Focal brain lesions induced with ultraviolet irradiation.

PubMed

Nakata, Mariko; Nagasaka, Kazuaki; Shimoda, Masayuki; Takashima, Ichiro; Yamamoto, Shinya

2018-05-22

Lesion and inactivation methods have played important roles in neuroscience studies. However, traditional techniques for creating a brain lesion are highly invasive, and control of lesion size and shape using these techniques is not easy. Here, we developed a novel method for creating a lesion on the cortical surface via 365 nm ultraviolet (UV) irradiation without breaking the dura mater. We demonstrated that 2.0 mWh UV irradiation, but not the same amount of non-UV light irradiation, induced an inverted bell-shaped lesion with neuronal loss and accumulation of glial cells. Moreover, the volume of the UV irradiation-induced lesion depended on the UV light exposure amount. We further succeeded in visualizing the lesioned site in a living animal using magnetic resonance imaging (MRI). Importantly, we also observed using an optical imaging technique that the spread of neural activation evoked by adjacent cortical stimulation disappeared only at the UV-irradiated site. In summary, UV irradiation can induce a focal brain lesion with a stable shape and size in a less invasive manner than traditional lesioning methods. This method is applicable to not only neuroscientific lesion experiments but also studies of the focal brain injury recovery process.

Brain injury in sports.

PubMed

Lloyd, John; Conidi, Frank

2016-03-01

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. 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. 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. 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 brain injuries for football players of

Focal stimulation of the brain by entirely extracranial means. An example of radiation controlled focal pharmacology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Remler, M.P.

A method for focal stimulation of the brain by entirely extracranial means is presented. A focal x ray lesion of cortex was made that reduces the blood-brain barrier in that area. Then parenteral penicillin was administered. Penicillin is primarily confined to the vascular space by the blood-brain barrier in all parts of the brain except for some leakage into the brain at higher doses. An increased concentration of penicillin is created in the irradiated cortex. The penicillin creates a focal epileptic lesion in the irradiated area. This is an example of radiation-controlled focal pharmacology in the central nervous system. (auth)

Investigation of blast-induced traumatic brain injury.

PubMed

Taylor, Paul A; Ludwigsen, John S; Ford, Corey C

2014-01-01

Many troops deployed in Iraq and Afghanistan have sustained blast-related, closed-head injuries from being within non-lethal distance of detonated explosive devices. Little is known, however, about the mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI). This study attempts to identify the precise conditions of focused stress wave energy within the brain, resulting from blast exposure, which will correlate with a threshold for persistent brain injury. This study developed and validated a set of modelling tools to simulate blast loading to the human head. Using these tools, the blast-induced, early-time intracranial wave motions that lead to focal brain damage were simulated. The simulations predict the deposition of three distinct wave energy components, two of which can be related to injury-inducing mechanisms, namely cavitation and shear. Furthermore, the results suggest that the spatial distributions of these damaging energy components are independent of blast direction. The predictions reported herein will simplify efforts to correlate simulation predictions with clinical measures of TBI and aid in the development of protective headwear.

Investigation of blast-induced traumatic brain injury

PubMed Central

Ludwigsen, John S.; Ford, Corey C.

2014-01-01

Objective Many troops deployed in Iraq and Afghanistan have sustained blast-related, closed-head injuries from being within non-lethal distance of detonated explosive devices. Little is known, however, about the mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI). This study attempts to identify the precise conditions of focused stress wave energy within the brain, resulting from blast exposure, which will correlate with a threshold for persistent brain injury. Methods This study developed and validated a set of modelling tools to simulate blast loading to the human head. Using these tools, the blast-induced, early-time intracranial wave motions that lead to focal brain damage were simulated. Results The simulations predict the deposition of three distinct wave energy components, two of which can be related to injury-inducing mechanisms, namely cavitation and shear. Furthermore, the results suggest that the spatial distributions of these damaging energy components are independent of blast direction. Conclusions The predictions reported herein will simplify efforts to correlate simulation predictions with clinical measures of TBI and aid in the development of protective headwear. PMID:24766453

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

Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury.

PubMed

Ariza, Mar; Pueyo, Roser; Junqué, Carme; Mataró, María; Poca, María Antonia; Mena, Maria Pau; Sahuquillo, Juan

2006-09-01

The aim of the present study was to determine whether the type of lesion in a sample of moderate and severe traumatic brain injury (TBI) was related to material-specific memory impairment. Fifty-nine patients with TBI were classified into three groups according to whether the site of the lesion was right temporal, left temporal or diffuse. Six-months post-injury, visual (Warrington's Facial Recognition Memory Test and Rey's Complex Figure Test) and verbal (Rey's Auditory Verbal Learning Test) memories were assessed. Visual memory deficits assessed by facial memory were associated with right temporal lobe lesion, whereas verbal memory performance assessed with a list of words was related to left temporal lobe lesion. The group with diffuse injury showed both verbal and visual memory impairment. These results suggest a material-specific memory impairment in moderate and severe TBI after focal temporal lesions and a non-specific memory impairment after diffuse damage.

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

PubMed Central

Jansen, H M; van der Naalt, J; van Zomeren, A H; Paans, A M; Veenma-van der Duin, L; Hew, J M; Pruim, J; Minderhoud, J M; Korf, J

1996-01-01

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury. Images PMID:8708661

Overexpression of Thioredoxin in Transgenic Mice Attenuates Focal Ischemic Brain Damage

NASA Astrophysics Data System (ADS)

Takagi, Yasushi; Mitsui, Akira; Nishiyama, Akira; Nozaki, Kazuhiko; Sono, Hiroshi; Gon, Yasuhiro; Hashimoto, Nobuo; Yodoi, Junji

1999-03-01

Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.

Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

PubMed

Yamakami, I; Yamaura, A; Isobe, K

1993-01-01

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.

PubMed

Abu-Judeh, H H; Parker, R; Singh, M; el-Zeftawy, H; Atay, S; Kumar, M; Naddaf, S; Aleksic, S; Abdel-Dayem, H M

1999-06-01

We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the

T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

PubMed Central

Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

2014-01-01

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

The role of autophagy in acute brain injury: A state of flux?

PubMed

Wolf, Michael S; Bayır, Hülya; Kochanek, Patrick M; Clark, Robert S B

2018-04-26

It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Grammaticality Sensitivity in Children with Early Focal Brain Injury and Children with Specific Language Impairment

ERIC Educational Resources Information Center

Wulfeck, Beverly; Bates, Elizabeth; Krupa-Kwiatkowski, Magda; Saltzman, Danna

2004-01-01

Grammaticality judgments and processing times associated with violation detection were examined in typically developing children, children with focal brain lesions (FL) acquired early in life, and children with specific language impairment (SLI). Grammatical sensitivity in the FL group, while below typically developing children, was above levels…

Hitting a Moving Target: Basic Mechanisms of Recovery from Acquired Developmental Brain Injury

PubMed Central

Giza, Christopher C.; Kolb, Bryan; Harris, Neil G.; Asarnow, Robert F.; Prins, Mayumi L.

2009-01-01

Acquired brain injuries represent a major cause of disability in the pediatric population. Understanding responses to developmental acquired brain injuries requires knowledge of the neurobiology of normal development, age-at-injury effects and experience-dependent neuroplasticity. In the developing brain, full recovery cannot be considered as a return to the premorbid baseline, since ongoing maturation means that cerebral functioning in normal individuals will continue to advance. Thus, the recovering immature brain has to ‘hit a moving target’ to achieve full functional recovery, defined as parity with age-matched uninjured peers. This review will discuss the consequences of developmental injuries such as focal lesions, diffuse hypoxia and traumatic brain injury (TBI). Underlying cellular and physiological mechanisms relevant to age-at-injury effects will be described in considerable detail, including but not limited to alterations in neurotransmission, connectivity/network functioning, the extracellular matrix, response to oxidative stress and changes in cerebral metabolism. Finally, mechanisms of experience-dependent plasticity will be reviewed in conjunction with their effects on neural repair and recovery. PMID:19956795

Fractal dimension brain morphometry: a novel approach to quantify white matter in traumatic brain injury.

PubMed

Rajagopalan, Venkateswaran; Das, Abhijit; Zhang, Luduan; Hillary, Frank; Wylie, Glenn R; Yue, Guang H

2018-06-16

Traumatic brain injury (TBI) is the main cause of disability in people younger than 35 in the United States. The mechanisms of TBI are complex resulting in both focal and diffuse brain damage. Fractal dimension (FD) is a measure that can characterize morphometric complexity and variability of brain structure especially white matter (WM) structure and may provide novel insights into the injuries evident following TBI. FD-based brain morphometry may provide information on WM structural changes after TBI that is more sensitive to subtle structural changes post injury compared to conventional MRI measurements. Anatomical and diffusion tensor imaging (DTI) data were obtained using a 3 T MRI scanner in subjects with moderate to severe TBI and in healthy controls (HC). Whole brain WM volume, grey matter volume, cortical thickness, cortical area, FD and DTI metrics were evaluated globally and for the left and right hemispheres separately. A neuropsychological test battery sensitive to cognitive impairment associated with traumatic brain injury was performed. TBI group showed lower structural complexity (FD) bilaterally (p < 0.05). No significant difference in either grey matter volume, cortical thickness or cortical area was observed in any of the brain regions between TBI and healthy controls. No significant differences in whole brain WM volume or DTI metrics between TBI and HC groups were observed. Behavioral data analysis revealed that WM FD accounted for a significant amount of variance in executive functioning and processing speed beyond demographic and DTI variables. FD therefore, may serve as a sensitive marker of injury and may play a role in outcome prediction in TBI.

Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats.

PubMed

Wang, Yong; Ren, Qianyao; Zhang, Xing; Lu, Huiling; Chen, Jian

2018-01-01

Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways. A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-α in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses. The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-α significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-α. All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its anti-autophagic, anti-apoptotic and anti-inflammatory action. © 2018 The Author(s). Published by S. Karger AG, Basel.

Protective effect of protopine on the focal cerebral ischaemic injury in rats.

PubMed

Xiao, Xianghua; Liu, Juntian; Hu, Jingwen; Li, Tianxia; Zhang, Yuanhui

2007-08-01

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pre-treatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, antioxidation and depression of cell apoptosis.

Macrophagic and microglial responses after focal traumatic brain injury in the female rat

PubMed Central

2014-01-01

Background After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N = 72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. Results By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1α and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. Conclusions The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes. PMID:24761998

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 ...

Consequences of Traumatic Brain Injury for Human Vergence Dynamics

PubMed Central

Tyler, Christopher W.; Likova, Lora T.; Mineff, Kristyo N.; Elsaid, Anas M.; Nicholas, Spero C.

2015-01-01

Purpose: Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters. Methods: Disparity vergence eye movements were measured for a population of 123 normally sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI) in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions. Results: The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters. Conclusion: The results support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI. PMID:25691880

Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

DTIC Science & Technology

2017-10-01

subacute and chronic post -injury periods as a potential prognostic marker for PTE. The SNTF blood test is an electrochemiluminescence-based sandwich...contribution of each of these types of injury to epileptogenic brain activity and ultimately post traumatic epilepsy (PTE) is unclear, as are the mechanisms...nine months post injury, and blood biomarkers are being analyzed throughout in order to evaluate them as potential prognostic measures for the

A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis.

PubMed

Gutierrez, E; Huang, Y; Haglid, K; Bao, F; Hansson, H A; Hamberger, A; Viano, D

2001-03-01

Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.

Changes in event-related potential functional networks predict traumatic brain injury in piglets.

PubMed

Atlan, Lorre S; Lan, Ingrid S; Smith, Colin; Margulies, Susan S

2018-06-01

Traumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. None of the current diagnostic tools, such as quantitative cognitive and balance tests, have been validated to identify mild traumatic brain injury in infants, adults and animals. In this preliminary study, we report a novel, quantitative tool that has the potential to quickly and reliably diagnose traumatic brain injury and which can track the state of the brain during recovery across multiple ages and species. Using 32 scalp electrodes, we recorded involuntary auditory event-related potentials from 22 awake four-week-old piglets one day before and one, four, and seven days after two different injury types (diffuse and focal) or sham. From these recordings, we generated event-related potential functional networks and assessed whether the patterns of the observed changes in these networks could distinguish brain-injured piglets from non-injured. Piglet brains exhibited significant changes after injury, as evaluated by five network metrics. The injury prediction algorithm developed from our analysis of the changes in the event-related potentials functional networks ultimately produced a tool with 82% predictive accuracy. This novel approach is the first application of auditory event-related potential functional networks to the prediction of traumatic brain injury. The resulting tool is a robust, objective and predictive method that offers promise for detecting mild traumatic brain injury, in particular because collecting event-related potentials data is noninvasive and inexpensive. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

PubMed

Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

2014-07-01

Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

BDNF Polymorphism Predicts General Intelligence after Penetrating Traumatic Brain Injury

PubMed Central

Rostami, Elham; Krueger, Frank; Zoubak, Serguei; Dal Monte, Olga; Raymont, Vanessa; Pardini, Matteo; Hodgkinson, Colin A.; Goldman, David; Risling, Mårten; Grafman, Jordan

2011-01-01

Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10–15 years post-injury, and Phase III (30–35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery. PMID:22087305

Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

PubMed Central

Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

2014-01-01

Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

IMM-H004, A New Coumarin Derivative, Improved Focal Cerebral Ischemia via Blood-Brain Barrier Protection in Rats.

PubMed

Niu, Fei; Song, Xiu-Yun; Hu, Jin-Feng; Zuo, Wei; Kong, Ling-Lei; Wang, Xiao-Feng; Han, Ning; Chen, Nai-Hong

2017-10-01

IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood-brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection. Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins. Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection. IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study. Copyright © 2017. Published by Elsevier Inc.

The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats.

PubMed

Sun, Baozhu; Chen, Lin; Wei, Xinbing; Xiang, Yanxiao; Liu, Xiaoqian; Zhang, Xiumei

2011-06-17

Apoptosis is one of the major mechanisms of cell death during cerebral ischemia and reperfusion injury. Flurbiprofen has been shown to reduce cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanism remains unclear. This study aimed to investigate the potential association between the neuroprotective effect of flurbiprofen and the apoptosis inhibiting signaling pathways, in particularly the Akt/GSK-3β pathway. A focal cerebral ischemia rat model was subjected to middle cerebral artery occlusion (MCAO) for 120 min and then treated with flurbiprofen at the onset of reperfusion. The infarct volume and the neurological deficit scores were evaluated at 24h after reperfusion. Cell apoptosis, apoptosis-related proteins and the levels of p-Akt and p-GSK-3β in ischemic penumbra were measured using TUNEL and western blot. The results showed that administration of flurbiprofen at the doses of 5 and 10mg/kg significantly attenuated brain ischemia/reperfusion injury, as shown by a reduction in the infarct volume, neurological deficit scores and cell apoptosis. Moreover, flurbiprofen not only inhibited the expression of Bax protein and p-GSK-3β, but also increased the expression of Bcl-2 protein, the ratio of Bcl-2/Bax as well as the P-Akt level. Taken together, these results suggest that flurbiprofen protects the brain from ischemia/reperfusion injury by reducing apoptosis and this neuroprotective effect may be partly due to the activation of Akt/GSK-3β signaling pathway. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

P43/pro-EMAPII: A Potential Biomarker for Discriminating Traumatic Versus Ischemic Brain Injury

PubMed Central

Yao, Changping; Williams, Anthony J.; Ottens, Andrew K.; Lu, X.-C. May; Liu, Ming Cheng; Hayes, Ronald L.; Wang, Kevin K.; Tortella, Frank C.

2009-01-01

Abstract To gain additional insights into the pathogenic cellular and molecular mechanisms underlying different types of brain injury (e.g., trauma versus ischemia), recently attention has focused on the discovery and study of protein biomarkers. In previous studies, using a high-throughput immunoblotting (HTPI) technique, we reported changes in 29 out of 998 proteins following acute injuries to the rat brain (penetrating traumatic versus focal ischemic). Importantly, we discovered that one protein, endothelial monocyte-activating polypeptide II precursor (p43/pro-EMAPII), was differentially expressed between these two types of brain injury. Among other functions, p43/pro-EMAPII is a known pro-inflammatory cytokine involved in the progression of apoptotic cell death. Our current objective was to verify the changes in p43/pro-EMAPII expression, and to evaluate the potentially important implications that the differential regulation of this protein has on injury development. At multiple time points following either a penetrating ballistic-like brain injury (PBBI), or a transient middle cerebral artery occlusion (MCAo) brain injury, tissue samples (6–72 h), CSF samples (24 h), and blood samples (24 h) were collected from rats for analysis. Changes in protein expression were assessed by Western blot analysis and immunohistochemistry. Our results indicated that p43/pro-EMAPII was significantly increased in brain tissues, CSF, and plasma following PBBI, but decreased after MCAo injury compared to their respective sham control samples. This differential expression of p43/pro-EMAPII may be a useful injury-specific biomarker associated with the underlying pathologies of traumatic versus ischemic brain injury, and provide valuable information for directing injury-specific therapeutics. PMID:19317603

Network measures predict neuropsychological outcome after brain injury

PubMed Central

Warren, David E.; Power, Jonathan D.; Bruss, Joel; Denburg, Natalie L.; Waldron, Eric J.; Sun, Haoxin; Petersen, Steven E.; Tranel, Daniel

2014-01-01

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury. PMID:25225403

Acute Traumatic Brain Injury Does Not Exacerbate Amyotrophic Lateral Sclerosis in the SOD1G93A Rat Model1,2,3

PubMed Central

Thomsen, Gretchen M.

2015-01-01

Abstract 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

Productive Use of the English Past Tense in Children with Focal Brain Injury and Specific Language Impairment

ERIC Educational Resources Information Center

Marchman, Virginia A.; Saccuman, Cristina; Wulfeck, Beverly

2004-01-01

In this study, 22 children with early left hemisphere (LHD) or right hemisphere (RHD) focal brain lesions (FL, n=14 LHD, n=8 RHD) were administered an English past tense elicitation test (M=6.5 years). Proportion correct and frequency of overregularization and zero-marking errors were compared to age-matched samples of children with specific…

Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

PubMed

Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

2015-07-28

Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

Brain injury - discharge

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000163.htm Brain injury - discharge To use the sharing features on ... know was in the hospital for a serious brain injury. At home, it will take time for ...

Traumatic Brain Injury and Blood-Brain Barrier Cross-Talk.

PubMed

Nasser, Mohammad; Bejjani, Fabienne; Raad, Mohamad; Abou-El-Hassan, Hadi; Mantash, Sarah; Nokkari, Amaly; Ramadan, Naify; Kassem, Nouhad; Mondello, Stefania; Hamade, Eva; Darwish, Hala; Zibara, Kazem; Kobeissy, Firas

2016-01-01

Traumatic brain injury, often referred to as the "silent epidemic," is a nondegenerative, non-congenital insult to the brain due to a blow or penetrating object that disrupts the function of the brain leading to permanent or temporary impairment of cognition, physical and psychosocial functions. Traumatic brain injury usually has poor prognosis for long-term treatment and is a major cause of mortality and morbidity worldwide; approximately 10 million deaths and/or hospitalizations annually are directly related to traumatic brain injury. Traumatic brain injury involves primary and secondary insults. Primary injury occurs during the initial insult, and results from direct or indirect force applied to the physical structures of the brain. Secondary injury is characterized by longer-term degeneration of neurons, glial cells, and vascular tissues due to activation of several proteases, glutamate and pro-inflammatory cytokine secretion. In addition, there is growing evidence that the blood-brain barrier is involved in the course of traumatic brain injury pathophysiology and has detrimental effects on the overall pathology of brain trauma, as will be discussed in this work.

Injury-Related Production of Cysteinyl Leukotrienes Contributes to Brain Damage following Experimental Traumatic Brain Injury

PubMed Central

Farias, Santiago; Frey, Lauren C.; Murphy, Robert C.

2009-01-01

Abstract The leukotrienes belong to a family of biologically active lipids derived from arachidonate that are often involved in inflammatory responses. In the central nervous system, a group of leukotrienes, known as the cysteinyl leukotrienes, is generated in brain tissue in response to a variety of acute brain injuries. Although the exact clinical significance of this excess production remains unclear, the cysteinyl leukotrienes may contribute to injury-related disruption of the brain-blood barrier and exacerbate secondary injury processes. In the present study, the formation and role of cysteinyl leukotrienes was explored in the fluid percussion injury model of traumatic brain injury in rats. The results showed that levels of the cysteinyl leukotrienes were elevated after fluid percussion injury with a maximal formation 1 hour after the injury. Neutrophils contributed to cysteinyl leukotriene formation in the injured brain hemisphere, potentially through a transcellular biosynthetic mechanism. Furthermore, pharmacological reduction of cysteinyl leukotriene formation after the injury, using MK-886, resulted in reduction of brain lesion volumes, suggesting that the cysteinyl leukotrienes play an important role in traumatic brain injury. PMID:19886806

Hydroquinone Strongly Alleviates Focal Ischemic Brain Injury via Blockage of Blood-Brain Barrier Disruption in Rats.

PubMed

Ha Park, Joon; Yoo, Ki-Yeon; Hye Kim, In; Cho, Jeong-Hwi; Lee, Jae-Chul; Hyeon Ahn, Ji; Jin Tae, Hyun; Chun Yan, Bing; Won Kim, Dae; Kyu Park, Ok; Kwon, Seung-Hae; Her, Song; Su Kim, Jin; Hoon Choi, Jung; Hyun Lee, Choong; Koo Hwang, In; Youl Cho, Jae; Hwi Cho, Jun; Kwon, Young-Guen; Ryoo, Sungwoo; Kim, Young-Myeong; Won, Moo-Ho; Jun Kang, Il

2016-12-01

Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion. Neuroprotection by treatment with 100 mg/kg of HQ was shown using evaluation of neurological deficits, positron-emission tomography (PET) and 2,3,5-triphenyltetrazoliumchloride (TTC) staining. In addition, HQ treatment significantly attenuated ischemia-induced Evans blue dye extravasation from blood vessels and significantly increased immunoreactivities of SMI-71 (an endothelial BBB marker) and glucose transporter-1 (GLUT-1, an endothelial cell marker) in ischemic cortex compared to the vehicle-treated ischemia-operated group. Confocal microscopy and western blot analysis also showed that HQ treatment maintained expressions of tight junction proteins (zonula occludens-1 and occludin) in the ischemic cortex. Post-treatment with HQ protected neurons from transient focal cerebral ischemic injury and the neuroprotective effect of HQ might be closely associated with prevention of BBB disruption via maintaining SMI-71 and GLUT-1 expressions as well as prevention of the degradation of zonula occludens-1 and occludin proteins. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

"Frog, Where Are You?" Narratives in Children with Specific Language Impairment, Early Focal Brain Injury, and Williams Syndrome

ERIC Educational Resources Information Center

Reilly, Judy; Losh, Molly; Bellugi, Ursula; Wulfeck, Beverly

2004-01-01

In this cross-population study, we use narratives as a context to investigate language development in children from 4 to 12 years of age from three experimental groups: children with early unilateral focal brain damage (FL; N=52); children with specific language impairment (SLI; N=44); children with Williams syndrome (WMS; N=36), and typically…

The neural basis of impaired self-awareness after traumatic brain injury

PubMed Central

Ham, Timothy E.; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H.; Leech, Robert

2014-01-01

Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at ‘rest’. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self

The neural basis of impaired self-awareness after traumatic brain injury.

PubMed

Ham, Timothy E; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H; Leech, Robert; Sharp, David J

2014-02-01

Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at 'rest'. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self

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 ...

Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

PubMed

Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

2016-06-01

Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

PubMed Central

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

2011-01-01

skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20. We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. PMID:21876530

Lateral fluid percussion: model of traumatic brain injury in mice.

PubMed

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

2011-08-22

mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

Ethanol-induced hyponatremia augments brain edema after traumatic brain injury.

PubMed

Katada, Ryuichi; Watanabe, Satoshi; Ishizaka, Atsushi; Mizuo, Keisuke; Okazaki, Shunichiro; Matsumoto, Hiroshi

2012-04-01

Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.

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

Traumatic brain injury and delayed sequelae: a review--traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia.

PubMed

Kiraly, Michael; Kiraly, Stephen J

2007-11-12

Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

PubMed

Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

2013-06-10

The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

[Quantitative evaluation of visual gnosis in children with focal brain lesions].

PubMed

Pencheva, S; Zaprianova, L

1983-01-01

Bearing in mind the opinion of many authors on a great plasticity and interchangeability of the brain cortical functional systems in children the authors have carried out an experiment with 40 children with focal damages of the brain hemispheres, in 20 of whom the right, and in the other 20 the left hemisphere was affected. Use was made of the method of visual gnosis quantitative assessment in the modification of Pencheva and Mavlov (1975). In the children with the focal damages, more or less marked disturbances of the visual gnosis were revealed, however, no statistically significant relationship between the disturbances and the brain side were disclosed. The agnostic disorders were equally frequent in the children of both groups.

Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis.

PubMed

Nakayama, N; Okumura, A; Shinoda, J; Nakashima, T; Iwama, T

2006-07-01

The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.

Attention and driving in traumatic brain injury: a question of coping with time-pressure.

PubMed

Brouwer, Wiebo H; Withaar, Frederiec K; Tant, Mark L M; van Zomeren, Adriaan H

2002-02-01

Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task analysis of driving skill. Specifically, we focus on slow information processing, divided attention, and the development of procedural knowledge. Also the effects of a combination of diffuse and focal dysfunctions, specifically homonymous hemianopia and the dysexecutive syndrome, are discussed. Finally, we turn to problems and challenges with regard to assessment and rehabilitation methods in the areas of driving and fitness to drive.

