findings that are statistically associated with increased mortality and morbidity. Conclusions: The care of severe traumatic brain injuries is challenging and dynamic. This case highlights the unexpected recovery of a patient and serves as a reminder that there is variability among patients. PMID:27005826

  1. Paclitaxel improves outcome from traumatic brain injury

    PubMed Central

    Cross, Donna J.; Garwin, Gregory G.; Cline, Marcella M.; Richards, Todd L.; Yarnykh, Vasily; Mourad, Pierre D.; Ho, Rodney J.Y.; Minoshima, Satoshi

    2016-01-01

    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

  2. First aid for acute sports injuries.

    PubMed

    Bull, R C

    1987-09-01

    This article deals with management of acute sports injuries on the field or on the ice and in the dressing room or in the arena's first-aid room. Its most vital message is "Be prepared". A team approach and suitable ambulance and hospital back-up are mandatory. Individual management of a specific acute injury should be approached with a practice plan. Collars, splints, back board, doctor's bag, ambu bag, suture tray and emergency medications should be at hand. Care must be taken that no long-term harm befalls the player. The attending physician must be knowledgeable about preventive equipment and immediate institution of rehabilitation procedures, and must try to inform the coach or trainer and parent as to when the athlete can safely return to play. It is important that the athlete not return to play until he/she is 100% fit. PMID:21263977

  3. Sodium hypochlorite-induced acute kidney injury.

    PubMed

    Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul

    2014-03-01

    Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis. PMID:24626008

  4. Neuroimaging in Pediatric Traumatic Brain Injury: Current and Future Predictors of Functional Outcome

    ERIC Educational Resources Information Center

    Suskauer, Stacy J.; Huisman, Thierry A. G. M.

    2009-01-01

    Although neuroimaging has long played a role in the acute management of pediatric traumatic brain injury (TBI), until recently, its use as a tool for understanding and predicting long-term brain-behavior relationships after TBI has been limited by the relatively poor sensitivity of routine clinical imaging for detecting diffuse axonal injury…

  5. Ischaemic Markers in Acute Hepatic Injury

    PubMed Central

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  6. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  7. Neuropsychiatry of Pediatric Traumatic Brain Injury

    PubMed Central

    Max, Jeffrey E.

    2014-01-01

    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

  8. Biomarkers in traumatic brain injury: a review.

    PubMed

    Toman, Emma; Harrisson, S; Belli, T

    2016-04-01

    Biomarkers allow physiological processes to be monitored, in both health and injury. Multiple attempts have been made to use biomarkers in traumatic brain injury (TBI). Identification of such biomarkers could allow improved understanding of the pathological processes involved in TBI, diagnosis, prognostication and development of novel therapies. This review article aims to cover both established and emerging TBI biomarkers along with their benefits and limitations. It then discusses the potential value of TBI biomarkers to military, civilian and sporting populations and the future hopes for developing a role for biomarkers in head injury management. PMID:26527607

  9. Antioxidant therapies in traumatic brain and spinal cord injury*

    PubMed Central

    Bains, Mona; Hall, Edward D.

    2011-01-01

    Free radical formation and oxidative damage have been extensively investigated and validated as important contributors to the pathophysiology of acute central nervous system injury. The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following injury occurring within minutes of mechanical impact. A key component in this event is peroxynitrite-induced lipid peroxidation. As discussed in this review, peroxynitrite formation and lipid peroxidation irreversibly damages neuronal membrane lipids and protein function, which results in subsequent disruptions in ion homeostasis, glutamate-mediated excitotoxicity, mitochondrial respiratory failure and microvascular damage. Antioxidant approaches include the inhibition and/or scavenging of superoxide, peroxynitrite, or carbonyl compounds, the inhibition of lipid peroxidation and the targeting of the endogenous antioxidant defense system. This review covers the preclinical and clinical literature supporting the role of ROS and RNS and their derived oxygen free radicals in the secondary injury response following acute traumatic brain injury (TBI) and spinal cord injury (SCI) and reviews the past and current trends in the development of antioxidant therapeutic strategies. Combinatorial treatment with the suggested mechanistically complementary antioxidants will also be discussed as a promising neuroprotective approach in TBI and SCI therapeutic research. This article is part of a Special Issue entitled: Antioxidants and antioxidant treatment in disease. PMID:22080976

  10. Normobaric oxygen worsens outcome after a moderate traumatic brain injury.

    PubMed

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-07-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI. PMID:25690469

  11. Normobaric oxygen worsens outcome after a moderate traumatic brain injury

    PubMed Central

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-01-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n=8) or normal air (n=8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI. PMID:25690469

  12. Modulation of acute lung injury by integrins.

    PubMed

    Sheppard, Dean

    2012-07-01

    Acute lung injury is a common disorder with a high mortality rate, but previous efforts to develop drugs to treat this disorder have been unsuccessful. In an effort to develop more effective treatments, we have been studying the molecular pathways that regulate the dysfunction of alveolar epithelial cells and endothelial cells that serve as a final common pathway leading to alveolar flooding. Using integrin subunit knockout mice and antibodies we developed by immunizing these mice, we have found important and distinct roles for the αvβ6 integrin on epithelial cells and the αvβ5 integrin on endothelial cells in mediating increases in alveolar permeability in multiple models of acute lung injury. We have also found therapeutic effects of αvβ5 inhibition in two models of septic shock even when the antibody was administered to animals that were obviously ill. These results identify αvβ6 and αvβ5 as promising therapeutic targets for the treatment of acute lung injury and septic shock. PMID:22802286

  13. Acute kidney injury due to rhabdomyolysis.

    PubMed

    Lima, Rafael Siqueira Athayde; da Silva Junior, Geraldo Bezerra; Liborio, Alexandre Braga; Daher, Elizabeth De Francesco

    2008-09-01

    Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal muscle cells disrupt and release creatine phosphokinase (CK), lactate dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The main causes of rhabdomyolysis include direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50% of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal injury are renal vasoconstriction, intraluminal cast formation, and direct myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome with AKI and high mortality. Serum CK five times higher than the normal value usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may reduce the risk of AKI. Further studies are necessary to establish the importance of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis. PMID:18711286

  14. Money, Language Barriers Can Affect Kids' Brain Injury Care

    MedlinePlus

    ... 159124.html Money, Language Barriers Can Affect Kids' Brain Injury Care Those on Medicaid have less access ... May 31, 2016 (HealthDay News) -- Children with traumatic brain injuries may be less likely to receive rehabilitation ...

  15. Kids' Mild Brain Injury Can Have Long-Term Effects

    MedlinePlus

    ... medlineplus.gov/news/fullstory_160606.html Kids' Mild Brain Injury Can Have Long-Term Effects Early head ... 000 Swedes who suffered at least one traumatic brain injury (TBI) before age 25 with their unaffected ...

  16. Mechanisms and Potential Therapeutic Applications of Microglial Activation after Brain Injury

    PubMed Central

    Kim, Jong Youl; Kim, Nuri; Yenari, Midori A.

    2014-01-01

    As the resident immune cells of the central nervous system, microglia rapidly respond to brain insults, including stroke and traumatic brain injury. Microglial activation plays a major role in neuronal cell damage and death by releasing a variety of inflammatory and neurotoxic mediators. Their activation is an early response that may exacerbate brain injury and many other stressors, especially in the acute stages, but are also essential to brain recovery and repair. The full range of microglial activities is still not completely understood, but there is accumulating knowledge about their role following brain injury. We review recent progress related to the deleterious and beneficial effects of microglia in the setting of acute neurological insults, and the current literature surrounding pharmacological interventions for intervention. PMID:25475659

  17. Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury.

    PubMed

    Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent

    2012-09-01

    Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. PMID:25624828

  18. Traumatic Brain Injury: Empirical Family Assessment Techniques.

    ERIC Educational Resources Information Center

    Bishop, Duane S.; Miller, Ivan W.

    1988-01-01

    Methods are described for quantifying and formalizing assessment of traumatic brain injury patient families. The advantages and disadvantages of empirical and clinical assessment are outlined, and four family assessment methods are reviewed: self-report, interview, observation, and laboratory. Specific assessment instruments are noted along with…

  19. Academic Placement after Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Donders, Jacques

    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…

  20. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

    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.…

  1. Traumatic Brain Injury and Vocational Rehabilitation.

    ERIC Educational Resources Information Center

    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…

  2. School Reentry Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Deidrick, Kathleen K. M.; Farmer, Janet E.

    2005-01-01

    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…

  3. Reality Lessons in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Adams, Elaine Parker; Adams, Albert A., Jr.

    2008-01-01

    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…

  4. Traumatic Brain Injury: Perspectives from Educational Professionals

    ERIC Educational Resources Information Center

    Mohr, J. Darrell; Bullock, Lyndal M.

    2005-01-01

    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…

  5. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    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…

  6. Psychiatric disorders and traumatic brain injury

    PubMed Central

    Schwarzbold, Marcelo; Diaz, Alexandre; Martins, Evandro Tostes; Rufino, Armanda; Amante, Lúcia Nazareth; Thais, Maria Emília; Quevedo, João; Hohl, Alexandre; Linhares, Marcelo Neves; Walz, Roger

    2008-01-01

    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

  7. Defense and Veterans Brain Injury Center

    MedlinePlus

    ... Are you or a loved one in a crisis and need help? Call the Military Crisis Line at 800-273-8255, press 1 to ... blog articles » Defense and Veterans Brain Injury Center Crisis Intervention (24/7) Department of Veterans Affairs Military & ...

  8. Mild Traumatic Brain Injury: Facilitating School Success.

    ERIC Educational Resources Information Center

    Hux, Karen; Hacksley, Carolyn

    1996-01-01

    A case study is used to demonstrate the effects of mild traumatic brain injury on educational efforts. Discussion covers factors complicating school reintegration, ways to facilitate school reintegration, identification of cognitive and behavioral consequences, minimization of educators' discomfort, reintegration program design, and family…

  9. Narrative Language in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio

    2011-01-01

    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…

  10. Working with Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

    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…

  11. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  12. Discriminating military and civilian traumatic brain injuries.

    PubMed

    Reid, Matthew W; Velez, Carmen S

    2015-05-01

    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'. PMID:25827093

  13. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

    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

  14. Traumatic Brain Injury as a Cause of Behavior Disorders.

    ERIC Educational Resources Information Center

    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.,…

  15. The Impact of Traumatic Brain Injury on the Aging Brain.

    PubMed

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident. PMID:27432348

  16. Contrasting Acute and Slow-Growing Lesions: A New Door to Brain Plasticity

    ERIC Educational Resources Information Center

    Desmurget, Michel; Bonnetblanc, FranCois; Duffau, Hugues

    2007-01-01

    The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated "eloquent" areas and (ii) that…

  17. Epidemiology of Overuse and Acute Injuries Among Competitive Collegiate Athletes

    PubMed Central

    Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin

    2012-01-01

    Context: Although overuse injuries are gaining attention, epidemiologic studies on overuse injuries in male and female collegiate athletes are lacking. (70.7%) acute injuries were reported. The overall injury rate was Objective: To report the epidemiology of overuse injuries sustained by collegiate athletes and to compare the rates of overuse and acute injuries. Design: Descriptive epidemiology study. Setting: A National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 1317 reported injuries sustained by 573 male and female athletes in 16 collegiate sports teams during the 2005–2008 seasons. Main Outcome Measure(s): The injury and athlete-exposure (AE) data were obtained from the Sports Injury Monitoring System. An injury was coded as either overuse or acute based on the nature of injury. Injury rate was calculated as the total number of overuse (or acute) injuries during the study period divided by the total number of AEs during the same period. Results: A total of 386 (29.3%) overuse injuries and 931 63.1 per 10000 AEs. The rate ratio (RR) of acute versus overuse injuries was 2.34 (95% confidence interval [CI] = 2.05, 2.67). Football had the highest RR (RR = 8.35, 95% CI = 5.38, 12.97), and women's rowing had the lowest (RR = 0.75, 95% CI = 0.51, 1.10). Men had a higher acute injury rate than women (49.8 versus 38.6 per 10000 AEs). Female athletes had a higher rate of overuse injury than male athletes (24.6 versus 13.2 per 10000 AEs). More than half of the overuse injuries (50.8%) resulted in no time loss from sport. Conclusions: Additional studies are needed to examine why female athletes are at greater risk for overuse injuries and identify the best practices for prevention and rehabilitation of overuse injuries. PMID:22488286

  18. Chronic cerebrovascular dysfunction after traumatic brain injury.

    PubMed

    Jullienne, Amandine; Obenaus, Andre; Ichkova, Aleksandra; Savona-Baron, Catherine; Pearce, William J; Badaut, Jerome

    2016-07-01

    Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc. PMID:27117494

  19. Extracellular N-Acetylaspartate in Human Traumatic Brain Injury

    PubMed Central

    Shannon, Richard J.; Carter, Eleanor L.; Jalloh, Ibrahim; Menon, David K.; Hutchinson, Peter J.; Carpenter, Keri L.H.

    2016-01-01

    Abstract 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. PMID:26159566

  20. Forensic Pathology of Traumatic Brain Injury.

    PubMed

    Finnie, J W

    2016-09-01

    Traumatic brain injury constitutes a significant proportion of cases requiring forensic examination, and it encompasses (1) blunt, nonmissile head injury, especially involving motor vehicle accidents, and (2) penetrating, missile injury produced by a range of high- and lower-velocity projectiles. This review examines the complex pathophysiology and biomechanics of both types of neurotrauma and assesses the macroscopic and histologic features of component lesions, which may be used to determine the cause and manner of death resulting from an intentional assault or accident. Estimation of the survival time postinjury by pathologic examination is also important where malicious head injury is suspected, in an attempt to ascertain a time at which the traumatic event might have been committed, thereby evaluating the authenticity of statements made by the alleged perpetrator. PMID:26578643

  1. Simvastatin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Mountney, Andrea; Bramlett, Helen M; Dixon, C Edward; Mondello, Stefania; Dietrich, W Dalton; Wang, Kevin K W; Caudle, Krista; Empey, Philip E; Poloyac, Samuel M; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M; Shear, Deborah A

    2016-03-15

    Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post-TBI using the oral route of administration and, as such, it will not be further pursued by OBTT. PMID:26541177

  2. Inflammatory sequences in acute pulmonary radiation injury.

    PubMed Central

    Slauson, D. O.; Hahn, F. F.; Benjamin, S. A.; Chiffelle, T. L.; Jones, R. K.

    1976-01-01

    The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1258976

  3. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

    Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

    2015-01-01

    Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

  4. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  5. Recovery of resting brain connectivity ensuing mild traumatic brain injury

    PubMed Central

    Bharath, Rose D.; Munivenkatappa, Ashok; Gohel, Suril; Panda, Rajanikant; Saini, Jitender; Rajeswaran, Jamuna; Shukla, Dhaval; Bhagavatula, Indira D.; Biswal, Bharat B.

    2015-01-01

    Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function. PMID:26441610

  6. Temporal assessment of nanoparticle accumulation after experimental brain injury: Effect of particle size

    PubMed Central

    Bharadwaj, Vimala N.; Lifshitz, Jonathan; Adelson, P. David; Kodibagkar, Vikram D.; Stabenfeldt, Sarah E.

