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Brain Injury (brain + injury)
Kinds of Brain Injury Selected AbstractsCURRENT CONTROVERSIES IN THE MANAGEMENT OF PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURYANZ JOURNAL OF SURGERY, Issue 3 2006Alexios A. Adamides Background: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the ,cerebral perfusion pressure-targeted' and ,volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy. Methods: A review of the literature was performed to examine the evidence base behind each intervention. Results: There is no class I evidence to support the routine use of any of the therapies examined. Conclusion: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful. [source] Newborn Brain Injuries During ChildbirthNURSING FOR WOMENS HEALTH, Issue 3 2003Carolyn Davis Cockey MLS executive editor No abstract is available for this article. [source] Ethnic and Racial Disparities in Emergency Department Care for Mild Traumatic Brain InjuryACADEMIC EMERGENCY MEDICINE, Issue 11 2003Jeffrey J. Bazarian MD Abstract Objectives: To identify racial, ethnic, and gender disparities in the emergency department (ED) care for mild traumatic brain injury (mTBI). Methods: A secondary analysis of ED visits in the National Hospital Ambulatory Medical Care Survey for the years 1998 through 2000 was performed. Cases of mTBI were identified using ICD-9 codes 800.0, 800.5, 850.9, 801.5, 803.0, 803.5, 804.0, 804.5, 850.0, 850.1, 850.5, 850.9, 854.0, and 959.01. ED care variables related to imaging, procedures, treatments, and disposition were analyzed along racial, ethnic, and gender categories. The relationship between race, ethnicity, and selected ED care variables was analyzed using multivariate logistic regression with control for associated injuries, geographic region, and insurance type. Results: The incidence of mTBI was highest among men (590/100,000), Native Americans/Alaska Natives (1026.2/100,000), and non-Hispanics (391.1/100,000). After controlling for important confounders, Hispanics were more likely than non-Hispanics to receive a nasogastric tube (OR, 6.36; 95% CI = 1.2 to 33.6); nonwhites were more likely to receive ED care by a resident (OR, 3.09; 95% CI = 1.9 to 5.0) and less likely to be sent back to the referring physician after ED discharge (OR, 0.47; 95% CI = 0.3 to 0.9). Men and women received equivalent ED care. Conclusions: There are significant racial and ethnic but not gender disparities in ED care for mTBI. The causes of these disparities and the relationship between these disparities and post-mTBI outcome need to be examined. [source] Blood Pressure and Brain Injury in Older Adults: Findings from a Community-Based Autopsy StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2009Lucy Y. Wang MD OBJECTIVES: To examine correlations between blood pressure (BP) and dementia-related pathological brain changes in a community-based autopsy sample. DESIGN: Prospective cohort study. SETTING: A large health maintenance organization in Seattle, Washington. PARTICIPANTS: A cohort of 250 participants aged 65 and older and cognitively normal at time of enrollment in the Adult Changes in Thought (ACT) Study and who underwent autopsy. MEASUREMENTS: BP and history of antihypertensive treatment were taken at enrollment. A linear regression model was used to examine the relationship between BP (systolic (SBP) and diastolic (DBP)) at enrollment and pathological changes in the cerebrum (cystic macroscopic infarcts, microinfarcts, neuritic plaques, neurofibrillary tangles, and cortical Lewy bodies). RESULTS: The presence of more than 2 microinfarcts, but not any other pathological change, was independently associated with SBP in younger participants (65,80, n=137) but not in older participants (>80, n=91). The relative risk (RR) for more than two microinfarcts with each 10-mmHg increase in SBP was 1.15 (95% confidence interval (CI)=1.00,1.33) in the younger participants, adjusted for age at entry, sex, and time to death. This RR was particularly strong in younger participants not taking antihypertensive medications (RR=1.48, 95% CI=1.21, 1.81); significant associations were not observed in participants treated for hypertension. Findings for DBP were negative. CONCLUSION: The association between high SBP and cerebrovascular damage in untreated older adults (65,80) suggests that adequate hypertension treatment may reduce dementia risk by minimizing microvascular injury to cerebrum. [source] Oxidative Stress Following Traumatic Brain Injury in RatsJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Detection of Free Radical Intermediates, Quantitation of Biomarkers Abstract: Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8- epi -prostaglandin F2,, was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N -oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury. [source] Mothers' Experience of Helping Young Adults With Traumatic Brain InjuryJOURNAL OF NURSING SCHOLARSHIP, Issue 1 2005Suporn Wongvatunyu Purpose:To describe mothers' experience of helping young adults with traumatic brain injury (TBI). Design:Descriptive. Methods:A convenience sample of participants from support groups for parents of young adults with TBI met the criteria of engaging in regular interaction or helping their children (aged 20 to 36 years). These young adults had suffered moderate or severe TBI from a motor vehicle collisions, sports-related injuries, or recreation-related injuries more than 6 months earlier. A descriptive