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:…

Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity.

PubMed

Li, Minshu; Li, Zhiguo; Yao, Yang; Jin, Wei-Na; Wood, Kristofer; Liu, Qiang; Shi, Fu-Dong; Hao, Junwei

2017-01-17

Astrocytes are believed to bridge interactions between infiltrating lymphocytes and neurons during brain ischemia, but the mechanisms for this action are poorly understood. Here we found that interleukin-15 (IL-15) is dramatically up-regulated in astrocytes of postmortem brain tissues from patients with ischemic stroke and in a mouse model of transient focal brain ischemia. We generated a glial fibrillary acidic protein (GFAP) promoter-controlled IL-15-expressing transgenic mouse (GFAP-IL-15 tg ) line and found enlarged brain infarcts, exacerbated neurodeficits after the induction of brain ischemia. In addition, knockdown of IL-15 in astrocytes attenuated ischemic brain injury. Interestingly, the accumulation of CD8 + T and natural killer (NK) cells was augmented in these GFAP-IL-15 tg mice after brain ischemia. Of note, depletion of CD8 + T or NK cells attenuated ischemic brain injury in GFAP-IL-15 tg mice. Furthermore, knockdown of the IL-15 receptor α or blockade of cell-to-cell contact diminished the activation and effector function of CD8 + T and NK cells in GFAP-IL-15 tg mice, suggesting that astrocytic IL-15 is delivered in trans to target cells. Collectively, these findings indicate that astrocytic IL-15 could aggravate postischemic brain damage via propagation of CD8 + T and NK cell-mediated immunity.

Mild Traumatic Brain Injury

MedlinePlus

... Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity of TBI Symptoms ... across the country. National Center for Telehealth and Technology t2health.dcoe.mil The National Center for Telehealth ...

COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats.

PubMed

Günther, Mattias; Plantman, Stefan; Davidsson, Johan; Angéria, Maria; Mathiesen, Tiit; Risling, Mårten

2015-04-01

Traumatic brain injury is followed by secondary neuronal degeneration, largely dependent on an inflammatory response. This response is probably gender specific, since females are better protected than males in experimental models. The reasons are not fully known. We examined aspects of the inflammatory response following experimental TBI in male and female rats to explore possible gender differences at 24 h and 72 h after trauma, times of peak histological inflammation and neuronal degeneration. A penetrating brain injury model was used to produce penetrating focal TBI in 20 Sprague-Dawley rats, 5 males and 5 females for each time point. After 24 and 72 h the brains were removed and subjected to in situ hybridization and immunohistochemical analyses for COX-2, iNOS, osteopontin, glial fibrillary acidic protein, 3-nitrotyrosine, TUNEL and Fluoro-Jade. COX-2 mRNA and protein levels were increased in the perilesional area compared to the uninjured contralateral side and significantly higher in males at 24 h and 72 h (p < 0.05). iNOS mRNA was significantly increased in females at 24 h (p < 0.05) although protein was not. TUNEL was increased in male rats after 24 h (p < 0.05). Glial fibrillary acidic protein, osteopontin, 3-nitrotyrosine and Fluoro-Jade stained degenerating neurons were increased in the perilesional area, showing no difference between genders. COX-2 regulation differed between genders after TBI. The increased COX-2 expression in male rats correlated with increased apoptotic cell death detected by increased TUNEL staining at 24 h, but not with neuronal necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ, confirming a comparable level of trauma. The gender-specific trait of the secondary inflammatory response may be connected to prostaglandin regulation, which may partially explain gender variances in outcome after TBI.

Diffuse optical systems and methods to image physiological changes of the brain in response to focal TBI (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abookasis, David; Volkov, Boris; Kofman, Itamar

2017-02-01

During the last four decades, various optical techniques have been proposed and intensively used for biomedical diagnosis and therapy both in animal model and in human. These techniques have several advantages over the traditional existing methods: simplicity in structure, low-cost, easy to handle, portable, can be used repeatedly over time near the patient bedside for continues monitoring, and offer high spatiotemporal resolution. In this work, we demonstrate the use of two optical imaging modalities namely, spatially modulated illumination and dual-wavelength laser speckle to image the changes in brain tissue chromophores, morphology, and metabolic before, during, and after the onset of focal traumatic brain injury in intact mouse head (n=15). Injury was applied in anesthetized mice by weight-drop apparatus using 50gram metal rod striking the mouse's head. Following data analysis, we show a series of hemodynamic and structural changes over time including higher deoxyhemoglobin, reduction in oxygen saturation and blood flow, cell swelling, etc., in comparison with baseline measurements. In addition, to validate the monitoring of cerebral blood flow by the imaging system, measurements with laser Doppler flowmetry were also performed (n=5), which confirmed reduction in blood flow following injury. Overall, our result demonstrates the capability of diffuse optical modalities to monitor and map brain tissue optical and physiological properties following brain trauma.

Secondary brain injuries in thalamus and hippocampus after focal ischemia caused by mild, transient extradural compression of the somatosensori cortex in the rat.

PubMed

Holmberg, Per; Liljequist, Sture; Wägner, Anna

2009-02-01

The development and distribution of secondary brain lesions, subsequent to ischemic stroke, are of considerable clinical interest but so far only a limited number of studies have investigated the distribution and development of these secondary lesions in detail. In this study, we used an animal model of focal ischemia caused by extradural compression of the sensorimotor cortex. This paradigm of focal ischemia was shown to produce a consistent pattern of secondary lesions located distally from the primary lesion. Functionally the primary brain lesion produced a transient neurological deficit, which was evaluated by daily beam walking tests. Morphological changes were assessed in parallel after the ischemic event using Fluoro-Jade (FJ) staining as a marker of neuronal cell death. Secondary brain lesions were observed in the thalamus as well as in the hippocampus. The first sign of the slowly developing secondary brain lesions was present on day 3 with subsequent lesions being identified until day 16 after the primary ischemia. In addition to the identification of neuronal cell death by the FJ assays, immunostaining for parvalbumin (PA), a marker of GABAergic interneurons, revealed a loss of PA-staining in the pyramidal layer of CA1 on day 3, thus showing a similar time pattern for loss of PA-staining as for the loss of FJ stained cells. Based upon our present results, we suggest that the current animal model of focal ischemia represents a valuable tool for studies concerning the development of secondary remote brain lesions and their association to impaired motor and cognitive functions.

Left hemisphere regions are critical for language in the face of early left focal brain injury.

PubMed

Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L

2010-06-01

A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.

Twitter and traumatic brain injury: A content and sentiment analysis of tweets pertaining to sport-related brain injury

PubMed Central

Workewych, Adriana M; Ciuffetelli Muzzi, Madeline; Jing, Rowan; Zhang, Stanley; Topolovec-Vranic, Jane; Cusimano, Michael D

2017-01-01

Objectives: Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player’s life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users’ messages often reflects the prevailing culture related to a particular event or health issue. Methods: We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter® tweets related to traumatic brain injuries in sports collected during June and July 2013. Results: We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. Conclusion: While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies. PMID:28890783

Twitter and traumatic brain injury: A content and sentiment analysis of tweets pertaining to sport-related brain injury.

PubMed

Workewych, Adriana M; Ciuffetelli Muzzi, Madeline; Jing, Rowan; Zhang, Stanley; Topolovec-Vranic, Jane; Cusimano, Michael D

2017-01-01

Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player's life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users' messages often reflects the prevailing culture related to a particular event or health issue. We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter ® tweets related to traumatic brain injuries in sports collected during June and July 2013. We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies.

Traumatic brain injury.

PubMed

Barlow, Karen Maria

2013-01-01

In childhood, traumatic brain injury (TBI) poses the unique challenges of an injury to a developing brain and the dynamic pattern of recovery over time, inflicted TBI and its medicolegal ramifications. The mechanisms of injury vary with age, as do the mechanisms that lead to the primary brain injury. As it is common, and is the leading cause of death and disability in the USA and Canada, prevention is the key, and we may need increased legislation to facilitate this. Despite its prevalence, there is an almost urgent need for research to help guide the optimal management and improve outcomes. Indeed, contrary to common belief, children with severe TBI have a worse outcome and many of the consequences present in teenage years or later. The treatment needs, therefore, to be multifaceted and starts at the scene of the injury and extends into the home and school. In order to do this, the care needs to be multidisciplinary from specialists with a specific interest in TBI and to involve the family, and will often span many decades. Copyright © 2013 Elsevier B.V. All rights reserved.

Preservation of General Intelligence following Traumatic Brain Injury: Contributions of the Met66 Brain-Derived Neurotrophic Factor

PubMed Central

Barbey, Aron K.; Colom, Roberto; Paul, Erick; Forbes, Chad; Krueger, Frank; Goldman, David; Grafman, Jordan

2014-01-01

Brain-derived neurotrophic factor (BDNF) promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the preservation of general intelligence following TBI. We genotyped a sample of male Vietnam combat veterans (n = 156) consisting of a frontal lobe lesion group with focal penetrating head injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI. However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI. These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI. PMID:24586380

Perinatal Brain Injury: Mechanisms, Prevention, and Outcomes.

PubMed

Novak, Christopher M; Ozen, Maide; Burd, Irina

2018-06-01

Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants with perinatal brain injury. The effects of hypoxia-ischemia, inflammation, and infection during critical periods of development can lead to a common pathway of perinatal brain injury marked by neuronal excitotoxicity, cellular apoptosis, and microglial activation. Various interventions can prevent or improve the outcomes of different types of perinatal brain injury. The objective of this article is to review the mechanisms of perinatal brain injury, approaches to prevention, and outcomes among children with perinatal brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Late-onset social anxiety disorder following traumatic brain injury.

PubMed

Chaves, Cristiano; Trzesniak, Clarissa; Derenusson, Guilherme Nogueira; Araújo, David; Wichert-Ana, Lauro; Machado-de-Sousa, João Paulo; Carlotti, Carlos Gilberto; Nardi, Antonio E; Zuardi, Antônio W; de S Crippa, José Alexandre; Hallak, Jaime E C

2012-01-01

Neuropsychiatric sequelae are the predominant long-term disability after traumatic brain injury (TBI). This study reports a case of late-onset social anxiety disorder (SAD) following TBI. A patient that was spontaneous and extroverted up to 18-years-old started to exhibit significant social anxiety symptoms. These symptoms became progressively worse and he sought treatment at age 21. He had a previous history of traumatic brain injury (TBI) at age 17. Neuroimaging investigations (CT, SPECT and MRI) showed a bony protuberance on the left frontal bone, with mass effect on the left frontal lobe. He had no neurological signs or symptoms. The patient underwent neurosurgery with gross total resection of the lesion and the pathological examination was compatible with intradiploic haematoma. Psychiatric symptoms may be the only findings in the initial manifestation of slowly growing extra-axial space-occupying lesions that compress the frontal lobe from the outside. Focal neurological symptoms may occur only when the lesion becomes large. This case report underscores the need for careful exclusion of general medical conditions and TBI history in cases of late-onset SAD and may also contribute to the elucidation of the neurobiology of this disorder.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.

PubMed

Bisicchia, Elisa; Sasso, Valeria; Catanzaro, Giuseppina; Leuti, Alessandro; Besharat, Zein Mersini; Chiacchiarini, Martina; Molinari, Marco; Ferretti, Elisabetta; Viscomi, Maria Teresa; Chiurchiù, Valerio

2018-01-22

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

Dysautonomia after pediatric brain injury

PubMed Central

KIRK, KATHERINE A; SHOYKHET, MICHAEL; JEONG, JONG H; TYLER-KABARA, ELIZABETH C; HENDERSON, MARYANNE J; BELL, MICHAEL J; FINK, ERICKA L

2012-01-01

AIM Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of brain-injured adults and is associated with poor outcome. We hypothesized that brain-injured children with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features. METHOD We developed a database of children (n=249, 154 males, 95 females; mean (SD) age 11y 10mo [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted to The Children’s Institute of Pittsburgh for rehabilitation between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia. RESULTS Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001). INTERPRETATION Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes. PMID:22712762

Employment outcome four years after a severe traumatic brain injury: results of the Paris severe traumatic brain injury study.

PubMed

Ruet, Alexis; Jourdan, Claire; Bayen, Eléonore; Darnoux, Emmanuelle; Sahridj, Dalila; Ghout, Idir; Azerad, Sylvie; Pradat Diehl, Pascale; Aegerter, Philippe; Charanton, James; Vallat Azouvi, Claire; Azouvi, Philippe

2017-05-18

To describe employment outcome four years after a severe traumatic brain injury by the assessment of individual patients' preinjury sociodemographic data, injury-related and postinjury factors. A prospective, multicenter inception cohort of 133 adult patients in the Paris area (France) who had received a severe traumatic brain injury were followed up postinjury at one and four years. Sociodemographic data, factors related to injury severity and one-year functional and cognitive outcomes were prospectively collected. The main outcome measure was employment status. Potential predictors of employment status were assessed by univariate and multivariate analysis. At the four-year follow-up, 38% of patients were in paid employment. The following factors were independent predictors of unemployment: being unemployed or studying before traumatic brain injury, traumatic brain injury severity (i.e., a lower Glasgow Coma Scale score upon admission and a longer stay in intensive care) and a lower one-year Glasgow Outcome Scale-Extended score. This study confirmed the low rate of long-term employment amongst patients after a severe traumatic brain injury. The results illustrated the multiple determinants of employment outcome and suggested that students who had received a traumatic brain injury were particularly likely to be unemployed, thus we propose that they may require specific support to help them find work. Implications for rehabilitation Traumatic brain injury is a leading cause of persistent disablity and can associate cognitive, emotional, physical and sensory impairments, which often result in quality-of-life reduction and job loss. Predictors of post-traumatic brain injury unemployment and job loss remains unclear in the particular population of severe traumatic brain injury patients. The present study highlights the post-traumatic brain injury student population require a close follow-up and vocational rehabilitation. The study suggests that return to work post

A review of mild traumatic brain injury diagnostics: current perspectives, limitations, and emerging technology.

PubMed

Cook, Glen A; Hawley, Jason S

2014-10-01

Mild traumatic brain injury (mTBI) or concussion is a common battlefield and in-garrison injury caused by transmission of mechanical forces to the head. The energy transferred in such events can cause structural and/or functional changes in the brain that manifest as focal neurological, cognitive, or behavioral dysfunction. Current diagnostic criteria for mTBI are highly limited, variable, and based on subjective self-report. The subjective nature of the symptoms, both in quantity and quality, together with their large overlap in other physical and behavioral maladies, limit the clinician's ability to accurately diagnose, treat, and make prognostic decisions after such injuries. These diagnostic challenges are magnified in an operational environment as well. The Department of Defense has invested significant resources into improving the diagnostic tools and accuracy for mTBI. This focus has been to supplement the clinician's examination with technology that is better able to objectify brain dysfunction after mTBI. Through this review, we discuss the current state of three promising technologies--soluble protein biomarkers, advanced neuroimaging, and quantitative electroencephalography--that are of particular interest within military medicine. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Narratives of Focal Brain Injured Individuals: A Macro-Level Analysis

PubMed Central

Karaduman, Ayşenur; Göksun, Tilbe; Chatterjee, Anjan

2017-01-01

Focal brain injury can have detrimental effects on the pragmatics of communication. This study examined narrative production by unilateral brain damaged people (n= 36) and healthy controls and focused on the complexity (content and coherence) and the evaluative aspect of their narratives to test the general hypothesis that the left hemisphere is biased to process microlinguistic information and the right hemisphere is biased to process macrolinguistic information. We found that people with left hemisphere damage’s (LHD) narratives were less likely to maintain the overall theme of the story and produced fewer evaluative comments in their narratives. These deficits correlated with their performances on microlinguistic linguistic tasks. People with the right hemisphere damage (RHD) seemed to be preserved in expressing narrative complexity and evaluations as a group. Yet, single case analyses revealed that particular regions in the right hemisphere such as damage to the dorsolateral prefrontal cortex (DLPFC), the anterior and superior temporal gyrus, the middle temporal gyrus, and the supramarginal gyrus lead to problems in creating narratives. Our findings demonstrate that both hemispheres are necessary to produce competent narrative production. LHD people’s poor production is related to their microlinguistic language problems whereas RHD people’s impaired abilities can be associated with planning and working memory abilities required to relate events in a narrative. PMID:28347806

Nicotinamide attenuates the ischemic brain injury-induced decrease of Akt activation and Bad phosphorylation.

PubMed

Koh, Phil-Ok

2011-07-08

Nicotinamide protects cortical neuronal cells against cerebral ischemic injury through activation of various cytoprotective mechanisms. Here, this study confirmed the neuroprotective effects of nicotinamide in focal cerebral ischemic injury and investigated whether nicotinamide modulates a crucial survival pathway, Akt and its downstream targets. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2h after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. Nicotinamide significantly reduced the infarct volume in the cerebral cortex. Potential activation was measured by phosphorylation of PDK1 at Ser(241), Akt at Ser(473), and Bad at Ser(136) using Western blot analysis. Nicotinamide prevented the injury-induced decrease of pPDK1, pAkt, and pBad levels. 14-3-3 levels were not different between vehicle- and nicotinamide-treated animals. However, pBad and 14-3-3 interaction levels decreased during MCAO, but were maintained in the presence of nicotinamide, compared to levels in control animals. These findings suggest that nicotinamide attenuates cell death due to focal cerebral ischemic injury and that neuroprotective effects are mediated through the Akt signaling pathway, thus enhancing neuronal survival. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging

PubMed Central

LEVINE, BRIAN; FUJIWARA, ESTHER; O’CONNOR, CHARLENE; RICHARD, NADINE; KOVACEVIC, NATASA; MANDIC, MARINA; RESTAGNO, ADRIANA; EASDON, CRAIG; ROBERTSON, IAN H.; GRAHAM, SIMON J.; CHEUNG, GORDON; GAO, FUQIANG; SCHWARTZ, MICHAEL L.; BLACK, SANDRA E.

2007-01-01

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior. PMID:17020478

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

PubMed

Wolf, Amparo; Donahue, Bernadine; Silverman, Joshua S; Chachoua, Abraham; Lee, Jean K; Kondziolka, Douglas

2017-08-01

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372 mm 3 and the median margin dose was 16 Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.

A mouse model of human repetitive mild traumatic brain injury

PubMed Central

Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

2011-01-01

A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

Neuroprotective effect of oxaloacetate in a focal brain ischemic model in the rat.

PubMed

Knapp, L; Gellért, L; Kocsis, K; Kis, Z; Farkas, T; Vécsei, L; Toldi, J

2015-01-01

During an ischemic event, the well-regulated glutamate (Glu) homeostasis is disturbed, which gives rise to extremely high levels of this excitatory neurotransmitter in the brain tissues. It was earlier reported that the administration of oxaloacetate (OxAc) as a Glu scavenger reduces the Glu level in the brain by enhancing the brain-to-blood Glu efflux. Here, we studied the neuroprotective effect of OxAc administration in a new focal ischemic model in rats. Occlusion of the middle cerebral artery resulted in immediate reduction of the somatosensory-evoked responses (SERs), and the amplitudes remained at the reduced level throughout the whole ischemic period. On reperfusion, the SERs started to increase, but never reached the control level. OxAc proved to be protective, since the amplitudes started to recover even during the ischemia, and finally fully regained the control level. The findings of the histological measurements were in accordance with the electrophysiological data. After Fluoro Jade C staining, significantly fewer labeled cells were detected in the OxAc-treated group relative to the control. These results provide new evidence of the neuroprotective effect of OxAc against ischemic injury, which strengthens the likelihood of its future applicability as a novel neuroprotective agent for the treatment of ischemic stroke patients.

Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

PubMed Central

Ostrowski, Robert P.; Stępień, Katarzyna; Pucko, Emanuela; Matyja, Ewa

2016-01-01

The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering. PMID:27826422

Concussion and Traumatic Brain Injury

MedlinePlus

... please turn JavaScript on. Feature: Concussion Concussion and Traumatic Brain Injury Past Issues / Summer 2015 Table of Contents Children ... Flutie: "Be on the Safe Side." / Concussion and Traumatic Brain Injury Summer 2015 Issue: Volume 10 Number 2 Page ...

Blockade of Central Angiotensin II AT1 Receptor Protects the Brain from Ischemia/Reperfusion Injury in Normotensive Rats.

PubMed

Panahpour, Hamdolah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-11-01

Stroke is the third leading cause of invalidism and death in industrialized countries. There are conflicting reports about the effects of Angiotensin II on ischemia-reperfusion brain injuries and most data have come from chronic hypertensive rats. In this study, hypotensive and non-hypotensive doses of candesartan were used to investigate the effects of angiotensin II AT1 receptor blockade by transient focal cerebral ischemia in normotensive rats. In this experimental study, 48 male Sprague-Dawley rats were randomly divided into four groups (n=12). Sham group, the control ischemic group, and two ischemic groups received candesartan at doses of 0.1 or 0.5 mg/kg at one hour before ischemia. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 h reperfusion. The neurological deficit score was evaluated at the end of the reperfusion period. The total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride staining technique. Tissue swelling was calculated for the investigation of ischemic brain edema formation. In comparison with the control ischemic group, AT1 receptor blockade with both doses of candesartan (0.1 or 0.5 mg/kg) significantly improved neurological deficit and lowered cortical and striatal infarct sizes. In addition, pretreatment with candesartan significantly reduced ischemia induced tissue swelling. Angiotensin II by stimulating AT1 receptors, participates in ischemia-reperfusion injuries and edema formation. AT1 receptor blockade with candesartan decreased ischemic brain injury and edema and improved neurological outcome.

Brain injury and altered brain growth in preterm infants: predictors and prognosis.

PubMed

Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

2014-08-01

To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

PubMed

Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

2014-09-05

Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (p<0.05). Immunostaining results showed that the microvessel density in the peri-focal region of metformin treated mice was greatly increased compared to the control (p<0.05). Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p<0.05). Furthermore, we demonstrated that metformin treatment activated AMPK signaling pathway and promoted eNOS phosphorylation. Thus, we concluded that metformin promoted focal angiogenesis and neurogenesis and attenuated ischemia-induced brain injury in mice after middle cerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Back to the future: estimating pre-injury brain volume in patients with traumatic brain injury.

PubMed

Ross, David E; Ochs, Alfred L; D Zannoni, Megan; Seabaugh, Jan M

2014-11-15

A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin

PubMed Central

2017-01-01

Abstract Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others. PMID:29085896

Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin.

PubMed

Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

2017-01-01

Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others.

Integrating Traumatic Brain Injury Model Systems Data into the Federal Interagency Traumatic Brain Injury Research Informatics Systems

DTIC Science & Technology

2016-10-01

Traumatic Brain Injury Research Informatics Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0564 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...AWARD NUMBER: W81XWH-14-1-0564 TITLE: Integrating Traumatic Brain Injury Model Systems Data into the Federal Interagency Traumatic Brain Injury...Research Informatics Systems PRINCIPAL INVESTIGATOR: Cynthia Harrison-Felix, PhD CONTRACTING ORGANIZATION: Craig Hospital Englewood, CO 80113

SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.

PubMed

Abdel-Dayem, H M; Abu-Judeh, H; Kumar, M; Atay, S; Naddaf, S; El-Zeftawy, H; Luo, J Q

1998-05-01

The purpose of this atlas is to present a review of the literature showing the advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or MRI. The authors also present the technical recommendations for SPECT brain perfusion currently practiced at their center. For the radiopharmaceutical of choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc-99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD. Recommendations regarding standardizing intravenous injection, the acquisition, processing parameters, and interpretation of scans using a ten grade color scale, and use of the cerebellum as the reference organ are presented. SPECT images of 228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI and no significant medical history that interfered with the results of the SPECT BP were reviewed. The etiology of the trauma was in the following order of frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a fall (19%). Frequency of the symptoms was headache (60.9%), memory problems (27.6%), dizziness (26.7%), and sleep disorders (8.7%). Comparison between patients imaged early (<3 months) versus those imaged delayed (>3 months) from the time of the accident, showed that early imaging detected more lesions (4.2 abnormal lesions per study compared to 2.7 in those imaged more than 3 months after the accident). Of 41 patients who had mild traumatic injury without loss of consciousness and had normal CT, 28 studies were abnormal. Focal areas of hypoperfusion were seen in 77% (176 patients, 612 lesions) of the group of 228 patients. The sites of abnormalities were in the following order: basal ganglia and thalami, 55.2%, frontal lobes, 23.8%, temporal lobes, 13%, parietal, 3.7%, insular and occipital

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…

Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

PubMed

Lindsberg, P J; Sirén, A L; Hallenbeck, J M

1997-01-01

Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping

Development of brain injury criteria (BrIC).

PubMed

Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

2013-11-01

Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship

Functional MRI in the Investigation of Blast-Related Traumatic Brain Injury

PubMed Central

Graner, John; Oakes, Terrence R.; French, Louis M.; Riedy, Gerard

2012-01-01

This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries. PMID:23460082

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…

Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

PubMed

Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

2015-01-01

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding

PubMed Central

Pedersen, Mangor; Omidvarnia, Amir H.; Walz, Jennifer M.; Jackson, Graeme D.

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications. PMID:26110111

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

PubMed

Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

Assessing Quantitative Changes in Intrinsic Thalamic Networks in Blast and Nonblast Mild Traumatic Brain Injury: Implications for Mechanisms of Injury.