    2016-01-01

    Nanoparticle (NP) based therapeutic and theranostic agents have been developed for various diseases, yet application to neural disease/injury is restricted by the blood-brain-barrier (BBB). Traumatic brain injury (TBI) results in a host of pathological alterations, including transient breakdown of the BBB, thus opening a window for NP delivery to the injured brain tissue. This study focused on investigating the spatiotemporal accumulation of different sized NPs after TBI. Specifically, animal cohorts sustaining a controlled cortical impact injury received an intravenous injection of PEGylated NP cocktail (20, 40, 100, and 500 nm, each with a unique fluorophore) immediately (0 h), 2 h, 5 h, 12 h, or 23 h after injury. NPs were allowed to circulate for 1 h before perfusion and brain harvest. Confocal microscopy demonstrated peak NP accumulation within the injury penumbra 1 h post-injury. An inverse relationship was found between NP size and their continued accumulation within the penumbra. NP accumulation preferentially occurred in the primary motor and somatosensory areas of the injury penumbra as compared to the parietal association and visual area. Thus, we characterized the accumulation of particles up to 500 nm at different times acutely after injury, indicating the potential of NP-based TBI theranostics in the acute period after injury. PMID:27444615

  7. Temporal assessment of nanoparticle accumulation after experimental brain injury: Effect of particle size.

    PubMed

    Bharadwaj, Vimala N; Lifshitz, Jonathan; Adelson, P David; Kodibagkar, Vikram D; Stabenfeldt, Sarah E

    2016-01-01

    Nanoparticle (NP) based therapeutic and theranostic agents have been developed for various diseases, yet application to neural disease/injury is restricted by the blood-brain-barrier (BBB). Traumatic brain injury (TBI) results in a host of pathological alterations, including transient breakdown of the BBB, thus opening a window for NP delivery to the injured brain tissue. This study focused on investigating the spatiotemporal accumulation of different sized NPs after TBI. Specifically, animal cohorts sustaining a controlled cortical impact injury received an intravenous injection of PEGylated NP cocktail (20, 40, 100, and 500 nm, each with a unique fluorophore) immediately (0 h), 2 h, 5 h, 12 h, or 23 h after injury. NPs were allowed to circulate for 1 h before perfusion and brain harvest. Confocal microscopy demonstrated peak NP accumulation within the injury penumbra 1 h post-injury. An inverse relationship was found between NP size and their continued accumulation within the penumbra. NP accumulation preferentially occurred in the primary motor and somatosensory areas of the injury penumbra as compared to the parietal association and visual area. Thus, we characterized the accumulation of particles up to 500 nm at different times acutely after injury, indicating the potential of NP-based TBI theranostics in the acute period after injury. PMID:27444615

  8. Neuropathology of explosive blast traumatic brain injury.

    PubMed

    Magnuson, John; Leonessa, Fabio; Ling, Geoffrey S F

    2012-10-01

    During the conflicts of the Global War on Terror, which are Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF), there have been over a quarter of a million diagnosed cases of traumatic brain injury (TBI). The vast majority are due to explosive blast. Although explosive blast TBI (bTBI) shares many clinical features with closed head TBI (cTBI) and penetrating TBI (pTBI), it has unique features, such as early cerebral edema and prolonged cerebral vasospasm. Evolving work suggests that diffuse axonal injury (DAI) seen following explosive blast exposure is different than DAI from focal impact injury. These unique features support the notion that bTBI is a separate and distinct form of TBI. This review summarizes the current state of knowledge pertaining to bTBI. Areas of discussion are: the physics of explosive blast generation, blast wave interaction with the bony calvarium and brain tissue, gross tissue pathophysiology, regional brain injury, and cellular and molecular mechanisms of explosive blast neurotrauma. PMID:22836523

  9. Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up

    PubMed Central

    Cho, Young-Eun; Latour, Lawrence L.; Kim, Hyungsuk; Turtzo, L. Christine; Olivera, Anlys; Livingston, Whitney S.; Wang, Dan; Martin, Christiana; Lai, Chen; Cashion, Ann; Gill, Jessica

    2016-01-01

    Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging. PMID

  10. Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up.

    PubMed

    Cho, Young-Eun; Latour, Lawrence L; Kim, Hyungsuk; Turtzo, L Christine; Olivera, Anlys; Livingston, Whitney S; Wang, Dan; Martin, Christiana; Lai, Chen; Cashion, Ann; Gill, Jessica

    2016-01-01

    Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging. PMID

  11. Cognitive and psychopathological sequelae of pediatric traumatic brain injury.

    PubMed

    Beauchamp, M H; Anderson, V

    2013-01-01

    Childhood traumatic brain injury (TBI) is a frequent cause of acquired disability in childhood and can have a serious impact on development across the lifespan. The consequences of early TBI vary according to injury severity, with severe injuries usually resulting in more serious physical, cognitive and behavioral sequelae. Both clinical and research reports document residual deficits in a range of skills, including intellectual function, attention, memory, learning, and executive function. In addition, recent investigations suggest that early brain injury also affects psychological and social development and that problems in these domains may increase in the long term postinjury. Together, these deficits affect children's ability to function effectively at school, in the home, and in their social environment, resulting in impaired acquisition of knowledge, psychological and social problems, and overall reduced quality of life. Ultimately, recovery from childhood TBI depends on a range of complex biological, developmental, and psychosocial factors making prognosis difficult to predict. This chapter will detail the cognitive (intellectual, attentional, mnesic, executive, educational, and vocational) and psychopathological (behavioral, adaptive, psychological, social) sequelae of childhood TBI with a particular focus on postinjury recovery patterns in the acute, short-, and long-term phases, as well as into adulthood. PMID:23622301

  12. Screening for Traumatic Brain Injury: Findings and Public Health Implications

    PubMed Central

    Dams-O’Connor, Kristen; Cantor, Joshua B.; Brown, Margaret; Dijkers, Marcel P.; Spielman, Lisa A.; Gordon, Wayne A.

    2016-01-01

    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

  13. A Novel Mouse Model of Penetrating Brain Injury

    PubMed Central

    Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

    2014-01-01

    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

  14. Respiratory mechanics in brain injury: A review.

    PubMed

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-02-01

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients. PMID:26855895

  15. Respiratory mechanics in brain injury: A review

    PubMed Central

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-01-01

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients. PMID:26855895

  16. Acute kidney injury in patients with acute coronary syndromes.

    PubMed

    Marenzi, Giancarlo; Cosentino, Nicola; Bartorelli, Antonio L

    2015-11-01

    Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACSs). This condition has a complex pathogenesis, an incidence that can reach 30% and it is associated with higher short-term and long-term morbidity and mortality. Nevertheless, AKI is still characterised by lack of a single accepted definition, unclear pathophysiology understanding and insensitive diagnostic tools that make its detection difficult, particularly in the setting of ACS. Recent data suggested that patients with AKI during ACS, even those in whom renal function seems to fully recover, face an increased, persisting risk of future AKI and may develop chronic kidney disease. Thus, in these patients, nephrology follow-up, after hospital discharge, and secondary preventive measures should possibly be implemented. In this review, we aim at providing a framework of knowledge to increase cardiologists' awareness of AKI, with the goal of improving the outcome of patients with ACS. PMID:26243789

  17. Diffuse traumatic brain injury induces prolonged immune dysregulation and potentiates hyperalgesia following a peripheral immune challenge

    PubMed Central

    Rowe, Rachel K; Ellis, Gavin I; Harrison, Jordan L; Bachstetter, Adam D; Corder, Gregory F; Van Eldik, Linda J; Taylor, Bradley K; Marti, Francesc

    2016-01-01

    Background Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. Results To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1–9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). Conclusions We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are

  18. Acute kidney injury: A rare cause.

    PubMed

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  19. Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury

    PubMed Central

    Bao, Hai-jun; Qiu, Hai-yang; Kuai, Jin-xia; Song, Cheng-jie; Wang, Shao-xian; Wang, Chao-qun; Peng, Hua-bin; Han, Wen-can; Wu, Yong-ping

    2016-01-01

    The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

  20. Low Level Primary Blast Injury in Rodent Brain

    PubMed Central

    Pun, Pamela B. L.; Kan, Enci Mary; Salim, Agus; Li, Zhaohui; Ng, Kian Chye; Moochhala, Shabbir M.; Ling, Eng-Ang; Tan, Mui Hong; Lu, Jia

    2011-01-01

    The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure (BOP) exposure of either 48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross histopathology of the brains showed that cortical neurons were “darkened” and shrunken with narrowed vasculature in the cerebral cortex day 1 after blast with signs of recovery at day 4 and day 7 after blast. TUNEL-positive cells were predominant in the white matter of the brain at day 1 after blast and double-labeling of brain tissue showed that these DNA-damaged cells were both oligodendrocytes and astrocytes but were mainly not apoptotic due to the low caspase-3 immunopositivity. There was also an increase in amyloid precursor protein immunoreactive cells in the white matter which suggests acute axonal damage. In contrast, Iba-1 staining for macrophages or microglia was not different from control post-blast. Blast exposure altered the expression of over 5786 genes in the brain which occurred mostly at day 1 and day 4 post-blast. These genes were narrowed down to 10 overlapping genes after time-course evaluation and functional analyses. These genes pointed toward signs of repair at day 4 and day 7 post-blast. Our findings suggest that the BOP levels in the study resulted in mild cellular injury to the brain as evidenced by acute neuronal, cerebrovascular, and white matter perturbations that showed signs of resolution. It is unclear whether these perturbations exist at a milder level or normalize completely and will need more investigation. Specific changes in gene expression may be further evaluated to understand the mechanism of blast-induced neurotrauma. PMID

  1. Nicotinamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Shear, Deborah A; Dixon, C Edward; Bramlett, Helen M; Mondello, Stefania; Dietrich, W Dalton; Deng-Bryant, Ying; Schmid, Kara E; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Kochanek, Patrick M; Tortella, Frank C

    2016-03-15

    Nicotinamide (vitamin B3) was the first drug selected for cross-model testing by the Operation Brain Trauma Therapy (OBTT) consortium based on a compelling record of positive results in pre-clinical models of traumatic brain injury (TBI). Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Nicotinamide (50 or 500 mg/kg) was delivered intravenously at 15 min and 24 h after injury with subsequent behavioral, biomarker, and histopathological outcome assessments. There was an intermediate effect on balance beam performance with the high (500 mg/kg) dose in the CCI model, but no significant therapeutic benefit was detected on any other motor task across the OBTT TBI models. There was an intermediate benefit on working memory with the high dose in the FPI model. A negative effect of the low (50 mg/kg) dose, however, was observed on cognitive outcome in the CCI model, and no cognitive improvement was observed in the PBBI model. Lesion volume analysis showed no treatment effects after either FPI or PBBI, but the high dose of nicotinamide resulted in significant tissue sparing in the CCI model. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-1 (UCH-L1) in blood at 4 or 24 h after injury. Negative effects (both doses) were detected on biomarker levels of GFAP after FPI and on biomarker levels of UCH-L1 after PBBI. The high dose of nicotinamide, however, reduced GFAP levels after both PBBI and CCI. Overall, our results showed a surprising lack of benefit from the low dose nicotinamide. In contrast, and partly in keeping with the literature, some benefit was achieved with the high dose. The marginal benefits achieved with nicotinamide, however, which appeared sporadically across the TBI models, has reduced enthusiasm for further investigation by the OBTT Consortium

  2. Clinical Scenarios in Acute Kidney Injury: Parenchymal Acute Kidney Injury-Tubulo-Interstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria; Ronco, Claudio

    2016-01-01

    Acute tubular necrosis (ATN) is the most common type of acute kidney injury (AKI) related to parenchymal damage (90% of cases). It may be due to a direct kidney injury, such as sepsis, drugs, toxins, contrast media, hemoglobinuria and myoglobinuria, or it may be the consequence of a prolonged systemic ischemic injury. Conventional ultrasound (US) shows enlarged kidneys with hypoechoic pyramids. Increased volume is largely sustained by the increase of anteroposterior diameter, while longitudinal axis usually maintains its normal length. Despite the role of color Doppler in AKI still being debated, many studies demonstrate that renal resistive indexes (RIs) vary on the basis of primary disease. Moreover, several studies assessed that higher RI values are predictive of persistent AKI. Nevertheless, due to the marked heterogeneity among the studies, further investigations focused on timing of RI measurement and test performances are needed. Acute interstitial nephritis is also a frequent cause of AKI, mainly due to non-steroidal anti-inflammatory drugs and antibiotics administration. The development of acute interstitial nephritis is due to an immunological reaction against nephritogenic exogenous antigens, processed by tubular cells. In acute interstitial nephritis, as well as in ATN, conventional US does not allow a definitive diagnosis. Kidneys appear enlarged and widely hyperechoic due to interstitial edema and inflammatory infiltration. Also, in this condition, hemodynamic changes are closely correlated to the severity and the progression of the anatomical damage. PMID:27169885

  3. Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

    PubMed Central

    Stemper, Brian D.; Shah, Alok S.; Budde, Matthew D.; Olsen, Christopher M.; Glavaski-Joksimovic, Aleksandra; Kurpad, Shekar N.; McCrea, Michael; Pintar, Frank A.

    2016-01-01

    Mild traumatic brain injury (mTBI) can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW) Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements. PMID:27014184

  4. The Role of Markers of Inflammation in Traumatic Brain Injury

    PubMed Central

    Woodcock, Thomas; Morganti-Kossmann, Maria Cristina

    2013-01-01

    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

  5. Diagnosing pseudobulbar affect in traumatic brain injury

    PubMed Central

    Engelman, William; Hammond, Flora M; Malec, James F

    2014-01-01

    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

  6. Mild Traumatic Brain Injury in Translation

    PubMed Central

    Robertson, Claudia S.

    2013-01-01

    Abstract This Introduction to a Special Issue on Mild Traumatic Brain Injury (mTBI) highlights the methodological challenges in outcome studies and clinical trials involving patients who sustain mTBI. Recent advances in brain imaging and portable, computerized cognitive tasks have contributed to protocols that are sensitive to the effects of mTBI and efficient in time for completion. Investigation of civilian mTBI has been extended to single and repeated injuries in athletes and blast-related mTBI in service members and veterans. Despite differences in mechanism of injury, there is evidence for similar effects of acceleration-deceleration and blast mechanisms of mTBI on cognition. Investigation of repetitive mTBI suggests that the effects may be cumulative and that repeated mTBI and repeated subconcussive head trauma may lead to neurodegenerative conditions. Although animal models of mTBI using cortical impact and fluid percussion injury in rodents have been able to reproduce some of the cognitive deficits frequently exhibited by patients after mTBI, modeling post-concussion symptoms is difficult. Recent use of closed head and blast injury animal models may more closely approximate clinical mTBI. Translation of interventions that are developed in animal models to patients with mTBI is a priority for the research agenda. This Special Issue on mTBI integrates basic neuroscience studies using animal models with studies of human mTBI, including the cognitive sequelae, persisting symptoms, brain imaging, and host factors that facilitate recovery. PMID:23046349

  7. Acute complications of spinal cord injuries.

    PubMed

    Hagen, Ellen Merete

    2015-01-18

    The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation. PMID:25621207

  8. Human models of acute lung injury

    PubMed Central

    Proudfoot, Alastair G.; McAuley, Danny F.; Griffiths, Mark J. D.; Hind, Matthew

    2011-01-01

    Acute lung injury (ALI) is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome. PMID:21357760

  9. Acute complications of spinal cord injuries

    PubMed Central

    Hagen, Ellen Merete

    2015-01-01

    The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation. PMID:25621207

  10. Mild traumatic brain injury in a gymnast.

    PubMed

    Knight, Debra; Dewitt, Rachel; Moser, Sharon

    2016-07-01

    Primary care providers often are responsible for the initial evaluation and management plan of young patients with mild traumatic brain injury (mild TBI, also called concussion), and need to be familiar with new protocols and how to incorporate them into a patient's treatment plan. This article describes a patient who suffered a mild TBI and returned to sports too early, and discusses the appropriate protocols for managing concussion in children. PMID:27351644

  11. Psychotic disorder caused by traumatic brain injury.

    PubMed

    Fujii, Daryl E; Ahmed, Iqbal

    2014-03-01

    Psychosis is a rare and severe sequela of traumatic brain injury (TBI). This article assists clinicians in differential diagnosis by providing literature-based guidance with regard to use of the Diagnostic and Statistical Manual for Mental Disorders 5 criteria for this condition. This article also describes potential relationships between TBI and the development of a psychosis within the conceptualization of psychosis as a neurobehavioral syndrome. PMID:24529427

  12. Emerging Therapies in Traumatic Brain Injury

    PubMed Central

    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

    2015-01-01

    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

  13. Traumatic brain injury in modern war

    NASA Astrophysics Data System (ADS)

    Ling, Geoffrey S. F.; Hawley, Jason; Grimes, Jamie; Macedonia, Christian; Hancock, James; Jaffee, Michael; Dombroski, Todd; Ecklund, James M.

    2013-05-01

    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 [1] and mild TBI/concussion [2] 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.

  14. Cerebral Lactate Metabolism After Traumatic Brain Injury.

    PubMed

    Patet, Camille; Suys, Tamarah; Carteron, Laurent; Oddo, Mauro

    2016-04-01

    Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome. PMID:26898683

  15. Substance P Mediates Reduced Pneumonia Rates After Traumatic Brain Injury

    PubMed Central

    Yang, Sung; Stepien, David; Hanseman, Dennis; Robinson, Bryce; Goodman, Michael D.; Pritts, Timothy A.; Caldwell, Charles C.; Remick, Daniel G.; Lentsch, Alex B.