phenomenological method was used. Three in-depth interviews were done with each mother over a 2-month period. Data were the mothers' perceptions, actions, and intentions pertaining to their experiences of helping the young adults. Findings:Five phenomena that were structures of the experience were discerned, discussed with participants to obtain their feedback, and compared to the relevant literature. The five phenomena of the mothers' experiences were: reconnecting my child's brain, considering my child's safety, making our lives as normal as possible, dealing with our biggest problem, and advocating for my child. Conclusions:The mothers continued rehabilitation efforts with the young adults, even when only minimal services were available to support their efforts. Mothers needed interventions to enhance their knowledge, and they and the young adults with TBI needed expanded community services. [source] Chronic Stress, Sense of Belonging, and Depression Among Survivors of Traumatic Brain InjuryJOURNAL OF NURSING SCHOLARSHIP, Issue 3 2002Esther Bay Purpose: To test whether chronic stress, interpersonal relatedness, and cognitive burden could explain depression after traumatic brain injury (TBI). Design: A nonprobability sample of 75 mild-to-moderately injured TBI survivors and their significant others, were recruited from five TBI day-rehabilitation programs. All participants were within 2 years of the date of injury and were living in the community. Methods: During face-to-face interviews, demographic information, and estimates of brain injury severity were obtained and participants completed a cognitive battery of tests of directed attention and short-term memory, responses to the Perceived Stress Scale, Interpersonal Relatedness Inventory, Sense of Belonging Instrument, Neurobehavioral Functioning Inventory, and Center for Epidemiological Studies Depression Scale;. Findings: Chronic stress was significantly and positively related to post-TBI depression. Depression and postinjury sense of belonging were negatively related. Social support and results from the cognitive battery did not explain depression. Conclusions: Postinjury chronic stress and sense of belonging were strong predictors of post-injury depression and are variables amenable to interventions by nurses in community health, neurological centers, or rehabilitation clinics. Future studies are needed to examine how these variables change over time during the recovery process. [source] SPECIAL ARTICLE: A review of the International Brain Research Foundation novel approach to mild traumatic brain injury presented at the International Conference on Behavioral Health and Traumatic Brain InjuryJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 9 2010MSN (Doctoral Student), Mary Zemyan Polito CRNP Abstract "The International Conference on Behavioral Health and Traumatic Brain Injury" held at St. Joseph's Regional Medical Center in Paterson, NJ., from October 12 to 15, 2008, included a presentation on the novel assessment and treatment approach to mild traumatic brain injury (mTBI) by Philip A. DeFina, PhD, of the International Brain Research Foundation (IBRF). Because of the urgent need to treat a large number of our troops who are diagnosed with mTBI and post-traumatic stress disorder (PTSD), the conference was held to create a report for Congress titled "Recommendations to Improve the Care of Wounded Warriors NOW. March 12, 2009." This article summarizes and adds greater detail to Dr. DeFina's presentation on the current standard and novel ways to approach assessment and treatment of mTBI and PTSD. Pilot data derived from collaborative studies through the IBRF have led to the development of clinical and research protocols utilizing currently accepted, valid, and reliable neuroimaging technologies combined in novel ways to develop "neuromarkers." These neuromarkers are being evaluated in the context of an "Integrity-Deficit Matrix" model to demonstrate their ability to improve diagnostic accuracy, guide treatment programs, and possibly predict outcomes for patients suffering from traumatic brain injury. [source] A Prospective Controlled Study in the Prevalence of Posttraumatic Headache Following Mild Traumatic Brain InjuryPAIN MEDICINE, Issue 8 2008S. Faux FAFRM (RACP) FFPMANZCA ABSTRACT Objective., To establish the prevalence of post traumatic headache, persisting at 3 months following minor traumatic brain injury. Design., A prospective controlled study of patients admitted with a diagnosis of mild traumatic brain injury and matched orthopedic controls over 12 months during 2004. Setting., A level two inner city Emergency Department in Sydney, Australia. Patients., One hundred eligible sequential admissions with mild traumatic brain injury as defined by American Congress of Rehabilitation Medicine, 1993, and 100 matched minor injury controls with nondeceleration injuries. Interventions., Subjects were part of a study on prediction of postconcussive syndrome and had neuropsychological tests, balance test and pain recordings taken at the time of injury, at 1 month and at 3 months post injury. Outcome Measures., Main measures were the reporting of headache "worse than prior to the injury" and concordant with the definition of Posttraumatic Headache according to International Headache Society Classification of Headache Disorders 2003. Results., 15.34% of those with minor head injury continued to complain of perisistant posttraumatic headache at 3 months compared to 2.2% of the