PubMed

Nathan, Dominic E; Bellgowan, Julie F; Oakes, Terrence R; French, Louis M; Nadar, Sreenivasan R; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

2016-06-01

In the global war on terror, the increased use of improvised explosive devices has resulted in increased incidence of blast-related mild traumatic brain injury (mTBI). Diagnosing mTBI is both challenging and controversial due to heterogeneity of injury location, trauma intensity, transient symptoms, and absence of focal biomarkers on standard clinical imaging modalities. The goal of this study is to identify a brain biomarker that is sensitive to mTBI injury. Research suggests the thalamus may be sensitive to changes induced by mTBI. A significant number of connections to and from various brain regions converge at the thalamus. In addition, the thalamus is involved in information processing, integration, and regulation of specific behaviors and mood. In this study, changes in task-free thalamic networks as quantified by graph theory measures in mTBI blast (N = 186), mTBI nonblast (N = 80), and controls (N = 21) were compared. Results show that the blast mTBI group had significant hyper-connectivity compared with the controls and nonblast mTBI group. However, after controlling for post-traumatic stress symptoms (PTSS), the blast mTBI group was not different from the controls, but the nonblast mTBI group showed significant hypo-connectivity. The results suggest that there are differences in the mechanisms of injury related to mTBI as reflected in the architecture of the thalamic networks. However, the effect of PTSS and its relationship to mTBI is difficult to distinguish and warrants more research.

Blockade of Central Angiotensin II AT1 Receptor Protects the Brain from Ischemia/Reperfusion Injury in Normotensive Rats

PubMed Central

Panahpour, Hamdolah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-01-01

Background: Stroke is the third leading cause of invalidism and death in industrialized countries. There are conflicting reports about the effects of Angiotensin II on ischemia-reperfusion brain injuries and most data have come from chronic hypertensive rats. In this study, hypotensive and non-hypotensive doses of candesartan were used to investigate the effects of angiotensin II AT1 receptor blockade by transient focal cerebral ischemia in normotensive rats. Methods: In this experimental study, 48 male Sprague-Dawley rats were randomly divided into four groups (n=12). Sham group, the control ischemic group, and two ischemic groups received candesartan at doses of 0.1 or 0.5 mg/kg at one hour before ischemia. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 h reperfusion. The neurological deficit score was evaluated at the end of the reperfusion period. The total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride staining technique. Tissue swelling was calculated for the investigation of ischemic brain edema formation. Results: In comparison with the control ischemic group, AT1 receptor blockade with both doses of candesartan (0.1 or 0.5 mg/kg) significantly improved neurological deficit and lowered cortical and striatal infarct sizes. In addition, pretreatment with candesartan significantly reduced ischemia induced tissue swelling. Conclusion: Angiotensin II by stimulating AT1 receptors, participates in ischemia-reperfusion injuries and edema formation. AT1 receptor blockade with candesartan decreased ischemic brain injury and edema and improved neurological outcome. PMID:25429176

45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

PubMed

Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

2015-10-01

Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.

PubMed

Wang, Na; Guo, Qu-lian; Ye, Zhi; Xia, Ping-ping; Wang, E; Yuan, Ya-jing

2011-07-05

Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

Netrin-1 Preserves Blood-Brain Barrier Integrity Through Deleted in Colorectal Cancer/Focal Adhesion Kinase/RhoA Signaling Pathway Following Subarachnoid Hemorrhage in Rats.

PubMed

Xie, Zongyi; Enkhjargal, Budbazar; Reis, Cesar; Huang, Lei; Wan, Weifeng; Tang, Jiping; Cheng, Yuan; Zhang, John H

2017-05-19

Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH. Recombinant NTN-1 was administered intravenously 1 hour after SAH induction. NTN-1 small interfering RNA or Deleted in Colorectal Cancer small interfering RNA was administered intracerebroventricular at 48 hours before SAH. Focal adhesion kinase inhibitor was administered by intraperitoneal injection at 1 hour prior to SAH. Neurological scores, brain water content, BBB permeability, RhoA activity, Western blot, and immunofluorescence staining were evaluated. The expression of endogenous NTN-1 and its receptor Deleted in Colorectal Cancer were increased after SAH. Administration of exogenous NTN-1 significantly reduced brain water content and BBB permeability and ameliorated neurological deficits at 24 and 72 hours after SAH. Exogenous NTN-1 treatment significantly promoted phosphorylated focal adhesion kinase activation and inhibited RhoA activity, as well as upregulated the expression of ZO-1 and Occludin. Conversely, depletion of endogenous NTN-1 aggravated BBB breakdown and neurological impairments at 24 hours after SAH. The protective effects of NTN-1 at 24 hours after SAH were also abolished by pretreatment with Deleted in Colorectal Cancer small interfering RNA and focal adhesion kinase inhibitor. NTN-1 treatment preserved BBB integrity and improved neurological functions through a Deleted in Colorectal Cancer/focal adhesion kinase/RhoA signaling pathway after SAH. Thus, NTN-1 may serve as a promising treatment to alleviate early brain injury following SAH. © 2017 The Authors. Published on behalf of the American Heart

Brain Injury Alters Volatile Metabolome

PubMed Central

Cohen, Akiva S.; Gordon, Amy R.; Opiekun, Maryanne; Martin, Talia; Elkind, Jaclynn; Lundström, Johan N.; Beauchamp, Gary K.

2016-01-01

Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function—which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. PMID:26926034

Hypersomnia Following Traumatic Brain Injury

PubMed Central

Watson, Nathaniel F; Dikmen, Sureyya; Machamer, Joan; Doherty, Michael; Temkin, Nancy

2007-01-01

Study Objectives: To evaluate the prevalence and natural history of sleepiness following traumatic brain injury. Methods: This prospective cohort study used the Sickness Impact Profile to evaluate sleepiness in 514 consecutive subjects with traumatic brain injury (TBI), 132 non-cranial trauma controls, and 102 trauma-free controls 1 month and 1 year after injury. Results: Fifty-five percent of TBI subjects, 41% of non-cranial trauma controls, and 3% of trauma-free controls endorsed 1 or more sleepiness items 1 month following injury (p < .001). One year following injury, 27% of TBI subjects, 23% of non-cranial trauma controls, and 1% of trauma-free controls endorsed 1 or more sleepiness items (p < .001). Patients with TBI were sleepier than non-cranial trauma controls at 1 month (p < .02) but not 1 year after injury. Brain-injured subjects were divided into injury-severity groups based on time to follow commands (TFC). At 1 month, the non-cranial trauma controls were less sleepy than the 1- to 6-day (p < .05), 7- to 13-day (p < .01), and 14-day or longer (p < .01) TFC groups. In addition, the ≤ 24-hour group was less sleepy then the 7- to 13-day and 14-day or longer groups (each p < .05). At 1 year, the non-cranial trauma control group (p < .05) and the ≤ 24-hour TFC group (p < .01) were less sleepy than the 14-day or longer TFC group. Sleepiness improved in 84% to 100% of subjects in the TBI TFC groups, as compared with 78% of the non-cranial trauma control group (p < .01). Conclusions: Sleepiness is common following traumatic injury, particularly TBI, with more severe injuries resulting in greater sleepiness. Sleepiness improves in many patients, particularly those with TBI. However, about a quarter of TBI subjects and non-cranial trauma control subjects remained sleepy 1 year after injury. Citation: Watson NF; Dikmen S; Machamer J et al. Hypersomnia following traumatic brain injury. J Clin Sleep Med 2007;3(4):363-368. PMID:17694724

Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

PubMed

Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

2009-03-01

Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

Resilience in mathematics after early brain injury: The roles of parental input and early plasticity.

PubMed

Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C

2018-04-01

Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.

PubMed

Scheibel, Randall S; Newsome, Mary R; Wilde, Elisabeth A; McClelland, Michelle M; Hanten, Gerri; Krawczyk, Daniel C; Cook, Lori G; Chu, Zili D; Vásquez, Ana C; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V; Levin, Harvey S

2011-01-01

The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

Safe and stable noninvasive focal gene delivery to the mammalian brain following focused ultrasound.

PubMed

Stavarache, Mihaela A; Petersen, Nicholas; Jurgens, Eric M; Milstein, Elizabeth R; Rosenfeld, Zachary B; Ballon, Douglas J; Kaplitt, Michael G

2018-04-27

OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation. The objective of the current study was to evaluate the efficiency, safety, and long-term stability of MRgFUS-mediated noninvasive gene therapy in the mammalian brain. METHODS Focused ultrasound under the control of MRI, in combination with microbubbles consisting of albumin-coated gas microspheres, was applied to rat striatum, followed by intravenous infusion of an adeno-associated virus serotype 1/2 (AAV1/2) vector expressing green fluorescent protein (GFP) as a marker. Following recovery, animals were followed from several hours up to 15 months. Immunostaining for GFP quantified transduction efficiency and stability of expression. Quantification of neuronal markers was used to determine histological safety over time, while inflammatory markers were examined for evidence of immune responses. RESULTS Transitory disruption of the BBB by MRgFUS resulted in efficient delivery of the AAV1/2 vector to the targeted rodent striatum, with 50%-75% of striatal neurons transduced on average. GFP transgene expression appeared to be stable over extended periods of time, from 2 weeks to 6 months, with evidence of ongoing stable expression as long as 16 months in a smaller cohort of animals. No evidence of substantial toxicity, tissue injury, or neuronal loss was observed. While transient inflammation from BBB disruption alone was noted for the first few days, consistent

Educational professionals' understanding of childhood traumatic brain injury.

PubMed

Linden, Mark A; Braiden, Hannah-Jane; Miller, Sarah

2013-01-01

To determine the understanding of educational professionals around the topic of childhood brain injury and explore the factor structure of the Common Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI). Cross-sectional postal survey. The CM-TBI was posted to all educational establishments in one region of the UK. One representative from each school was asked to complete and return the questionnaire (n = 388). Differences were demonstrated between those participants who knew someone with a brain injury and those who did not, with a similar pattern being shown for those educators who had taught a child with brain injury. Participants who had taught a child with brain injury demonstrated greater knowledge in areas such as seatbelts/prevention, brain damage, brain injury sequelae, amnesia, recovery and rehabilitation. Principal components analysis suggested the existence of four factors and the discarding of half the original items of the questionnaire. In the first European study to explore this issue, it is highlighted that teachers are ill-prepared to cope with children who have sustained a brain injury. Given the importance of a supportive school environment in return to life following hospitalization, the lack of understanding demonstrated by teachers in this research may significantly impact on a successful return to school.

[Prognosis in pediatric traumatic brain injury. A dynamic cohort study].

PubMed

Vázquez-Solís, María G; Villa-Manzano, Alberto I; Sánchez-Mosco, Dalia I; Vargas-Lares, José de Jesús; Plascencia-Fernández, Irma

2013-01-01

traumatic brain injury is a main cause of hospital admission and death in children. Our objective was to identify prognostic factors of pediatric traumatic brain injury. this was a dynamic cohort study of traumatic brain injury with 6 months follow-up. The exposition was: mild or moderate/severe traumatic brain injury, searching for prognosis (morbidity-mortality and decreased Glasgow scale). Relative risk and logistic regression was estimated for prognostic factors. we evaluated 440 patients with mild traumatic brain injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %. There were no deaths. Prognostic factors for moderate/severe traumatic brain injury were associated injuries (RR = 133), fractures (RR = 60), street accidents (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2). Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR = 1.6). there should be a prognosis established based on kinetic energy of the injury and not only with Glasgow Scale.

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

PubMed

Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

2016-01-01

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

Cost-appropriateness of whole body vs limited bone imaging for suspected focal sports injuries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagle, C.E.

Bone imaging has been recognized as a useful diagnostic tool in detecting the presence of focal musculoskeletal injury when radiographs are normal. A retrospective review of bone images in a small number of amateur athletes indicates that secondary injuries were commonly detected at sites different from the site of musculoskeletal pain being evaluated for injury. While a larger study will be necessary to confirm the data, this review suggests that it is medically justified and cost-appropriate to perform imaging of the entire skeleton as opposed to imaging limited to the anatomic site of pain and suspected injury.

Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

PubMed

Carroll, Linda J; Cassidy, J David; Holm, Lena; Kraus, Jess; Coronado, Victor G

2004-02-01

The WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury performed a comprehensive search and critical review of the literature published between 1980 and 2002 to assemble the best evidence on the epidemiology, diagnosis, prognosis and treatment of mild traumatic brain injury. Of 743 relevant studies, 313 were accepted on scientific merit and comprise our best-evidence synthesis. The current literature on mild traumatic brain injury is of variable quality and we report the most common methodological flaws. We make recommendations for avoiding the shortcomings evident in much of the current literature and identify topic areas in urgent need of further research. This includes the need for large, well-designed studies to support evidence-based guidelines for emergency room triage of children with mild traumatic brain injury and to explore more fully the issue of prognosis after mild traumatic brain injury in the elderly population. We also advocate use of standard criteria for defining mild traumatic brain injury and propose a definition.

Transcranial magnetic stimulation in brain injury.

PubMed

Castel-Lacanal, E; Tarri, M; Loubinoux, I; Gasq, D; de Boissezon, X; Marque, P; Simonetta-Moreau, M

2014-02-01

Transcranial magnetic stimulations (TMS) have been used for many years as a diagnostic tool to explore changes in cortical excitability, and more recently as a tool for therapeutic neuromodulation. We are interested in their applications following brain injury: stroke, traumatic and anoxic brain injury. Following brain injury, there is decreased cortical excitability and changes in interhemispheric interactions depending on the type, the severity, and the time-lapse between the injury and the treatment implemented. rTMS (repetitive TMS) is a therapeutic neuromodulation tool which restores the interhemispheric interactions following stroke by inhibiting the healthy cortex with frequencies ≤1Hz, or by exciting the lesioned cortex with frequencies between 3 and 50Hz. Results in motor recovery are promising and those in improving aphasia or visuospatial neglect are also encouraging. Finally, the use of TMS is mainly limited by the risk of seizure, and is therefore contraindicated for many patients. TMS is a useful non-invasive brain stimulation tool to diagnose the effects of brain injury, to study the mechanisms of recovery and a non-invasive neuromodulation promising tool to influence the post-lesional recovery. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

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.

White matter injury in term newborns with neonatal encephalopathy.

PubMed

Li, Amanda M; Chau, Vann; Poskitt, Kenneth J; Sargent, Michael A; Lupton, Brian A; Hill, Alan; Roland, Elke; Miller, Steven P

2009-01-01

White matter injury (WMI) is the characteristic pattern of brain injury detected on magnetic resonance imaging in the premature newborn. Focal noncystic WMI is increasingly recognized in populations of term newborns. The aim of this study was to describe the occurrence of focal noncystic WMI in a cohort of 48 term newborns with encephalopathy studied with magnetic resonance imaging at 72 +/- 12 h of life, and to identify clinical risk factors for this pattern of injury. Eleven newborns (23%; 95% CI 11-35) were found to have WMI (four minimal, three moderate, and four severe). In 10 of the 11 newborns, the WMI was associated with restricted diffusion on apparent diffusion coefficient maps. An increasing severity of WMI was associated with lower gestational age at birth (p = 0.05), but not lower birth weight. Newborns with WMI had milder encephalopathy and fewer clinical seizures relative to other newborns in the cohort. Other brain injuries were seen in three of the 11 newborns: basal nuclei predominant pattern of injury in one and cortical strokes in two. These findings suggest that WMI in the term newborn is acquired near birth and that the state of brain maturation is an important determinant of this pattern of brain injury.

Brain imaging and behavioral outcome in traumatic brain injury.

PubMed

Bigler, E D

1996-09-01

Brain imaging studies have become an essential diagnostic assessment procedure in evaluating the effects of traumatic brain injury (TBI). Such imaging studies provide a wealth of information about structural and functional deficits following TBI. But how pathologic changes identified by brain imaging methods relate to neurobehavioral outcome is not as well known. Thus, the focus of this article is on brain imaging findings and outcome following TBI. The article starts with an overview of current research dealing with the cellular pathology associated with TBI. Understanding the cellular elements of pathology permits extrapolation to what is observed with brain imaging. Next, this article reviews the relationship of brain imaging findings to underlying pathology and how that pathology relates to neurobehavioral outcome. The brain imaging techniques of magnetic resonance imaging, computerized tomography, and single photon emission computed tomography are reviewed. Various image analysis procedures, and how such findings relate to neuropsychological testing, are discussed. The importance of brain imaging in evaluating neurobehavioral deficits following brain injury is stressed.

The neuropathology of traumatic brain injury.

PubMed

Mckee, Ann C; Daneshvar, Daniel H

2015-01-01

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at

Annexin A7 Levels Increase in Rats With Traumatic Brain Injury and Promote Secondary Brain Injury.

PubMed

Gao, Fan; Li, Di; Rui, Qin; Ni, Haibo; Liu, Huixiang; Jiang, Feng; Tao, Li; Gao, Rong; Dang, Baoqi

2018-01-01

The incidence of traumatic brain injury (TBI) has been increasing annually. Annexin A7 is a calcium-dependent phospholipid binding protein. It can promote melting of the cell membrane. Recent studies have shown that it plays an important role in atherosclerosis, other cardiovascular diseases, and a variety of tumors. However, few studies of ANXA7 in TBI have been performed. We here observed how ANXA7 changes after TBI and discuss whether brain injury is associated with the use of ANXA7 antagonist intervention. Experimental Results: 1. After TBI, ANXA7 levels were higher than in the sham group, peaking 24 h after TBI. 2. The use of siA7 was found to reduce the expression of A7 in the injured brain tissue, and also brain edema, BBB damage, cell death, and apoptosis relative to the sham group. Conclusion: ANXA7 promotes the development of secondary brain injury (SBI) after TBI.

Reactive astrocytes and therapeutic potential in focal ischemic stroke

PubMed Central

Choudhury, Gourav Roy; Ding, Shinghua

2015-01-01

Astrocytes are specialized and the most abundant cell type in the central nervous system (CNS). They play important roles in the physiology of the brain. Astrocytes are also critically involved in many CNS disorders including focal ischemic stroke, the leading cause of brain injury and death in patients. One of the prominent pathological features of a focal ischemic stroke is reactive astrogliosis and glial scar formation. Reactive astrogliosis is accompanied with changes in morphology, proliferation and gene expression in the reactive astrocytes. This study provides an overview of the most recent advances in astrocytic Ca2+ signaling, spatial and temporal dynamics of the morphology and proliferation of reactive astrocytes as well as signaling pathways involved in the reactive astrogliosis after ischemic stroke based on results from experimental studies performed in various animal models. This review also discusses the therapeutic potential of reactive astrocytes in a focal ischemic stroke. As reactive astrocytes exhibit high plasticity, we suggest that modulation of local reactive astrocytes is a promising strategy for cell-based stroke therapy. PMID:25982835

Clinical trials in mild traumatic brain injury.

PubMed

Hoffer, Michael E; Szczupak, Mikhaylo; Balaban, Carey

2016-10-15

Traumatic brain injury is an increasingly prevalent injury seen in both civilian and military populations. Regardless of the mechanisms of injury, the most common sub-type of injury continues to be mild traumatic brain injury. Within the last decade, there has been tremendous growth in the literature regarding this disease entity. To describe the obstacles necessary to overcome in performing a rigorous and sound clinical research study investigating mild traumatic brain injury. This examination begins by a consideration of changing standards for good faith open and total reporting of any and all conflicts of interest or commitment. This issue is particularly critical in mTBI research. We next examine obstacles that include but are not limited to diagnostic criteria, inclusion/exclusion criteria, source of injury, previous history of injury, presence of comorbid conditions and proper informed consent of participants. Frequently, multi-center studies are necessary for adequate subject accrual with the added challenges of site coordination, data core management and site specific study conduct. We propose a total reversal to the traditional translational research approach where clinical studies drive new concepts for future basic science studies. There have been few mild traumatic brain injury clinical trials in the literature with treatments/interventions that have been able to overcome many of these described obstacles. We look forward to the results of current and ongoing clinical mild traumatic brain injury studies providing the tools necessary for the next generation of basic science projects. Copyright © 2016 Elsevier B.V. All rights reserved.

[Traumatic brain injuries--forensic and expertise aspects].

PubMed

Vuleković, Petar; Simić, Milan; Misić-Pavkov, Gordana; Cigić, Tomislav; Kojadinović, Zeljko; Dilvesi, Dula

2008-01-01

Traumatic brain injuries have major socio-economic importance due to their frequency, high mortality and serious consequences. According to their nature the consequences of these injuries may be classified as neurological, psychiatric and esthetic. Various lesions of brain structures cause neurological consequences such as disturbance of motor functions, sensibility, coordination or involuntary movements, speech disturbances and other deviations, as well as epilepsy. Psychiatric consequences include cognitive deficit, emotional disturbances and behavior disturbances. CRIMINAL-LEGAL ASPECT OF TRAUMATIC BRAIN INJURIES AND LITIGATION: Criminal-legal aspect of traumatic brain injuries expertise understands the qualification of these injuries as mild, serious and qualified serious body injuries as well as the expertise about the mechanisms of their occurrence. Litigation expertise includes the estimation of pain, fear, diminished, i.e. lost vital activity and disability, esthetic marring, and psychological suffer based on the diminished general vital activity and esthetic marring. Evaluation of consequences of traumatic brain injuries should be performed only when it can be positively confirmed that they are permanent, i.e. at least one year after the injury. Expertise of these injuries is interdisciplinary. Among clinical doctors the most competent medical expert is the one who is in charge for diagnostics and injury treatment, with the recommendation to avoid, if possible, the doctor who conducted treatment. For the estimation of general vital activity, the neurological consequences, pain and esthetic marring expertise, the most competent doctors are neurosurgeon and neurologist. Psychological psychiatric consequences and fear expertise have to be performed by the psychiatrist. Specialists of forensic medicine contribute with knowledge of criminal low and legal expertise.

Lesion Size Is Exacerbated in Hypoxic Rats Whereas Hypoxia-Inducible Factor-1 Alpha and Vascular Endothelial Growth Factor Increase in Injured Normoxic Rats: A Prospective Cohort Study of Secondary Hypoxia in Focal Traumatic Brain Injury.

PubMed

Thelin, Eric Peter; Frostell, Arvid; Mulder, Jan; Mitsios, Nicholas; Damberg, Peter; Aski, Sahar Nikkhou; Risling, Mårten; Svensson, Mikael; Morganti-Kossmann, Maria Cristina; Bellander, Bo-Michael

2016-01-01

Hypoxia following traumatic brain injury (TBI) is a severe insult shown to exacerbate the pathophysiology, resulting in worse outcome. The aim of this study was to investigate the effects of a hypoxic insult in a focal TBI model by monitoring brain edema, lesion volume, serum biomarker levels, immune cell infiltration, as well as the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Female Sprague-Dawley rats (n = 73, including sham and naive) were used. The rats were intubated and mechanically ventilated. A controlled cortical impact device created a 3-mm deep lesion in the right parietal hemisphere. Post-injury, rats inhaled either normoxic (22% O2) or hypoxic (11% O2) mixtures for 30 min. The rats were sacrificed at 1, 3, 7, 14, and 28 days post-injury. Serum was collected for S100B measurements using ELISA. Ex vivo magnetic resonance imaging (MRI) was performed to determine lesion size and edema volume. Immunofluorescence was employed to analyze neuronal death, changes in cerebral macrophage- and neutrophil infiltration, microglia proliferation, apoptosis, complement activation (C5b9), IgG extravasation, HIF-1α, and VEGF. The hypoxic group had significantly increased blood levels of lactate and decreased pO2 (p < 0.0001). On MRI post-traumatic hypoxia resulted in larger lesion areas (p = 0.0173), and NeuN staining revealed greater neuronal loss (p = 0.0253). HIF-1α and VEGF expression was significantly increased in normoxic but not in hypoxic animals (p < 0.05). A trend was seen for serum levels of S100B to be higher in the hypoxic group at 1 day after trauma (p = 0.0868). No differences were observed between the groups in cytotoxic and vascular edema, IgG extravasation, neutrophils and macrophage aggregation, microglia proliferation, or C5b-9 expression. Hypoxia following focal TBI exacerbated the lesion size and neuronal loss. Moreover, there was a tendency to higher levels

Predictors of Hypopituitarism in Patients with Traumatic Brain Injury.

PubMed

Silva, Paula P B; Bhatnagar, Saurabha; Herman, Seth D; Zafonte, Ross; Klibanski, Anne; Miller, Karen K; Tritos, Nicholas A

2015-11-15

Hypopituitarism may often occur in association with traumatic brain injury (TBI). Identification of reliable predictors of pituitary dysfunction is of importance in order to establish a rational testing approach. We searched the records of patients with TBI, who underwent neuroendocrine evaluation in our institution between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months (0.2-430.4).Of these, 31% had ≥1 pituitary deficiency, including 29% of patients with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were more likely to have suffered a motor vehicle accident (MVA, p = 0.04), experienced post-traumatic seizures (p = 0.04), demonstrated any intracranial hemorrhage (p = 0.05), petechial brain hemorrhages (p = 0.017), or focal cortical parenchymal contusions (p = 0.02). Central hypothyroidism occurred in 8% and central hypogonadism in 12%; the latter subgroup had higher BMI (p = 0.03), were less likely to be working after TBI (p = 0.002), and had lower Global Assessment of Functioning (GAF) scores (p = 0.03). Central diabetes insipidus (DI) occurred in 6%, who were more likely to have experienced MVA (p < 0.001) or sustained moderate/severe TBI (p < 0.001). Patients with MVA and those with post-traumatic seizures, intracranial hemorrhage, petechial brain hemorrhages, and/or focal cortical contusions are at particular risk for serious pituitary dysfunction, including adrenal insufficiency and DI, and should be referred for neuroendocrine testing. However, a substantial proportion of patients without these risk factors also developed hypopituitarism.