    2014-01-01

    Objectives Traumatic brain injury results in significant morbidity and mortality and is associated with infectious complications, particularly pneumonia. However, whether traumatic brain injury directly impacts the host response to pneumonia is unknown. The objective of this study was to determine the nature of the relationship between traumatic brain injury and the prevalence of pneumonia in trauma patients and investigate the mechanism of this relationship using a murine model of traumatic brain injury with pneumonia. Design Data from the National Trauma Data Bank and a murine model of traumatic brain injury with postinjury pneumonia. Setting Academic medical centers in Cincinnati, OH, and Boston, MA. Patients/Subjects Trauma patients in the National Trauma Data Bank with a hospital length of stay greater than 2 days, age of at least 18 years at admission, and a blunt mechanism of injury. Subjects were female ICR mice 8–10 weeks old. Interventions Administration of a substance P receptor antagonist in mice. Measurements and Main Results Pneumonia rates were measured in trauma patients before and after risk adjustment using propensity scoring. In addition, survival and pulmonary inflammation were measured in mice undergoing traumatic brain injury with or without pneumonia. After risk adjustment, we found that traumatic brain injury patients had significantly lower rates of pneumonia compared to blunt trauma patients without traumatic brain injury. A murine model of traumatic brain injury reproduced these clinical findings with mice subjected to traumatic brain injury demonstrating increased bacterial clearance and survival after induction of pneumonia. To determine the mechanisms responsible for this improvement, the substance P receptor was blocked in mice after traumatic brain injury. This treatment abrogated the traumatic brain injury–associated increases in bacterial clearance and survival. Conclusions The data demonstrate that patients with traumatic

  16. Acute Kidney Injury Subsequent to Cardiac Surgery

    PubMed Central

    Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.

    2015-01-01

    Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  17. Acute Kidney Injury Subsequent to Cardiac Surgery.

    PubMed

    Kramer, Robert S; Herron, Crystal R; Groom, Robert C; Brown, Jeremiah R

    2015-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor shortand long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  18. [Intensive care of traumatic brain injury in children].

    PubMed

    Kizilov, A V; Babaev, B D; Malov, A G; Ermolaev, V V; Mikhaĭlov, E V; Ostreĭkov, I F

    2011-01-01

    Traumatic brain injury among other injuries of human body reaches up to 30-50% and, according to the WHO, it grows by 2%. Severe traumatic brain injury (such as severe brain contusion, epidural, subdural and intracerebral hematoma, intracerebral hygroma, diffuse axonal injury) in the structure of general trauma amounts 4-20%. The prognosis of traumatic brain injury mainly depends on the timeliness of the first aid. The therapeutic measures usually begin at the place of the accident or in the ambulance vehicle (hence the clear role of the specialist team). It is advised for children with severe traumatic brain injury to be directed to specialized neurosurgical or trauma hospitals, where it is possible to provide them with adequate medical care. This work is dedicated to the enhancement of the intensive care quality during severe traumatic brain injury in children of Chuvash Republic, by the means of integrated patient assessment. PMID:21513069

  19. Controlled Cortical Impact Traumatic Brain Injury in 3xTg-AD Mice Causes Acute Intra-axonal Amyloid-beta Accumulation and Independently Accelerates the Development of Tau Abnormalities

    PubMed Central

    Tran, Hien T; LaFerla, Frank M.; Holtzman, David M.; Brody, David L.

    2011-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in approximately 30% of human subjects following severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between Aβ and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Aβ accumulations and increased phospho-tau immunoreactivity at 24 hours and up to 7 days post TBI. Given these findings, we investigated the relationship between Aβ and tau pathologies following trauma in this model by systemic treatment of Compound E to inhibit γ-secrectase activity, a proteolytic process required for Aβ production. Compound E treatment successfully blocked post-traumatic Aβ accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies, and suggest that TBI may independently affect Aβ and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies. PMID:21715616

  20. Traumatic Brain Injury: A Guidebook for Idaho Educators.

    ERIC Educational Resources Information Center

    Carter, Susanne

    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…

  1. [Pre-hospital care management of acute spinal cord injury].

    PubMed

    Hess, Thorsten; Hirschfeld, Sven; Thietje, Roland; Lönnecker, Stefan; Kerner, Thoralf; Stuhr, Markus

    2016-04-01

    Acute injury to the spine and spinal cord can occur both in isolation as also in the context of multiple injuries. Whereas a few decades ago, the cause of paraplegia was almost exclusively traumatic, the ratio of traumatic to non-traumatic causes in Germany is currently almost equivalent. In acute treatment of spinal cord injury, restoration and maintenance of vital functions, selective control of circulation parameters, and avoidance of positioning or transport-related additional damage are in the foreground. This article provides information on the guideline for emergency treatment of patients with acute injury of the spine and spinal cord in the preclinical phase. PMID:27070515

  2. Traumatic brain injury: Does gender influence outcomes?

    PubMed Central

    Munivenkatappa, Ashok; Agrawal, Amit; Shukla, Dhaval P.; Kumaraswamy, Deepika; Devi, Bhagavatula Indira

    2016-01-01

    Background: Traumatic brain injury (TBI) is a major public health problem. Both genders are affected, but little is known about female TBI. The present study exclusively explores epidemiological, clinical, imaging, and death aspects of female TBI, and how it differs from males. Methods: It is a retrospective study. Data were documented from a tertiary institute during January 2010 to March 2010. All variables were documented on standard proforma. The data were analyzed using R statistics software. Age group was categorized into pediatric (<18 years), middle (19–60 years) and elderly (>61 years). Significance was tested using Chi-square test at the significance level of P < 0.05. Results: Data of 1627 TBI patients were recorded. Of the total, female TBIs contributed nearly 20%. Compared to males, female patients reported higher percentages in manifesting symptoms (84.3% vs. 82.6%), injuries due to fall (32.1% vs. 24.4%), and surgical interventions (11.6% vs. 10.4%). Female patients were significantly higher in mild head injury group (76.8% vs. 69.5%, P - 0.016) and mortality (3.4% vs. 1.6%, P - 0.048). Number of patients and deaths was more among females than males in pediatric and elderly age group. Severities of injuries were more among female patients than male patients in middle and elder age groups. Conclusion: The study results observe that female TBI group differ significantly in the severity of injury and mortality. PMID:27308254

  3. Babesiosis-induced acute kidney injury with prominent urinary macrophages.

    PubMed

    Luciano, Randy L; Moeckel, Gilbert; Palmer, Matthew; Perazella, Mark A

    2013-10-01

    Babesia is an obligate intracellular erythrocyte parasite that can infect humans. Severe symptomatic disease from massive hemolysis and multiorgan system failure, including acute kidney injury (AKI), occurs. Acute tubular injury from a combination of volume depletion and heme pigment toxicity from profound hemolysis is the most common cause of AKI. We present a case of severe babesiosis complicated by dialysis-requiring AKI with the unique finding of large macrophages containing engulfed erythrocyte fragments in urine sediment. This urinary finding raised the possibility of another diagnosis distinct from acute tubular injury. Subsequent kidney biopsy demonstrated infection-associated acute interstitial nephritis. PMID:23643302

  4. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  5. Neuroimaging in adult penetrating brain injury: a guide for radiographers.

    PubMed

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  6. Therapies targeting lipid peroxidation in traumatic brain injury.

    PubMed

    Anthonymuthu, Tamil Selvan; Kenny, Elizabeth Megan; Bayır, Hülya

    2016-06-01

    Lipid peroxidation can be broadly defined as the process of inserting a hydroperoxy group into a lipid. Polyunsaturated fatty acids present in the phospholipids are often the targets for peroxidation. Phospholipids are indispensable for normal structure of membranes. The other important function of phospholipids stems from their role as a source of lipid mediators - oxygenated free fatty acids that are derived from lipid peroxidation. In the CNS, excessive accumulation of either oxidized phospholipids or oxygenated free fatty acids may be associated with damage occurring during acute brain injury and subsequent inflammatory responses. There is a growing body of evidence that lipid peroxidation occurs after severe traumatic brain injury in humans and correlates with the injury severity and mortality. Identification of the products and sources of lipid peroxidation and its enzymatic or non-enzymatic nature is essential for the design of mechanism-based therapies. Recent progress in mass spectrometry-based lipidomics/oxidative lipidomics offers remarkable opportunities for quantitative characterization of lipid peroxidation products, providing guidance for targeted development of specific therapeutic modalities. In this review, we critically evaluate previous attempts to use non-specific antioxidants as neuroprotectors and emphasize new approaches based on recent breakthroughs in understanding of enzymatic mechanisms of lipid peroxidation associated with specific death pathways, particularly apoptosis. We also emphasize the role of different phospholipases (calcium-dependent and -independent) in hydrolysis of peroxidized phospholipids and generation of pro- and anti-inflammatory lipid mediators. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26872597

  7. Traumatic Brain Injury: An Educator's Manual. [Revised Edition.

    ERIC Educational Resources Information Center

    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…

  8. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

    PubMed

    Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

    2016-01-01

    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

  9. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury

    PubMed Central

    Andrews, Allison M.; Lutton, Evan M.; Merkel, Steven F.; Razmpour, Roshanak; Ramirez, Servio H.

    2016-01-01

    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

  10. Concussive brain injury from explosive blast

    PubMed Central

    de Lanerolle, Nihal C; Hamid, Hamada; Kulas, Joseph; Pan, Jullie W; Czlapinski, Rebecca; Rinaldi, Anthony; Ling, Geoffrey; Bandak, Faris A; Hetherington, Hoby P

    2014-01-01

    Objective Explosive blast mild traumatic brain injury (mTBI) is associated with a variety of symptoms including memory impairment and posttraumatic stress disorder (PTSD). Explosive shock waves can cause hippocampal injury in a large animal model. We recently reported a method for detecting brain injury in soldiers with explosive blast mTBI using magnetic resonance spectroscopic imaging (MRSI). This method is applied in the study of veterans exposed to blast. Methods The hippocampus of 25 veterans with explosive blast mTBI, 20 controls, and 12 subjects with PTSD but without exposure to explosive blast were studied using MRSI at 7 Tesla. Psychiatric and cognitive assessments were administered to characterize the neuropsychiatric deficits and compare with findings from MRSI. Results Significant reductions in the ratio of N-acetyl aspartate to choline (NAA/Ch) and N-acetyl aspartate to creatine (NAA/Cr) (P < 0.05) were found in the anterior portions of the hippocampus with explosive blast mTBI in comparison to control subjects and were more pronounced in the right hippocampus, which was 15% smaller in volume (P < 0.05). Decreased NAA/Ch and NAA/Cr were not influenced by comorbidities – PTSD, depression, or anxiety. Subjects with PTSD without blast had lesser injury, which tended to be in the posterior hippocampus. Explosive blast mTBI subjects had a reduction in visual memory compared to PTSD without blast. Interpretation The region of the hippocampus injured differentiates explosive blast mTBI from PTSD. MRSI is quite sensitive in detecting and localizing regions of neuronal injury from explosive blast associated with memory impairment. PMID:25493283

  11. Sleep disruption and the sequelae associated with traumatic brain injury

    PubMed Central

    Lucke-Wold, Brandon P.; Smith, Kelly E.; Nguyen, Linda; Turner, Ryan C.; Logsdon, Aric F.; Jackson, Garrett J.; Huber, Jason D.; Rosen, Charles L.; Miller, Diane B.

    2016-01-01

    Sleep disruption, which includes a loss of sleep as well as poor quality fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a large number of patients each year in the United States. Fragmented and/or disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive decline. The most common sleep disruption following TBI is insomnia, which is difficulty staying asleep. The consequences of disrupted sleep following injury range from deranged metabolomics and blood brain barrier compromise to altered neuroplasticity and degeneration. There are several theories for why sleep is necessary (e.g., glymphatic clearance and metabolic regulation) and these may help explain how sleep disruption contributes to degeneration within the brain. Experimental data indicate disrupted sleep allows hyperphosphorylated tau and amyloid β plaques to accumulate. As sleep disruption may act as a cellular stressor, target areas warranting further scientific investigation include the increase in endoplasmic reticulum and oxidative stress following acute periods of sleep deprivation. Potential treatment options for restoring the normal sleep cycle include melatonin derivatives and cognitive behavioral therapy. PMID:25956251

  12. Sleep disruption and the sequelae associated with traumatic brain injury.

    PubMed

    Lucke-Wold, Brandon P; Smith, Kelly E; Nguyen, Linda; Turner, Ryan C; Logsdon, Aric F; Jackson, Garrett J; Huber, Jason D; Rosen, Charles L; Miller, Diane B

    2015-08-01

    Sleep disruption, which includes a loss of sleep as well as poor quality fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a large number of patients each year in the United States. Fragmented and/or disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive decline. The most common sleep disruption following TBI is insomnia, which is difficulty staying asleep. The consequences of disrupted sleep following injury range from deranged metabolomics and blood brain barrier compromise to altered neuroplasticity and degeneration. There are several theories for why sleep is necessary (e.g., glymphatic clearance and metabolic regulation) and these may help explain how sleep disruption contributes to degeneration within the brain. Experimental data indicate disrupted sleep allows hyperphosphorylated tau and amyloid β plaques to accumulate. As sleep disruption may act as a cellular stressor, target areas warranting further scientific investigation include the increase in endoplasmic reticulum and oxidative stress following acute periods of sleep deprivation. Potential treatment options for restoring the normal sleep cycle include melatonin derivatives and cognitive behavioral therapy. PMID:25956251

  13. Traumatic brain injury results in rapid pericyte loss followed by reactive pericytosis in the cerebral cortex.

    PubMed

    Zehendner, Christoph M; Sebastiani, Anne; Hugonnet, André; Bischoff, Florian; Luhmann, Heiko J; Thal, Serge C

    2015-01-01

    Accumulating evidence suggests a pivotal role of PDGFRß positive cells, a specific marker for central nervous system (CNS) pericytes, in tissue scarring. Identification of cells that contribute to tissue reorganization in the CNS upon injury is a crucial step to develop novel treatment strategies in regenerative medicine. It has been shown that pericytes contribute to scar formation in the spinal cord. It is further known that ischemia initially triggers pericyte loss in vivo, whilst brain trauma is capable of inducing pericyte detachment from cerebral vessels. These data point towards a significant role of pericytes in CNS injury. The temporal and spatial dynamics of PDGFRß cells and their responses in traumatic brain injury are poorly understood. Here we show that PDGFRß positive cells initially decline in the acute phase following experimental traumatic brain injury. However, PDGFRß positive cells increase significantly in the trauma zone days after brain injury. Using various pericyte markers we identify these cells to be pericytes that are demarcated by reactive gliosis. Our data indicate that brain trauma causes a biphasic response of pericytes in the early phase of brain trauma that may be of relevance for the understanding of pathological cellular responses in traumatic brain injury. PMID:26333872

  14. Traumatic brain injury results in rapid pericyte loss followed by reactive pericytosis in the cerebral cortex

    PubMed Central

    Zehendner, Christoph M.; Sebastiani, Anne; Hugonnet, André; Bischoff, Florian; Luhmann, Heiko J.; Thal, Serge C.

    2015-01-01

    Accumulating evidence suggests a pivotal role of PDGFRß positive cells, a specific marker for central nervous system (CNS) pericytes, in tissue scarring. Identification of cells that contribute to tissue reorganization in the CNS upon injury is a crucial step to develop novel treatment strategies in regenerative medicine. It has been shown that pericytes contribute to scar formation in the spinal cord. It is further known that ischemia initially triggers pericyte loss in vivo, whilst brain trauma is capable of inducing pericyte detachment from cerebral vessels. These data point towards a significant role of pericytes in CNS injury. The temporal and spatial dynamics of PDGFRß cells and their responses in traumatic brain injury are poorly understood. Here we show that PDGFRß positive cells initially decline in the acute phase following experimental traumatic brain injury. However, PDGFRß positive cells increase significantly in the trauma zone days after brain injury. Using various pericyte markers we identify these cells to be pericytes that are demarcated by reactive gliosis. Our data indicate that brain trauma causes a biphasic response of pericytes in the early phase of brain trauma that may be of relevance for the understanding of pathological cellular responses in traumatic brain injury. PMID:26333872

  15. Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

    PubMed

    Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

    2015-10-01

    Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

  16. Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging

    PubMed Central

    Paveliev, Mikhail; Kislin, Mikhail; Molotkov, Dmitry; Yuryev, Mikhail; Rauvala, Heikki; Khiroug, Leonard

    2014-01-01

    Although acute brain trauma often results from head damage in different accidents and affects a substantial fraction of the population, there is no effective treatment for it yet. Limitations of currently used animal models impede understanding of the pathology mechanism. Multiphoton microscopy allows studying cells and tissues within intact animal brains longitudinally under physiological and pathological conditions. Here, we describe two models of acute brain injury studied by means of two-photon imaging of brain cell behavior under posttraumatic conditions. A selected brain region is injured with a sharp needle to produce a trauma of a controlled width and depth in the brain parenchyma. Our method uses stereotaxic prick with a syringe needle, which can be combined with simultaneous drug application. We propose that this method can be used as an advanced tool to study cellular mechanisms of pathophysiological consequences of acute trauma in mammalian brain in vivo. In this video, we combine acute brain injury with two preparations: cranial window and skull thinning. We also discuss advantages and limitations of both preparations for multisession imaging of brain regeneration after trauma. PMID:24748024

  17. Optical microangiography enabling visualization of change in meninges after traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.