minor injury controls. Conclusions., To the authors' knowledge this is the first controlled prospective study in the prevalence of posttraumatic headache following mild traumatic brain injury. [source] Cell Death Mechanisms Following Traumatic Brain InjuryBRAIN PATHOLOGY, Issue 2 2004Ramesh Raghupathi PhD Neuronal and glial cell death and traumatic axonal injury contribute to the overall pathology of traumatic brain injury (TBI) in both humans and animals. In both head-injured humans and following experimental brain injury, dying neural cells exhibit either an apoptotic or a necrotic morphology. Apoptotic and necrotic neurons have been identified within contusions in the acute post-traumatic period, and in regions remote from the site of impact in the days and weeks after trauma, while degenerating oligodendrocytes and astrocytes have been observed within injured white matter tracts. We review and compare the regional and temporal patterns of apoptotic and necrotic cell death following TBI and the possible mechanisms underlying trauma-induced cell death. While excitatory amino acids, increases in intracellular calcium and free radicals can all cause cells to undergo apoptosis, in vitro studies have determined that neural cells can undergo apoptosis via many other pathways. It is generally accepted that a shift in the balance between pro- and anti-apoptotic protein factors towards the expression of proteins that promote death may be one mechanism underlying apoptotic cell death. The effect of TBI on cellular expression of survival promoting-proteins such as Bcl-2, Bcl-xL, and extracellular signal-regulated kinases, and death-inducing proteins such as Bax, c-Jun N-terminal kinase, tumor-suppressor gene, p53, and the calpain and caspase families of proteases are reviewed. In light of pharmacologic strategies that have been devised to reduce the extent of apoptotic cell death in animal models of TBI, our review also considers whether apoptosis may serve a protective role in the injured brain. Together, these observations suggest that cell death mechanisms may be representative of a continuum between apoptotic and necrotic pathways. [source] Aromatase expression and cell proliferation following injury of the adult zebra finch hippocampusDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2007R. Scott Peterson Abstract Estrogens can be neuroprotective following traumatic brain injury. Immediately after trauma to the zebra finch hippocampus, the estrogen-synthetic enzyme aromatase is rapidly upregulated in astrocytes and radial glia around the lesion site. Brain injury also induces high levels of cell proliferation. Estrogens promote neuronal differentiation, migration, and survival naturally in the avian brain. We suspect that glia are a source of estrogens promoting cell proliferation after neural injury. To explore this hypothesis, we examined the spatial and temporal relationship between glial aromatase expression and cell proliferation after neural injury in adult female zebra finches. Birds were ovariectomized and given a blank implant or one filled with estradiol; some birds were also administered an aromatase inhibitor or vehicle. All birds received penetrating injuries to the right hippocampus. Twenty-four hours after lesioning, birds were injected once with BrdU to label mitotically active cells and euthanized 2 h, 24 h, or 7 days later. The brains were processed for double-label BrdU and aromatase immunocytochemistry. Injury-induced glial aromatase expression was unaffected by survival time and aromatase inhibition. BrdU labeling was significantly reduced at 24 h by ovariectomy and by aromatase inhibition; effects were partially reversed by E2 replacement. Irrespective of ovariectomy, the densities of aromatase immunoreactive astrocytes and BrdU-labeled cells at known distances from the lesion site were highly correlated. These data suggest that injury-induced glial aromatization may influence the reorganization of injured tissue by providing a rich estrogenic environment available to influence cellular incorporation. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Fall-related brain injuries and the risk of dementia in elderly people: a population-based studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2005H. Luukinen Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of ,26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35,5.81). In a population scoring ,28 points in the baseline MMSE an apolipoprotein E (ApoE) ,4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35,9.34), and the effect of brain injury and ApoE ,4 phenotype was synergistic; 7.68 (2.32,25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE ,4 allele. [source] Minocycline attenuates hypoxia,ischemia-induced neurological dysfunction and brain injury in the juvenile ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Lir-Wan Fan Abstract To investigate whether minocycline provides long-lasting protection against neonatal hypoxia,ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague,Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic,ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic,ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia,ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia,ischemia-induced brain injury and the associated neurological dysfunction. [source] GP IIb-IIIa Receptor Blockers Minimize Vascular and Perivascular Damage in the Hippocampus after Cardiopulmonary Bypass ManagementANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005S. Arnhold Brain injury remains a significant and potentially devastating outcome of cardiopulmonary bypass (CPB) under circulatory arrest. These outcomes caused by a microvasculature embolization are associated with increased mortality, longer hospital stays and increased use of intermediate or long term care facilities. The administration of heparin in heart surgery during deep hypothermic cardiopulmonary bypass is the basic prophylactic strategy for reducing or even preventing, microvasculature embolization. Unfortunately, an incidence of neuropsychological impairments (NPI) is found in as many as 25 % of the survivors. As it is suspected that these impairments are correlated with morphological alterations, in our study we use the GP IIb-IIIa receptor blocker Eptifibatide for the inhibition of platelet aggregation, in order to look for a reduction of tissue damage compared to the standard treatment. Two groups of 11 piglets (mean body weight of 15±5 kg) underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass, 60-minutes deep hypothermic circulatory arrest (DHCA) at 15°C, and 40-minute rewarming to 37°C. Group 1 was treated only with unfractionated heparin (UFH), whereas Group 2 was medicated with Eptifibatide, in addition to the UFH-treatment group 1. After rewarming, all animals underwent bilateral carotid perfusion with 4% paraformaldehyde. Histological investigations of semi thin sections reveal a marked decrease of hippocampal alterations by using the GP IIb-IIIa receptor blocker in addition to standard UFH treatment. We detect a reduction of degenerative areas in perivascular (vessels with 10,30 ,m in diameter) tissue. These semi-quantitative data are confirmed by ultrastructural findings. [source] A critical evaluation of the evidence supporting the practice of behavioural vision therapyOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 1 2009Brendan T. Barrett Abstract In 2000, the UK's College of Optometrists commissioned a report to critically evaluate the theory and practice of behavioural optometry. The report which followed Jennings (2000; Behavioural optometry , a critical review. Optom. Pract. 1: 67) concluded that there was a lack of controlled clinical trials to support behavioural management strategies. The purpose of this report was to evaluate the evidence in support of behavioural approaches as it stands in 2008. The available evidence was reviewed under 10 headings, selected because they represent patient groups/conditions that behavioural optometrists are treating, or because they represent approaches to treatment that have been advocated in the behavioural literature. The headings selected were: (1) vision therapy for accommodation/vergence disorders; (2) the underachieving child; (3) prisms for near binocular disorders and for producing postural change; (4) near point stress and low-plus prescriptions; (5) use of low-plus lenses at near to slow the progression of myopia; (6) therapy to reduce myopia; (7) behavioural approaches to the treatment of strabismus and amblyopia; (8) training central and peripheral awareness and syntonics; (9) sports vision therapy; (10) neurological disorders and neuro-rehabilitation after trauma/stroke. There is a continued paucity of controlled trials in the literature to support behavioural optometry approaches. Although there are areas where the available evidence is consistent with claims made by behavioural optometrists (most notably in relation to the treatment of convergence insufficiency, the use of yoked prisms in neurological patients, and in vision rehabilitation after brain disease/injury), a large majority of behavioural management approaches are not evidence-based, and thus cannot be advocated. [source] Prevalence and correlates of traumatic brain injury among delinquent youthsCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 4 2008Brian E. Perron Background,Delinquent youth frequently exhibit high-risk behaviours that can result in serious injury. However, little is known about traumatic brain injuries (TBIs) and their correlates in this population. Aims,To examine the period prevalence and correlates of TBIs in delinquent youths. Method,Interviews were conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services rehabilitation facilities between March 1 and May 31, 2003. Participants [mean age (Mage) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures assessing TBI, substance use, psychiatric symptoms, and antisocial traits/behaviours. TBI was defined as ever having sustained a head injury causing unconsciousness for more than 20 minutes. Results,Nearly one-in-five youths (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely than youths without to be male, have received a psychiatric diagnosis, report an earlier onset of criminal behaviour/substance use and more lifetime substance use problems and past-year criminal acts, evidence psychiatric symptoms, report lifetime suicidality, be impulsive, fearless, and external in locus of control and criminally victimized in the year preceding incarceration. Male gender and frequency of own criminal victimization were important predictors of TBI in multivariate analyses. Regression analyses adjusted for demographic factors, indicated that youths with TBIs were at significantly elevated risk for current depressive/anxious symptoms, antisocial behaviour, and substance abuse problems. Conclusions,TBI is common among delinquent youth and associated with wide ranging