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…

Substance P mediates reduced pneumonia rates after traumatic brain injury.

PubMed

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

2014-09-01

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. Data from the National Trauma Data Bank and a murine model of traumatic brain injury with postinjury pneumonia. Academic medical centers in Cincinnati, OH, and Boston, MA. 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. Administration of a substance P receptor antagonist in mice. 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. The data demonstrate that patients with traumatic brain injury have lower rates of pneumonia compared to non-head-injured trauma patients and suggest that the

Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

PubMed

Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P

2012-04-01

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 dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

PubMed Central

Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

2018-01-01

Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

Traumatic Brain Injury: Effects on the Endocrine System

MedlinePlus

Fact Sheet BTrarainumInajutircy: Effects on the Endocrine System What is traumatic brain injury? Traumatic brain injury, also called TBI, is sudden damage to the brain. It happens when the head hits ...

Defense.gov Special Report: Traumatic Brain Injury

Science.gov Websites

Excellence TBI Resources Brainline Military The Michael E. DeBakey VA Medical Center Congressionally Directed Medical Research Program NIH: National Institute of Neurological Disorders NIH: Traumatic Brain Injury Research CDC: Give Brain Injury a Voice Center for Medical Excellence for Multimedia Brainline.org - Brain

Comparison of the anti-apoptotic effects of 15- and 35-minute suspended moxibustion after focal cerebral ischemia/reperfusion injury.

PubMed

Xiao, Ai-Jiao; He, Lin; Ouyang, Xin; Liu, Jie-Min; Chen, Ming-Ren

2018-02-01

Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion (usually from 30 minutes to 1 hour) is longer than traditional suspended moxibustion (usually 15 minutes). However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebral ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui (GV14) in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the injury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expression was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.

The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.

PubMed

Zhao, Li-xia; Liu, An-chang; Yu, Shu-wen; Wang, Zeng-xin; Lin, Xiao-qian; Zhai, Guang-xi; Zhang, Qing-zhu

2013-01-01

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.

Dementia resulting from traumatic brain injury

PubMed Central

Ramalho, Joana; Castillo, Mauricio

2015-01-01

Traumatic brain injury (TBI) represents a significant public health problem in modern societies. It is primarily a consequence of traffic-related accidents and falls. Other recently recognized causes include sports injuries and indirect forces such as shock waves from battlefield explosions. TBI is an important cause of death and lifelong disability and represents the most well-established environmental risk factor for dementia. With the growing recognition that even mild head injury can lead to neurocognitive deficits, imaging of brain injury has assumed greater importance. However, there is no single imaging modality capable of characterizing TBI. Current advances, particularly in MR imaging, enable visualization and quantification of structural and functional brain changes not hitherto possible. In this review, we summarize data linking TBI with dementia, emphasizing the imaging techniques currently available in clinical practice along with some advances in medical knowledge. PMID:29213985

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

Beneficial effects of n-acetylcysteine on ischaemic brain injury

PubMed Central

Cuzzocrea, Salvatore; Mazzon, Emanuela; Costantino, Giuseppina; Serraino, Ivana; Dugo, Laura; Calabrò, Giusy; Cucinotta, Giovanni; De Sarro, Angela; Caputi, A P

2000-01-01

Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia.Treatment of gerbils with NAC (20 mg kg−1 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content.NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia.Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC.NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion.Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC.These results show that NAC improves brain injury induced by transient cerebral ischaemia. PMID:10903958

Clinical review: Ketones and brain injury

PubMed Central

2011-01-01

Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury. PMID:21489321

Lateral automobile impacts and the risk of traumatic brain injury.

PubMed

Bazarian, Jeffrey J; Fisher, Susan Gross; Flesher, William; Lillis, Robert; Knox, Kerry L; Pearson, Thomas A

2004-08-01

We determine the relative risk and severity of traumatic brain injury among occupants of lateral impacts compared with occupants of nonlateral impacts. This was a secondary analysis of the National Highway Traffic Safety Administration's National Automotive Sampling System, Crashworthiness Data Systems for 2000. Analysis was restricted to occupants of vehicles in which at least 1 person experienced an injury with Abbreviated Injury Scale score greater than 2. Traumatic brain injury was defined as an injury to the head or skull with an Abbreviated Injury Scale score greater than 2. Outcomes were analyzed using the chi2 test and multivariate logistic regression, with adjustment of variance to account for weighted probability sampling. Of the 1,115 occupants available for analysis, impact direction was lateral for 230 (18.42%) occupants and nonlateral for 885 (81.58%) occupants. One hundred eighty-seven (16.07%) occupants experienced a traumatic brain injury, 14.63% after lateral and 16.39% after nonlateral impact. The unadjusted relative risk of traumatic brain injury after lateral impact was 0.89 (95% confidence interval [CI] 0.51 to 1.56). After adjusting for several important crash-related variables, the relative risk of traumatic brain injury was 2.60 (95% CI 1.1 to 6.0). Traumatic brain injuries were more severe after lateral impact according to Abbreviated Injury Scale and Glasgow Coma Scale scores. The proportion of fatal or critical crash-related traumatic brain injuries attributable to lateral impact was 23.5%. Lateral impact is an important independent risk factor for the development of traumatic brain injury after a serious motor vehicle crash. Traumatic brain injuries incurred after lateral impact are more severe than those resulting from nonlateral impact. Vehicle modifications that increase head protection could reduce crash-related severe traumatic brain injuries by up to 61% and prevent up to 2,230 fatal or critical traumatic brain injuries each year

Protective effect of chlorogenic acid on the focal cerebral ischemia reperfusion rat models.

PubMed

Miao, Mingsan; Cao, Lihua; Li, Ruiqi; Fang, Xiaoyan; Miao, Yanyan

2017-05-01

The aim of the study was to investigate the protective characteristic of chlorogenic acid, a natural glucosyl xanthone found in Lonicera Japonica on the cerebral ischemia reperfusion injury and the underlying mechanism. Focal cerebral ischemia reperfusion model was built by blocking the left middle cerebral artery in rats by using the suture-occluded method. Before operation, the corresponding drugs were given for each group once a day for 7 days. After 1 h of final administration, the model was built, after operation, reperfusion was conducted for 22 h, Before the reperfusion 10 min tail vein injection of large, medium and small dose of chlorogenic acid and then mortality was calculated, and Neurological deficit score (NDS) was conducted, and serum was collected to measure the NSE level; a 2 mm thick brain slice located at the intersection of optic nerves was collected for TTC staining, and the percentage of cerebral infarction area was calculated; brain homogenate was collected to measure the ICAM-1, VCAM-1, EPO and HIF-1α levels in brain tissue of cerebral ischemia reperfusion rat models; NGF was detected using immunohistochemical method; the morphological changes in brain tissue was observed with HE staining. All focal cerebral ischemia reperfusion rat models were duplicated successfully. Every chlorogenic acid group with different dosage can significantly reduce the mortality, NDS and cerebral infarction area of rats, and significantly increase the EPO, HIF-1α and NGF levels in brain tissue; significantly improve the pathological lesions of hippocampus and cortex in brain tissue. The results showed that chlorogenic acid could protect the focal cerebral ischemia reperfusion injury rat models by adjusting the inflammatory factor, hypoxia factor and nerve growth factor.

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 adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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…

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of

Brain MRI volumetry in a single patient with mild traumatic brain injury.

PubMed

Ross, David E; Castelvecchi, Cody; Ochs, Alfred L

2013-01-01

This letter to the editor describes the case of a 42 year old man with mild traumatic brain injury and multiple neuropsychiatric symptoms which persisted for a few years after the injury. Initial CT scans and MRI scans of the brain showed no signs of atrophy. Brain volume was measured using NeuroQuant®, an FDA-approved, commercially available software method. Volumetric cross-sectional (one point in time) analysis also showed no atrophy. However, volumetric longitudinal (two points in time) analysis showed progressive atrophy in several brain regions. This case illustrated in a single patient the principle discovered in multiple previous group studies, namely that the longitudinal design is more powerful than the cross-sectional design for finding atrophy in patients with traumatic brain injury.

Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

PubMed

Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

2015-01-01

Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not

Severe traumatic head injury: prognostic value of brain stem injuries detected at MRI.

PubMed

Hilario, A; Ramos, A; Millan, J M; Salvador, E; Gomez, P A; Cicuendez, M; Diez-Lobato, R; Lagares, A

2012-11-01

Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P < .05). Posterior location showed the best discriminatory capability in terms of outcome (OR 6.8, P < .05) and disability (OR 4.8, P < .01). The addition of nonhemorrhagic and anterior lesions or unilateral injuries showed the highest odds and best discriminatory capacity for good outcome. The prognosis worsens in direct relationship to the extent of traumatic injury. Posterior and bilateral brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

Subjective complaints after acquired brain injury: presentation of the Brain Injury Complaint Questionnaire (BICoQ).

PubMed

Vallat-Azouvi, Claire; Paillat, Cyrille; Bercovici, Stéphanie; Morin, Bénédicte; Paquereau, Julie; Charanton, James; Ghout, Idir; Azouvi, Philippe

2018-04-01

The objective of the present study was to present a new complaint questionnaire designed to assess a wide range of difficulties commonly reported by patients with acquired brain injury. Patients (n =  619) had been referred to a community re-entry service at a chronic stage after brain injury, mainly traumatic brain injury (TBI). The Brain Injury Complaint Questionnaire (BICoQ) includes 25 questions in the following domains: cognition, behavior, fatigue and sleep, mood, and somatic problems. A self and a proxy questionnaire were given. An additional question was given to the relative, about the patient's awareness of his difficulties. The questionnaires had a good internal coherence, as measured with Cronbach's alpha. The most frequent complaints were, in decreasing order, mental slowness, memory troubles, fatigue, concentration difficulties, anxiety, and dual tasking problems. Principal component analysis with varimax rotation yielded six underlying factors explaining 50.5% of total variance: somatic concerns, cognition, and lack of drive, lack of control, psycholinguistic disorders, mood, and mental fatigue/slowness. About 52% of patients reported fewer complaints than their proxy, suggesting lack of awareness. The total complaint scores were not significantly correlated with any injury severity measure, but were significantly correlated with disability and poorer quality of life (Note: only factor 2 [cognition/lack of drive] was significantly related to disability.) The BICoQ is a simple scale that can be used in addition to traditional clinical and cognitive assessment measures, and to assess awareness of everyday life problems. © 2017 Wiley Periodicals, Inc.

Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site.

PubMed

Harris, Katie; Armstrong, Scott P; Campos-Pires, Rita; Kiru, Louise; Franks, Nicholas P; Dickinson, Robert

2013-11-01

Xenon, the inert anesthetic gas, is neuroprotective in models of brain injury. The authors investigate the neuroprotective mechanisms of the inert gases such as xenon, argon, krypton, neon, and helium in an in vitro model of traumatic brain injury. The authors use an in vitro model using mouse organotypic hippocampal brain slices, subjected to a focal mechanical trauma, with injury quantified by propidium iodide fluorescence. Patch clamp electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate receptors and TREK-1 channels, two molecular targets likely to play a role in neuroprotection. Xenon (50%) and, to a lesser extent, argon (50%) are neuroprotective against traumatic injury when applied after injury (xenon 43±1% protection at 72 h after injury [N=104]; argon 30±6% protection [N=44]; mean±SEM). Helium, neon, and krypton are devoid of neuroprotective effect. Xenon (50%) prevents development of secondary injury up to 48 h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon (xenon 50±5% reduction in secondary injury at 72 h after injury [N=104]; argon 34±8% reduction [N=44]; mean±SEM). Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive inhibition at the N-methyl-D-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels. Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-D-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.

Tics after traumatic brain injury.

PubMed

Ranjan, Nishant; Nair, Krishnan Padmakumari Sivaraman; Romanoski, Charles; Singh, Rajiv; Venketswara, Guruprasad

2011-01-01

Tics are involuntary non-rhythmic, stereotyped muscle contractions which can be suppressed temporarily. Tics usually start during childhood as part of Tourette syndrome. Adult onset tics are infrequent. This study reports on an adult man who developed tics 1 year after severe traumatic brain injury (TBI). Case report and review of literature. A 19-year-old man sustained TBI following a road traffic accident. He did not have tics or features of obsessive compulsive disorder before the brain injury. A year after injury he developed motor and vocal tics. Magnetic resonance image of the brain showed lesions in the basal ganglia. A search of databases Medline, EMBASE and CINHAL found only four publications on tics in adults with TBI. None of these reported cases had lesions in the basal ganglia. Tics are a rare complication of TBI. People with early onset post-traumatic tics may have had a previously unrecognized, mild tic disorder or a genetic predisposition for tics, which was unmasked by the TBI. In contrast, late post-traumatic tics could be due to delayed effects of injury on neural circuits connecting the frontal cortex and basal ganglia.

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

PubMed

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

PubMed

Hamed, Sherifa A

2017-04-01

Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

Neuroprotection against Surgically-Induced Brain Injury

PubMed Central

Jadhav, Vikram; Solaroglu, Ihsan; Obenaus, Andre; Zhang, John H.

2007-01-01

Background Neurosurgical procedures are carried out routinely in health institutions across the world. A key issue to be considered during neurosurgical interventions is that there is always an element of inevitable brain injury that results from the procedure itself due to the unique nature of the nervous system. Brain tissue at the periphery of the operative site is at risk of injury by various means including incisions and direct trauma, electrocautery, hemorrhage, and retractor stretch. Methods/Results In the present review we will elaborate upon this surgically-induced brain injury and also present a novel animal model to study it. Additionally, we will summarize preliminary results obtained by pretreatment with PP1, a src tyrosine kinase inhibitor reported to have neuroprotective properties in in-vivo experimental studies. Any form of pretreatment to limit the damage to the susceptible functional brain tissue during neurosurgical procedures may have a significant impact on the patient recovery. Conclusion This brief review is intended to raise the question of ‘neuroprotection against surgically-induced brain injury’ in the neurosurgical scientific community and stimulate discussions. PMID:17210286

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…

Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases.

PubMed

Cruz-Haces, Marcela; Tang, Jonathan; Acosta, Glen; Fernandez, Joseph; Shi, Riyi

2017-01-01

Traumatic brain injury is among the most common causes of death and disability in youth and young adults. In addition to the acute risk of morbidity with moderate to severe injuries, traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration, the causative factors linking these processes have not yet been fully elucidated. Apart from removal from activity, few, if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist. Therefore, it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes. Oxidative stress, neuroinflammation, and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration. In particular, reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity. As such, it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration. Consequently, reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage. Furthermore, these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.

Focal brain inflammation and autism.

PubMed

Theoharides, Theoharis C; Asadi, Shahrzad; Patel, Arti B

2013-04-09

Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.

Biomarkers of brain injury in the premature infant.

PubMed

Douglas-Escobar, Martha; Weiss, Michael D

2012-01-01

The term "encephalopathy of prematurity" encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant's subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

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. © 2016 International Society for Neurochemistry.

Quantitative magnetic resonance imaging in traumatic brain injury.

PubMed

Bigler, E D

2001-04-01

Quantitative neuroimaging has now become a well-established method for analyzing magnetic resonance imaging in traumatic brain injury (TBI). A general review of studies that have examined quantitative changes following TBI is presented. The consensus of quantitative neuroimaging studies is that most brain structures demonstrate changes in volume or surface area after injury. The patterns of atrophy are consistent with the generalized nature of brain injury and diffuse axonal injury. Various clinical caveats are provided including how quantitative neuroimaging findings can be used clinically and in predicting rehabilitation outcome. The future of quantitative neuroimaging also is discussed.

Selective Vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury

PubMed Central

Marmarou, Christina R.; Liang, Xiuyin; Abidi, Naqeeb H.; Parveen, Shanaz; Taya, Keisuke; Henderson, Scott C.; Young, Harold F.; Filippidis, Aristotelis S.; Baumgarten, Clive M.

2014-01-01

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5 h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm2) versus sham groups (78.3±0.1%; 9.5±0.9 µm2), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8 µm2). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03± 0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema. PMID:24933327

Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury.

PubMed

Marmarou, Christina R; Liang, Xiuyin; Abidi, Naqeeb H; Parveen, Shanaz; Taya, Keisuke; Henderson, Scott C; Young, Harold F; Filippidis, Aristotelis S; Baumgarten, Clive M

2014-09-18

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm(2)) versus sham groups (78.3±0.1%; 9.5±0.9 µm(2)), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8µm(2)). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03±0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence of Brain Injuries among Children with Special Healthcare Needs.

PubMed

Lebrun-Harris, Lydie A; Parasuraman, Sarika Rane; Desrocher, Rebecca

2018-06-06

To investigate differences in brain injury prevalence among US children by special healthcare needs status, accounting for sociodemographic and family characteristics, and to examine correlated health conditions among children with special healthcare needs (CSHCN). We conducted cross-sectional analyses using parent/caregiver responses to the 2016 National Survey of Children's Health (n = 50 212 children). CSHCN status was based on responses to a 5-item tool designed to identify children through assessment of functional limitations, prescription medication use, elevated service use or need, use of specialized therapies, and ongoing emotional, developmental, or behavioral conditions. Brain injury history was reported by parents/caregivers based on healthcare provider diagnosis. Bivariate and multivariable analyses were conducted. Lifetime history of brain injury was significantly higher among CSHCN than non-CSHCN (6.7% vs 2.3%, P < .001). CSHCN make up 19% of the total US child population but comprise 42% of children with lifetime brain injuries. In addition, the prevalence of a number of comorbid conditions and functional limitations was significantly higher among CSHCN with lifetime brain injury vs those without brain injury. The prevalence of lifetime history of brain injury is nearly 3 times greater among CSHCN than among non-CSHCN. Several comorbid conditions among CSHCN are significantly associated with lifetime history of brain injury. Further studies are needed to examine the extent to which brain injury in CSHCN may exacerbate or be misdiagnosed as other comorbid conditions. Published by Elsevier Inc.

Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

PubMed

Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

2014-06-01

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

[Protein S100b in differential diagnosis of brain concussion and superficial scalp injury in inebriated patients].

PubMed

Matek, J; Vajtr, D; Krška, Z; Springer, D; Filip, M; Zima, T

2012-10-01

Concussion cannot be differentiated from superficial scalp injury, especially in inebriated or uncooperative patients. This can have serious medical or forensic consequences. The aim of the study was to determine whether serum concentrations of S-100b in mild traumatic brain injury (MTBI) patients are significantly higher than those in patients with superficial scalp injury with scalp wound and alcohol intoxication. A total of 50 patients with head injury, 25 with mild concussion without scalp wound and alcohol intoxication, 25 superficial scalp injury patients with scalp wound and clinical signs of inebriety. Neurological status and cranial CT scan were evaluated 60-120 minutes after injury in all the 50 patients to exclude focal cerebral injury or skull fracture. The serum levels of S-100b were significantly increased in patients with concussion (median 0.36 ± 0.15 μg/l ) in comparison with the group of patients with scalp injury and alcohol intoxication (median 0.09 ± 0.002 μg/l). All 50 patients had a normal cranial CT finding and neurological status. In all superficial scalp injury patients alcohol intoxication was confirmed (0.96 - 3.11š). We proved significantly higher values of S-100b in patients with brain concussion. Diagnostically decisive value of S-100b concentration in the serum was set at 146 μg/l and higher (94% sensitivity and 100% specificity). Alcohol intoxication (up to 3.11 š) and scalp wound seem to have had no crucial impact on serum S-100b level.

Standardizing Data Collection in Traumatic Brain Injury

DTIC Science & Technology

2010-01-01

om th is p ro of . 15 Definitions of mild TBI vary considerably across studies ( Comper et al 2005). The American Congress of Rehabilitation...451-627. Comper P, Bisschop S, Carnide N, Tricco A (2005). A Systematic Review of Treatments for Mild Traumatic Brain Injury. Brain Injury 19, 863

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…

Brain injury patterns in hypoglycemia in neonatal encephalopathy.

PubMed

Wong, D S T; Poskitt, K J; Chau, V; Miller, S P; Roland, E; Hill, A; Tam, E W Y

2013-07-01

Low glucose values are often seen in term infants with NE, including HIE, yet the contribution of hypoglycemia to the pattern of neurologic injury remains unclear. We hypothesized that MR features of neonatal hypoglycemia could be detected, superimposed on the predominant HIE injury pattern. Term neonates (n = 179) with NE were prospectively imaged with day-3 MR studies and had glucose data available for review. The predominant imaging pattern of HIE was recorded as watershed, basal ganglia, total, focal-multifocal, or no injury. Radiologic hypoglycemia was diagnosed on the basis of selective edema in the posterior white matter, pulvinar, and anterior medial thalamic nuclei. Clinical charts were reviewed for evidence of NE, HIE, and hypoglycemia (<46 mg/dL). The predominant pattern of HIE injury imaged included 17 watershed, 25 basal ganglia, 10 total, 42 focal-multifocal, and 85 cases of no injury. A radiologic diagnosis of hypoglycemia was made in 34 cases. Compared with laboratory-confirmed hypoglycemia, MR findings had a positive predictive value of 82% and negative predictive value of 78%. Sixty (34%) neonates had clinical hypoglycemia before MR imaging. Adjusting for 5-minute Apgar scores and umbilical artery pH with logistic regression, clinical hypoglycemia was associated with a 17.6-fold higher odds of MR imaging identification (P < .001). Selective posterior white matter and pulvinar edema were most predictive of clinical hypoglycemia, and no injury (36%) or a watershed (32%) pattern of injury was seen more often in severe hypoglycemia. In term infants with NE and hypoglycemia, specific imaging features for both hypoglycemia and hypoxia-ischemia can be identified.

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

Levetiracetam-induced neutropenia following traumatic brain injury.

PubMed

Bunnell, Kristen; Pucci, Francesco

2015-01-01

Levetiracetam is being increasingly utilized for post-traumatic brain injury seizure prophylaxis, in part because of its more favourable adverse effect profile compared to other anti-epileptics. This report highlights an unusual, clinically significant adverse drug reaction attributed to levetiracetam use in a patient with blunt traumatic brain injury. This study describes a case of isolated neutropenia associated with levetiracetam in a 52-year-old man with traumatic brain injury. The patient developed neutropenia on day 3 of therapy with levetiracetam, with an absolute neutrophil count nadir of 200. There were no other medications that may have been implicated in the development of this haematological toxicity. Neutropenia rapidly resolved upon cessation of levetiracetam therapy. Clinicians should be aware of potentially serious adverse reactions associated with levetiracetam in patients with neurological injury.

Metabolic alterations in developing brain after injury – knowns and unknowns

PubMed Central

McKenna, Mary C.; Scafidi, Susanna; Robertson, Courtney L.

2016-01-01

Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID:26148530

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

PubMed Central

Zhang, Nannan; Ding, Shinghua

2015-01-01

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.

PubMed

Hamberger, Anders; Viano, David C; Säljö, Annette; Bolouri, Hayde

2009-06-01

An animal model of concussions in National Football League players has been described in a previous study. It involves a freely moving 300-g Wistar rat impacted on the side of the head at velocities of 7.4 to 11.2 m/s with a 50-g impactor. The impact causes a 6% to 28% incidence of meningeal hemorrhages and 0.1- to 0.3-mm focal petechiae depending on the impact velocity. This study addresses the immunohistochemical responses of the brain. Twenty-seven tests were conducted with a 50-g impactor and velocities of 7.4, 9.3, or 11.2 m/s. The left temporal region of the helmet-protected head was hit 1 or 3 times. Thirty-one additional tests were conducted with a 100-g impactor. Diffuse axonal injury in distant regions of the brain was assessed with immunohistochemistry for NF-200, the heaviest neurofilament subunit, and glial fibrillary acidic protein, an intermediate filament protein in astrocytes. Hemorrhages were analyzed by unspecific peroxidase. There were 10 controls. A single impact at 7.4 and 9.3 m/s velocity with the 50-g impactor causes minimal neuronal injury and astrocytosis. Repeat impacts with 11.2 m/s velocity and more than 9.3-m/s impacts with 100 g cause diffuse axonal injury and distant injury bilaterally in the cerebral cortex, the subcortical, the white matter, the hippocampus CA1, the corpus callosum, and the striatum, as indicated by NF-200 accumulation in neuronal perikarya 10 days after impact. It also causes reactive astrocytosis in the midline regions of the cerebral cortex and periventricularly. Regions with erythrocyte-loaded blood capillaries indicated brain edema in regions of the cerebral cortex, the brainstem, and the cerebellum. When the immunohistochemical results are extrapolated to professional football players, concussions result in no or minimal brain injury. Repeat impacts at higher velocity or with a heavier mass impactor cause extensive and distant diffuse axonal injury. Based on this model, the threshold for diffuse axonal injury

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.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

PubMed Central

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

PubMed

Chen, Xin-ran; Liao, Song-jie; Ye, Lan-xiang; Gong, Qiong; Ding, Qiao; Zeng, Jin-sheng; Yu, Jian

2014-01-16

Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction. © 2013 Published by Elsevier B.V.

Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

PubMed Central

Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

2011-01-01

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

Transforming Research and Clinical Knowledge in Traumatic Brain Injury

DTIC Science & Technology

2016-12-01

Szuflita, N., Orman, J., and Schwab, K. (2010). Advancing integrated research in psychological health and traumatic brain injury: common data ele- ments...Szuflita N, Orman J, et al. Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements. Arch Phys Med Rehabil...R, Gleason T, et al. Advancing integrated research in psychological health and traumatic brain injury: common data elements. Arch Phys Med Rehabil

Stereotypic movement disorder after acquired brain injury.

PubMed

McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A

2002-05-01

Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.

[Ischemic brain injury and hepatocyte growth factor].

PubMed

Takeo, Satoshi; Takagi, Norio; Takagi, Keiko

2007-11-01

Cerebral ischemia causes an irreversible and neurodegenerative disorder that may lead to progressive dementia and global cognitive deterioration. Since the overall process of ischemic brain injuries is extremely complex, treatment with endogenous multifunctional factors would be better choices for preventing complicated ischemic brain injuries. Hepatocyte growth factor, HGF, is a multifunctional cytokine originally identified and purified as a potent mitogen for hepatocyte. The activation of the c-Met/HGF receptor evokes diverse cellular responses, including mitogenic, morphogenic, angiogenic and anti-apoptotic activities in various types of cell. Previous studies showed that HGF and c-Met were expressed in various brain regions under normal conditions and that HGF enhanced the survival of hippocampal and cortical neurons during the aging of cells in culture. The protective effects of HGF on in vivo ischemic brain injuries and their mechanisms have not fully understood. To elucidate therapeutic potencies of HGF for ischemic brain injuries, we examined effects of HGF on ischemia-induced learning and memory dysfunction, neuronal cell death and endothelial cell damage by using the 4-vessel occlusion model and the microsphere embolism model in rats. Our findings suggested that treatment with HGF was capable of protecting hippocampal neurons against ischemia-induced cell death through the prevention of apoptosis-inducing factor translocation to the nucleus. Furthermore, we demonstrated that HGF had the ability to prevent tissue degeneration and improved learning and memory function after cerebral embolism, possibly through prevention of cerebral vessel injuries. As HGF has a potent cerebroprotective effect, it could be a prospective agent for the therapy against complicated ischemic brain diseases.

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

PubMed

Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-07-01

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Blunt splenic injury and severe brain injury: a decision analysis and implications for care

PubMed Central

Alabbasi, Thamer; Nathens, Avery B.; Tien, Col Homer

2015-01-01

Background The initial nonoperative management (NOM) of blunt splenic injuries in hemodynamically stable patients is common. In soldiers who experience blunt splenic injuries with concomitant severe brain injury while on deployment, however, NOM may put the injured soldier at risk for secondary brain injury from prolonged hypotension. Methods We conducted a decision analysis using a Markov process to evaluate 2 strategies for managing hemodynamically stable patients with blunt splenic injuries and severe brain injury — immediate splenectomy and NOM — in the setting of a field hospital with surgical capability but no angiography capabilities. We considered the base case of a 40-year-old man with a life expectancy of 78 years who experienced blunt trauma resulting in a severe traumatic brain injury and an isolated splenic injury with an estimated failure rate of NOM of 19.6%. The primary outcome measured was life expectancy. We assumed that failure of NOM would occur in the setting of a prolonged casualty evacuation, where surgical capability was not present. Results Immediate splenectomy was the slightly more effective strategy, resulting in a very modest increase in overall survival compared with NOM. Immediate splenectomy yielded a survival benefit of only 0.4 years over NOM. Conclusion In terms of overall survival, we would not recommend splenectomy unless the estimated failure rate of NOM exceeded 20%, which corresponds to an American Association for the Surgery of Trauma grade III splenic injury. For military patients for whom angiography may not be available at the field hospital and who require prolonged evacuation, immediate splenectomy should be considered for grade III–V injuries in the presence of severe brain injury. PMID:26100770

Blunt splenic injury and severe brain injury: a decision analysis and implications for care.

PubMed

Alabbasi, Thamer; Nathens, Avery B; Tien, Homer

2015-06-01

The initial nonoperative management (NOM) of blunt splenic injuries in hemodynamically stable patients is common. In soldiers who experience blunt splenic injuries with concomitant severe brain injury while on deployment, however, NOM may put the injured soldier at risk for secondary brain injury from prolonged hypotension. We conducted a decision analysis using a Markov process to evaluate 2 strategies for managing hemodynamically stable patients with blunt splenic injuries and severe brain injury--immediate splenectomy and NOM--in the setting of a field hospital with surgical capability but no angiography capabilities. We considered the base case of a 40-year-old man with a life expectancy of 78 years who experienced blunt trauma resulting in a severe traumatic brain injury and an isolated splenic injury with an estimated failure rate of NOM of 19.6%. The primary outcome measured was life expectancy. We assumed that failure of NOM would occur in the setting of a prolonged casualty evacuation, where surgical capability was not present. Immediate splenectomy was the slightly more effective strategy, resulting in a very modest increase in overall survival compared with NOM. Immediate splenectomy yielded a survival benefit of only 0.4 years over NOM. In terms of overall survival, we would not recommend splenectomy unless the estimated failure rate of NOM exceeded 20%, which corresponds to an American Association for the Surgery of Trauma grade III splenic injury. For military patients for whom angiography may not be available at the field hospital and who require prolonged evacuation, immediate splenectomy should be considered for grade III-V injuries in the presence of severe brain injury.

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…

What Are Common Traumatic Brain Injury (TBI) Symptoms?

MedlinePlus

... NICHD Research Information Find a Study More Information Traumatic Brain Injury (TBI) Condition Information NICHD Research Information Find a ... Care Providers Home Health A to Z List Traumatic Brain Injury (TBI) Condition Information What are common symptoms? Share ...

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

Childhood motocross truncal injuries: high-velocity, focal force to the chest and abdomen

PubMed Central

Kennedy, Raelene D; Potter, D Dean; Osborn, John B; Zietlow, Scott; Zarroug, Abdalla E; Moir, Christopher R; Ishitani, Michael B; McIntosh, Amy

2012-01-01

Objectives To review the need for operative intervention and critical care services for motocross truncal injuries in children. Design cohort Retrospective review of patients identified via the hospital trauma registry. Setting Our Level 1 Pediatric Trauma Center serves five motocross tracks. These patients require frequent medical care for injuries. Participants All patients ≤17 years of age with truncal injuries sustained during motocross activities, between 2000 and 2011, were identified through the trauma registry. Primary and secondary outcome measures Operative intervention, intensive care unit (ICU) admission, length of stay, morbidity and demographics were reviewed. Results Motocross injured 162 children. Thirty (18.5%) were thoracic or abdominal injuries. Operative intervention was required in eight (27%) patients. Mean injury severity score (ISS) was 11.8. ICU admission was required in 50% and average hospital length of stay was 4.1 days. The most common injuries include pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects suffered truncal injury from motocross on more than one occasion. Conclusions Paediatric motocross-related truncal injuries are significant. Surgical intervention is required in 27% of patients. The lower ISS incurred from motocross combined with high surgical and ICU admission rates suggests focal high-impact injuries to the chest and abdomen. Despite significant injury, 13% of motocross patients suffer recurrent injuries. Parents and children need injury prevention education. PMID:23166134

Imaging of Traumatic Brain Injury.

PubMed

Bodanapally, Uttam K; Sours, Chandler; Zhuo, Jiachen; Shanmuganathan, Kathirkamanathan

2015-07-01

Imaging plays an important role in the management of patients with traumatic brain injury (TBI). Computed tomography (CT) is the first-line imaging technique allowing rapid detection of primary structural brain lesions that require surgical intervention. CT also detects various deleterious secondary insults allowing early medical and surgical management. Serial imaging is critical to identifying secondary injuries. MR imaging is indicated in patients with acute TBI when CT fails to explain neurologic findings. However, MR imaging is superior in patients with subacute and chronic TBI and also predicts neurocognitive outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein profiling in serum after traumatic brain injury in rats reveals potential injury markers.

PubMed

Thelin, Eric Peter; Just, David; Frostell, Arvid; Häggmark-Månberg, Anna; Risling, Mårten; Svensson, Mikael; Nilsson, Peter; Bellander, Bo-Michael

2018-03-15

The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. Sprague Dawley rats (n=73) received a 3mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O 2 ) or hypoxic (11% O 2 ) air mixture for 30min before resuscitation. The rats were sacrificed at day 1, 3, 7, 14 and 28 after trauma. A total of 204 antibodies targeting 143 unique proteins of interest in TBI research, were selected. The sample proteome was analyzed in a suspension bead array set-up. Comparative statistics and factor analysis were used to detect differences as well as variance in the data. We found that complement factor 9 (C9), complement factor B (CFB) and aldolase c (ALDOC) were detected at higher levels the first days after trauma. In contrast, hypoxia inducing factor (HIF)1α, amyloid precursor protein (APP) and WBSCR17 increased over the subsequent weeks. S100A9 levels were higher in hypoxic-compared to normoxic rats, together with a majority of the analyzed proteins, albeit few reached statistical significance. The principal component analysis revealed a variance in the data, highlighting clusters of proteins. Protein profiling of serum following TBI using an antibody based microarray revealed temporal changes of several proteins over an extended period of up to four weeks. Further studies are warranted to confirm our findings. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

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

Predictors for traumatic brain injuries evaluated through accident reconstructions.

PubMed

Kleiven, Svein

2007-10-01

The aim of this study is to evaluate all the 58 available NFL cases and compare various predictors for mild traumatic brain injuries using a detailed and extensively validated finite element model of the human head. Global injury measures such as magnitude in angular and translational acceleration, change in angular velocity, head impact power (HIP) and HIC were also investigated with regard to their ability to predict the intracranial pressure and strains associated with injury. The brain material properties were modeled using a hyperelastic and viscoelastic constitutive law. Also, three different stiffness parameters, encompassing a range of published brain tissue properties, were tested. 8 tissue injury predictors were evaluated for 6 different regions, covering the entire cerebrum, as well as for the whole brain. In addition, 10 head kinematics based predictors were evaluated both for correlation with injury as well as with strain and pressure. When evaluating the results, a statistical correlation between strain, strain rate, product of strain and strain rate, Cumulative Strain Damage Measure (CSDM), strain energy density, maximum pressure, magnitude of minimum pressure, as well as von Mises effective stress, with injury was found when looking into specific regions of the brain. However, the maximal pressure in the gray matter showed a higher correlation with injury than other evaluated measures. On the other hand, it was possible, through the reconstruction of a motocross accident, to re-create the injury pattern in the brain of the injured rider using maximal principal strain. It was also found that a simple linear combination of peak change in rotational velocity and HIC showed a high correlation (R=0.98) with the maximum principal strain in the brain, in addition to being a significant predictor of injury. When applying the rotational and translational kinematics separately for one of the cases, it was found that the translational kinematics contribute

Prehospital Tranexamic Acid Use for Traumatic Brain Injury

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-2-0090 TITLE: Prehospital Tranexamic Acid Use for Traumatic Brain...2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Prehospital Tranexamic Acid Use for Traumatic Brain Injury 5a. CONTRACT NUMBER 5b...N/A 7. Appendices-N/A Page 7 Early Tranexamic Acid Use for Traumatic Brain Injury DMRDP Funding Opportunity Number: W81XWH-12-CCCJPC

Multi-Tiered Analysis of Brain Injury in Neonates with Congenital Heart Disease

PubMed Central

Mulkey, Sarah B.; Swearingen, Christopher J.; Melguizo, Maria S.; Schmitz, Michael L.; Ou, Xiawei; Ramakrishnaiah, Raghu H.; Glasier, Charles M.; Schaefer, G. Bradley; Bhutta, Adnan T.

2014-01-01

Early brain injury occurs in newborns with congenital heart disease (CHD) placing them at risk for impaired neurodevelopmental outcomes. Predictors for preoperative brain injury have not been well described in CHD newborns. This study aimed to analyze, retrospectively, brain magnetic resonance imaging (MRI) in a heterogeneous group of newborns who had CHD surgery during the first month of life using a detailed qualitative CHD MRI Injury Score, quantitative imaging assessments (regional apparent diffusion coefficient [ADC] values and brain volumes), and clinical characteristics. Seventy-three newborns that had CHD surgery at 8 ± 5 (mean ± standard deviation) days of life and preoperative brain MRI were included; 38 also had postoperative MRI. Thirty-four (34/73, 47%) had at least 1 type of preoperative brain injury, and 28/38 (74%) had postoperative brain injury. The 5-minute APGAR score was negatively associated with preoperative injury, but there was no difference between CHD types. Infants with intraparenchymal hemorrhage, deep gray matter injury, and/or watershed infarcts had the highest CHD MRI Injury Scores. ADC values and brain volumes were not different in infants with different CHD types, or in those with and without brain injury. In a mixed group of CHD newborns, brain injury was found preoperatively on MRI in almost 50%, and there were no significant baseline characteristic differences to predict this early brain injury, except 5-minute APGAR score. We conclude that all infants, regardless of CHD type, who require early surgery, should be evaluated with MRI as they are all at high risk for brain injury. PMID:23652966

[Stress adaptive effects after traumatic brain injury].

PubMed

Teryaeva, N B; Moshkin, A V

Neuroendocrine dysfunction, in particular impaired synthesis of anterior pituitary hormones, is a common complication of traumatic brain injury. Deficiency of tropic pituitary hormones entails a hypofunction of the related peripheral endocrine glands and can be accompanied by persistent endocrine and metabolic disorders. In particular, the hypophyseal mechanisms are the key ones in implementation of most stress effects. Adequate implementation of these mechanisms largely determines a favorable outcome in the acute stage of disease. Traumatic brain injury (as well as any significant injury) initiates a stress response that can not develop in full in the case of pituitary gland failure. It is logical to suppose that the course of the acute phase of stress in the presence of hypopituitarism is different to a certain extent from the typical course, which inevitably affects certain adaptation elements. In this review, we analyzed the adaptive effects of stress after traumatic brain injury.

The role of inflammation in perinatal brain injury.

PubMed

Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M; Vannucci, Susan J; Levison, Steven W; Vexler, Zinaida S; Gressens, Pierre

2015-04-01

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals.

The role of inflammation in perinatal brain injury

PubMed Central

Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M.; Vannucci, Susan J.; Levison, Steven W.; Vexler, Zinaida S.; Gressens, Pierre

2015-01-01

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals. PMID:25686754

Polyamine catabolism is enhanced after traumatic brain injury.

PubMed

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I

2010-03-01

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N(1)-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6-24 h), then increased by approximately 50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain

Traumatic Brain Injury (TBI) in Kids

MedlinePlus

... Information Share Facebook Twitter Pinterest Email Print Traumatic Brain Injury (TBI): Condition Information What is TBI? TBI ... external force that affects the functioning of the brain. It can be caused by a bump or ...

Aggressive behaviour of inpatients with acquired brain injury.

PubMed

Visscher, Ada J M; van Meijel, Berno; Stolker, Joost J; Wiersma, Jan; Nijman, Henk

2011-12-01

To study the prevalence, nature and determinants of aggression among inpatients with acquired brain injury. Patients with acquired brain injury often have difficulty in controlling their aggressive impulses. A prospective observational study design. By means of the Staff Observation Aggression Scale-Revised, the prevalence, nature and severity of aggressive behaviour of inpatients with acquired brain injury was assessed on a neuropsychiatric treatment ward with 45 beds. Additional data on patient-related variables were gathered from the patients' files. In total, 388 aggressive incidents were recorded over 17 weeks. Of a total of 57 patients included, 24 (42%) patients had engaged in aggressive behaviour on one or more occasions. A relatively small proportion of patients (n=8; 14%) was found to be responsible for the majority of incidents (n=332; 86%). The vast majority of aggression incidents (n=270; 70%) were directly preceded by interactions between patients and nursing staff. In line with this, most incidents occurred at times of high contact intensity. Aggressive behaviour was associated with male gender, length of stay at the ward, legal status and hypoxia as the cause of brain injury. Aggression was found to be highly prevalent among inpatients with acquired brain injury. The results suggest that for the prevention of aggression on the ward, it may be highly effective to develop individually tailored interventions for the subgroup with serious aggression problems. Insight into the frequency, nature and determinants of aggressive behaviour in inpatients with acquired brain injury provides nurses with tools for the prevention and treatment of aggressive behaviour. © 2011 Blackwell Publishing Ltd.

Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

NASA Astrophysics Data System (ADS)

Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

2011-03-01

The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

Catecholamines and cognition after traumatic brain injury

PubMed Central

Jenkins, Peter O.; Mehta, Mitul A.

2016-01-01

Abstract 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

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…

Evaluation of shock wave lithotripsy injury in the pig using a narrow focal zone lithotriptor.

PubMed

Connors, Bret A; McAteer, James A; Evan, Andrew P; Blomgren, Philip M; Handa, Rajash K; Johnson, Cynthia D; Gao, Sujuan; Pishchalnikov, Yuri A; Lingeman, James E

2012-11-01

What's known on the subject? and What does the study add? Of all the SW lithotriptors manufactured to date, more research studies have been conducted on and more is known about the injury (both description of injury and how to manipulate injury size) produced by the Dornier HM-3 than any other machine. From this information have come suggestions for treatment protocols to reduce shock wave (SW)-induced injury for use in stone clinics. By contrast, much less is known about the injury produced by narrow-focus and high-pressure lithotriptors like the Storz Modulith SLX. In fact, a careful study looking at the morphology of the injury produced by the SLX itself is lacking, as is any study exploring ways to reduce renal injury by manipulating SW delivery variables of this lithotriptor. The present study quantitates the lesion size and describes the morphology of the injury produced by the SLX. In addition, we report that reducing the SW delivery rate, a manoeuvre known to lower injury in the HM-3, does not reduce lesion size in the SLX. • To assess renal injury in a pig model after treatment with a clinical dose of shock waves using a narrow focal zone (≈3 mm) lithotriptor (Modulith SLX, Karl Storz Lithotripsy). • The left kidney of anaesthetized female pigs were treated with 2000 or 4000 shock waves (SWs) at 120 SWs/min, or 2000 SWs at 60 SWs/min using the Storz SLX. • Measures of renal function (glomerular filtration rate and renal plasma flow) were collected before and 1 h after shock wave lithotripsy (SWL) and the kidneys were harvested for histological analysis and morphometric quantitation of haemorrhage in the renal parenchyma with lesion size expressed as a percentage of functional renal volume (FRV). • A fibre-optic probe hydrophone was used to determine acoustic output and map the focal width of the lithotriptor. • Data for the SLX were compared with data from a previously published study in which pigs of the same age (7-8 weeks) were treated (2000

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.

Rehabilitation of discourse impairments after acquired brain injury

PubMed Central

Gindri, Gigiane; Pagliarin, Karina Carlesso; Casarin, Fabíola Schwengber; Branco, Laura Damiani; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz

2014-01-01

Language impairments in patients with acquired brain injury can have a negative impact on social life as well as on other cognitive domains. Discourse impairments are among the most commonly reported communication deficits among patients with acquired brain damage. Despite advances in the development of diagnostic tools for detecting such impairments, few studies have investigated interventions to rehabilitate patients presenting with these conditions. Objective The aim of this study was to present a systematic review of the methods used in the rehabilitation of discourse following acquired brain injury. Methods The PubMed database was searched for articles using the following keywords: "rehabilitation", "neurological injury", "communication" and "discursive abilities". Results A total of 162 abstracts were found, but only seven of these met criteria for inclusion in the review. Four studies involved samples of individuals with aphasia whereas three studies recruited samples of individuals with traumatic brain injury. Conclusion All but one article found that patient performance improved following participation in a discourse rehabilitation program. PMID:29213880

Functional Status after Blast-Plus-Impact Complex Concussive Traumatic Brain Injury in Evacuated United States Military Personnel

PubMed Central

MacDonald, Christine L.; Johnson, Ann M.; Nelson, Elliot C.; Werner, Nicole J.; Fang, Raymond; Flaherty, Stephen F.

2014-01-01

Abstract Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such “blast-plus” concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6–12 months after injury indicated a moderate overall disability in 41/47 (87%) blast-plus TBI subjects and a substantial but smaller number (11/18, 61%, p=0.018) of demographically similar US military controls without TBI evacuated for other medical reasons. Cognitive function assessed with a neuropsychological test battery was not different between blast-plus TBI subjects and controls; performance of both groups was generally in the normal range. No subject was found to have focal neurological deficits. However, 29/47 (57%) of blast-plus subjects with TBI met all criteria for post-traumatic stress disorder (PTSD) versus 5/18 (28%) of controls (p=0.014). PTSD was highly associated with overall disability; 31/34 patients with PTSD versus 19/31 patients who did not meet full PTSD criteria had moderate to severe disability (p=0.0003). Symptoms of depression were also more severe in the TBI group (p=0.05), and highly correlated with PTSD severity (r=0.86, p<0.0001). Thus, in summary, high rates of PTSD and depression but not cognitive impairment or focal neurological deficits were observed 6–12 months after concussive blast-plus-impact complex TBI. Overall disability was substantially greater than typically reported in civilian non-blast concussive (“mild”) patients with TBI, even with polytrauma. The relationship between these clinical outcomes and specific blast-related aspects of brain injuries versus other combat-related factors remains unknown. PMID:24367929

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…

Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

PubMed Central

Mac Donald, Christine L.; Johnson, Ann M.; Cooper, Dana; Nelson, Elliot C.; Werner, Nicole J.; Shimony, Joshua S.; Snyder, Abraham Z.; Raichle, Marcus E.; Witherow, John R.; Fang, Raymond; Flaherty, Stephen F.; Brody, David L.

2011-01-01

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast

Acute pathophysiological processes after ischaemic and traumatic brain injury.

PubMed

Kunz, Alexander; Dirnagl, Ulrich; Mergenthaler, Philipp

2010-12-01

Ischaemic stroke and brain trauma are among the leading causes of mortality and long-term disability in the western world. Enormous endeavours have been made to elucidate the complex pathophysiology of ischaemic and traumatic brain injury with the intention of developing new therapeutic strategies for patients suffering from these devastating diseases. This article reviews the current knowledge on cascades that are activated after ischaemic and traumatic brain injury and that lead to progression of tissue damage. Main attention will be on pathophysiological events initiated after ischaemic stroke including excitotoxicity, oxidative/nitrosative stress, peri-infarct depolarizations, apoptosis and inflammation. Additionally, specific pathophysiological aspects after traumatic brain injury will be discussed along with their similarities and differences to ischaemic brain injury. This article provides prerequisites for understanding the therapeutic strategies for stroke and trauma patients which are addressed in other articles of this issue. Copyright © 2010 Elsevier Ltd. All rights reserved.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Traumatic Brain Injury Rehabilitation Comparative Effectiveness Research: Introduction to the Traumatic Brain Injury-Practice Based Evidence Archives Supplement.

PubMed

Horn, Susan D; Corrigan, John D; Dijkers, Marcel P

2015-08-01

This supplement of the Archives of Physical Medicine and Rehabilitation is devoted to the Traumatic Brain Injury-Practice Based Evidence study, the first practice-based evidence study, to our knowledge, of traumatic brain injury rehabilitation. The purpose of this preface is to place this study in the broader context of comparative effectiveness research and introduce the articles in the supplement. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Porphyrin-laser photodynamic induction of focal brain necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stroop, W.G.; Battles, E.J.; Townsend, J.J.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and bymore » edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.« less

Synaptic Mechanisms of Blast-Induced Brain Injury

PubMed Central

Przekwas, Andrzej; Somayaji, Mahadevabharath R.; Gupta, Raj K.

2016-01-01

Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro–in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

Traumatic Brain Injury in the United States: An Epidemiologic Overview

DTIC Science & Technology

2009-01-01

discussed. Mt Sinai J Med 76:105–110, 2009.  2009 Mount Sinai School of Medicine Key Words: epidemiology, head injury, traumatic brain injury. A...traumatic brain injury in the civilian population of the United States. J Head Trauma Rehabil 2008; 23: 394–400. 3. Sosin DM, Sniezek JE, Thurman DJ...consciousness, a practical scale. Lancet 1974; 2: 81–84. 5. Kay T, Harrington DE, Adams R, et al. Definition of mild traumatic brain injury. J Head

Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury.

PubMed

Xia, Yang; Kong, Liang; Yao, Yingjia; Jiao, Yanan; Song, Jie; Tao, Zhenyu; You, Zhong; Yang, Jingxian

2015-09-04

Neuroendoscopy is an innovative technique for neurosurgery that can nonetheless result in traumatic brain injury. The accompanying neuroinflammation may lead to secondary tissue damage, which is the major cause of delayed neuronal death after surgery. The present study investigated the capacity of osthole to prevent secondary brain injury and the underlying mechanism of action in a mouse model of stab wound injury. A mouse model of cortical stab wound injury was established by inserting a needle into the cerebral cortex for 20 min to mimic neuroendoscopy. Mice received an intraperitoneal injection of osthole 30 min after surgery and continued for 14 days. Neurological severity was evaluated 12 h and up to 21 days after the trauma. Brains were collected 3-21 days post-injury for histological analysis, immunocytochemistry, quantitative real-time PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and enzyme-linked immunosorbent assays. Neurological function improved in mice treated with osthole and was accompanied by reduced brain water content and accelerated wound closure relative to untreated mice. Osthole treatment reduced the number of macrophages/microglia and peripheral infiltrating of neutrophils and lowered the level of the proinflammatory cytokines interleukin-6 and tumor necrosis factor α in the lesioned cortex. Osthole-treated mice had fewer TUNEL+ apoptotic neurons surrounding the lesion than controls, indicating increased neuronal survival. Osthole reduced secondary brain damage by suppressing inflammation and apoptosis in a mouse model of stab wound injury. These results suggest a new strategy for promoting neuronal survival and function after neurosurgery to improve long-term patient outcome.