    2016-03-01

    Traumatic brain injury (TBI) is a form of brain injury caused by sudden impact on brain by an external mechanical force. Following the damage caused at the moment of injury, TBI influences pathophysiology in the brain that takes place within the minutes or hours involving alterations in the brain tissue morphology, cerebral blood flow (CBF), and pressure within skull, which become important contributors to morbidity after TBI. While many studies for the TBI pathophysiology have been investigated with brain cortex, the effect of trauma on intracranial tissues has been poorly studied. Here, we report use of high-resolution optical microangiography (OMAG) to monitor the changes in cranial meninges beneath the skull of mouse after TBI. TBI is induced on a brain of anesthetized mouse by thinning the skull using a soft drill where a series of drilling exert mechanical stress on the brain through the skull, resulting in mild brain injury. Intracranial OMAG imaging of the injured mouse brain during post-TBI phase shows interesting pathophysiological findings in the meningeal layers such as widening of subdural space as well as vasodilation of subarachnoid vessels. These processes are acute and reversible within hours. The results indicate potential of OMAG to explore mechanism involved following TBI on small animals in vivo.

  18. Molecular mechanisms of cognitive dysfunction following traumatic brain injury

    PubMed Central

    Walker, Kendall R.; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

  19. Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury

    PubMed Central

    Iverson, Grant L.; Lange, Rael T.; Wäljas, Minna; Liimatainen, Suvi; Dastidar, Prasun; Hartikainen, Kaisa M.; Soimakallio, Seppo; Öhman, Juha

    2012-01-01

    Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures. Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan. Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75–14.75, range = 0–77) off work compared to a median of 36 days (IQR = 13.5–53, range = 3–315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures. Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs. PMID:22577556

  20. Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury.

    PubMed

    Iverson, Grant L; Lange, Rael T; Wäljas, Minna; Liimatainen, Suvi; Dastidar, Prasun; Hartikainen, Kaisa M; Soimakallio, Seppo; Ohman, Juha

    2012-01-01

    Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures. Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan. Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75-14.75, range = 0-77) off work compared to a median of 36 days (IQR = 13.5-53, range = 3-315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures. Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs. PMID:22577556

  1. Acute Kidney Injury Associated with Linagliptin.

    PubMed

    Nandikanti, Deepak K; Gosmanova, Elvira O; Gosmanov, Aidar R

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  2. Contrast Medium-Induced Acute Kidney Injury

    PubMed Central

    Sadat, Umar; Usman, Ammara; Boyle, Jonathan R.; Hayes, Paul D.; Solomon, Richard J.

    2015-01-01

    Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of hospital-acquired renal insufficiency. With an increasing number of contrast medium-enhanced radiological procedures being performed in a rapidly increasing ageing population in the Western world, it is imperative that more attention is given to understand the aetiology of CI-AKI to devise novel diagnostic methods and to formulate effective prophylactic and therapeutic regimens to reduce its incidence and its associated morbidity and mortality. This article presents high-yield information on the above-mentioned aspects of CI-AKI, primarily based on results of randomised controlled trials, meta-analyses, systematic reviews and international consensus guidelines. PMID:26195974

  3. Acute Kidney Injury Associated with Linagliptin

    PubMed Central

    Nandikanti, Deepak K.; Gosmanova, Elvira O.; Gosmanov, Aidar R.

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  4. Transfusion-related acute lung injury (TRALI).

    PubMed

    Roberts, George H

    2004-01-01

    Transfusion is an inevitable event in the life of many individuals. Transfusion medicine personnel attempt to provide blood products that will result in a safe and harmless transfusion. However, this is not always possible since no laboratory test gives totally accurate and reliable results all the time and testing in routine transfusion services is devoted primarily to the identification of red blood cell problems. Thus, when patients are transfused, several possible adverse effects may occur in the transfused patient even though quality testing indicates no potential problem. These adverse events include infectious complications, hemolytic reactions, anaphylaxis, urticaria, circulatory overload, transfusion-associated graft-versus-host disease, chills and fever, immunomodulation, and transfusion-related acute lung injury (TRALI). PMID:15314887

  5. Acute kidney injury in HCT: an update.

    PubMed

    Lopes, J A; Jorge, S; Neves, M

    2016-06-01

    Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short- and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. PMID:26855155

  6. Traumatic brain injury: a review of characteristics, molecular basis and management.

    PubMed

    Wang, Ke; Cui, Daming; Gao, Liang

    2016-01-01

    Traumatic brain injury (TBI) is a critical cause of hospitalization, disability, and death worldwide. The global increase in the incidence of TBI poses a significant socioeconomic burden. Guidelines for the management of acute TBI mostly pertain to emergency treatment. Comprehensive gene expression analysis is currently available for several animal models of TBI, along with enhanced understanding of the molecular mechanisms activated during injury and subsequent recovery. The current review focuses on the characteristics, molecular basis and management of TBI. PMID:27100477

  7. Spillway-induced salmon head injury triggers the generation of brain alphaII-spectrin breakdown product biomarkers similar to mammalian traumatic brain injury.

    PubMed

    Miracle, Ann; Denslow, Nancy D; Kroll, Kevin J; Liu, Ming Cheng; Wang, Kevin K W

    2009-01-01

    Recent advances in biomedical research have resulted in the development of specific biomarkers for diagnostic testing of disease condition or physiological risk. Of specific interest are alphaII-spectrin breakdown products (SBDPs), which are produced by proteolytic events in traumatic brain injury and have been used as biomarkers to predict the severity of injury in humans and other mammalian brain injury models. This study describes and demonstrates the successful use of antibody-based mammalian SBDP biomarkers to detect head injury in migrating juvenile Chinook salmon (Oncorhynchus tshawytscha) that have been injured during passage through high-energy hydraulic environments present in spillways under different operational configurations. Mortality and injury assessment techniques currently measure only near-term direct mortality and easily observable acute injury. Injury-based biomarkers may serve as a quantitative indicator of subacute physical injury and recovery, and aid hydropower operators in evaluation of safest passage configuration and operation actions for migrating juvenile salmonids. We describe a novel application of SBDP biomarkers for head injury for migrating salmon. To our knowledge, this is the first documented cross-over use of a human molecular biomarker in a wildlife and operational risk management scenario. PMID:19214235

  8. Spillway-Induced Salmon Head Injury Triggers the Generation of Brain αII-Spectrin Breakdown Product Biomarkers Similar to Mammalian Traumatic Brain Injury

    PubMed Central

    Miracle, Ann; Denslow, Nancy D.; Kroll, Kevin J.; Liu, Ming Cheng; Wang, Kevin K. W.

    2009-01-01

    Recent advances in biomedical research have resulted in the development of specific biomarkers for diagnostic testing of disease condition or physiological risk. Of specific interest are αII-spectrin breakdown products (SBDPs), which are produced by proteolytic events in traumatic brain injury and have been used as biomarkers to predict the severity of injury in humans and other mammalian brain injury models. This study describes and demonstrates the successful use of antibody-based mammalian SBDP biomarkers to detect head injury in migrating juvenile Chinook salmon (Oncorhynchus tshawytscha) that have been injured during passage through high-energy hydraulic environments present in spillways under different operational configurations. Mortality and injury assessment techniques currently measure only near-term direct mortality and easily observable acute injury. Injury-based biomarkers may serve as a quantitative indicator of subacute physical injury and recovery, and aid hydropower operators in evaluation of safest passage configuration and operation actions for migrating juvenile salmonids. We describe a novel application of SBDP biomarkers for head injury for migrating salmon. To our knowledge, this is the first documented cross-over use of a human molecular biomarker in a wildlife and operational risk management scenario. PMID:19214235

  9. Time Dysperception Perspective for Acquired Brain Injury

    PubMed Central

    Piras, Federica; Piras, Fabrizio; Ciullo, Valentina; Danese, Emanuela; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-01-01

    Distortions of time perception are presented by a number of neuropsychiatric illnesses. Here we survey timing abilities in clinical populations with focal lesions in key brain structures recently implicated in human studies of timing. We also review timing performance in amnesic and traumatic brain injured patients in order to identify the nature of specific timing disorders in different brain damaged populations. We purposely analyzed the complex relationship between both cognitive and contextual factors involved in time estimation, as to characterize the correlation between timed and other cognitive behaviors in each group. We assume that interval timing is a solid construct to study cognitive dysfunctions following brain injury, as timing performance is a sensitive metric of information processing, while temporal cognition has the potential of influencing a wide range of cognitive processes. Moreover, temporal performance is a sensitive assay of damage to the underlying neural substrate after a brain insult. Further research in neurological and psychiatric patients will clarify whether time distortions are a manifestation of, or a mechanism for, cognitive and behavioral symptoms of neuropsychiatric disorders. PMID:24454304

  10. The Anatomic Pattern of Injuries in Acute Inversion Ankle Sprains

    PubMed Central

    Khor, Yuet Peng; Tan, Ken Jin

    2013-01-01

    Background: There are little data on the incidence and patterns of injuries seen on magnetic resonance imaging (MRI) in acute inversion ankle sprains. This study may help in the understanding of the pathomechanics, natural history, and outcomes of this common injury. Study Design: Case series; Level of evidence, 4. Methods: From June 2011 to June 2013, a total of 64 consecutive patients had MRI of the ankle performed for acute inversion injury to the ankle. All injuries/pathologies reported were recorded. Results: Only 22% of patients had isolated lateral ligament complex injuries. Twenty-two percent of patients had other pathologies but no lateral ligament injury, and 53% had lateral ligament injuries in combination with other pathologies or injuries. The most common associated finding with lateral ligament injuries was bone bruising (76%) followed by deltoid ligament injury (50%). The overall incidence of bone bruising was 50%. Thirty percent of ankles had tendon pathology, 27% had deltoid ligament injury, and 22% had occult fractures. Conclusion: Isolated lateral ligament ankle injury is not as common as is believed. The pattern of injury seems complex, and most patients appear to have more injuries than expected. MRI reveals additional information that may have significance in terms of diagnosis, treatment, and prognosis in this common injury. PMID:26535261

  11. [Delayed brain abscess after penetrating transorbital injury].

    PubMed

    Hiraishi, Tetsuya; Tomikawa, Masaru; Kobayashi, Tsutomu; Kawaguchi, Tadashi

    2007-05-01

    We report a case of brain abscess caused by a penetrating head injury that occurred 9 years earlier. A 14-year-old girl presenting with fever, headache, and stiff neck was admitted to our hospital. She was diagnosed with aseptic meningitis and treated conservatively. Seven days after admission she became stuporous and showed left hemiparesis. Computed tomography (CT) revealed two ring-enhancing masses with perifocal edema in the right frontal lobe. We diagnosed brain abscess and performed right fronto-temporal decompressive craniectomy and stereotactic aspiration, followed by systemic antibiotic therapy. Post-surgery bone window CT revealed a well-defined, low-density foreign body passing from the left orbita to the right frontal lobe through the ethmoid sinus. We learned that the patient had been struck with a plastic chopstick in the left medial eyelid at the age of 5 years. No particular symptoms developed during the following 9 years. After the cerebral edema had diminished over the next 10 days, a second surgery was performed to remove the residual chopstick, repair the fistula at the base of the skull, and perform cranioplasty. The patient was discharged with only slight hyposmia after a 4-week course of antibiotics. This case showed that it is necessary to remove a residual foreign body and to close the dural fistula if there is a possibility of recurrent central nervous system infection. When a child presents with brain abscess, previous penetrating head injury should be considered. PMID:17491344

  12. Pathophysiology of battlefield associated traumatic brain injury.

    PubMed

    Duckworth, Josh L; Grimes, Jamie; Ling, Geoffrey S F

    2013-02-01

    As more data is accumulated from Operation Iraqi Freedom and Operation Enduring Freedom (OEF in Afghanistan), it is becoming increasing evident that traumatic brain injury (TBI) is a serious and highly prevalent battle related injury. Although traditional TBIs such as closed head and penetrating occur in the modern battle space, the most common cause of modern battle related TBI is exposure to explosive blast. Many believe that explosive blast TBI is unique from the other forms of TBI. This is because the physical forces responsible for explosive blast TBI are different than those for closed head TBI and penetrating TBI. The unique force associated with explosive blast is the blast shock pressure wave. This shock wave occurs over a very short period, milliseconds, and has a specific profile known as the Freidlander curve. This pressure-time curve is characterized by an initial very rapid up-rise followed by a longer decay that reaches a negative inflection point before returning to baseline. This is important as the effect of this shock pressure on brain parenchyma is distinct. The diffuse interaction of the pressure wave with the brain leads to a complex cascade of events that affects neurons, axons, glia cells, and vasculature. It is only by properly studying this disease will meaningful therapies be realized. PMID:22703708

  13. Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat

    PubMed Central

    van Bregt, Daniel R.; Thomas, Theresa Currier; Hinzman, Jason M.; Cao, Tuoxin; Liu, Mei; Bing, Guoying; Gerhardt, Greg A.; Pauly, James R.; Lifshitz, Jonathan

    2012-01-01

    Dementia and parkinsonism are late-onset symptoms associated with repetitive head injury, as documented in multiple contact-sport athletes. Clinical symptomatology is the likely phenotype of chronic degeneration and circuit disruption in the substantia nigra (SN). To investigate the initiating neuropathology, we hypothesize that a single diffuse brain injury is sufficient to initiate SN neuropathology including neuronal loss, vascular disruption and microglial activation, contributing to neurodegeneration and altered dopamine regulation. Adult, male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury. Stereological estimates indicated a significant 44% loss of the estimated total neuron number in the SN at 28-days post-injury, without atrophy of neuronal nuclear volumes, including 25% loss of tyrosine hydroxylase positive neurons by 28-days post-injury. Multi-focal vascular compromise occurred 1–2 days post-injury, with ensuing microglial activation (significant 40% increase at 4-days). Neurodegeneration (silver-stain technique) encompassed on average 21% of the SN by 7-days post-injury and increased to 29% by 28-days compared to sham (1%). Whole tissue SN, but not striatum, dopamine metabolism was altered at 28-days post-injury, without appreciable gene or protein changes in dopamine synthesis or regulation elements. Together, single moderate diffuse brain injury resulted in SN neurovascular pathology potentially associated with neuroinflammation or dopamine dysregulation. Compensatory mechanisms may preserve dopamine signaling acutely, but subsequent SN damage with aging or additional injury may expose clinical symptomatology of motor ataxias and dementia. PMID:22178300

  14. Hypersexuality or altered sexual preference following brain injury.

    PubMed Central

    Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

    1986-01-01

    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

  15. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury.

    PubMed

    Shlosberg, Dan; Benifla, Mony; Kaufer, Daniela; Friedman, Alon

    2010-07-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults and children. The treatment of TBI in the acute phase has improved substantially; however, the prevention and management of long-term complications remain a challenge. Blood-brain barrier (BBB) breakdown has often been documented in patients with TBI, but the role of such vascular pathology in neurological dysfunction has only recently been explored. Animal studies have demonstrated that BBB breakdown is involved in the initiation of transcriptional changes in the neurovascular network that ultimately lead to delayed neuronal dysfunction and degeneration. Brain imaging data have confirmed the high incidence of BBB breakdown in patients with TBI and suggest that such pathology could be used as a biomarker in the clinic and in drug trials. Here, we review the neurological consequences of TBI, focusing on the long-term complications of such injuries. We present the clinical evidence for involvement of BBB breakdown in TBI and examine the primary and secondary mechanisms that underlie such pathology. We go on to consider the consequences of BBB injury, before analyzing potential mechanisms linking vascular pathology to neuronal dysfunction and degeneration, and exploring possible targets for treatment. Finally, we highlight areas for future basic research and clinical studies into TBI. PMID:20551947

  16. Cardiac Surgery-Associated Acute Kidney Injury

    PubMed Central

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  17. Septic acute kidney injury: the glomerular arterioles.