psychiatric dysfunction; however, the causal role of TBIs in the pathogenesis of co-morbid conditions remains unclear. Copyright © 2008 John Wiley & Sons, Ltd. [source] Customized mandibular orthotics in the prevention of concussion/mild traumatic brain injury in football players: a preliminary studyDENTAL TRAUMATOLOGY, Issue 5 2009G. Dave Singh However, previous investigations have primarily studied non-customized mouthguards without dental/temporo-mandibular joint examinations of the subjects. Therefore, the aim of this study is to determine whether the use of a customized mandibular orthotic after temporo-mandibular joint assessment reduces the incidence of concussion/mild traumatic brain injuries in high-school football players. Materials and methods:, Using a longitudinal, retrospective design, data were collected from a cohort of football players (n = 28) over three seasons using a questionnaire. The mean age of the sample prior to the use of the customized mandibular orthotic was 17.3 years ± 1.9. Prior to deployment, dental records and temporo-mandibular joint evaluations were undertaken, as well as neurocognitive assessment, including history of concussion/mild traumatic brain injuries. After establishing optimal jaw position, a customized mandibular orthotic was fabricated to the new spatial relations. Results:, The mean age of the sample after three seasons was 19.7 years ± 2.0. Prior to the use of the customized mandibular orthotic, the mean self-reported incidence of concussion/mild traumatic brain injuries was 2.1 ± 1.4 concussive events. After the deployment of the customized mandibular orthotic the number of concussive events fell to 0.11 ± 0.3 with an odds ratio of 38.33 (95% CI 8.2,178.6), P < 0.05. Conclusion:, The preliminary results of this study suggest that a customized mandibular orthotic may decrease the incidence of concussion/mild traumatic brain injuries in high- school football athletes, but a comprehensive study is required to confirm these initial findings. Furthermore, additional research is necessary to indicate the possible mode(s) of action of a customized mandibular orthotic in the prevention of concussion/mild traumatic brain injuries. [source] Microglia and inflammation: Impact on developmental brain injuriesDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2006Li-Jin Chew Abstract 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 central nervous system and play a critical role in the development of an inflammatory response within the brain. Microglia are critically involved with both the innate and adaptive immune system, regulating inflammation and cell damage within the brain via activation of Toll-like receptors, production of cytokines, and a myriad of other intracellular and intercellular processes. In this article, microglial physiology is reviewed along with the role of microglia in developmental brain injuries in humans and animal models. Last, microglial functions within the innate and adaptive immune system will be summarized. Understanding the processes of inflammation and microglial activation is critical for formulating effective preventative and therapeutic strategies for developmental brain injuries. MRDD Research Reviews 2006;12:105,112. © 2006 Wiley-Liss, Inc. [source] Patterns of motor disability in very preterm childrenDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2002Melanie Bracewell Abstract Motor development in very preterm children differs in several important ways from that of children born at full term. Variability is common, although the anatomic and physiologic bases for that variability are often poorly understood. Motor patterns over the first postnatal year may depend on behaviours learned during often long periods of neonatal intensive care. The normal pattern of development may be modified by disturbances of brain function caused both by the interruption of normal brain maturation ex-utero and the superimposition of focal brain injuries following very preterm birth. Abnormal patterns of development over the first year may evolve into clear neuromotor patterns of cerebral palsy or resolve, as "transient dystonias." Cerebral palsy is associated with identified patterns of brain injury secondary to ischaemic or haemorrhagic lesions, perhaps modified by activation of inflammatory cytokines. Cerebral palsy rates have not fallen as might be expected over the past 10 years as survival has improved, perhaps because of increasing survival at low gestations, which is associated with the highest prevalence of cerebral palsy. Children who escape cerebral palsy are also at risk of motor impairments during the school years. The relationship of these impairments to perinatal factors or to neurological progress over the first postnatal year is debated. Neuromotor abnormalities are the most frequent of the "hidden disabilities" among ex-preterm children and are thus frequently associated with poorer cognitive ability and attention deficit disorders. Interventions to prevent cerebral palsy or to reduce these late disabilities in very preterm children are needed. MRDD Research Reviews 2002;8:241,248. © 2002 Wiley-Liss, Inc. [source] Fall-related brain injuries and the risk of dementia in elderly people: a population-based studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2005H. Luukinen Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of ,26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35,5.81). In a population scoring ,28 points in the baseline MMSE