The profile of head injuries and traumatic brain injury deaths in Kashmir.

PubMed

Yattoo, Gh; Tabish, Amin

2008-06-21

This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI) deaths were also studied retrospectively for a period of eight years (1996 to 2003).The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21-30 years (18.8%), followed by 11-20 years age group (17.8%) and 31-40 years (14.3%). The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas.To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres) need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients.

Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury.

PubMed

Taylor, Paul A; Ford, Corey C

2009-06-01

The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm3 voxels) five material model of the human head was created by segmentation of color cryosections from the Visible Human Female data set. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior, and lateral directions. Three-dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric stress within the first 2 ms of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 ms time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early-time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

EPO improved neurologic outcome in rat pups late after traumatic brain injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Rodesch, Christopher K

2018-05-01

In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. Rats pups received erythropoietin or vehicle at 1, 24, and 48 h and 7 days after injury or sham surgery followed by histology at 35 days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The possibility of application of spiral brain computed tomography to traumatic brain injury.

PubMed

Lim, Daesung; Lee, Soo Hoon; Kim, Dong Hoon; Choi, Dae Seub; Hong, Hoon Pyo; Kang, Changwoo; Jeong, Jin Hee; Kim, Seong Chun; Kang, Tae-Sin

2014-09-01

The spiral computed tomography (CT) with the advantage of low radiation dose, shorter test time required, and its multidimensional reconstruction is accepted as an essential diagnostic method for evaluating the degree of injury in severe trauma patients and establishment of therapeutic plans. However, conventional sequential CT is preferred for the evaluation of traumatic brain injury (TBI) over spiral CT due to image noise and artifact. We aimed to compare the diagnostic power of spiral facial CT for TBI to that of conventional sequential brain CT. We evaluated retrospectively the images of 315 traumatized patients who underwent both brain CT and facial CT simultaneously. The hemorrhagic traumatic brain injuries such as epidural hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, and contusional hemorrhage were evaluated in both images. Statistics were performed using Cohen's κ to compare the agreement between 2 imaging modalities and sensitivity, specificity, positive predictive value, and negative predictive value of spiral facial CT to conventional sequential brain CT. Almost perfect agreement was noted regarding hemorrhagic traumatic brain injuries between spiral facial CT and conventional sequential brain CT (Cohen's κ coefficient, 0.912). To conventional sequential brain CT, sensitivity, specificity, positive predictive value, and negative predictive value of spiral facial CT were 92.2%, 98.1%, 95.9%, and 96.3%, respectively. In TBI, the diagnostic power of spiral facial CT was equal to that of conventional sequential brain CT. Therefore, expanded spiral facial CT covering whole frontal lobe can be applied to evaluate TBI in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

Seizures and the Role of Anticonvulsants After Traumatic Brain Injury.

PubMed

Zimmermann, Lara L; Diaz-Arrastia, Ramon; Vespa, Paul M

2016-10-01

Posttraumatic seizures are a common complication of traumatic brain injury. Posttraumatic epilepsy accounts for 20% of symptomatic epilepsy in the general population and 5% of all epilepsy. Early posttraumatic seizures occur in more than 20% of patients in the intensive care unit and are associated with secondary brain injury and worse patient outcomes. Most posttraumatic seizures are nonconvulsive and therefore continuous electroencephalography monitoring should be the standard of care for patients with moderate or severe brain injury. The literature shows that posttraumatic seizures result in secondary brain injury caused by increased intracranial pressure, cerebral edema and metabolic crisis. Copyright © 2016 Elsevier Inc. All rights reserved.

Polyamine Catabolism Is Enhanced after Traumatic Brain Injury

PubMed Central

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A.

2010-01-01

Abstract Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6–24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6–24 h), then increased by ∼50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6–72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24–72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally

Diagnostic imaging of traumatic brain injury.

PubMed

Furlow, Bryant

2006-01-01

In this Directed Reading, the history and epidemiology of traumatic brain injury (TBI) will be briefly introduced, the physical and physiological nature of TBI reviewed and the role of imaging in the assessment of TBI patients described. New imaging techniques and recent findings about the neurological correlates of TBI symptoms and outcomes from studies using different imaging modalities and techniques will also be discussed. This directed reading will focus on closed-head TBI; penetrating missile brain injuries, such as those caused by bullet wounds, will not be reviewed.

Clinics in diagnostic imaging (153). Severe hypoxic ischaemic brain injury.

PubMed Central

Chua, Wynne; Lim, Boon Keat; Lim, Tchoyoson Choie Cheio

2014-01-01

A 58-year-old Indian woman presented with asystole after an episode of haemetemesis, with a patient downtime of 20 mins. After initial resuscitation efforts, computed tomography of the brain, obtained to evaluate neurological injury, demonstrated evidence of severe hypoxic ischaemic brain injury. The imaging features of hypoxic ischaemic brain injury and the potential pitfalls with regard to image interpretation are herein discussed. PMID:25091891

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

PubMed

Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

2017-11-01

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of severity of traumatic brain injury and brain reserve on cognitive-control related brain activation.

PubMed

Scheibel, Randall S; Newsome, Mary R; Troyanskaya, Maya; Steinberg, Joel L; Goldstein, Felicia C; Mao, Hui; Levin, Harvey S

2009-09-01

Functional magnetic resonance imaging (fMRI) has revealed more extensive cognitive-control related brain activation following traumatic brain injury (TBI), but little is known about how activation varies with TBI severity. Thirty patients with moderate to severe TBI and 10 with orthopedic injury (OI) underwent fMRI at 3 months post-injury using a stimulus response compatibility task. Regression analyses indicated that lower total Glasgow Coma Scale (GCS) and GCS verbal component scores were associated with higher levels of brain activation. Brain-injured patients were also divided into three groups based upon their total GCS score (3-4, 5-8, or 9-15), and patients with a total GCS score of 8 or less produced increased, diffuse activation that included structures thought to mediate visual attention and cognitive control. The cingulate gyrus and thalamus were among the areas showing greatest increases, and this is consistent with vulnerability of these midline structures in severe, diffuse TBI. Better task performance was associated with higher activation, and there were differences in the over-activation pattern that varied with TBI severity, including greater reliance upon left-lateralized brain structures in patients with the most severe injuries. These findings suggest that over-activation is at least partially effective for improving performance and may be compensatory.

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…

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

PubMed

Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

2017-01-01

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

PubMed Central

Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

2017-01-01

Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate

Memory and anatomical change in severe non missile traumatic brain injury: ∼1 vs. ∼8 years follow-up.

PubMed

Tomaiuolo, Francesco; Bivona, Umberto; Lerch, Jason P; Di Paola, Margherita; Carlesimo, Giovanni A; Ciurli, Paola; Matteis, Mariella; Cecchetti, Luca; Forcina, Antonio; Silvestro, Daniela; Azicnuda, Eva; Sabatini, Umberto; Di Giacomo, Dina; Caltagirone, Carlo; Petrides, Michael; Formisano, Rita

2012-03-10

In previous studies, we investigated a group of subjects who had suffered from a severe non missile traumatic brain injury (nmTBI) without macroscopic focal lesions and we found brain atrophy involving the hippocampus, fornix, corpus callosum, optic chiasm, and optic radiations. Memory test scores correlated mainly with fornix volumes [37,38]. In the present study, we re-examined 11 of these nmTBI subjects approximately 8 yr later. High-spatial resolution T1 weighted magnetic resonance images of the brain (1mm(3)) and standardised memory tests were performed once more in order to compare brain morphology and memory performance originally assessed 3-13 months after head injury (first study) and after 8-10 yr (present study). An overall improvement of memory test performance was demonstrated in the latest assessment, indicating that cognitive recovery in severe nmTBI subjects had not been completed within 3-13 months post-injury. It is notable that the volumes of the fornix and the hippocampus were reduced significantly from normal controls, but these volumes do not differ appreciatively between nmTBI subjects at first (after ∼1 yr) and at second (after ∼8 yr) scans. On the contrary, a clear reduction in the volume of the corpus callosus can be observed after ∼1 yr and a further significant reduction is evident after ∼8 yr, indicating that the neural degeneration in severe nmTBI continues long after the head trauma and relates to specific structures and not to the overall brain. Copyright © 2012 Elsevier Inc. All rights reserved.

Central diabetes insipidus in pediatric severe traumatic brain injury.

PubMed

Alharfi, Ibrahim M; Stewart, Tanya Charyk; Foster, Jennifer; Morrison, Gavin C; Fraser, Douglas D

2013-02-01

To determine the occurrence rate of central diabetes insipidus in pediatric patients with severe traumatic brain injury and to describe the clinical, injury, biochemical, imaging, and intervention variables associated with mortality. Retrospective chart and imaging review. Children's Hospital, level 1 trauma center. Severely injured (Injury Severity Score ≥ 12) pediatric trauma patients (>1 month and <18 yr) with severe traumatic brain injury (presedation Glasgow Coma Scale ≤ 8 and head Maximum Abbreviated Injury Scale ≥ 4) that developed acute central diabetes insipidus between January 2000 and December 2011. Of 818 severely injured trauma patients, 180 had severe traumatic brain injury with an overall mortality rate of 27.2%. Thirty-two of the severe traumatic brain injury patients developed acute central diabetes insipidus that responded to desamino-8-D-arginine vasopressin and/or vasopressin infusion, providing an occurrence rate of 18%. At the time of central diabetes insipidus diagnosis, median urine output and serum sodium were 6.8 ml/kg/hr (interquartile range = 5-11) and 154 mmol/L (interquartile range = 149-159), respectively. The mortality rate of central diabetes insipidus patients was 87.5%, with 71.4% declared brain dead after central diabetes insipidus diagnosis. Early central diabetes insipidus onset, within the first 2 days of severe traumatic brain injury, was strongly associated with mortality (p < 0.001), as were a lower presedation Glasgow Coma Scale (p = 0.03), a lower motor Glasgow Coma Scale (p = 0.01), an occurrence of fixed pupils (p = 0.04), and a prolonged partial thromboplastin time (p = 0.04). Cerebral edema on the initial computed tomography, obtained in the first 24 hrs after injury, was the only imaging finding associated with death (p = 0.002). Survivors of central diabetes insipidus were more likely to have intracranial pressure monitoring (p = 0.03), have thiopental administered to induce coma (p = 0.04) and have received a

Fever and therapeutic normothermia in severe brain injury: an update.

PubMed

Bohman, Leif-Erik; Levine, Joshua M

2014-04-01

Fever is common in the ICU among patients with severe brain injury. Fever has been consistently shown to exacerbate brain injuries in animal models and has been consistently associated with poor outcome in human studies. However, whether fever control improves outcome and the ideal means of fever control remain unknown. This review will address recent literature on the impact of fever on severe brain injury and on interventions to maintain normothermia. Current guidelines generally recommend maintenance of normothermia after brain injury but have scant recommendations on methods to do this. Observational trials have continued to demonstrate the association between fever and poor outcome after severe brain injury. Recent trials have shown the efficacy of more aggressive approaches to fever reduction, whereas a large randomized trial showed the relative ineffectiveness of acetaminophen alone for fever control. Several studies have also described the impact of fever and of fever control on brain physiology. The value of therapeutic normothermia in the neurocritical care unit (NCCU) is increasingly accepted, yet prospective trials that demonstrate a functional benefit to patients are lacking.

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

PubMed

Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

2017-01-01

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

[Brain injury knowledge in family members of neurosurgical patients].

PubMed

Navarro-Main, Blanca; Castaño-León, Ana M; Munarriz, Pablo M; Gómez, Pedro A; Rios-Lago, Marcos; Lagares, Alfonso

Several studies have shown misconceptions about brain injury in different populations. The aim of this study was to assess the knowledge and perceptions about brain injury of family members of neurosurgical patients in our hospital. The participants (n=81) were relatives of patients admitted to the neurosurgery department between February and August 2016. They voluntarily completed a 19-item true-false format survey about brain injury based on a translation of other questionnaires used in previous studies from other countries (USA, Canada, UK, Ireland and New Zealand). Also, some sociodemographic data were collected (age, sex, education level and the patient's pathology). Data analysis was developed through graphical modelling with a regularisation parameter plotted on a network representing the association of the items of the questionnaire from the response pattern of participants. Data analysis showed two conceptual areas with a high rate of wrong answers: behaviour and management of patients, and expectations about acquired brain injury recovery. The results obtained in this study would enable us to objectify misconceptions about acquired brain injury in patients' relatives attended in the neurosurgery department. This lack of knowledge could be a great obstacle in patients' recovery process. Therefore, we suggest placing the emphasis on the provision of information on brain injury to patients' families, especially with regard to its symptoms and course of development. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

SPECT brain perfusion findings in mild or moderate traumatic brain injury.

PubMed

Abu-Judeh, H H; Parker, R; Aleksic, S; Singh, M L; Naddaf, S; Atay, S; Kumar, M; Omar, W; El-Zeftawy, H; Luo, J Q; Abdel-Dayem, H M

2000-01-01

The purpose of this manuscript is to present the findings in the largest series of SPECT brain perfusion imaging reported to date for mild or moderate traumatic brain injury. This is a retrospective evaluation of 228 SPECT brain perfusion-imaging studies of patients who suffered mild or moderate traumatic brain injury with or without loss of consciousness (LOC). All patients had no past medical history of previous brain trauma, neurological, or psychiatric diseases, HIV, alcohol or drug abuse. The patient population included 135 males and 93 females. The ages ranged from 11-88 years (mean 40.8). The most common complaints were characteristic of the postconcussion syndrome: headaches 139/228 (61%); dizziness 61/228 (27%); and memory problems 63/228 (28%). LOC status was reported to be positive in 121/228 (53%), negative in 41/228 (18%), and unknown for 63/228 (28%). Normal studies accounted for 52/228 (23%). For abnormal studies (176/228 or 77%) the findings were as follows: basal ganglia hypoperfusion 338 lesions (55.2%); frontal lobe hypoperfusion 146 (23.8%); temporal lobes hypoperfusion 80 (13%); parietal lobes hypoperfusion 20 (3.7%); insular and or occipital lobes hypoperfusion 28 (4.6%). Patients' symptoms correlated with the SPECT brain perfusion findings. The SPECT BPI studies in 122/228 (54%) were done early within 3 months of the date of the accident, and for the remainder, 106/228 (46%) over 3 months and less than 3 years from the date of the injury. In early imaging, 382 lesions were detected; in 92 patients (average 4.2 lesions per study) imaging after 3 months detected 230 lesions: in 84 patients (average 2.7 lesions per study). Basal ganglia hypoperfusion is the most common abnormality following mild or moderate traumatic brain injury (p = 0.006), and is more common in patients complaining of memory problem (p = 0.0005) and dizziness (p = 0.003). Early imaging can detect more lesions than delayed imaging (p = 0.0011). SPECT brain perfusion

BPSD following traumatic brain injury.

PubMed

Anghinah, Renato; Freire, Fabio Rios; Coelho, Fernanda; Lacerda, Juliana Rhein; Schmidt, Magali Taino; Calado, Vanessa Tomé Gonçalves; Ianof, Jéssica Natuline; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Basile, Luis Fernando Hindi; Paiva, Wellingson Silva; Amorim, Robson Luis

2013-01-01

Annually, 700,000 people are hospitalized with brain injury acquired after traumatic brain injury (TBI) in Brazil. We aim to review the basic concepts related to TBI, and the most common Behavioral and Psychological Symptoms of Dementia (BPSD) findings in moderate and severe TBI survivors. We also discussed our strategies used to manage such patients in the post-acute period. Fifteen TBI outpatients followed at the Center for Cognitive Rehabilitation Post-TBI of the Clinicas Hospital of the University of São Paulo were submitted to a neurological, neuropsychological, speech and occupational therapy evaluation, including the Mini-Mental State Examination. Rehabilitation strategies will then be developed, together with the interdisciplinary team, for each patient individually. Where necessary, the pharmacological approach will be adopted. Our study will discuss options of pharmacologic treatment choices for cognitive, behavioral, or affective disorders following TBI, providing relevant information related to a structured cognitive rehabilitation service and certainly will offer an alternative for patients and families afflicted by TBI. Traumatic brain injury can cause a variety of potentially disabling psychiatric symptoms and syndromes. Combined behavioral and pharmacological strategies, in the treatment of a set of highly challenging behavioral problems, appears to be essential for good patient recovery.

New Antioxidant Drugs for Neonatal Brain Injury

PubMed Central

Tataranno, Maria Luisa; Longini, Mariangela; Buonocore, Giuseppe

2015-01-01

The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment. PMID:25685254

Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury

DTIC Science & Technology

2014-11-01

Award Number: W81XWH-11-2-0011 TITLE: Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury PRINCIPAL INVESTIGATOR...Oct 2014 4. TITLE AND SUBTITLE Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...fluid percussion, traumatic brain injury, blood brain barrier, neuroinflammation, neurological dysfunction, endocannabinoids , microglia and 16

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

PubMed

Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in

Pathophysiology of Blood-Brain Barrier in Brain Injury in Cold and Hot Environments: Novel Drug Targets for Neuroprotection.

PubMed

Sharma, Hari Shanker; Muresanu, Dafin F; Lafuente, José V; Nozari, Ala; Patnaik, Ranjana; Skaper, Stephen D; Sharma, Aruna

2016-01-01

The blood-brain barrier (BBB) plays a pivotal role in the maintenance of central nervous system function in health and disease. Thus, in almost all neurodegenerative, traumatic or metabolic insults BBB breakdown occurs, allowing entry of serum proteins into the brain fluid microenvironment with subsequent edema formation and cellular injury. Accordingly, pharmacological restoration of BBB function will lead to neurorepair. However, brain injury which occurs following blast, bullet wounds, or knife injury appears to initiate different sets of pathophysiological responses. Moreover, other local factors at the time of injury such as cold or elevated ambient temperatures could also impact the final outcome. Obviously, drug therapy applied to different kinds of brain trauma occurring at either cold or hot environments may respond differently. This is largely due to the fact that internal defense mechanisms of the brain, gene expression, release of neurochemicals and binding of drugs to specific receptors are affected by external ambient temperature changes. These factors may also affect BBB function and development of edema formation after brain injury. In this review, the effects of seasonal exposure to heat and cold on traumatic brain injury using different models i.e., concussive brain injury and cerebral cortical lesion, on BBB dysfunction in relation to drug therapy are discussed. Our observations clearly suggest that closed head injury and open brain injury are two different entities and the external hot or cold environments affect both of them remarkably. Thus, effective pharmacological therapeutic strategies should be designed with these views in mind, as military personnel often experience blunt or penetrating head injuries in either cold or hot environments.

Combat-related headache and traumatic brain injury.

PubMed

Waung, Maggie W; Abrams, Gary M

2012-12-01

Post-traumatic headache is a commonly described complication of traumatic brain injury. Recent studies highlight differences between headache features of combat veterans who suffered traumatic brain injury compared to civilians. Not surprisingly, there is a higher rate of associated PTSD and sleep disturbances among veterans. Factors of lower socioeconomic status, rank, and multiple head injuries appear to have a similar effect on post-traumatic headache in combat-related traumatic brain injury. Areas of discordance in the literature include the effect of prolonged loss of consciousness and the prevalence of specific headache phenotypes following head trauma. To date, there have been no randomized trials of treatment for post-traumatic headache. This may be related to the variability of headache features and uncertainty of pathophysiologic mechanisms. Given this lack of data, many practitioners follow treatment guidelines for primary headaches. Additionally, because of mounting data linking PTSD to post-traumatic headache in combat veterans, it may be crucial to choose multimodal agents and take a multidisciplinary approach to combat-related headache.

Neuroprotection of Osthole against Cerebral Ischemia/Reperfusion Injury through an Anti-apoptotic Pathway in Rats.

PubMed

Li, Kang; Ding, Dun; Zhang, Ming

2016-01-01

Cerebral ischemia/reperfusion (I/R) injury is a major cause of acute brain injury. The pathogenetic mechanisms underlying I/R injury involve apoptosis, inflammation and oxidative stress. Osthole-a plant coumarin compound-has been reported to protect against focal cerebral I/R-induced injury in rats. However, the mechanism remains unknown. Here we hypothesize that osthole acts through inhibition of apoptosis during focal cerebral I/R injury in rats. We induced cerebral I/R injury by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. We randomly assigned 60 rats to three groups (20 rats per group): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intraperitoneally with osthole (40 mg/kg) or vehicle 30 min before cerebral ischemia. We harvested the brains for infarct volume, brain water content, histological changes and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining as well as cleaved caspase-3, bax, and bcl-2 levels 24 h after reperfusion. Osthole treatment significantly attenuated cerebral dysfunction and histologic damage induced by I/R injury. Moreover, osthole-treated rats had a dramatic decrease in apoptotic neuronal cells along with a decrease in bax and cleaved caspase-3. The bcl-2 levels increased. Osthole treatment protects the brain from cerebral I/R injury by suppressing cell apoptosis. Thus, osthole may represent a novel practical strategy to prevent cerebral I/R injury.

Identity, grief and self-awareness after traumatic brain injury.

PubMed

Carroll, Emma; Coetzer, Rudi

2011-06-01

The objective of this study was to investigate perceived identity change in adults with traumatic brain injury (TBI) and explore associations between identity change, grief, depression, self-esteem and self-awareness. The participants were 29 adults with TBI who were being followed up by a community brain injury rehabilitation service. Participants were longer post-injury than those more commonly studied. Time since injury ranged from 2.25 to 40 years (mean = 11.17 years, SD = 11.4 years). Participants completed a battery of questionnaires. Significant others and clinicians completed a parallel version of one of these measures. Questionnaires included the Head Injury Semantic Differential Scale (HISDS-III), Brain Injury Grief Inventory (BIGI), Hospital Anxiety and Depression Scale - Depression, Rosenberg Self-Esteem Scale (RSES) and the Awareness Questionnaire (Self/Significant other/Clinician versions). The main findings were that participants reported significant changes in self-concept with current self being viewed negatively in comparison to pre-injury self. Perceived identity change was positively associated with depression and grief and negatively associated with self-esteem and awareness. Awareness was negatively associated with self-esteem and positively associated with depression. These findings were consistent with previous research, revealing changes in identity following TBI. Further research is needed to increase our understanding of the psychological factors involved in emotional adjustment after TBI and to inform brain injury rehabilitation interventions, including psychotherapy approaches.

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…

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. Copyright © 2016 Elsevier Ltd

Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology

DTIC Science & Technology

2014-11-01

GF, Moss WC, Cleveland RO, Tanzi RE, Stanton PK, McKee AC. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast... traumatic brain injury (bTBI) is largely undefined. Along with reducing mortality, in preliminary experiments Kevlar vests significantly protected...mitigation strategies. 15. SUBJECT TERMS Traumatic Brain Injury (TBI), Kevlar Vests, Neuroprotection 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain.

PubMed

Campbell, John N; Register, David; Churn, Severn B

2012-01-20

Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.

Caring for Patients with traumatic brain injury: a survey of nurses' perceptions.

PubMed

Oyesanya, Tolu O; Brown, Roger L; Turkstra, Lyn S

2017-06-01

The purpose of this study was to determine nurses' perceptions about caring for patients with traumatic brain injury. Annually, it is estimated that over 10 million people sustain a traumatic brain injury around the world. Patients with traumatic brain injury and their families are often concerned with expectations about recovery and seek information from nurses. Nurses' perceptions of care might influence information provided to patients and families, particularly if inaccurate knowledge and perceptions are held. Thus, nurses must be knowledgeable about care of these patients. A cross-sectional survey, the Perceptions of Brain Injury Survey (PBIS), was completed electronically by 513 nurses between October and December 2014. Data were analysed with structural equation modelling, factor analysis, and pairwise comparisons. Using latent class analysis, authors were able to divide nurses into three homogeneous sub-groups based on perceived knowledge: low, moderate and high. Findings showed that nurses who care for patients with traumatic brain injury the most have the highest perceived confidence but the lowest perceived knowledge. Nurses also had significant variations in training. As there is limited literature on nurses' perceptions of caring for patients with traumatic brain injury, these findings have implications for training and educating nurses, including direction for development of nursing educational interventions. As the incidence of traumatic brain injury is growing, it is imperative that nurses be knowledgeable about care of patients with these injuries. The traumatic brain injury PBIS can be used to determine inaccurate perceptions about caring for patients with traumatic brain injury before educating and training nurses. © 2016 John Wiley & Sons Ltd.

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.

The relation between persistent coma and brain ischemia after severe brain injury.

PubMed

Cheng, Quan; Jiang, Bing; Xi, Jian; Li, Zhen Yan; Liu, Jin Fang; Wang, Jun Yu

2013-12-01

To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.

Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

PubMed Central

Jiang, Xiaoyan; Zhang, Lili; Pu, Hongjian; Hu, Xiaoming; Zhang, Wenting; Cai, Wei; Gao, Yanqin; Leak, Rehana K.; Keep, Richard F.; Bennett, Michael V. L.; Chen, Jun

2017-01-01

The damage borne by the endothelial cells (ECs) forming the blood–brain barrier (BBB) during ischemic stroke and other neurological conditions disrupts the structure and function of the neurovascular unit and contributes to poor patient outcomes. We recently reported that structural aberrations in brain microvascular ECs—namely, uncontrolled actin polymerization and subsequent disassembly of junctional proteins, are a possible cause of the early onset BBB breach that arises within 30–60 min of reperfusion after transient focal ischemia. Here, we investigated the role of heat shock protein 27 (HSP27) as a direct inhibitor of actin polymerization and protectant against BBB disruption after ischemia/reperfusion (I/R). Using in vivo and in vitro models, we found that targeted overexpression of HSP27 specifically within ECs—but not within neurons—ameliorated BBB impairment 1–24 h after I/R. Mechanistically, HSP27 suppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein translocation in brain microvascular ECs, independent of its protective actions against cell death. By preserving BBB integrity after I/R, EC-targeted HSP27 overexpression attenuated the infiltration of potentially destructive neutrophils and macrophages into brain parenchyma, thereby improving long-term stroke outcome. Notably, early poststroke administration of HSP27 attached to a cell-penetrating transduction domain (TAT-HSP27) rapidly elevated HSP27 levels in brain microvessels and ameliorated I/R-induced BBB disruption and subsequent neurological deficits. Thus, the present study demonstrates that HSP27 can function at the EC level to preserve BBB integrity after I/R brain injury. HSP27 may be a therapeutic agent for ischemic stroke and other neurological conditions involving BBB breakdown. PMID:28137866

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Cerebrovascular regulation, exercise, and mild traumatic brain injury

PubMed Central

Meehan, William P.; Iverson, Grant L.; Taylor, J. Andrew

2014-01-01

A substantial number of people who sustain a mild traumatic brain injury report persistent symptoms. Most common among these symptoms are headache, dizziness, and cognitive difficulties. One possible contributor to sustained symptoms may be compromised cerebrovascular regulation. In addition to injury-related cerebrovascular dysfunction, it is possible that prolonged rest after mild traumatic brain injury leads to deconditioning that may induce physiologic changes in cerebral blood flow control that contributes to persistent symptoms in some people. There is some evidence that exercise training may reduce symptoms perhaps because it engages an array of cerebrovascular regulatory mechanisms. Unfortunately, there is very little work on the degree of impairment in cerebrovascular control that may exist in patients with mild traumatic brain injury, and there are no published studies on the subacute phase of recovery from this injury. This review aims to integrate the current knowledge of cerebrovascular mechanisms that might underlie persistent symptoms and seeks to synthesize these data in the context of exploring aerobic exercise as a feasible intervention to treat the underlying pathophysiology. PMID:25274845

Traumatic Brain Injury - Multiple Languages

MedlinePlus

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Role of Interleukin-10 in Acute Brain Injuries

PubMed Central

Garcia, Joshua M.; Stillings, Stephanie A.; Leclerc, Jenna L.; Phillips, Harrison; Edwards, Nancy J.; Robicsek, Steven A.; Hoh, Brian L.; Blackburn, Spiros; Doré, Sylvain

2017-01-01

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation. PMID:28659854

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats

PubMed Central

Fang, Mingchu; Jiang, Huai; Ye, Lixia; Cai, Chenchen; Hu, Yingying; Pan, Shulin; Li, Peijun; Xiao, Jian; Lin, Zhenlang

2017-01-01

Neonatal hypoxic-ischemic (HI) brain injury is a devastating disease that often leads to death and detrimental neurological deficits. The present study was designed to evaluate the ability of metformin to provide neuroprotection in a model of neonatal hypoxic-ischemic brain injury and to study the associated molecular mechanisms behind these protective effects. Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of metformin was associated with inhibition of neuronal apoptosis, suppression of the neuroinflammation and amelioration of the blood brain barrier breakdown. Additionally, metformin treatment conferred long-term protective against brain damage at 7 d after HI injury. Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease. PMID:29088867

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

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

2016-02-04

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.

Medical Management of the Severe Traumatic Brain Injury Patient.

PubMed

Marehbian, Jonathan; Muehlschlegel, Susanne; Edlow, Brian L; Hinson, Holly E; Hwang, David Y

2017-12-01

Severe traumatic brain injury (sTBI) is a major contributor to long-term disability and a leading cause of death worldwide. Medical management of the sTBI patient, beginning with prehospital triage, is aimed at preventing secondary brain injury. This review discusses prehospital and emergency department management of sTBI, as well as aspects of TBI management in the intensive care unit where advances have been made in the past decade. Areas of emphasis include intracranial pressure management, neuromonitoring, management of paroxysmal sympathetic hyperactivity, neuroprotective strategies, prognostication, and communication with families about goals of care. Where appropriate, differences between the third and fourth editions of the Brain Trauma Foundation guidelines for the management of severe traumatic brain injury are highlighted.

[Value of computer tomography in the managment of brain injuries].

PubMed

Keita, A D; Toure, M; Sissako, A; Doumbia, S; Coulibaly, Y; Doumbia, D; Kane, M; Diallo, A K; Toure, A A; Traore, I

2005-11-01

The purpose of this prospective study conducted from January 2001 to December 2001 was to ascertain the value of computer tomography for evaluation of brain injuries. Computer tomography was performed using a Toshiba X VID system with contiguous 5 mm axial sections through the posterior fossa and 10 mm contiguous axial sections through the subtentorial region without contrast injection. A total of 107 patients with brain injuries were enrolled over the one-year study period. These patients accounted for 0.8% of all admissions to surgical emergency unit of Gabriel Toure Hospital in Bamako, Mali. The predominant age group for brain injuries was the 20- to 29-year-old group (35 cases). The male-to-female sex ratio was 5:1. Vehicular accident was the most frequent cause of brain injury (76 cases). Trauma was severe in 48 patients with a Glasgow score less than 8. Coma occurred immediately after injury in 90 cases. Ventricular hemorrhage led to coma in 100% of cases whereas brain hemorrhage and hematoma led to coma in 93.3% and 83.3% of cases respectively. Treatment was medical in 99 cases and neurosurgical in 8. The mortality rate was 34% and the morbidity rate (permanent sequels) was 36%. Computer tomography is a valuable tool for therapeutic decision-making in medico-surgical emergencies involving brain injuries.

Sex, Gender, and Traumatic Brain Injury: A Commentary.

PubMed

Colantonio, Angela

2016-02-01

The goal of this supplemental issue is to address major knowledge, research, and clinical practice gaps regarding the limited focus on brain injury in girls and women as well as limited analysis of the effect of sex and gender in research on acquired brain injury. Integrating sex and gender in research is recognized as leading to better science and, ultimately, to better clinical practice. A sex and gender analytical approach to rehabilitation research is crucial to understanding traumatic brain injury and improving quality of life outcomes for survivors. Put another way, the lack of focus on sex and gender reduces the rigor of research design, the generalizability of study findings, and the effectiveness of clinical implementation and knowledge dissemination practices. The articles in this supplement examine sex and gender using a variety of methodological approaches and research contexts. Recommendations for future research on acquired brain injury that consciously incorporates sex and gender are made throughout this issue. This supplement is a product of the Girls and Women with ABI Task Force of the American Congress of Rehabilitation Medicine. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

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

[CT scans in children with head/brain injury: five years after the revision of the guideline on "mild traumatic head/brain injury"].

PubMed

Hageman, G Gerard

2015-01-01

In 2010 the guideline on mild traumatic head/ brain injury for both adults and children was revised under the supervision of the Dutch Neurology Society. The revised guideline endorsed rules for decisions on whether to carry out diagnostic imaging investigations (brain CT scanning) and formulates indications for admission. Unfortunately, 5 years after its introduction, it is clear that the guideline rules result in excessive brain CT scanning, in which no more serious head injury is diagnosed. Brain injury may be present in (small) children even if symptoms are absent at first presentation. Also, clinical signs do not predict intracranial complications. This was nicely demonstrated in a study by Tilma, Bekhof and Brand of 410 children with mTBI: no clinical symptom or sign reliably predicted the risk of intracranial bleeding. They advise hospitalisation for observation instead of brain CT scanning. It may be necessary to review part of the Dutch guideline on mTBI.

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,…

Traumatic brain injury: an overview of pathobiology with emphasis on military populations

PubMed Central

Cernak, Ibolja; Noble-Haeusslein, Linda J

2010-01-01

This review considers the pathobiology of non-impact blast-induced neurotrauma (BINT). The pathobiology of traumatic brain injury (TBI) has been historically studied in experimental models mimicking features seen in the civilian population. These brain injuries are characterized by primary damage to both gray and white matter and subsequent evolution of secondary pathogenic events at the cellular, biochemical, and molecular levels, which collectively mediate widespread neurodegeneration. An emerging field of research addresses brain injuries related to the military, in particular blast-induced brain injuries. What is clear from the effort to date is that the pathobiology of military TBIs, particularly BINT, has characteristics not seen in other types of brain injury, despite similar secondary injury cascades. The pathobiology of primary BINT is extremely complex. It comprises systemic, local, and cerebral responses interacting and often occurring in parallel. Activation of the autonomous nervous system, sudden pressure-increase in vital organs such as lungs and liver, and activation of neuroendocrine-immune system are among the most important mechanisms significantly contributing to molecular changes and cascading injury mechanisms in the brain. PMID:19809467

Word Finding in Children and Adolescents with a History of Brain Injury.

ERIC Educational Resources Information Center

Dennis, Maureen

1992-01-01

Word finding in relation to brain injury is discussed for children and adolescents with unilateral congenital malformations of the brain, early hydrocephalus, childhood-acquired left hemisphere stroke, and acquired traumatic head injury. Studies examining the recovery of word-finding deficits after brain injury are discussed, along with…

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.

Estrone is neuroprotective in rats after traumatic brain injury.

PubMed

Gatson, Joshua W; Liu, Ming-Mei; Abdelfattah, Kareem; Wigginton, Jane G; Smith, Scott; Wolf, Steven; Simpkins, James W; Minei, Joseph P

2012-08-10

In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (p<0.01) and neuronal injury (p<0.001), and it reduced cerebral cortical levels of TUNEL-positive staining (p<0.0001), and decreased numbers of TUNEL-positive cells in the corpus callosum (p<0.03). We assessed the levels of β-amyloid in the injured animals and found that estrone significantly decreased the cortical levels of β-amyloid after brain injury. Cortical levels of phospho-ERK1/2 were significantly (p<0.01) increased by estrone. This increase was associated with an increase in phospho-CREB levels (p<0.021), and brain-derived neurotrophic factor (BDNF) expression (p<0.0006). In conclusion, estrone given acutely after injury increases the signaling of protective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury

PubMed Central

Hay, Jennifer; Johnson, Victoria E.; Smith, Douglas H.; Stewart, William

2017-01-01

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 non-boxers 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

Surgical Treatment of Severe Traumatic Brain Injury in Switzerland: Results from a Multicenter Study.

PubMed

Rossi-Mossuti, Frédéric; Fisch, Urs; Schoettker, Patrick; Gugliotta, Marinella; Morard, Marc; Schucht, Philippe; Schatlo, Bawarjan; Levivier, Marc; Walder, Bernhard; Fandino, Javier

2016-01-01

Since the introduction of modern surgical techniques and monitoring tools for the treatment of severe traumatic brain injury (TBI) in Switzerland, standardized nationwide operative procedures are still lacking. This study aimed to assess surgical management and monitoring strategies in patients admitted throughout Switzerland with severe TBI. Demographic, clinical, and radiologic data from a prospective national cohort study on severe brain-injured patients (Patient-relevant Endpoints after Brain Injury from Traumatic Accidents [PEBITA]) were collected during a 3-year period. This study evaluated patients admitted to 7 of the 11 trauma centers included in PEBITA. We retrospectively analyzed surgery-related computed tomography (CT) findings prior to and after treatment, intracranial pressure (ICP) monitoring, size and technical features of craniotomy, as well as surgical complications. ResULTS: This study included 353 of the 921 patients enrolled in PEBITA who underwent surgical treatment for severe TBI. At admission, acute subdural hematoma was the most frequent focal lesion diagnosed (n = 154 [44%]), followed by epidural hematoma (n = 96 [27%]) and intracerebral hematoma (n = 84 [24%]). A total of 198 patients (61%) presented with midline shift. Clinical deterioration in terms of Glasgow Coma Scale scores or intractable ICP values as an indication for surgical evacuation or decompression were documented in 20% and 6%, respectively. A total of 97 (27.5%) only received a catheter/probe for ICP monitoring. Surgical procedures to treat a focal lesion or decompress the cerebrum were performed in 256 patients (72.5%). Of the 290 surgical procedures (excluding ICP probe implantation), craniotomy (137 [47.2%]) or decompressive craniectomy (133 [45.9%]) were performed most frequently. The mean size of craniectomy in terms of maximal linear width on the CT axial slice was 8.4 ± 2.9 cm. Intraoperative ICP monitoring was reported in 61% of the interventions. Significant

EEG dynamical correlates of focal and diffuse causes of coma.

PubMed

Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

2017-11-15

Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

Definition of Traumatic Brain Injury, Neurosurgery, Trauma Orthopedics, Neuroimaging, Psychology, and Psychiatry in Mild Traumatic Brain Injury.

PubMed

Pervez, Mubashir; Kitagawa, Ryan S; Chang, Tiffany R

2018-02-01

Traumatic brain injury (TBI) disrupts the normal function of the brain. This condition can adversely affect a person's quality of life with cognitive, behavioral, emotional, and physical symptoms that limit interpersonal, social, and occupational functioning. Although many systems exist, the simplest classification includes mild, moderate, and severe TBI depending on the nature of injury and the impact on the patient's clinical status. Patients with TBI require prompt evaluation and multidisciplinary management. Aside from the type and severity of the TBI, recovery is influenced by individual patient characteristics, social and environmental factors, and access to medical and rehabilitation services. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of chorioamnionitis on brain development and injury in premature newborns.

PubMed

Chau, Vann; Poskitt, Kenneth J; McFadden, Deborah E; Bowen-Roberts, Tim; Synnes, Anne; Brant, Rollin; Sargent, Michael A; Soulikias, Wendy; Miller, Steven P

2009-08-01

The association of chorioamnionitis and noncystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced magnetic resonance imaging. Ninety-two preterm newborns (24-32 weeks gestation) were studied at a median age of 31.9 weeks and again at 40.3 weeks gestation. Histopathological chorioamnionitis and white matter injury were scored using validated systems. Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on magnetic resonance spectroscopy, and microstructure (average diffusivity and fractional anisotropy) on diffusion tensor imaging were calculated from predefined brain regions. Thirty-one (34%) newborns were exposed to histopathological chorioamnionitis, and 26 (28%) had white matter injury. Histopathological chorioamnionitis was not associated with an increased risk of white matter injury (relative risk: 1.2; p = 0.6). Newborns with postnatal infections and hypotension requiring therapy were at higher risk of white matter injury (p < 0.03). Adjusting for gestational age at scan and regions of interest, histopathological chorioamnionitis did not significantly affect brain metabolic and microstructural development (p > 0.1). In contrast, white matter injury was associated with lower N-acetylaspartate/choline (-8.9%; p = 0.009) and lower white matter fractional anisotropy (-11.9%; p = 0.01). Histopathological chorioamnionitis does not appear to be associated with an increased risk of white matter injury on magnetic resonance imaging or with abnormalities of brain development. In contrast, postnatal infections and hypotension are associated with an increased risk of white matter injury in the premature newborn.

Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury.

PubMed

Hagos, Fanuel T; Empey, Philip E; Wang, Pengcheng; Ma, Xiaochao; Poloyac, Samuel M; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J; Clark, Robert S B

2018-05-07

To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment. Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board-approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009). Thirty-six-bed PICU in a university-affiliated children's hospital. Twelve children 2-18 years old after severe traumatic brain injury and five age-matched control subjects. Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube. The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation. This proof

Intranasal epidermal growth factor treatment rescues neonatal brain injury.

PubMed

Scafidi, Joseph; Hammond, Timothy R; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J; Hyder, Fahmeed; Horvath, Tamas L; Gallo, Vittorio

2014-02-13

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Intranasal epidermal growth factor treatment rescues neonatal brain injury

NASA Astrophysics Data System (ADS)

Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

2014-02-01

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

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,…

Synergistic Mechanisms Between Traumatic Brain Injury and Migraine

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-15-1-0209 TITLE: Synergistic Mechanisms Between Traumatic Brain Injury and Migraine PRINCIPAL INVESTIGATOR: Amynah Pradhan...SUBTITLE Synergistic Mechanisms Between Traumatic Brain Injury and Migraine 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0209 5c. PROGRAM ELEMENT...and can persist for months after the initial trauma. The most severe and long lasting posttraumatic headaches are usually classified as migraine ; and

Focal Experimental Injury Leads to Widespread Gene Expression and Histologic Changes in Equine Flexor Tendons

PubMed Central

Jacobsen, Else; Dart, Andrew J.; Mondori, Takamitsu; Horadogoda, Neil; Jeffcott, Leo B.; Little, Christopher B.; Smith, Margaret M.

2015-01-01

It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral) tendons were regionally sampled (medial and lateral halves each divided into six 3cm regions) for histologic (scoring and immunohistochemistry) and gene expression (real time PCR) analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03) with no differences between overstressed (medial) and stress-deprived (lateral) tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02), with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02) and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001). Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001), whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001). In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes and re-injury

Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice

PubMed Central

Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.

2017-01-01

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1–2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries. SIGNIFICANCE STATEMENT During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca2

Disconnection of network hubs and cognitive impairment after traumatic brain injury.

PubMed

Fagerholm, Erik D; Hellyer, Peter J; Scott, Gregory; Leech, Robert; Sharp, David J

2015-06-01

Traumatic brain injury affects brain connectivity by producing traumatic axonal injury. This disrupts the function of large-scale networks that support cognition. The best way to describe this relationship is unclear, but one elegant approach is to view networks as graphs. Brain regions become nodes in the graph, and white matter tracts the connections. The overall effect of an injury can then be estimated by calculating graph metrics of network structure and function. Here we test which graph metrics best predict the presence of traumatic axonal injury, as well as which are most highly associated with cognitive impairment. A comprehensive range of graph metrics was calculated from structural connectivity measures for 52 patients with traumatic brain injury, 21 of whom had microbleed evidence of traumatic axonal injury, and 25 age-matched controls. White matter connections between 165 grey matter brain regions were defined using tractography, and structural connectivity matrices calculated from skeletonized diffusion tensor imaging data. This technique estimates injury at the centre of tract, but is insensitive to damage at tract edges. Graph metrics were calculated from the resulting connectivity matrices and machine-learning techniques used to select the metrics that best predicted the presence of traumatic brain injury. In addition, we used regularization and variable selection via the elastic net to predict patient behaviour on tests of information processing speed, executive function and associative memory. Support vector machines trained with graph metrics of white matter connectivity matrices from the microbleed group were able to identify patients with a history of traumatic brain injury with 93.4% accuracy, a result robust to different ways of sampling the data. Graph metrics were significantly associated with cognitive performance: information processing speed (R(2) = 0.64), executive function (R(2) = 0.56) and associative memory (R(2) = 0.25). These

Virtual reality in the assessment of selected cognitive function after brain injury.

PubMed

Zhang, L; Abreu, B C; Masel, B; Scheibel, R S; Christiansen, C H; Huddleston, N; Ottenbacher, K J

2001-08-01

To assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. A computer-simulated virtual kitchen was used to assess the ability of 30 patients with brain injury and 30 volunteers without brain injury to process and sequence information. The overall assessment score was based on the number of correct responses and the time needed to complete daily living tasks. Identical daily living tasks were tested and scored in participants with and without brain injury. Each subject was evaluated twice within 7 to 10 days. A total of 30 tasks were categorized as follows: information processing, problem solving, logical sequencing, and speed of responding. Persons with brain injuries consistently demonstrated a significant decrease in the ability to process information (P = 0.04-0.01), identify logical sequencing (P = 0.04-0.01), and complete the overall assessment (P < 0.01), compared with volunteers without brain injury. The time needed to process tasks, representing speed of cognitive responding, was also significantly different between the two groups (P < 0.01). A computer-generated virtual reality environment represents a reproducible tool to assess selected cognitive functions and can be used as a supplement to traditional rehabilitation assessment in persons with acquired brain injury.

The structural basis of moderate disability after traumatic brain damage

PubMed Central

Adams, J; Graham, D; Jennett, B

2001-01-01

The objective was to discover the nature of brain damage in survivors of head injury who are left with moderate disability. Macroscopic and microscopic examination was carried out on the brains of 20 persons who had died long after a head injury that had been treated in a neurosurgical unit. All had become independent but had various disabilities (moderate disability on the Glasgow outcome scale) Most deaths had been sudden, which had led to their referral from forensic pathologists. Post-traumatic epilepsy was a feature in 75%. An intracranial haematoma had been evacuated in 75%, and in 11 of the 15 with epilepsy. Diffuse axonal injury was found in six patients, five of the mildest type (grade 1) and one of grade 2. No patient had diffuse thalamic damage but one had a small focal ischaemic lesion in the thalamus. No patient had severe ischaemic brain damage, but three had moderate lesions which were bilateral in only one. No patient had severe cortical contusions. In conclusion, the dominant lesion was focal damage from an evacuated intracranial haematoma. Severe diffuse damage was not found, with diffuse axonal injury only mild and thalamic damage in only one patient.

 PMID:11561038

Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase and S6 phosphorylation.

PubMed

Koh, Phil-Ok

2013-10-25

Ferulic acid exhibits neuroprotective effects against focal cerebral ischemia. PI3/K and Akt signaling pathways play an essential role in protecting against cerebral ischemia. Mammalian target of rapamycin (mTOR), a major downstream target of Akt, regulates p70S6 kinase and S6, both of which are involved in ribosomal biogenesis and protein synthesis. I investigated whether ferulic acid regulates mTOR, p70S6 kinase, and S6 phosphorylation during brain ischemic injury. Rats were treated immediately with vehicle or ferulic acid (100mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were removed at 24h after the onset of MCAO and the cerebral cortex regions were collected. Ferulic acid reduced the MCAO-induced infarct volume. I showed previously that ferulic acid prevents the MCAO injury-induced decrease of Akt phosphorylation. In this study, MCAO injury induced decreases in mTOR, p70S6 kinase, and S6 phosphorylation levels, while ferulic acid attenuated the injury-induced decreases. Immunohistochemical staining demonstrated that ferulic acid prevented the MCAO-induced reduction in the number of positive cells for phosphorylated p70S6 kinase and phosphorylated S6. These findings suggest that ferulic acid has a neuroprotective function against focal cerebral ischemia by modulating p70S6 kinase expression and S6 phosphorylation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats

PubMed Central

BAN, JU YEON; KANG, SUNG WOOK; LEE, JONG SEOK; CHUNG, JOO-HO; KO, YOUNG GWAN; CHOI, HAN SUNG

2012-01-01

In the present study, we investigated the neuroprotective effect of Korean red ginseng (KRG) following focal brain ischemia/reperfusion injury, in relation to its antioxidant activities. The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats was employed. The KRG extract (100 mg/kg, perorally) was administered once daily for 7 days following MCAO/R. The elevated levels of lipid peroxidation in the MCAO/R group were attenuated significantly in the KRG-administered group. The significantly depleted activity of the antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase was prevented in the KRG-administered group. In the neurobehavioral evaluation expressed as the modified neurological severity score and corner-turn test, the daily intake of KRG showed consistent and significant improvement in the neurological deficits for 7 days following MCAO/R injury. These results indicate that KRG has a neuroprotective effect against ischemia/reperfusion brain injury by reducing the level of lipid peroxidation and increasing the endogenous antioxidant enzymatic activity. PMID:22969953

Investigation of the relationship between facial injuries and traumatic brain injuries using a realistic subject-specific finite element head model.

PubMed

Tse, Kwong Ming; Tan, Long Bin; Lee, Shu Jin; Lim, Siak Piang; Lee, Heow Pueh

2015-06-01

In spite of anatomic proximity of the facial skeleton and cranium, there is lack of information in the literature regarding the relationship between facial and brain injuries. This study aims to correlate brain injuries with facial injuries using finite element method (FEM). Nine common impact scenarios of facial injuries are simulated with their individual stress wave propagation paths in the facial skeleton and the intracranial brain. Fractures of cranio-facial bones and intracranial injuries are evaluated based on the tolerance limits of the biomechanical parameters. General trend of maximum intracranial biomechanical parameters found in nasal bone and zygomaticomaxillary impacts indicates that severity of brain injury is highly associated with the proximity of location of impact to the brain. It is hypothesized that the midface is capable of absorbing considerable energy and protecting the brain from impact. The nasal cartilages dissipate the impact energy in the form of large scale deformation and fracture, with the vomer-ethmoid diverging stress to the "crumpling zone" of air-filled sphenoid and ethmoidal sinuses; in its most natural manner, the face protects the brain. This numerical study hopes to provide surgeons some insight in what possible brain injuries to be expected in various scenarios of facial trauma and to help in better diagnosis of unsuspected brain injury, thereby resulting in decreasing the morbidity and mortality associated with facial trauma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

PubMed Central

Clifton, Guy L; Valadka, Alex; Zygun, David; Coffey, Christopher S; Drever, Pamala; Fourwinds, Sierra; Janis, L Scott; Wilde, Elizabeth; Taylor, Pauline; Harshman, Kathy; Conley, Adam; Puccio, Ava; Levin, Harvey S; McCauley, Stephen R; Bucholz, Richard D; Smith, Kenneth R; Schmidt, John H; Scott, James N; Yonas, Howard; Okonkwo, David O

2013-01-01

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative

Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

DTIC Science & Technology

2011-06-02

hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging ( DTI ), an advanced form of magnetic... DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mecha- nism of injury (e.g...other injuries but no clinical diagnosis of traumatic brain injury. Results Abnormalities revealed on DTI were consistent with traumatic axonal injury in

Glucose and oxygen metabolism after penetrating ballistic-like brain injury.