    PubMed

    Bellomo, Rinaldo; Wan, Li; Langenberg, Christoph; Ishikawa, Ken; May, Clive N

    2011-01-01

    Acute kidney injury (AKI) is a serious condition that affects many intensive care unit (ICU) patients. The most common causes of AKI in the ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to tubular injury, which, in turn, has been considered secondary to renal ischemia. This belief is curious because the hallmark of septic AKI and AKI in general is the loss of glomerular filtration rate (GFR). It would seem logical, therefore, to focus on the glomerulus in trying to understand why such loss of GFR occurs. Recent experimental observations suggest that, at least in the initial phases of septic AKI, profound changes occur which involve glomerular hemodynamics and lead to loss of GFR. These observations imply that changes in the vasoconstrictor tone of both the afferent and efferent arterioles are an important component of the pathogenesis of septic AKI. PMID:21921614

  18. Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Alobaidi, Rashid; Basu, Rajit K.; Goldstein, Stuart L.; Bagshaw, Sean M.

    2015-01-01

    Summary Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment. PMID:25795495

  19. [Transfusion-related acute lung injury].

    PubMed

    Tank, S; Sputtek, A; Kiefmann, R

    2013-04-01

    Transfusion-related acute lung injury (TRALI) developed into the leading cause of transfusion-related morbidity and mortality after the first description by Popovsky et al. approximately three decades ago. It was the most frequent reason for transfusion-related fatalities worldwide before implementation of risk minimization strategies by donor selection. Plasma-rich blood products, such as fresh frozen plasma and apheresis platelets seem to be the leading triggers of TRALI. Hypoxemia and development of pulmonary edema within 6 h of transfusion are the diagnostic criteria for TRALI. The differentiation between cardiac failure and other transfusion-related lung injuries, such astransfusion-associated circulatory overload ( TACO) is difficult and causal treatment is not available. Therapy is based on supportive measures, such as oxygen insufflationor mechanical ventilation. The exactly pathogenesis is still unknown but the most propagated hypothesis is the two-event-model. Neutrophils are primed by the underlying condition, e.g. sepsis or trauma during the first event and these primed neutrophils are activated by transfused leukoagglutinating antibodies (immunogen) or bioreactive mediators (non-immunogen) during the second-event. Transfusion of leukoagglutinating antibodies from female donors with one or more previous pregnancies is the most frequent reason. No more TRALI fatalities were reported after implementation of the donor selection in Germany in 2009. PMID:23558721

  20. Cardiac surgery-associated acute kidney injury.

    PubMed

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-10-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  1. Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

    PubMed Central

    Watts, Ryan P.; Thom, Ogilvie; Fraser, John F.

    2013-01-01

    Brain death is associated with dramatic and serious pathophysiologic changes that adversely affect both the quantity and quality of organs available for transplant. To fully optimise the donor pool necessitates a more complete understanding of the underlying pathophysiology of organ dysfunction associated with transplantation. These injurious processes are initially triggered by catastrophic brain injury and are further enhanced during both brain death and graft transplantation. The activated inflammatory systems then contribute to graft dysfunction in the recipient. Inflammatory mediators drive this process in concert with the innate and adaptive immune systems. Activation of deleterious immunological pathways in organ grafts occurs, priming them for further inflammation after engraftment. Finally, posttransplantation ischaemia reperfusion injury leads to further generation of inflammatory mediators and consequent activation of the recipient's immune system. Ongoing research has identified key mediators that contribute to the inflammatory milieu inherent in brain dead organ donation. This has seen the development of novel therapies that directly target the inflammatory cascade. PMID:23691272

  2. Extending the viability of acute brain slices.

    PubMed

    Buskila, Yossi; Breen, Paul P; Tapson, Jonathan; van Schaik, André; Barton, Matthew; Morley, John W

    2014-01-01

    The lifespan of an acute brain slice is approximately 6-12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research. PMID:24930889

  3. [Mental disorders after mild traumatic brain injury].

    PubMed

    Gonschorek, A S; Schwenkreis, P; Guthke, T

    2016-05-01

    Mild traumatic brain injury (mTBI) is a frequent neurological disorder following a closed head injury. It is often accompanied by temporary changes of consciousness as well as cognitive, emotional and physical symptoms. These symptoms subside in the vast majority of affected persons within a few weeks; however, in recent years it has become increasingly more apparent that functionally significant long-term effects can remain after an initially diagnosed mTBI. In these cases mental disorders, such as impairment of cognitive and emotional functions as well as somatic disorders play an important role. This article presents the frequency, diagnosis, therapy and possible mechanisms of cognitive and emotional dysfunction after mTBI, including medicolegal aspects. PMID:27119532

  4. Aggression after Traumatic Brain Injury: Prevalence & Correlates

    PubMed Central

    Rao, Vani; Rosenberg, Paul; Bertrand, Melaine; Salehinia, Saeed; Spiro, Jennifer; Vaishnavi, Sandeep; Rastogi, Pramit; Noll, Kathy; Schretlen, David J; Brandt, Jason; Cornwell, Edward; Makley, Michael; Miles, Quincy Samus

    2010-01-01

    Aggression after traumatic brain injury (TBI) is common but not well defined. Sixty-seven participants with first-time TBI were seen within three months of injury and evaluated for aggression. The prevalence of aggression was found to be 28.4% and to be predominantly verbal aggression. Post-TBI aggression was associated with new-onset major depression (p=0.02), poorer social functioning (p=0.04), and increased dependency on activities of daily living (p=0.03), but not with a history of substance abuse or adult/childhood behavioral problems. Implications of the study include early screening for aggression, evaluation for depression, and consideration of psychosocial support in aggressive patients. PMID:19996251

  5. Acute renal injury after partial hepatectomy

    PubMed Central

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-01-01

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  6. Acute renal injury after partial hepatectomy.

    PubMed

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-07-28

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  7. Cannabinoids: well-suited candidates for the treatment of perinatal brain injury.

    PubMed

    Fernández-López, David; Lizasoain, Ignacio; Moro, Maria Angeles; Martínez-Orgado, José

    2013-01-01

    Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth, including neonatal asphyxia, neonatal hypoxia-ischemia and stroke-induced focal ischemia. Typical manifestations of these conditions are the presence of glutamate excitoxicity, neuroinflammation and oxidative stress, the combination of which can potentially result in apoptotic-necrotic cell death, generation of brain lesions and long-lasting functional impairment. In spite of the high incidence of perinatal brain injury, the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair. The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier. The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species. Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies. This review addresses the particular effects of several drugs that modulate the activity of the endocannabinoid system on the progression of different manifestations of perinatal brain injury during both the acute and chronic recovery phases using

  8. Wasp sting-induced acute kidney injury

    PubMed Central

    Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Sakthirajan, Ramanathan; Shankar, Palaniselvam; Gopalakrishnan, Natarajan; Balasubramaniyan, Thoppalan

    2016-01-01

    Background Wasp stings are a common form of envenomation in tropical countries, especially in farmers. The aim of this study was to document the clinical presentation, treatment and outcomes of patients with acute kidney injury (AKI) due to multiple wasp stings in a tertiary care hospital. Methods We conducted a retrospective observational study of patients with multiple wasp stings and AKI at the Department of Nephrology between July 2011 and August 2015. The clinical features, laboratory data, treatment details and outcomes were noted. Results A total of 11 patients were included. All were from rural areas. All of them were males with age ranging from 21 to 70 years, mean age 45 ± 23 years. Six had oliguria and two had hypotension. All 11 patients had evidence of rhabdomyolysis and three also had hemolysis. Ten patients required hemodialysis with a mean number of hemodialysis sessions of 8.7 ± 2.8. Renal biopsy carried out on four patients, showed acute interstitial nephritis (AIN) in one patient, acute tubular necrosis (ATN) in two patients, and one patient had both AIN and ATN. The two patients with AIN were given steroids, while all other patients were managed with supportive measures. One patient died within 48 h of presentation due to shock. At a mean follow-up of 24 months, one had progressed to chronic kidney disease and the remaining nine had normal renal function. Conclusions Wasp sting is an occupational hazard. AKI was most commonly due to rhabdomyolysis. Early renal biopsy is indicated in those patients who do not respond to supportive measures. Timely dialysis and steroid in the case of AIN improves renal survival. PMID:26985369

  9. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    PubMed Central

    Guan, Li; Zhang, Yan-Lin; Li, Zong-Yang; Zhu, Ming-Xia; Yao, Wei-Juan; Zhao, Jin-Yuan

    2015-01-01

    Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning. PMID:25705671

  10. Headache management in concussion and mild traumatic brain injury.

    PubMed

    Lucas, Sylvia

    2011-10-01

    Headache is one of the most common symptoms after traumatic brain injury (TBI), and posttraumatic headache (PTH) may be part of a constellation of symptoms that is seen in the postconcussive syndrome. PTH has no defining clinical features; currently it is classified as a secondary headache based on its close temporal relationship to the injury. A growing number of studies are characterizing PTH by using primary headache classifications. Moderate to severe PTH that is often disabling may be classified as migraine or probable migraine and is found in substantial numbers of individuals. Recent data from civilian adult, pediatric, and military populations all find that PTH may be more of a chronic problem than previously thought, with a prevalence of close to half of the injured population. In addition, if PTH definitions are strictly adhered to, then many cases of PTH may be missed, thus underestimating the scope of the problem. New headaches may be reported well after the 7 days required for diagnosis of PTH by the guidelines of the International Classification of Headache Disorders, 2nd edition. A history of headache before a head injury occurs and female gender are possible risk factors for headache after TBI. Treatment of PTH may be acute or preventive, and recommendations are made for the use of migraine-specific acute therapy when indicated. Preventive therapy may be considered when PTH is frequent, disabling, or refractory to acute therapies. Comorbid conditions should be considered when choosing an appropriate preventive therapy. The symptom of headache as a "return to play" or "return to duty" barrier must be viewed in the context of other symptoms of mild TBI. PMID:22035683

  11. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  12. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

    PubMed

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  13. Leukocyte Recruitment and Ischemic Brain Injury

    PubMed Central

    Yilmaz, Gokhan

    2010-01-01

    Leukocytes are recruited into the cerebral microcirculation following an ischemic insult. The leukocyte–endothelial cell adhesion manifested within a few hours after ischemia (followed by reperfusion, I/R) largely reflects an infiltration of neutrophils, while other leukocyte populations appear to dominate the adhesive interactions with the vessel wall at 24 h of reperfusion. The influx of rolling and adherent leukocytes is accompanied by the recruitment of adherent platelets, which likely enhances the cytotoxic potential of the leukocytes to which they are attached. The recruitment of leukocytes and platelets in the postischemic brain is mediated by specific adhesion glycoproteins expressed by the activated blood cells and on cerebral microvascular endothelial cells. This process is also modulated by different signaling pathways (e.g., CD40/CD40L, Notch) and cytokines (e.g., RANTES) that are activated/released following I/R. Some of the known risk factors for cardiovascular disease, including hypercholesterolemia and obesity appear to exacerbate the leukocyte and platelet recruitment elicited by brain I/R. Although lymphocyte–endothelial cell and –platelet interactions in the postischemic cerebral microcirculation have not been evaluated to date, recent evidence in experimental animals implicate both CD4+ and CD8+ T-lymphocytes in the cerebral microvascular dysfunction, inflammation, and tissue injury associated with brain I/R. Evidence implicating regulatory T-cells as cerebroprotective modulators of the inflammatory and tissue injury responses to brain I/R support a continued focus on leukocytes as a target for therapeutic intervention in ischemic stroke. PMID:19579016

  14. A study of rotational brain injury.

    PubMed

    Misra, J C; Chakravarty, S

    1984-01-01

    Of concern in the paper is an investigation on brain injuries which may occur owing to an input angular acceleration of the head. The study is based on the use of an improved mathematical model for the cranium. The eccentricity of the braincase is incorporated through the consideration of a prolate spheroidal shell as the representative of the skull. Also the dissipative mechanical behaviour of the brain material (as per the observations of experimenters) has been accounted for by considering the material contained in the shell as viscoelastic. The problem is formulated in terms of prolate spheroidal coordinates. The singularities of the governing equations of motion (when expressed in the prolate coordinate system) are removed by a suitable transformation of the concerned dependent variable, viz. the one that stands for the angular displacement of a representative point of the system. In the first place the solution of the boundary value problem is sought in the Laplace transform space, by employing a finite difference technique. Use of the alternating-direction-implicit method together with Thomas algorithm was made for obtaining the angular acceleration in the transformed space. The Laplace inversion is also carried out with the help of numerical procedures (Gauss quadrature formula is used for this purpose). The results of the parametric study are presented through graphs. The plots illustrate the shear stresses and strains in the brain medium. A meaningful comparison of the computational results with those of previous investigations indicate that the eccentricity of the braincase plays a significant role in causing injury to the brain. PMID:6480621

  15. Violence-related mild traumatic brain injury in women: identifying a triad of postinjury disorders.

    PubMed

    Davis, Alice

    2014-01-01

    Violence against women whether from domestic partner abuse, sex trafficking injuries, or sexual assault is a pervasive health problem without racial or social boundaries. Regardless of cause, violence results in a complex triad of physical, emotional, and psychological injuries. There is clear evidence that female victims of violence or "battered women" experience brain injury. What is less certain is whether the constellations of events surrounding brain injury including postconcussion syndrome, depression, and posttraumatic stress disorder are acute symptoms after the brain injury, premorbid as a result of persistent abuse, or a synergistic triad of combined disorders as a result of the injuries. The purpose of this article is to examine the relationship between physical violence-associated mild traumatic brain injury (MTBI) and postinjury cognitive, emotional, and psychological disorders. The review of the literature addresses epidemiological factors associated with domestic partners and sexual violence, abuse and health outcomes in women, physical injury, and its consequences. Along with MTBI, a triad of disorders is hypothesized that includes postconcussion syndrome, depression, and posttraumatic stress disorder. Screening for MTBI and the triad of disorders is advocated, and assessment methods are offered. PMID:25397339

  16. Erythropoietin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Bramlett, Helen M; Dietrich, W Dalton; Dixon, C Edward; Shear, Deborah A; Schmid, Kara E; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Experimental studies targeting traumatic brain injury (TBI) have reported that erythropoietin (EPO) is an endogenous neuroprotectant in multiple models. In addition to its neuroprotective effects, it has also been shown to enhance reparative processes including angiogenesis and neurogenesis. Based on compelling pre-clinical data, EPO was tested by the Operation Brain Trauma Therapy (OBTT) consortium to evaluate therapeutic potential in multiple TBI models along with biomarker assessments. Based on the pre-clinical TBI literature, two doses of EPO (5000 and 10,000 IU/kg) were tested given at 15 min after moderate fluid percussion brain injury (FPI), controlled cortical impact (CCI), or penetrating ballistic-like brain injury (PBBI) with subsequent behavioral, histopathological, and biomarker outcome assessments. There was a significant benefit on beam walk with the 5000 IU dose in CCI, but no benefit on any other motor task across models in OBTT. Also, no benefit of EPO treatment across the three TBI models was noted using the Morris water maze to assess cognitive deficits. Lesion volume analysis showed no treatment effects after either FPI or CCI; however, with the 5000 IU/kg dose of EPO, a paradoxical increase in lesion volume and percent hemispheric tissue loss was seen after PBBI. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No treatment effects were seen on biomarker levels after FPI, whereas treatment at either dose exacerbated the increase in GFAP at 24 h in PBBI but attenuated 24-4 h delta UCH-L1 levels at high dose in CCI. Our data indicate a surprising lack of efficacy of EPO across three established TBI models in terms of behavioral, histopathological, and biomarker assessments. Although we cannot rule out the possibility that other doses or more prolonged treatment could show different effects, the lack of efficacy of EPO reduced

  17. Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury.