an apolipoprotein E (ApoE) ,4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35,9.34), and the effect of brain injury and ApoE ,4 phenotype was synergistic; 7.68 (2.32,25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE ,4 allele. [source] Oxidized low-density lipoprotein induces matrix metalloproteinase-9 expression via a p42/p44 and JNK-dependent AP-1 pathway in brain astrocytesGLIA, Issue 1 2009Hui-Hsin Wang Abstract Upregulation of matrix metalloproteinases (MMPs), especially MMP-9, by oxidized low-density lipoprotein (oxLDL) is implicated in many inflammatory diseases including brain injury. However, the signaling mechanisms underlying oxLDL-induced MMP-9 expression in astrocytes largely remain unknown. Here we report that oxLDL induces expression of proMMP-9 via a MAPK-dependent AP-1 activation in rat brain astrocyte (RBA)-1 cells. Results revealed by gelatin zymography, RT-PCR, and Western blotting analyses showed that oxLDL-induced proMMP-9 gene expression was mediated through Akt, JNK1/2, and p42/p44 MAPK phosphorylation in RBA-1 cells. These responses were attenuated by inhibitors of PI3K (LY294002), JNK (SP600125), and p42/p44 MAPK (PD98059), or transfection with dominant negative mutants and short hairpin RNA. Moreover, we demonstrated that AP-1 (i.e., c-Fos/c-Jun) is crucial for oxLDL-induced proMMP-9 expression which was attenuated by pretreatment with AP-1 inhibitor (curcumin). The regulation of MMP-9 gene transcription by AP-1 was confirmed by oxLDL-stimulated MMP-9 luciferase activity which was totally lost in cells transfected with the AP-1 binding site-mutated MMP-9 promoter construct (mt-AP1-MMP-9). These results suggested that oxLDL-induced proMMP-9 expression is mediated through PI3K/Akt, JNK1/2, and p42/p44 MAPK leading to AP-1 activation. Understanding the regulatory mechanisms underlying oxLDL-induced MMP-9 expression in astrocytes might provide a new therapeutic strategy of brain injuries and diseases. © 2008 Wiley-Liss, Inc. [source] Involvement of ,1 integrin in microglial chemotaxis and proliferation on fibronectin: Different regulations by ADP through PKAGLIA, Issue 2 2005Kaoru Nasu-Tada Abstract Microglia are immune cells in the brain; their activation, migration, and proliferation have pivotal roles in brain injuries and diseases. Microglia are known to attach firmly to fibronectin, the upregulation of which is associated with several pathological conditions in the CNS, through ,1 integrin and become activated. Extracellular nucleotides can serve as potent signaling molecules. Recently, ATP and ADP were revealed to possess chemoattractive properties to microglia via Gi-coupled P2Y receptors. In the present study, we report that the ADP-induced chemotaxis of microglia is mediated by P2Y12/13 receptors and is ,1 integrin-dependent in the presence of fibronectin. Signals from P2Y12/13 receptors also cause ,1 integrin translocation to the membrane ruffle regions, but this redistribution was lost when the intracellular cyclic AMP (cAMP) was increased by forskolin or dibutyryl cAMP. This inhibitory effect of cAMP-elevating agents did not appear when microglia were co-incubated with a protein kinase A (PKA) inhibitor, KT-5720, suggesting that PKA is a negative regulator of the ,1 integrin translocation. We also show that the engagement of ,1 integrin enhanced microglial proliferation. Signals from P2Y12/13 receptors attenuated the proliferation, whereas ADP itself had no effect on microglial growth. Furthermore, ,1 integrin-induced proliferation is positively regulated by the cAMP-dependent PKA. Together, these results indicate the involvement of ,1 integrin in microglial proliferation and chemotaxis, both of which have clinical importance. The data also suggest that PKA is inversely involved in these two cellular functions. © 2005 Wiley-Liss, Inc. [source] Differential regulation of NMDA receptor function by DJ-1 and PINK1AGING CELL, Issue 5 2010Ning Chang Summary Dysfunction of PTEN-induced kinase 1 (PINK1) or DJ-1 promotes neuronal death and is implicated in the pathogenesis of Parkinson's disease, but the underlying mechanisms remain unclear. Given the roles of N -methyl- d- aspartate receptor (NMDAr)-mediated neurotoxicity in various brain disorders including cerebral ischemia and neurodegenerative diseases, we investigated the effects of PINK1 and DJ-1 on NMDAr function. Using protein overexpression and knockdown approaches, we showed that PINK1 increased NMDAr-mediated whole-cell currents by enhancing the function of NR2A-containing NMDAr subtype (NR2ACNR). However, DJ-1 decreased NMDAr-mediated currents, which was mediated through the inhibition of both NR2ACNR and NR2B-containing NMDAr subtype (NR2BCNR). We revealed that the knockdown of DJ-1 enhanced PTEN expression, which not only potentiated NR2BCNR function but also increased PINK1 expression that led to NR2ACNR potentiation. These results indicate that NMDAr function is differentially regulated by DJ-1-dependent signal pathways DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR. Our results further showed that the suppression of DJ-1, while promoted NMDA-induced neuronal death through the overactivation of PTEN/NR2BCNR-dependent cell death pathway, induced a neuroprotective effect to counteract DJ-1 dysfunction-mediated neuronal death signaling through activating PTEN/PINK1/NR2ACNR cell survival,promoting pathway. Thus, PINK1 acts with DJ-1 in a common pathway to regulate NMDAr-mediated neuronal death. This study suggests that the DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR pathways may represent potential therapeutic targets for the development of neuroprotection strategy in the treatment of brain injuries and neurodegenerative diseases such as Parkinson's disease. [source] MRI of late microstructural and metabolic alterations in radiation-induced brain injuriesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2009Kevin C. Chan BEng Abstract Purpose To evaluate the late effects of radiation-induced damages in the rat brain by means of in vivo multiparametric MRI. Materials and Methods The right hemibrains of seven Sprague-Dawley rats were irradiated with a highly collimated 6 MV photon beam at a single dose of approximately 28 Gy. Diffusion tensor imaging (DTI), proton MR spectroscopy (1H-MRS), T2-weighted imaging, and T1-weighted imaging were performed to the same animals 12 months after radiation treatment. Results Compared with the contralateral side, a significantly higher percentage decrease in fractional anisotropy was observed in the ipsilateral fimbria of hippocampus (29%) than the external capsule (8%) in DTI, indicating the selective vulnerability of fimbria to radiation treatment. Furthermore, in 1H-MRS, significantly higher choline, glutamate, lactate, and taurine peaks by 24%, 25%, 87%, and 58%, respectively, were observed relative to creatine in the ipsilateral brain. Postmortem histology confirmed these white matter degradations as well as glial fibrillary acidic protein and glutamine synthetase immunoreactivity increase in the ipsilateral brain. Conclusion The microstructural and metabolic changes in late radiation-induced brain injuries were documented in vivo. These multiparametric MRI measurements may help understand the white matter changes and neurotoxicity upon radiation treatment in a single setting. J. Magn. Reson. Imaging 2009;29:1013,1020. © 2009 Wiley-Liss, Inc. [source] Traumatic brain injury in the United States: an epidemiologic overviewMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2009Carl R. Summers PhD Abstract A basic description of severity and frequency is needed for planning healthcare delivery for any disease process. In the case of traumatic brain injury, severity is typically categorized into mild, moderate, and severe with information from a combination of clinical observation and self-report methodologies. Recent US civilian epidemiological findings measuring the frequency of mortality and morbidity of traumatic brain injury are presented, including demographic and etiological breakdowns of the data. Falls, motor vehicle accidents, and being struck by objects are the major etiologies of traumatic brain injury. US civilian and Army hospitalization trends are discussed and compared. Features of traumatic brain injuries from Operation Iraqi Freedom and Operation Enduring Freedom are discussed. Mt Sinai J Med 76:105,110, 2009. © 2009 Mount Sinai School of Medicine [source] Assessment and Treatment of Pain Associated with Combat-Related PolytraumaPAIN MEDICINE, Issue 3 2009Michael E. Clark PhD ABSTRACT Due to the high rates of blast injuries sustained during operations in Iraq and Afghanistan, the number of soldiers returning with massive and multiple wounds is unprecedented. While casualty survival rates have improved dramatically, the extent and impact of these wounds on soldiers' functioning pose unique challenges for their rehabilitation. Pain is highly prevalent in these individuals with polytrauma injuries and is a source of suffering, as well as an impediment to rehabilitation. However, there are a number of obstacles to effective pain treatment in this group of war-injured, including their multiple and severe injuries, the high prevalence of brain injuries, cognitive impairments and emotional distress, the prolonged and intensive rehabilitation process, and the frequent need for repeated follow-up surgeries. As a result, we believe that a comprehensive, interdisciplinary approach to pain treatment is required. In this article we describe the model of pain care that has evolved at the Tampa Polytrauma Rehabilitation Center, which incorporates medical, rehabilitative, cognitive,behavioral, and interventional treatments targeting pain intensity as well as pain-related impairments and coping. We include a case study illustrating some key aspects of our approach. [source] Goal attainment for spasticity management using botulinum toxinPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 1 2006Stephen Ashford Abstract Background and Purpose. To determine whether goal attainment scaling (GAS) can demonstrate functional gains following injection of botulinum toxin (BTX) for spasticity in severely disabled patients. Method. Subjects were categorized as ,responder' (positive clinical outcome) and ,non-responder' (non-significant clinical outcome) on the basis of their overall clinical response. GAS scores for functional goals were calculated retrospectively and compared with standard outcome assessments undertaken at the time of intervention. Integrated care pathway (ICP) proformas were interrogated for 18 patients with acquired brain injuries. Mean age was 44.4 (SD 13.4) years. Results. Baseline GAS and Barthel scores were similar for the responder and non-responder groups. The outcome GAS score was significantly greater in the responder than in the non-responder group (Mann,Whitney U = 11.0; p = 0.011) as was the change in GAS score (Mann,Whitney U = 8.0; p = 0.004). GAS scores reflected change recorded in focal outcome measures. However, the Barthel Index measured change in only one case. Conclusions. This exploratory retrospective study provides preliminary support for the hypothesis that GAS provides a useful measure of functional gains in response to treatment with BTX, and is more sensitive than global measures such as the Barthel Index. Copyright © 2006 John Wiley & Sons, Ltd. [source] Practitioner Review: Beyond shaken baby syndrome: what influences the outcomes for infants following traumatic brain injury?THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2010Rebecca Ashton Background:, Traumatic brain injury (TBI) in infancy is relatively common, and is likely to lead to poorer outcomes than injuries sustained later in childhood. While the headlines have been grabbed by infant TBI caused by abuse, often known as shaken baby syndrome, the evidence base for how to support children following TBI in infancy is thin. These children are likely to benefit from ongoing assessment and intervention, because brain injuries sustained in the first year of life can influence development in different ways over many years. Methods:, A literature search was conducted and drawn together into a review aimed at informing practitioners working with children who had a brain injury in infancy. As there are so few evidence-based studies specifically looking at children who have sustained a TBI in infancy, ideas are drawn from a range of studies, including different age ranges and difficulties other than traumatic brain injury. Results:, This paper outlines the issues around measuring outcomes for children following TBI in the first year of life. An explanation of outcomes which are more likely for children following TBI in infancy is provided, in the areas of mortality; convulsions; endocrine problems; sensory and motor skills; cognitive processing; language; academic attainments; executive functions; and psychosocial difficulties. The key factors influencing these outcomes are then set out, including severity of injury; pre-morbid situation; genetics; family factors and interventions. Conclusions:, Practitioners need to take a long-term, developmental view when assessing, understanding and supporting children who have sustained a TBI in their first year of life. The literature suggests some interventions which may be useful in prevention, acute care and longer-term rehabilitation, and further research is needed to assess their effectiveness. [source] Practitioner Review: Early adversity and developmental disordersTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 5 2005Eric Taylor Background:, Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods:, This paper provides a selective, narrative review for clinicians of the effects of factors such as exposure to toxins and stresses in utero and in postnatal life; brain injuries and perinatal compromise; neglect, malnutrition and selective food deficiencies. It also considers what is known about the mechanisms through which early adversities operate. Results:, Gaps in the research are identified and suggestions made about clinical investigations. Several types of environmental adversity have associations with later disorders that suggest a causal role. The effects are often on a broad range of psychological processes, and are not always quickly reversible. Several adversities often coexist, calling for skilled judgement about priorities in treatment. Conclusions:, Individuals vary considerably in their exposure to adversity and their vulnerability to its effects, and genetic inheritance can influence both. [source] Historical perspective: Neurological advances from studies of war injuries and illnesses,ANNALS OF NEUROLOGY, Issue 4 2009Douglas J. Lanska MD Early in the 20th century during the Russo-Japanese War and World War I (WWI), some of the most important, lasting contributions to clinical neurology were descriptive clinical studies, especially those concerning war-related peripheral nerve disorders (eg, Hoffmann-Tinel sign, Guillain-Barré-Strohl syndrome [GBS]) and occipital bullet wounds (eg, the retinal projection on the cortex by Inouye and later by Holmes and Lister, and the functional partitioning of visual processes in the occipital cortex by Riddoch), but there were also other important descriptive studies concerning war-related aphasia, cerebellar injuries, and spinal cord injuries (eg, cerebellar injuries by Holmes, and autonomic dysreflexia by Head and Riddoch). Later progress, during and shortly after World War II (WWII), included major progress in understanding the pathophysiology of traumatic brain injuries by Denny-Brown, Russell, and Holbourn, pioneering accident injury studies by Cairns and Holbourn, promulgation of helmets to prevent motorcycle injuries by Cairns, development of comprehensive multidisciplinary neurorehabilitation by Rusk, and development of spinal cord injury care by Munro, Guttman, and Bors. These studies and developments were possible only because of the large number of cases that allowed individual physicians the opportunity to collect, collate, and synthesize observations of numerous cases in a short span of time. Such studies also required dedicated, disciplined, and knowledgeable investigators who made the most out of their opportunities to systematically assess large numbers of seriously ill and injured soldiers under stressful and often overtly dangerous situations. Ann Neurol 2009;66:444,459 [source] | ||||||||||||||||||||||||||||||||||||||||