    PubMed

    Skovira, Jacob W; Kabadi, Shruti V; Wu, Junfang; Zhao, Zaorui; DuBose, Joseph; Rosenthal, Robert; Fiskum, Gary; Faden, Alan I

    2016-07-15

    Aeromedical evacuation, an important component in the care of many patients with traumatic brain injury (TBI), particularly in war zones, exposes them to prolonged periods of hypobaria. The effects of such exposure on pathophysiological changes and outcome after TBI are largely unexplored. The objective of this study was to investigate whether prolonged hypobaria in rats subjected to TBI alters behavioral and histological outcomes. Adult male Sprague-Dawley rats underwent fluid percussion induced injury at 1.5-1.9 atmospheres of pressure. The effects of hypobaric exposure (6 h duration; equivalent to 0.75 atmospheres) at 6, 24, and 72 h, or 7 days after TBI were evaluated with regard to sensorimotor, cognitive, and histological changes. Additional groups were evaluated to determine the effects of two hypobaric exposures after TBI, representing primary simulated aeromedical evacuation (6 h duration at 24 h after injury) and secondary evacuation (10 h duration at 72 h after injury), as well as the effects of 100% inspired oxygen concentrations during simulated evacuation. Hypobaric exposure up to 7 days after injury significantly worsened cognitive deficits, hippocampal neuronal loss, and microglial/astrocyte activation in comparison with injured controls not exposed to hypobaria. Hyperoxia during hypobaric exposure or two exposures to prolonged hypobaric conditions further exacerbated spatial memory deficits. These findings indicate that exposure to prolonged hypobaria up to 7 days after TBI, even while maintaining physiological oxygen concentration, worsens long-term cognitive function and neuroinflammation. Multiple exposures or use of 100% oxygen further exacerbates these pathophysiological effects. PMID:26593382

  18. The History and Evolution of Experimental Traumatic Brain Injury Models.

    PubMed

    Povlishock, John

    2016-01-01

    This narrative provides a brief history of experimental animal model development for the study of traumatic brain injury. It draws upon a relatively rich history of early animal modeling that employed higher order animals to assess concussive brain injury while exploring the importance of head movement versus stabilization in evaluating the animal's response to injury. These themes are extended to the development of angular/rotational acceleration/deceleration models that also exploited brain movement to generate both the morbidity and pathology typically associated with human traumatic brain injury. Despite the significance of these early model systems, their limitations and overall practicality are discussed. Consideration is given to more contemporary rodent animal models that replicate individual/specific features of human injury, while via various transgenic technologies permitting the evaluation of injury-mediated pathways. The narrative closes on a reconsideration of higher order, porcine animal models of injury and their implication for preclinical/translational research. PMID:27604709

  19. Charting a course for erythropoietin in traumatic brain injury

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. PMID:27081573

  20. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence

    PubMed Central

    Li, Shasha; Zaninotto, Ana Luiza; Neville, Iuri Santana; Paiva, Wellingson Silva; Nunn, Danuza; Fregni, Felipe

    2015-01-01

    Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery. PMID:26170670

  1. Acute Kidney Injury: Quoi de Neuf?

    PubMed Central

    Reichel, Ronald R.

    2014-01-01

    Background Acute kidney injury (AKI) is frequently encountered in the nephrology practice. Serum creatinine, with its many shortcomings, is still the main biomarker used to detect AKI. Methods This review focuses on recent advances in definition, diagnosis, risk factors, and molecular mechanisms of AKI. In addition, specific AKI syndromes such as contrast-induced AKI, hepatorenal syndrome, and acute decompensated heart failure are discussed. The connection between AKI and subsequent chronic kidney disease and recent developments in renal replacement therapy are also covered. Results Novel biomarkers such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL) are being investigated to replace serum creatinine in the detection of AKI. Recent studies suggest that intravenous (IV) fluid use is beneficial for the prevention of contrast-induced AKI, while N-acetylcysteine use is not as well established. Diuretics are clearly beneficial in the treatment of acute decompensated heart failure. Ultrafiltration is less promising and can lead to adverse side effects. Although terlipressin use in hepatorenal syndrome is associated with reduced mortality, it is not available in the United States; combination therapy with midodrine, octreotide, and albumin provides an alternative. Fluid resuscitation is frequently used in critically ill patients with AKI; however, overly aggressive fluid resuscitation is frequently associated with an increased risk of mortality. A 3-step approach that combines guided fluid resuscitation, establishment of an even fluid balance, and an appropriate rate of fluid removal may be beneficial. If fluid resuscitation is needed, crystalloid solutions are preferred over hetastarch solutions. Renal replacement therapy is the last resort in AKI treatment, and timing, modality, and dosing are discussed. Research suggests that AKI leads to an increased incidence of subsequent chronic kidney disease. However, this relationship has not been fully

  2. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

    PubMed

    Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

    2015-12-01

    Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. PMID:26852688

  3. Role and Importance of IGF-1 in Traumatic Brain Injuries

    PubMed Central

    Mangiola, Annunziato; Vigo, Vera; Anile, Carmelo; De Bonis, Pasquale; Marziali, Giammaria; Lofrese, Giorgio

    2015-01-01

    It is increasingly affirmed that most of the long-term consequences of TBI are due to molecular and cellular changes occurring during the acute phase of the injury and which may, afterwards, persist or progress. Understanding how to prevent secondary damage and improve outcome in trauma patients, has been always a target of scientific interest. Plans of studies focused their attention on the posttraumatic neuroendocrine dysfunction in order to achieve a correlation between hormone blood level and TBI outcomes. The somatotropic axis (GH and IGF-1) seems to be the most affected, with different alterations between the acute and late phases. IGF-1 plays an important role in brain growth and development, and it is related to repair responses to damage for both the central and peripheral nervous system. The IGF-1 blood levels result prone to decrease during both the early and late phases after TBI. Despite this, experimental studies on animals have shown that the CNS responds to the injury upregulating the expression of IGF-1; thus it appears to be related to the secondary mechanisms of response to posttraumatic damage. We review the mechanisms involving IGF-1 in TBI, analyzing how its expression and metabolism may affect prognosis and outcome in head trauma patients. PMID:26417600

  4. Acute Methamphetamine Intoxication: Brain Hyperthermia, Blood-Brain Barrier and Brain Edema

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. PMID:19897075

  5. Ischemic preconditioning protects against ischemic brain injury.

    PubMed

    Ma, Xiao-Meng; Liu, Mei; Liu, Ying-Ying; Ma, Li-Li; Jiang, Ying; Chen, Xiao-Hong

    2016-05-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  6. Altered Calcium Signaling Following Traumatic Brain Injury

    PubMed Central

    Weber, John T.

    2012-01-01

    Cell death and dysfunction after traumatic brain injury (TBI) is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI. PMID:22518104

  7. MRI of radiation injury to the brain

    SciTech Connect

    Curnes, J.T.; Laster, D.W.; Ball, M.R.; Moody, D.M.; Witcofski, R.L.

    1986-07-01

    Nine patients with a history of radiation of 2400-6000 rad (24-60 Gy) to the brain were examined by magnetic resonance imaging (MRI) and computed tomography (CT). MRI demonstrated abnormalities in the periventricular white matter in all patients. The abnormal periventricular signal was characterized by a long T2 and was demonstrated best on coronal spin-echo (SE) 1000/80 images. A characteristic scalloped appearance at the junction of the gray-white matter was seen on MR images of seven patients, and represented extensive white-matter damage involving the more peripheral arcuate fiber systems. This differs from transependymal absorption, which is seen best on SE 3000/80 images and has a smooth peripheral margin. Cranial CT demonstrated white-matter lucencies in six cases but generally failed to display the extent of white-matter injury demonstrated by MRI. MRI is uniquely suited to detect radiation injury to the brain because of its extreme sensitivity to white-matter edema.

  8. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  9. Neuropsychological rehabilitation for traumatic brain injury patients.

    PubMed

    Chantsoulis, Marzena; Mirski, Andrzej; Rasmus, Anna; Kropotov, Juri D; Pachalska, Maria

    2015-01-01

    The aim of this review is to discuss the basic forms of neuropsychological rehabilitation for patients with traumatic brain injury (TBI). More broadly, we discussed cognitive rehabilitation therapy (CRT) which constitutes a fundamental component in therapeutic interaction at many centres worldwide. Equally presented is a comprehensive model of rehabilitation, the fundamental component of which is CRT. It should be noted that the principles of this approach first arose in Poland in the 1970s, in other words, several decades before their appearance in other programmemes. Taken into consideration are four factors conditioning the effectiveness of such a process: comprehensiveness, earlier interaction, universality and its individualized character. A comprehensive programmeme of rehabilitation covers: cognitive rehabilitation, individual and group rehabilitation with the application of a therapeutic environment, specialist vocational rehabilitation, as well as family psychotherapy. These training programmemes are conducted within the scope of the 'Academy of Life,' which provides support for the patients in their efforts and shows them the means by which they can overcome existing difficulties. Equally emphasized is the close cooperation of the whole team of specialists, as well as the active participation of the family as an essential condition for the effectiveness of rehabilitation and, in effect, a return of the patient to a relatively normal life. Also presented are newly developing neurothechnologies and the neuromarkers of brain injuries. This enables a correct diagnosis to be made and, as a result, the selection of appropriate methods for neuropsychological rehabilitation, including neurotherapy. PMID:26094541

  10. Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits

    PubMed Central

    Corser-Jensen, Chelsea E.; Goodell, Dayton J.; Freund, Ronald K.; Serbedzija, Predrag; Murphy, Robert C.; Farias, Santiago E.; Dell'Acqua, Mark L.; Frey, Lauren C.; Serkova, Natalie; Heidenreich, Kim A.

    2014-01-01

    Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11 weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arms water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits. PMID:24681156

  11. Ethics of neuroimaging after serious brain injury

    PubMed Central

    2014-01-01

    Background Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Methods/Design Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients’ interests, and we

  12. Brain injury, neuroinflammation and Alzheimer's disease

    PubMed Central

    Breunig, Joshua J.; Guillot-Sestier, Marie-Victoire; Town, Terrence

    2013-01-01

    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

  13. Traumatic brain injury brief outcome interview.

    PubMed

    Burton, Leslie A; Leahy, Derek M; Volpe, Bruce

    2003-01-01

    There is much evidence that deficits in physical and psychological functioning persist long after traumatic brain injury occurs. This paper presents a brief outcome interview (BOI) that can be administered in person or over the telephone, with evaluation of change in functioning in three areas: (a). occupational status, (b). mobility/activities of daily living (ADL), and (c). social relationships. Forty-four traumatic brain injury participants were evaluated at an average of 6.2 years postinjury with the present BOI as well as with the Glasgow Outcome Scale and Karnofsky Performance Scale (KPS). The BOI demonstrated strong concurrent validity with both scales, as well as strong test-retest reliability. IQ and memory scores obtained at an average of 4.1 months postinjury suggested that the injury was moderately severe. The average score on the GPS suggested "good recovery" and the average score on the KPS suggested "normal activity with effort, some signs or symptoms." These descriptions matched the BOI for the mobility/ADL dimension, for which all respondents reported some form of independent mobility, and 88.6% of the respondents reported no need for any kind of assistance in daily life functioning. However, significant long-term issues were seen for social and occupational functioning. Fifty-four percent said that they did not socialize as much as before their injury, and half of the participants reported not being involved in a romantic relationship in spite of an average age of 32 years. In terms of occupational status, 40.9% reported not working at all at any kind of job. Compared to before their injury, 47.7% said this was less time, 40.9% said that it was for a lower salary, and 54.5% said that their responsibilities were less. The stability of these social and occupational changes was indicated by high test-test reliabilities for the overall BOI score and the three subscale scores (r's ranged from.97 to 1.0). These stable long-term changes are consistent

  14. Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats

    PubMed Central

    Kizmazoglu, Ceren; Aydin, Hasan Emre; Sevin, Ismail Ertan; Yüceer, Nurullah; Atasoy, Metin Ant

    2015-01-01

    Background Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53. PMID:26819684

  15. Mechanisms of blast induced brain injuries, experimental studies in rats.

    PubMed

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. PMID:20493951

  16. Decompressive craniectomy following traumatic brain injury: developing the evidence base.

    PubMed

    Kolias, Angelos G; Adams, Hadie; Timofeev, Ivan; Czosnyka, Marek; Corteen, Elizabeth A; Pickard, John D; Turner, Carole; Gregson, Barbara A; Kirkpatrick, Peter J; Murray, Gordon D; Menon, David K; Hutchinson, Peter J

    2016-04-01

    In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of "opening the skull" in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented. PMID:26972805

  17. Decompressive craniectomy following traumatic brain injury: developing the evidence base

    PubMed Central

    Kolias, Angelos G.; Adams, Hadie; Timofeev, Ivan; Czosnyka, Marek; Corteen, Elizabeth A.; Pickard, John D.; Turner, Carole; Gregson, Barbara A.; Kirkpatrick, Peter J.; Murray, Gordon D.; Menon, David K.; Hutchinson, Peter J.

    2016-01-01

    Abstract In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of “opening the skull” in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented. PMID:26972805

  18. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

    2012-01-01

    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…

  19. Depression After Brain Injury: A Guide for Patients and Their Caregivers

    MedlinePlus

    ... a> Consumer Summary – Apr. 13, 2011 Depression After Brain Injury: A Guide for Patients and Their Caregivers ... productID=658 . Understanding Your Condition What is traumatic brain injury? Traumatic brain injury (TBI) is the medical ...

  20. Brain Injury among Children and Adolescents. Tip Cards.

    ERIC Educational Resources Information Center

    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…

  1. Community-Based Employment Following Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Thomas, Dale F., Ed.; And Others

    This collection of papers on vocational rehabilitation of persons impaired as a result of traumatic brain injury is designed to provide a resource for individuals concerned with community-based employment. The 11 papers include: "Training Persons with Traumatic Brain Injury for Complex Computer Jobs: The Domain-Specific Learning Approach"…

  2. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    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…

  3. Students with Acquired Brain Injury. The School's Response.

    ERIC Educational Resources Information Center

    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…

  4. Traumatic Brain Injury - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Traumatic Brain Injury URL of this page: https://www.nlm. ... W XYZ List of All Topics All Traumatic Brain Injury - Multiple Languages To use the sharing features on this page, ...

  5. Traumatic brain injury: a risk factor for neurodegenerative diseases.

    PubMed

    Gupta, Rajaneesh; Sen, Nilkantha

    2016-01-01

    Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages. PMID:26352199

  6. The role of the immune system in central nervous system plasticity after acute injury

    PubMed Central

    Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-01-01

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system. In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that ultimately are associated to intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  7. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  8. Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain

    PubMed Central

    Li, Nan; Yang, Ya; Glover, David P.; Zhang, Jiangyang; Saraswati, Manda; Robertson, Courtney

    2014-01-01

    Abstract The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. We investigated the altered cortical plasticity 2–3 weeks after injury in a pediatric rat model of TBI. Significant decreases in neurophysiological responses across the depth of the noninjured, primary somatosensory cortex (S1) in TBI rats, compared to age-matched controls, were detected with electrophysiological measurements of multi-unit activity (86.4% decrease), local field potential (75.3% decrease), and functional magnetic resonance imaging (77.6% decrease). Because the corpus callosum is a clinically important white matter tract that was shown to be consistently involved in post-traumatic axonal injury, we investigated its anatomical and functional characteristics after TBI. Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks. PMID:24050267

  9. MicroRNAs in acute kidney injury.

    PubMed

    Fan, Pei-Chun; Chen, Chia-Chun; Chen, Yung-Chang; Chang, Yu-Sun; Chu, Pao-Hsien

    2016-01-01

    Acute kidney injury (AKI) is an important clinical issue that is associated with significant morbidity and mortality. Despite research advances over the past decades, the complex pathophysiology of AKI is not fully understood. The regulatory mechanisms underlying post-AKI repair and fibrosis have not been clarified either. Furthermore, there is no definitively effective treatment for AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23 nucleotides that have been shown to be crucial to the post-transcriptional regulation of various cellular biological functions, including proliferation, differentiation, metabolism, and apoptosis. In addition to being fundamental to normal development and physiology, miRNAs also play important roles in various human diseases. In AKI, some miRNAs appear to act pathogenically by promoting inflammation, apoptosis, and fibrosis, while others may act protectively by exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenic effects. Thus, miRNAs have not only emerged as novel biomarkers for AKI; they also hold promise to be potential therapeutic targets. PMID:27608623

  10. Simultaneous cesarean delivery and craniotomy in a term pregnant patient with traumatic brain injury

    PubMed Central

    Tawfik, Mohamed Mohamed; Badran, Basma Abed; Eisa, Ahmed Amin; Barakat, Rafik Ibrahim

    2015-01-01

    The management of pregnant patients with traumatic brain injury is challenging. A multidisciplinary team approach is mandatory, and management should be individualized according to the type and extent of injury, maternal status, gestational age, and fetal status. We report a 27-year-old term primigravida presenting after head injury with Glasgow coma scale score 11 and anisocoria. Depressed temporal bone fracture and acute epidural hematoma were diagnosed, necessitating an urgent neurosurgery. Her fetus was viable with no signs of distress and no detected placental abnormalities. Cesarean delivery was performed followed by craniotomy in the same setting under general anesthesia with good outcome of the patient and her baby. PMID:25829914

  11. Pediatric Traumatic Brain Injury. Special Topic Report #3.

    ERIC Educational Resources Information Center

    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.,…

  12. Training to Optimize Learning after Traumatic Brain Injury

    PubMed Central

    Skidmore, Elizabeth R.

    2015-01-01

    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

  13. Severe physical exertion, oxidative stress, and acute lung injury.

    PubMed

    Shah, Nikunj R; Iqbal, M Bilal; Barlow, Andrew; Bayliss, John

    2011-11-01

    We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID:22064719

  14. Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury.

    PubMed

    Cartagena, Casandra M; Mountney, Andrea; Hwang, Hye; Swiercz, Adam; Rammelkamp, Zoe; Boutte, Angela M; Shear, Deborah A; Tortella, Frank C; Schmid, Kara E

    2016-01-01

    Traumatic brain injury (TBI) is an established risk factor for the development of Alzheimer's disease (AD). Here the effects of severe penetrating TBI on APP and tau cleavage processing were investigated in a rodent model of penetrating ballistic-like brain injury (PBBI). PBBI was induced by stereotactically inserting a perforated steel probe through the right frontal cortex of the anesthetized rat and rapidly inflating/deflating the probe's elastic tubing into an elliptical shaped balloon to 10% of total rat brain volume causing temporary cavitation injury. Separate animals underwent probe injury (PrI) alone without balloon inflation. Shams underwent craniectomy. Brain tissue was collected acutely (4h, 24h, 3d) and subacutely (7d) post-injury and analyzed by immunoblot for full length APP (APP-FL) and APP beta c-terminal fragments (βCTFs), full length tau (tau-FL) and tau truncation fragments and at 7d for cytotoxic Beta amyloid (Aβ) peptides Aβ40 and Aβ42 analysis. APP-FL was significantly decreased at 3d and 7d following PBBI whereas APP βCTFs were significantly elevated by 4h post-injury and remained elevated through 7d post-injury. Effects on βCTFs were mirrored with PrI, albeit to a lesser extent. Aβ40 and Aβ42 were significantly elevated at 7d following PBBI and PrI. Tau-FL decreased substantially 3d and 7d post-PBBI and PrI. Importantly, a 22 kDa tau fragment (tau22), similar to that found in AD, was significantly elevated by 4h and remained elevated through 7d post-injury. Thus both APP and tau cleavage was dramatically altered in the acute and subacute periods post-injury. As cleavage of these proteins has also been implicated in AD, TBI pathology shown here may set the stage for the later development of AD or other tauopathies. PMID:27428544

  15. Neuron specific enolase: a promising therapeutic target in acute spinal cord injury.

    PubMed

    Haque, Azizul; Ray, Swapan K; Cox, April; Banik, Naren L

    2016-06-01

    Enolase is a multifunctional protein, which is expressed abundantly in the cytosol. Upon stimulatory signals, enolase can traffic to cell surface and contribute to different pathologies including injury, autoimmunity, infection, inflammation, and cancer. Cell-surface expression of enolase is often detected on activated macrophages, microglia/macrophages, microglia, and astrocytes, promoting extracellular matrix degradation, production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury and inflammation. Inflammatory stimulation also induces translocation of enolase from the cytosolic pool to the cell surface where it can act as a plasminogen receptor and promote extracellular matrix degradation and tissue damage. Spinal cord injury (SCI) is a devastating debilitating condition characterized by progressive pathological changes including complex and evolving molecular cascades, and insights into the role of enolase in multiple inflammatory events have not yet been fully elucidated. Neuronal damage following SCI is associated with an elevation of neuron specific enolase (NSE), which is also known to play a role in the pathogenesis of hypoxic-ischemic brain injury. Thus, NSE is now considered as a biomarker in ischemic brain damage, and it has recently been suggested to be a biomarker in traumatic brain injury (TBI), stroke and anoxic encephalopathy after cardiac arrest and acute SCI as well. This review article gives an overview of the current basic research and clinical studies on the role of multifunctional enolase in neurotrauma, with a special emphasis on NSE in acute SCI. PMID:26847611

  16. [PARTICULAR QUALITIES OF DIAGNOSTIC ACUTE LATERAL ANKLE LIGAMENT INJURIES].

    PubMed

    Krasnoperov, S N; Shishka, I V; Golovaha, M L

    2015-01-01

    Delayed diagnosis of acute lateral ankle ligaments injury and subsequent inadequate treatment leads to the development of chronic instability and rapid progression of degenerative processes in the joint. The aim of our work was to improve treatment results by developing an diagnostic algorithm and treatment strategy of acute lateral ankle ligament injuries. The study included 48 patients with history of acute inversion ankle injury mechanism. Diagnostic protocol included clinical and radiological examination during 48 hours and after 7-10 days after injury. According to the high rate of inaccurate clinical diagnosis in the first 48 hours of the injury a short course of conservative treatment for 7-10 days is needed with follow-up and controlling clinical and radiographic instability tests. Clinical symptoms of ankle inversion injury showed that the combination of local tenderness in the projection of damaged ligaments, the presence of severe periarticular hematoma in the lateral department and positive anterior drawer and talar tilt tests in 7-10 days after the injury in 87% of cases shows the presence of ligament rupture. An algorithm for diagnosis of acute lateral ankle ligament injury was developed, which allowed us to determine differential indications for surgical repair of the ligaments and conservative treatment of these patients. PMID:27089717

  17. The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

    PubMed Central

    Sun, Dong

    2016-01-01

    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

  18. Rehospitalization During the 9-Months Following Inpatient Rehabilitation for Traumatic Brain Injury

    PubMed Central

    Hammond, Flora M.; Horn, Susan D.; Smout, Randall J.; Seel, Ronald T.; Beaulieu, Cynthia L.; Corrigan, John D.; Barrett, Ryan S.; Cullen, Nora; Sommerfeld, Teri; Brandstater, Murray E.

    2015-01-01

    Objective To investigate frequency of, causes for, and factors associated with acute rehospitalization following discharge from inpatient rehabilitation during the 9-months after traumatic brain injury (TBI). Design Multi-center observational cohort. Setting Community. Participants 1,850 individuals with TBI admitted for inpatient rehabilitation. Interventions Not applicable. Main Outcome Measure(s) Occurrences of proxy or self-report of post-rehabilitation acute care rehospitalization, and length of and causes for rehospitalizations. Results 510 participants (28%) had experienced 775 acute rehospitalizations. All experienced 1 admission (510 participants; 66%), while 154 (20%) had 2 admissions, 60 (8%) had 3, 23 (3%) had 4, 27 had between 5 and 11, and 1 had 12. The most common rehospitalization causes were: infection (15%), neurologic issues (13%), neurosurgical procedures (11%), injury (7%), psychiatric (7%), and orthopedic (7%). Mean days from rehabilitation discharge to first rehospitalization was 113 days. Mean rehospitalization duration was 6.5 days. Logistic regression revealed increasing age, history of seizures prior to injury or during acute care or rehabilitation, history of previous brain injuries, and non-brain injury medical severity increased the risk of rehospitalization. Injury etiology of motor vehicular crash and high motor functioning at discharge decreased rehospitalization risk. Conclusion(s) Approximately 28% of TBI patients were rehospitalized within 9-months of TBI rehabilitation discharge due to a wide variety of medical and surgical reasons. Future research should evaluate if some of these occurrences may be preventable (such as infections, injuries, and psychiatric readmissions), and should evaluate the extent that persons at risk may benefit from additional screening, surveillance, and treatment protocols. PMID:26212407

  19. MRI in acute ligamentous injuries of the ankle.

    PubMed

    Martella, Ilenia; Azzali, Emanuele; Milanese, Gianluca; Praticò, Francesco Emanuele; Ruggirello, Margherita; Trunfio, Vincenzo; Parziale, Raffaele; Corrado, Michele; Della Casa, Giovanni; Capasso, Raffaella; De Filippo, Massimo

    2016-01-01

    Ankle sprains are the most common lower limb injuries and affect more frequently young athletes; imaging is needed for an accurate diagnosis of such traumatic injuries. The purpose of this review is to analyse the magnetic resonance (MR) findings of both normal and pathological ankle's ligaments; indeed, MRI is the gold standard for the diagnosis of acute traumatic injuries and is useful for differentiation of the causes of ankle instability as well as for pre-operative planning. PMID:27467862

  20. Unique aspects of downhill ski injuries part 2: diagnosis and acute management of specific injuries.

    PubMed

    Buck, P G; Sophocles, A M; Beckenbaugh, R D

    1982-04-01

    As in many sports, a wide spectrum of injuries is seen in skiing (Table 1). This includes injuries to the upper and lower extremities as well as miscellaneous injuries and medical problems (frostbite, hypothermia, and high altitude effects). Six relatively unique injuries in skiing will be presented in detail. The discussion will focus on the acute management of these injuries: subluxing peroneal tendons, fibular stress fractures, tibial shaft fractures (spiral, transverse), medical compartment knee injuries, anterior shoulder dislocations with associated greater tuberosity fractures, and gamekeeper's thumb. PMID:24822536

  1. Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    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

    2016-03-15

    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. PMID:26671550

  2. Acute traumatic injuries in automotive manufacturing.

    PubMed

    Warner, M; Baker, S P; Li, G; Smith, G S

    1998-10-01

    Motor vehicle manufacturing, with its varied tasks, challenging work environment, and diverse worker populations, presents many hazards to employees. This study examined routinely collected surveillance data from a major motor vehicle manufacturer to identify injury types, high-risk workers, causes of injury, and factors associated with work loss. Injury and personnel data were used to calculate injury rates. Injury data were from the routinely collected medical and safety surveillance system on occupational injuries. The number of persons working in the plants was estimated using year-end personnel reports. Key word searches supplementing the analyses provided insight into the specific circumstances of injury. The most common injuries were sprains/strains (39% of the total), lacerations (22%), and contusions (15%). Forty-nine percent of the injuries resulted in one or more lost or restricted workdays; 25% resulted in 7 or more lost or restricted workdays. The injuries most likely to result in work loss were amputations, hernias and fractures. Sprains/strains accounted for 65% of all lost workdays. Injury rates ranged from 13.8 per 100 person-years at stamping plants to 28.7 at parts depots. Even within similar types of plants, injury rates varied widely, with a twofold difference among the individual assembly plants in overall injury rates. Injury surveillance systems with descriptive data on injury events shed light on the circumstances under which certain types of injuries occur and can provide the basis for preventive interventions. Sources of variation and potential biases are discussed, providing guidance for those interested in designing and using surveillance systems for occupational injuries. PMID:9750941

  3. Hyperbaric oxygen therapy for traumatic brain injury

    PubMed Central

    2011-01-01

    Traumatic brain injury (TBI) is a major public health issue. The complexity of TBI has precluded the use of effective therapies. Hyperbaric oxygen therapy (HBOT) has been shown to be neuroprotective in multiple neurological disorders, but its efficacy in the management of TBI remains controversial. This review focuses on HBOT applications within the context of experimental and clinical TBI. We also discuss its potential neuroprotective mechanisms. Early or delayed multiple sessions of low atmospheric pressure HBOT can reduce intracranial pressure, improve mortality, as well as promote neurobehavioral recovery. The complimentary, synergistic actions of HBOT include improved tissue oxygenation and cellular metabolism, anti-apoptotic, and anti-inflammatory mechanisms. Thus HBOT may serve as a promising neuroprotective strategy that when combined with other therapeutic targets for TBI patients which could improve long-term outcomes. PMID:22146562

  4. Demyelination as a rational therapeutic target for ischemic or traumatic brain injury.

    PubMed

    Shi, Hong; Hu, Xiaoming; Leak, Rehana K; Shi, Yejie; An, Chengrui; Suenaga, Jun; Chen, Jun; Gao, Yanqin

    2015-10-01

    Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients. PMID:25819104

  5. Iatrogenic traumatic brain injury during tooth extraction.

    PubMed

    Troxel, Mark

    2015-01-01

    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. PMID:25695556

  6. Sexual changes associated with traumatic brain injury.

    PubMed

    Ponsford, Jennie

    2003-01-01

    Findings from numerous outcome studies have suggested that people with traumatic brain injuries (TBI) experience relationship difficulties and changes in sexuality. However, there have been few investigations of these problems. This paper reports the results of a study of sexuality following TBI, which aimed to identify changes in sexual behaviour, affect, self-esteem, and relationship quality, and their inter-relationships. Two hundred and eight participants with moderate-to-severe TBI (69% males) completed a questionnaire 1-5 years post-injury. Their responses were compared with those of 150 controls, matched for age, gender, and education. Of TBI participants 36-54% reported: (1) A decrease in the importance of sexuality, opportunities, and frequency of engaging in sexual activities; (2) reduced sex drive; (3) a decline in their ability to give their partner sexual satisfaction and to engage in sexual intercourse; and (4) decreased enjoyment of sexual activity and ability to stay aroused and to climax. The frequencies of such negative changes were significantly higher than those reported by controls and far outweighed the frequency of increases on these dimensions. A significant proportion of TBI participants also reported decreased self-confidence, sex appeal, higher levels of depression, and decreased communication levels and relationship quality with their sexual partner. Factors associated with sexual problems in the TBI group are explored and implications of all findings discussed. PMID:21854338

  7. Recent advances in the understanding of acute kidney injury

    PubMed Central

    Tögel, Florian

    2014-01-01

    Acute kidney injury (AKI) is a common clinical entity associated with high morbidity and mortality and clinical costs. The pathophysiology is multifaceted and involves inflammation, tubular injury, and vascular damage. Recently identified components include necroptosis, a special form of cell death, and autophagy. Most of the pathophysiological knowledge is obtained from animal models but these do not directly reflect the reality of the clinical situation. Tubular cells have a remarkable capacity to regenerate, and the role of stem/progenitor cells is discussed. Acute kidney injury is frequently associated with chronic kidney disease, and the implications are widespread. PMID:25343040

  8. Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.

    PubMed

    Hanley, Daniel F; Chabot, Robert; Mould, W Andrew; Morgan, Timothy; Naunheim, Rosanne; Sheth, Kevin N; Chiang, William; Prichep, Leslie S

    2013-12-15

    This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity. PMID:24040943

  9. Microglia and Inflammation: Impact on Developmental Brain Injuries

    ERIC Educational Resources Information Center

    Chew, Li-Jin; Takanohashi, Asako; Bell, Michael

    2006-01-01

    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…

  10. Molecular determinants of acute kidney injury

    PubMed Central

    Husi, Holger; Human, Christin

    2015-01-01

    Abstract: Background: Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage. Methods: An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events. Results: The renin-angiotensin-aldosterone-system (RAAS) axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha (TNF α) and transforming growth factor beta (TGF β) signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor. Conclusions: Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically intervene in the

  11. Sports-related brain injuries: connecting pathology to diagnosis.

    PubMed

    Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

    2016-04-01

    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. PMID:27032917

  12. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury.

    PubMed

    Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H; Stewart, William

    2016-05-23

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article. PMID:26772317

  13. Molecular mediators of favism-induced acute kidney injury.

    PubMed

    García-Camín, Rosa María; Goma, Montserrat; Osuna, Rosa García; Rubio-Navarro, Alfonso; Buendía, Irene; Ortiz, Alberto; Egido, Jesús; Manzarbeitia, Félix; Chevarria, Julio Leonel; Gluksmann, María Constanza; Moreno, Juan Antonio

    2014-03-01

    Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury. PMID:23006341

  14. Experimental Traumatic Brain Injury Alters Ethanol Consumption and Sensitivity

    PubMed Central

    Lowing, Jennifer L.; Susick, Laura L.; Caruso, James P.; Provenzano, Anthony M.; Raghupathi, Ramesh

    2014-01-01

    Abstract Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of

  15. Erythropoietin as a Neuroprotectant for Neonatal Brain Injury: Animal Models

    PubMed Central

    Traudt, Christopher M.; Juul, Sandra E.

    2016-01-01

    Prematurity and perinatal hypoxia-ischemia are common problems that result in significant neurodevelopmental morbidity and high mortality worldwide. The Vannucci model of unilateral brain injury was developed to model perinatal brain injury due to hypoxia-ischemia. Because the rodent brain is altricial, i.e., it develops postnatally, investigators can model either preterm or term brain injury by varying the age at which injury is induced. This model has allowed investigators to better understand developmental changes that occur in susceptibility of the brain to injury, evolution of brain injury over time, and response to potential neuroprotective treatments. The Vannucci model combines unilateral common carotid artery ligation with a hypoxic insult. This produces injury of the cerebral cortex, basal ganglia, hippocampus, and periventricular white matter ipsilateral to the ligated artery. Varying degrees of injury can be obtained by varying the depth and duration of the hypoxic insult. This chapter details one approach to the Vannucci model and also reviews the neuroprotective effects of erythropoietin (Epo), a neuroprotective treatment that has been extensively investigated using this model and others. PMID:23456865

  16. Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

    PubMed Central

    Ma, H.; Sinha, B.; Pandya, R.S.; Lin, N.; Popp, A.J.; Li, J.; Yao, J.; Wang, X.

    2014-01-01

    Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury. PMID:22834830

  17. The incidence of acute hospital-treated eye injuries.

    PubMed

    Karlson, T A; Klein, B E

    1986-10-01

    Little information is available on the incidence and severity of eye injuries despite the disfigurement and vision loss they cause. From a population-based study in Dane County, Wisconsin, the incidence of acute hospital-treated eye injuries was 423/100,000 residents in 1979. The most common causes of eye injuries were assaults, work-related events, sports and recreational activities, motor vehicle crashes, and falls. Consumer products were involved in almost 70% (9/13) of severe eye injuries classified as severe. Injuries from fireworks were not found at all in this population. Implementing known strategies for eye injury prevention would substantially reduce their incidence. These include requiring certified eye protectors at workplaces and in sports activities whenever possible rather than making their use voluntary. For the preponderance of eye injuries, however, modifying potentially hazardous consumer products, including the interior of passenger cars, will be necessary. PMID:3767676

  18. Motor Vehicle Crash Brain Injury in Infants and Toddlers: A Suitable Model for Inflicted Head Injury?

    ERIC Educational Resources Information Center

    Shah, Mahim; Vavilala, Monica S.; Feldman, Kenneth W.; Hallam, Daniel K.

    2005-01-01

    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…

  19. Glucose and oxygen metabolism after penetrating ballistic-like brain injury

    PubMed Central

    Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

  20. DARPA challenge: developing new technologies for brain and spinal injuries

    NASA Astrophysics Data System (ADS)

    Macedonia, Christian; Zamisch, Monica; Judy, Jack; Ling, Geoffrey

    2012-06-01

    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.

  1. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury

    PubMed Central

    Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M.; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Thompson, Paul M.; Asarnow, Robert F.

    2016-01-01

    Abstract Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1–6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI. PMID:26393494

  2. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury.

    PubMed

    Dennis, Emily L; Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C; Thompson, Paul M; Asarnow, Robert F

    2016-05-01

    Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1-6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI. PMID:26393494

  3. Assessing neuro-systemic & behavioral components in the pathophysiology of blast-related brain injury.

    PubMed

    Kobeissy, Firas; Mondello, Stefania; Tümer, Nihal; Toklu, Hale Z; Whidden, Melissa A; Kirichenko, Nataliya; Zhang, Zhiqun; Prima, Victor; Yassin, Walid; Anagli, John; Chandra, Namas; Svetlov, Stan; Wang, Kevin K W

    2013-01-01

    Among the U.S. military personnel, blast injury is among the leading causes of brain injury. During the past decade, it has become apparent that even blast injury as a form of mild traumatic brain injury (mTBI) may lead to multiple different adverse outcomes, such as neuropsychiatric symptoms and long-term cognitive disability. Blast injury is characterized by blast overpressure, blast duration, and blast impulse. While the blast injuries of a victim close to the explosion will be severe, majority of victims are usually at a distance leading to milder form described as mild blast TBI (mbTBI). A major feature of mbTBI is its complex manifestation occurring in concert at different organ levels involving systemic, cerebral, neuronal, and neuropsychiatric responses; some of which are shared with other forms of brain trauma such as acute brain injury and other neuropsychiatric disorders such as post-traumatic stress disorder. The pathophysiology of blast injury exposure involves complex cascades of chronic psychological stress, autonomic dysfunction, and neuro/systemic inflammation. These factors render blast injury as an arduous challenge in terms of diagnosis and treatment as well as identification of sensitive and specific biomarkers distinguishing mTBI from other non-TBI pathologies and from neuropsychiatric disorders with similar symptoms. This is due to the "distinct" but shared and partially identified biochemical pathways and neuro-histopathological changes that might be linked to behavioral deficits observed. Taken together, this article aims to provide an overview of the current status of the cellular and pathological mechanisms involved in blast overpressure injury and argues for the urgent need to identify potential biomarkers that can hint at the different mechanisms involved. PMID:24312074

  4. Assessing Neuro-Systemic & Behavioral Components in the Pathophysiology of Blast-Related Brain Injury

    PubMed Central

    Kobeissy, Firas; Mondello, Stefania; Tümer, Nihal; Toklu, Hale Z.; Whidden, Melissa A.; Kirichenko, Nataliya; Zhang, Zhiqun; Prima, Victor; Yassin, Walid; Anagli, John; Chandra, Namas; Svetlov, Stan; Wang, Kevin K. W.

    2013-01-01

    Among the U.S. military personnel, blast injury is among the leading causes of brain injury. During the past decade, it has become apparent that even blast injury as a form of mild traumatic brain injury (mTBI) may lead to multiple different adverse outcomes, such as neuropsychiatric symptoms and long-term cognitive disability. Blast injury is characterized by blast overpressure, blast duration, and blast impulse. While the blast injuries of a victim close to the explosion will be severe, majority of victims are usually at a distance leading to milder form described as mild blast TBI (mbTBI). A major feature of mbTBI is its complex manifestation occurring in concert at different organ levels involving systemic, cerebral, neuronal, and neuropsychiatric responses; some of which are shared with other forms of brain trauma such as acute brain injury and other neuropsychiatric disorders such as post-traumatic stress disorder. The pathophysiology of blast injury exposure involves complex cascades of chronic psychological stress, autonomic dysfunction, and neuro/systemic inflammation. These factors render blast injury as an arduous challenge in terms of diagnosis and treatment as well as identification of sensitive and specific biomarkers distinguishing mTBI from other non-TBI pathologies and from neuropsychiatric disorders with similar symptoms. This is due to the “distinct” but shared and partially identified biochemical pathways and neuro-histopathological changes that might be linked to behavioral deficits observed. Taken together, this article aims to provide an overview of the current status of the cellular and pathological mechanisms involved in blast overpressure injury and argues for the urgent need to identify potential biomarkers that can hint at the different mechanisms involved. PMID:24312074

  5. Erythropoietin 2nd cerebral protection after acute injuries: a double-edged sword?

    PubMed

    Velly, L; Pellegrini, L; Guillet, B; Bruder, N; Pisano, P

    2010-12-01

    Over the past 15 years, a large body of evidence has revealed that the cytokine erythropoietin exhibits non-erythropoietic functions, especially tissue-protective effects. The discovery of EPO and its receptors in the central nervous system and the evidence that EPO is made locally in response to injury as a protective factor in the brain have raised the possibility that recombinant human EPO (rhEPO) could be administered as a cytoprotective agent after acute brain injuries. This review highlights the potential applications of rhEPO as a neuroprotectant in experimental and clinical settings such as ischemia, traumatic brain injury, and subarachnoid and intracerebral hemorrhage. In preclinical studies, EPO prevented apoptosis, inflammation, and oxidative stress induced by injury and exhibited strong neuroprotective and neurorestorative properties. EPO stimulates vascular repair by facilitating endothelial progenitor cell migration into the brain and neovascularisation, and it promotes neurogenesis. In humans, small clinical trials have shown promising results but large prospective randomized studies failed to demonstrate a benefit of EPO for brain protection and showed unwanted side effects, especially thrombotic complications. Recently, regions have been identified within the EPO molecule that mediate tissue protection, allowing the development of non-erythropoietic EPO variants for neuroprotection conceptually devoid of side effects. The efficacy and the safety profile of these new compounds are still to be demonstrated to obtain, in patients, the benefits observed in experimental studies. PMID:20732352

  6. Driving after traumatic brain injury: evaluation and rehabilitation interventions

    PubMed Central

    Schultheis, Maria T.; Whipple, Elizabeth

    2014-01-01

    The ability to return to driving is a common goal for individuals who have sustained a traumatic brain injury. However, specific and empirically validated guidelines for clinicians who make the return-to-drive decision are sparse. In this article, we attempt to integrate previous findings on driving after brain injury and detail the cognitive, motor, and sensory factors necessary for safe driving that may be affected by brain injury. Various forms of evaluation (both in clinic and behind-the-wheel) are discussed, as well as driver retraining and modifications that may be necessary. PMID:25436178

  7. Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury

    PubMed Central

    Schoch, Kathleen M.; Evans, Heather N.; Brelsfoard, Jennifer M.; Madathil, Sindhu K.; Takano, Jiro; Saido, Takaomi C.; Saatman, Kathryn E.

    2012-01-01

    Traumatic brain injury (TBI) results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Although the specific inhibitor of calpains, calpastatin, is present within neurons, normal levels of calpastatin are unable to fully prevent the damaging proteolytic activity of calpains after injury. In this study, increased calpastatin expression was achieved using transgenic mice that overexpress the human calpastatin (hCAST) construct under control of a calcium-calmodulin dependent kinase II α promoter. Naïve hCAST transgenic mice exhibited enhanced neuronal calpastatin expression and significantly reduced protease activity. Acute calpain-mediated spectrin proteolysis in the cortex and hippocampus induced by controlled cortical impact brain injury was significantly attenuated in calpastatin overexpressing mice. Aspects of posttraumatic motor and cognitive behavioral deficits were also lessened in hCAST transgenic mice compared to their wildtype littermates. However, volumetric analyses of neocortical contusion revealed no histological neuroprotection at either acute or long-term time points. Partial hippocampal neuroprotection observed at a moderate injury severity was lost after severe TBI. This study underscores the effectiveness of calpastatin overexpression in reducing calpain-mediated proteolysis and behavioral impairment after TBI, supporting the therapeutic potential for calpain inhibition. In addition, the reduction in spectrin proteolysis without accompanied neocortical neuroprotection suggests the involvement of other factors that are critical for neuronal survival after contusion brain injury. PMID:22572592

  8. Self-awareness and traumatic brain injury outcome

    PubMed Central

    Robertson, Kayela; Schmitter-Edgecombe, Maureen

    2016-01-01

    Primary Objective Impaired self-awareness following a traumatic brain injury (TBI) can reduce the effectiveness of rehabilitation, resulting in poorer outcomes. However, little is understood about how the multi-dimensional aspects of self-awareness may differentially change with recovery and impact outcome. Thus, we examined four self-awareness variables represented in the Dynamic Comprehensive Model of Awareness: metacognitive awareness, anticipatory awareness, error-monitoring, and self-regulation. Research Design We evaluated change of the self-awareness measures with recovery from TBI and whether the self-awareness measures predicted community reintegration at follow-up. Methods and Procedures Participants were 90 individuals with moderate to severe TBI who were tested acutely following injury and 90 age-matched controls. Forty-nine of the TBI participants and 49 controls were re-tested after 6 months. Main Outcome and Results Results revealed that the TBI group’s error-monitoring performance was significantly poorer than controls at both baseline and follow-up. Regression analyses revealed that the self-awareness variables at follow-up were predictive of community reintegration, with error-monitoring being a unique predictor. Conclusions Our results highlight the importance of error-monitoring and suggest that interventions targeted at improving error-monitoring may be particularly beneficial. Understanding the multi-dimensional nature of self-awareness will further improve rehabilitation efforts and understanding of the theoretical basis of self-awareness. PMID:25915097

  9. Traumatic brain injury, axonal injury and shaking in New Zealand sea lion pups.

    PubMed

    Roe, W D; Mayhew, I G; Jolly, R D; Marshall, J; Chilvers, B L

    2014-04-01

    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. PMID:24565687

  10. The interplay between neuropathology and activity based rehabilitation after traumatic brain injury.

    PubMed

    Kreber, Lisa A; Griesbach, Grace S

    2016-06-01

    Exercise has been shown to facilitate the release of molecules that support neuroplasticity and to offer protection from brain damage. This article addresses the mechanisms behind exercise׳s beneficial effects within the context of traumatic brain injury (TBI). First, we describe how ongoing metabolic, neuroendocrine and inflammatory alterations after TBI interact with exercise. Given the dynamic nature of TBI-initiated pathophysiological processes, the timing, intensity and type of exercise need to be considered when implementing exercise. These factors have been shown to be important in determining whether exercise enhances or impedes neuroplasticity after TBI. In point of fact, intense exercise during the acute post-injury period has been associated with worsened cognitive performance. Similarly, exercise that is associated with a pronounced increase of stress hormones can inhibit the expression of brain derived neurotrophic factor that is usually increased with exercise. Second, we describe the clinical implications of these findings in returning to play following TBI. Finally, we address therapeutic exercise interventions in the context of rehabilitation following TBI. Exercise is likely to play an important role in improving cognitive and affective outcome during post-acute rehabilitation. It is important to take into account relevant patient, injury, and exercise variables when utilizing exercise as a therapeutic intervention to ensure that physical exercise programs promote adaptive neuroplasticity and hence recovery. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26776479

  11. Brain injury causes loss of cardiovascular response to hemorrhagic shock.

    PubMed

    Fulton, R L; Flynn, W J; Mancino, M; Bowles, D; Cryer, H M

    1993-01-01

    The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective. PMID:8512886

  12. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  13. Brain injury tolerance limit based on computation of axonal strain.

    PubMed

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy

    2016-07-01

    Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI. PMID:27038501

  14. The King's Outcome Scale for Childhood Head Injury and Injury Severity and Outcome Measures in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Calvert, Sophie; Miller, Helen E.; Curran, Andrew; Hameed, Biju; McCarter, Renee; Edwards, Richard J.; Hunt, Linda; Sharples, Peta Mary

    2008-01-01

    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…

  15. Utility of EEG measures of brain function in patients with acute stroke.

    PubMed

    Wu, Jennifer; Srinivasan, Ramesh; Burke Quinlan, Erin; Solodkin, Ana; Small, Steven L; Cramer, Steven C

    2016-06-01

    EEG has been used to study acute stroke for decades; however, because of several limitations EEG-based measures rarely inform clinical decision-making in this setting. Recent advances in EEG hardware, recording electrodes, and EEG software could overcome these limitations. The present study examined how well dense-array (256 electrodes) EEG, acquired with a saline-lead net and analyzed with whole brain partial least squares (PLS) modeling, captured extent of acute stroke behavioral deficits and varied in relation to acute brain injury. In 24 patients admitted for acute ischemic stroke, 3 min of resting-state EEG was acquired at bedside, including in the ER and ICU. Traditional quantitative EEG measures (power in a specific lead, in any frequency band) showed a modest association with behavioral deficits [NIH Stroke Scale (NIHSS) score] in bivariate models. However, PLS models of delta or beta power across whole brain correlated strongly with NIHSS score (R(2) = 0.85-0.90) and remained robust when further analyzed with cross-validation models (R(2) = 0.72-0.73). Larger infarct volume was associated with higher delta power, bilaterally; the contralesional findings were not attributable to mass effect, indicating that EEG captures significant information about acute stroke effects not available from MRI. We conclude that 1) dense-array EEG data are feasible as a bedside measure of brain function in patients with acute stroke; 2) high-dimension EEG data are strongly correlated with acute stroke behavioral deficits and are superior to traditional single-lead metrics in this regard; and 3) EEG captures significant information about acute stroke injury not available from structural brain imaging. PMID:26936984

  16. Structural and functional connectivity in traumatic brain injury

    PubMed Central

    Xiao, Hui; Yang, Yang; Xi, Ji-hui; Chen, Zi-qian

    2015-01-01

    Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID:26889200

  17. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.