PubMed

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

2015-05-01

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.

Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Corey C.; Taylor, Paul Allen

The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots ofmore » maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.« less

The jungle book of neuropsychology: Disentangling the influence of feral childhood from adult brain injury in order to provide effective rehabilitation.

PubMed

McIntosh, C J; James, A I W

2018-03-01

This article considers the complexities of neuropsychological assessment and rehabilitation in brain injury when the client is illiterate, is from a foreign culture with English as a second language, and reports highly atypical childhood feral experiences prior to injury. MC was a 63-year-old woman referred for neuropsychological rehabilitation with a diagnosis of suspected St Louis encephalitis and global cognitive impairment. In formulating her clinical presentation, consideration was given to a reported history of feral childhood living with monkeys in the Colombian jungle and subsequent physical and emotional abuse. MC participated in comprehensive neuropsychological assessment and then targeted rehabilitation. Neuroimaging documented relatively focal damage in the right temporal lobe. MC's family described her as "the same but worse"; assessment and formulation indicated an exacerbation of attentional, pragmatic, arousal and executive weaknesses but with new memory and emotion recognition impairments. Rehabilitation techniques for communication and executive difficulties were successful despite the complexities of the case. The importance of carefully considered assessment and formulation in understanding MC's presentation is discussed. To the authors' knowledge, this is the only case of neuropsychological assessment and rehabilitation in brain injury involving a history of feral childhood.

PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia.

PubMed

Jansen, Laura A; Mirzaa, Ghayda M; Ishak, Gisele E; O'Roak, Brian J; Hiatt, Joseph B; Roden, William H; Gunter, Sonya A; Christian, Susan L; Collins, Sarah; Adams, Carissa; Rivière, Jean-Baptiste; St-Onge, Judith; Ojemann, Jeffrey G; Shendure, Jay; Hevner, Robert F; Dobyns, William B

2015-06-01

Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia type IIa. In addition, a germline PTEN mutation was identified in a male with hemimegalencephaly but no peripheral manifestations of the PTEN hamartoma tumour syndrome. A spectrum of clinical, imaging and pathological abnormalities was found in this cohort. While patients with more severe brain imaging abnormalities and systemic manifestations were more likely to have detected mutations, routine histopathological studies did not predict mutation status. In addition, elevated levels of phosphorylated S6 ribosomal protein were identified in both neurons and astrocytes of all hemimegalencephaly and focal cortical dysplasia type II specimens, regardless of the presence or absence of detected PI3K/AKT pathway mutations. In contrast, expression patterns of the T308 and S473 phosphorylated forms of AKT and in vitro AKT kinase activities discriminated between mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. Our findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum. © The Author (2015). Published by Oxford University Press

The BIG (brain injury guidelines) project: defining the management of traumatic brain injury by acute care surgeons.

PubMed

Joseph, Bellal; Friese, Randall S; Sadoun, Moutamn; Aziz, Hassan; Kulvatunyou, Narong; Pandit, Viraj; Wynne, Julie; Tang, Andrew; O'Keeffe, Terence; Rhee, Peter

2014-04-01

It is becoming a standard practice that any "positive" identification of a radiographic intracranial injury requires transfer of the patient to a trauma center for observation and repeat head computed tomography (RHCT). The purpose of this study was to define guidelines-based on each patient's history, physical examination, and initial head CT findings-regarding which patients require a period of observation, RHCT, or neurosurgical consultation. In our retrospective cohort analysis, we reviewed the records of 3,803 blunt traumatic brain injury patients during a 4-year period. We classified patients according to neurologic examination results, use of intoxicants, anticoagulation status, and initial head CT findings. We then developed brain injury guidelines (BIG) based on the individual patient's need for observation or hospitalization, RHCT, or neurosurgical consultation. A total of 1,232 patients had an abnormal head CT finding. In the BIG 1 category, no patients worsened clinically or radiographically or required any intervention. BIG 2 category had radiographic worsening in 2.6% of the patients. All patients who required neurosurgical intervention (13%) were in BIG 3. There was excellent agreement between assigned BIG and verified BIG. κ statistic is equal to 0.98. We have proposed BIG based on patient's history, neurologic examination, and findings of initial head CT scan. These guidelines must be used as supplement to good clinical examination while managing patients with traumatic brain injury. Prospective validation of the BIG is warranted before its widespread implementation. Epidemiologic study, level III.

Effects of early focal brain injury on memory for visuospatial patterns: selective deficits of global-local processing.

PubMed

Stiles, Joan; Stern, Catherine; Appelbaum, Mark; Nass, Ruth; Trauner, Doris; Hesselink, John

2008-01-01

Selective deficits in visuospatial processing are present early in development among children with perinatal focal brain lesions (PL). Children with right hemisphere PL (RPL) are impaired in configural processing, while children with left hemisphere PL (LPL) are impaired in featural processing. Deficits associated with LPL are less pervasive than those observed with RPL, but this difference may reflect the structure of the tasks used for assessment. Many of the tasks used to date may place greater demands on configural processing, thus highlighting this deficit in the RPL group. This study employed a task designed to place comparable demands on configural and featural processing, providing the opportunity to obtain within-task evidence of differential deficit. Sixty-two 5- to 14-year-old children (19 RPL, 19 LPL, and 24 matched controls) reproduced from memory a series of hierarchical forms (large forms composed of small forms). Global- and local-level reproduction accuracy was scored. Controls were equally accurate on global- and local-level reproduction. Children with RPL were selectively impaired on global accuracy, and children with LPL on local accuracy, thus documenting a double dissociation in global-local processing.

Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels.

PubMed

Yang, Zecheng; Chen, Yunbo; Zhang, Yan; Jiang, Yi; Fang, Xuedong; Xu, Jingwei

2014-03-01

Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain

Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia.

PubMed

Lennmyr, F; Ericsson, A; Gerwins, P; Ahlström, H; Terént, A

2003-11-01

Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.

Cannabinoids and brain injury: therapeutic implications.

PubMed

Mechoulam, Raphael; Panikashvili, David; Shohami, Esther

2002-02-01

Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumour necrosis factor-alpha and reactive oxygen intermediates, which are factors in causing neuronal damage. The formation of the endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly enhanced after brain injury, and there is evidence that these compounds reduce the secondary damage incurred. Some plant and synthetic cannabinoids, which do not bind to the cannabinoid receptors, have also been shown to be neuroprotective, possibly through their direct effect on the excitatory glutamate system and/or as antioxidants.

[Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration].

PubMed

Narberhaus, A; Segarra-Castells, M D; Verger-Maestre, K; Serra-Grabulosa, J M; Salgado-Pineda, P; Bartomeus-Jené, F; Mercader-Sobrequés, J M

Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

Big for small: Validating brain injury guidelines in pediatric traumatic brain injury.

PubMed

Azim, Asad; Jehan, Faisal S; Rhee, Peter; O'Keeffe, Terence; Tang, Andrew; Vercruysse, Gary; Kulvatunyou, Narong; Latifi, Rifat; Joseph, Bellal

2017-12-01

Brain injury guidelines (BIG) were developed to reduce overutilization of neurosurgical consultation (NC) as well as computed tomography (CT) imaging. Currently, BIG have been successfully applied to adult populations, but the value of implementing these guidelines among pediatric patients remains unassessed. Therefore, the aim of this study was to evaluate the established BIG (BIG-1 category) for managing pediatric traumatic brain injury (TBI) patients with intracranial hemorrhage (ICH) without NC (no-NC). We prospectively implemented the BIG-1 category (normal neurologic examination, ICH ≤ 4 mm limited to one location, no skull fracture) to identify pediatric TBI patients (age, ≤ 21 years) that were to be managed no-NC. Propensity score matching was performed to match these no-NC patients to a similar cohort of patients managed with NC before the implementation of BIG in a 1:1 ratio for demographics, severity of injury, and type as well as size of ICH. Our primary outcome measure was need for neurosurgical intervention. A total of 405 pediatric TBI patients were enrolled, of which 160 (NC, 80; no-NC, 80) were propensity score matched. The mean age was 9.03 ± 7.47 years, 62.1% (n = 85) were male, the median Glasgow Coma Scale score was 15 (13-15), and the median head Abbreviated Injury Scale score was 2 (2-3). A subanalysis based on stratifying patients by age groups showed a decreased in the use of repeat head CT (p = 0.02) in the no-NC group, with no difference in progression (p = 0.34) and the need for neurosurgical intervention (p = 0.9) compared with the NC group. The BIG can be safely and effectively implemented in pediatric TBI patients. Reducing repeat head CT in pediatric patients has long-term sequelae. Likewise, adhering to the guidelines helps in reducing radiation exposure across all age groups. Therapeutic/care management, level III.

A voxel-based lesion study on facial emotion recognition after penetrating brain injury

PubMed Central

Dal Monte, Olga; Solomon, Jeffrey M.; Schintu, Selene; Knutson, Kristine M.; Strenziok, Maren; Pardini, Matteo; Leopold, Anne; Raymont, Vanessa; Grafman, Jordan

2013-01-01

The ability to read emotions in the face of another person is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VLSM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network, including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings add empirical evidence that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving not only a common network that includes bilateral fronto-temporo-limbic lobes, but also other regions depending on emotional valence. PMID:22496440

Loss of Financial Management Independence After Brain Injury: Survivors' Experiences.

PubMed

Koller, Kathryn; Woods, Lindsay; Engel, Lisa; Bottari, Carolina; Dawson, Deirdre R; Nalder, Emily

2016-01-01

This pilot study explored the experiences of brain injury survivors after a change in financial management (FM) independence. Using a qualitative descriptive design, 6 participants with acquired brain injury were recruited from a community brain injury organization and participated in semistructured interviews. Data were analyzed using thematic analysis. Three themes emerged from the interviews: (1) trajectory of FM change, involving family members as key change agents; (2) current FM situation, involving FM strategies such as automatic deposits and restricted budgets; and (3) the struggle for control, in which survivors desired control while also accepting supports for FM. This study identifies some of the challenges brain injury survivors face in managing their finances and the adjustment associated with a loss of FM independence. Occupational therapists should be aware of clients' experiences when supporting them through a change in independence. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Magnetic resonance imaging spectrum of perinatal hypoxic-ischemic brain injury

PubMed Central

Varghese, Binoj; Xavier, Rose; Manoj, V C; Aneesh, M K; Priya, P S; Kumar, Ashok; Sreenivasan, V K

2016-01-01

Perinatal hypoxic–ischemic brain injury results in neonatal hypoxic–ischemic encephalopathy and serious long-term neurodevelopmental sequelae. Magnetic resonance imaging (MRI) of the brain is an ideal and safe imaging modality for suspected hypoxic–ischemic injury. The pattern of injury depends on brain maturity at the time of insult, severity of hypotension, and duration of insult. Time of imaging after the insult influences the imaging findings. Mild to moderate hypoperfusion results in germinal matrix hemorrhages and periventricular leukomalacia in preterm neonates and parasagittal watershed territory infarcts in full-term neonates. Severe insult preferentially damages the deep gray matter in both term and preterm infants. However, associated frequent perirolandic injury is seen in term neonates. MRI is useful in establishing the clinical diagnosis, assessing the severity of injury, and thereby prognosticating the outcome. Familiarity with imaging spectrum and insight into factors affecting the injury will enlighten the radiologist to provide an appropriate diagnosis. PMID:27857456

Hyperthermia and fever control in brain injury.

PubMed

Badjatia, Neeraj

2009-07-01

Fever in the neurocritical care setting is common and has a negative impact on outcome of all disease types. Meta-analyses have demonstrated that fever at onset and in the acute setting after ischemic brain injury, intracerebral hemorrhage, and cardiac arrest has a negative impact on morbidity and mortality. Data support that the impact of fever is sustained for longer durations after subarachnoid hemorrhage and traumatic brain injury. Recent advances have made eliminating fever and maintaining normothermia feasible. However, there are no prospective randomized trials demonstrating the benefit of fever control in these patient populations, and important questions regarding indications and timing remain. The purpose of this review is to analyze the data surrounding the impact of fever across a range of neurologic injuries to better understand the optimal timing and duration of fever control. Prospective randomized trials are needed to determine whether the beneficial impact of secondary injury prevention is outweighed by the potential risks of prolonged fever control.

Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?

PubMed Central

Li, Jingang; McDonald, Courtney A.; Fahey, Michael C.; Jenkin, Graham; Miller, Suzanne L.

2014-01-01

Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia–ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia–ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications. PMID:25346720

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.,…

Pathophysiology of hypopituitarism in the setting of brain injury

PubMed Central

Dusick, Joshua R.; Wang, Christina; Cohan, Pejman; Swerdloff, Ronald

2014-01-01

The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. PMID:18481181

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively

Brain lesion correlates of fatigue in individuals with traumatic brain injury.

PubMed

Schönberger, Michael; Reutens, David; Beare, Richard; O'Sullivan, Richard; Rajaratnam, Shantha M W; Ponsford, Jennie

2017-10-01

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

What Can I Do to Help Prevent Traumatic Brain Injury?

MedlinePlus

... terrain vehicle; Playing a contact sport, such as football, ice hockey, or boxing; Using in-line skates ... Brain Injury Awareness Additional Pevention Resources Childhood Injuries Concussion in Children and Teens Injuries from Violence Injuries ...

Longitudinal Examination of Resilience After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

PubMed

Marwitz, Jennifer H; Sima, Adam P; Kreutzer, Jeffrey S; Dreer, Laura E; Bergquist, Thomas F; Zafonte, Ross; Johnson-Greene, Douglas; Felix, Elizabeth R

2018-02-01

To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. Longitudinal analysis of an observational cohort. Five inpatient rehabilitation centers. Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. Not applicable. Connor-Davidson Resilience Scale. Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

PubMed Central

Lara-Celador, I.; Goñi-de-Cerio, F.; Alvarez, Antonia; Hilario, Enrique

2013-01-01

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death. Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes. Among them, the endocannabinoid system emerges as a natural system of neuroprotection. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury. PMID:25206720

Innate defense regulator peptide 1018 protects against perinatal brain injury.

PubMed

Bolouri, Hayde; Sävman, Karin; Wang, Wei; Thomas, Anitha; Maurer, Norbert; Dullaghan, Edie; Fjell, Christopher D; Ek, C Joakim; Hagberg, Henrik; Hancock, Robert E W; Brown, Kelly L; Mallard, Carina

2014-03-01

There is currently no pharmacological treatment that provides protection against brain injury in neonates. It is known that activation of an innate immune response is a key, contributing factor in perinatal brain injury; therefore, the neuroprotective therapeutic potential of innate defense regulator peptides (IDRs) was investigated. The anti-inflammatory effects of 3 IDRs was measured in lipopolysaccharide (LPS)-activated murine microglia. IDRs were then assessed for their ability to confer neuroprotection in vivo when given 3 hours after neonatal brain injury in a clinically relevant model that combines an inflammatory challenge (LPS) with hypoxia-ischemia (HI). To gain insight into peptide-mediated effects on LPS-induced inflammation and neuroprotective mechanisms, global cerebral gene expression patterns were analyzed in pups that were treated with IDR-1018 either 4 hours before LPS or 3 hours after LPS+HI. IDR-1018 reduced inflammatory mediators produced by LPS-stimulated microglia cells in vitro and modulated LPS-induced neuroinflammation in vivo. When administered 3 hours after LPS+HI, IDR-1018 exerted effects on regulatory molecules of apoptotic (for, eg, Fadd and Tnfsf9) and inflammatory (for, eg, interleukin 1, tumor necrosis factor α, chemokines, and cell adhesion molecules) pathways and showed marked protection of both white and gray brain matter. IDR-1018 suppresses proinflammatory mediators and cell injurious mechanisms in the developing brain, and postinsult treatment is efficacious in reducing LPS-induced hypoxic-ischemic brain damage. IDR-1018 is effective in the brain when given systemically, confers neuroprotection of both gray and white matter, and lacks significant effects on the brain under normal conditions. Thus, this peptide provides the features of a promising neuroprotective agent in newborns with brain injury. © 2014 Child Neurology Society/American Neurological Association.

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…

Mechanisms of gender-linked ischemic brain injury

PubMed Central

Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

2010-01-01

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

Improving client-centered brain injury rehabilitation through research-based theater.

PubMed

Kontos, Pia C; Miller, Karen-Lee; Gilbert, Julie E; Mitchell, Gail J; Colantonio, Angela; Keightley, Michelle L; Cott, Cheryl

2012-12-01

Traumatic brain injury often results in physical, behavioral, and cognitive impairments perceived by health care practitioners to limit or exclude clients' full participation in treatment decision making. We used qualitative methods to evaluate the short- and long-term impact of "After the Crash: A Play About Brain Injury," a research-based drama designed to teach client-centered care principles to brain injury rehabilitation staff. We conducted interviews and observations with staff of two inpatient neurorehabilitation units in Ontario, Canada. Findings demonstrate the effectiveness of the play in influencing practice through the avoidance of medical jargon to improve clients' understanding and participation in treatment; newfound appreciation for clients' needs for emotional expression and sexual intimacy; increased involvement of family caregivers; and avoidance of staff discussions as if clients were unaware. These findings suggest that research-based drama can effect reflexivity, empathy, and practice change to facilitate a client-centered culture of practice in brain injury rehabilitation.

Brain pathology after mild traumatic brain injury: an exploratory study by repeated magnetic resonance examination.

PubMed

Lannsjö, Marianne; Raininko, Raili; Bustamante, Mariana; von Seth, Charlotta; Borg, Jörgen

2013-09-01

To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination. A prospective follow-up study. Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15. The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE). At follow-up, 7 patients (37%) reported ≥  3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported < 3 symptoms and 1 ≥ 3 symptoms, all exhibiting GOSE scores of 8. Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.

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

A clinical comparison of penetrating and blunt traumatic brain injuries.

PubMed

Santiago, Luis A; Oh, Bryan C; Dash, Pramod K; Holcomb, John B; Wade, Charles E

2012-01-01

Traumatic brain injury (TBI) is a leading cause of injury death and long-term disability in the USA. It commonly results from blunt (closed) or penetrating trauma. The majority of civilian TBI is caused by falls or motor vehicle collisions, whereas military TBI mainly results from explosions. Although penetrating injuries are less common than closed injuries in the civilian population, they are far more lethal. Unfortunately, the pathophysiologic differences between penetrating and closed TBI remain poorly understood due to the lack of studies on the subject. Many studies on the prognostic factors of mortality and functional outcome after TBI exclude penetrating brain injuries from their series because they are believed to have a different pathophysiology. 125 Articles regarding brain injury were reviewed and summarized for this report. Despite the absence of a clear delineation between penetrating and blunt TBI, the current guidelines for penetrating TBI suggest defaulting to management strategies used for closed TBI with limited supportive evidence. Thus, injuries that appear to have different pathophysiologies and outcomes are managed equally and perhaps not optimally. In view of the incomplete understanding of the impact of mechanism of injury on TBI outcomes, as demonstrated in the current review, new research studies are required to improve evidence-based TBI guidelines tailored especially for penetrating injuries.

Plasma copeptin level predicts acute traumatic coagulopathy and progressive hemorrhagic injury after traumatic brain injury.

PubMed

Yang, Ding-Bo; Yu, Wen-Hua; Dong, Xiao-Qiao; Du, Quan; Shen, Yong-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie; Wang, Hao; Jiang, Li; Du, Yuan-Feng

2014-08-01

Higher plasma copeptin levels correlate with poor clinical outcomes after traumatic brain injury. Nevertheless, their links with acute traumatic coagulopathy and progressive hemorrhagic injury are unknown. Therefore, we aimed to investigate the relationship between plasma copeptin levels, acute traumatic coagulopathy and progressive hemorrhagic injury in patients with severe traumatic brain injury. We prospectively studied 100 consecutive patients presenting within 6h from head trauma. Progressive hemorrhagic injury was present when the follow-up computerized tomography scan reported any increase in size or number of the hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy was defined as an activated partial thromboplastic time greater than 40s and/or international normalized ratio greater than 1.2 and/or a platelet count less than 120×10(9)/L. We measured plasma copeptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression analysis, plasma copeptin level emerged as an independent predictor of progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver operating characteristic curves, we calculated areas under the curve for progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive performance of copeptin was similar to that of Glasgow Coma Scale score. However, copeptin did not obviously improve the predictive value of Glasgow Coma Scale score. Thus, copeptin may help in the prediction of progressive hemorrhagic injury and acute traumatic coagulopathy after traumatic brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Anti-epileptic drugs in pediatric traumatic brain injury.

PubMed

Tanaka, Tomoko; Litofsky, N Scott

2016-10-01

Pediatric post-traumatic epilepsy incidence varies depending on reporting mechanism and injury severity; anti-epileptic drug (AEDs) use also varies with lack of quality evidence-based data. Adverse AED effects are not negligible; some may negatively affect functional outcome. This review focuses on clarifying available data. This review discusses seizures associated with traumatic brain injury in children, including seizure incidence, relationship to severity of injury, potential detrimental effects of seizures, potential benefits of AED, adverse effects of AED, new developments in preventing epileptogenesis, and suggested recommendations for patient management. English language papers were identified from PubMed using search terms including but not excluding the following: adverse drug effects, anti-epileptic drugs, children, electroencephalogram, epilepsy, epileptogenesis, head injury, levetiracetam, pediatrics, phenytoin, post-traumatic epilepsy, prevention, prophylaxis, seizures, and traumatic brain injury. Expert commentary: Identification of high-risk patients for post-traumatic seizures is a key goal. Levetiracetam may prevent epileptogenesis, as may other developments.

Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair.

PubMed

Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S

2016-01-01

The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury

DTIC Science & Technology

2013-11-07

RE, Melo B, Christensen B, Ngo L-A, Monette G, Bradbury C. 2008. Measuring premorbid IQ in traumatic brain injury: An examination of the validity of...High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury by Brendan J. Finton Thesis...Mild Traumatic Brain Injury" is appropriately acknowledged and, beyond brief excerpts, is with the permission of the copyright owner. Brendan J

Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

PubMed

Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang

2018-06-01

Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.

Prevalence of traumatic brain injury in juvenile offenders: a meta-analysis.

PubMed

Farrer, Thomas J; Frost, R Brock; Hedges, Dawson W

2013-01-01

Studies of traumatic brain injury (TBI) among adult populations demonstrate that such injuries can lead to aggressive behaviors. Related findings suggest that incarcerated individuals have high rates of brain injuries. Such studies suggest that traumatic brain injury may be related to the etiology and recidivism of criminal behavior. Relatively few studies have examined the prevalence of TBI using a delinquent juvenile sample. In order to assess the relationship between TBI and juvenile offender status, the current study used meta-analytic techniques to examine the odds of having a TBI among juvenile offenders. Across 9 studies, we found that approximately 30% of juvenile offenders have sustained a previous brain injury. Across 5 studies that used a control group, a calculated summary odds ratio of 3.37 suggests that juvenile offenders are significantly more likely to have a TBI compared to controls. Results suggest that the rate of TBIs within the juvenile offender population is significant and that there may be a relationship between TBIs and juvenile criminal behavior.

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…

Effects of the Oral Ingestion of Probiotics on Brain Damage in a Transient Model of Focal Cerebral Ischemia in Mice

PubMed Central

Akhoundzadeh, Kobra; Vakili, Abedin; Shadnoush, Mahdi; Sadeghzadeh, Jafar

2018-01-01

Background: Probiotics are microorganisms that may influence brain function via altering brain neurochemistry. New research evidence suggests that probiotic bacteria might protect tissue damage through diminishing the production of free radicals and/or inflammatory cytokines. Therefore, this study was designed to evaluate the effects of probiotic bacteria on the prevention or reduction of brain damage in an experimental model of stroke in mice. Methods: In this study, 30 male BLC57 mice were randomly divided into 6 equal groups. Focal cerebral ischemia was induced via middle cerebral artery occlusion for 45 minutes, followed by 24 hours of reperfusion, in the mice. Probiotics at a concentration of 107 CFU/mL were administered by oral gavage daily for 14 days before ischemia. Infarct size, neurological outcome, and biochemical markers were measured 24 hours after brain ischemia. Statistical analysis were performed using the one-way ANOVA and/or Kruskal–Wallis ANOVA on rank by Sigma Stat (2.0; Jandel Scientific) software. Results: Our results indicated that pretreatment with probiotics significantly reduced infarct size by 52% (P=0.001) but could not improve neurological function (P=0.26). Moreover, the administration of probiotics significantly decreased the malondialdehyde content (P=0.001) and the tumor necrosis factor-alpha level (P=0.004) in the ischemic brain tissue. Conclusion: The findings of the present study showed that probiotic supplements might be useful in the prevention or attenuation of brain ischemic injury in patients at risk of stroke. Probiotics may open new therapeutic alternatives for the prevention of stroke. More preclinical and clinical studies are, however, needed to clarify their efficacy in cerebral stroke. PMID:29398750

The influence of victim characteristics on potential jurors' perceptions of brain damage in mild traumatic brain injury.

PubMed

Guilmette, T J; Temple, R O; Kennedy, M L; Weiler, M D; Ruffolo, L F; Dufresne, E

2005-11-01

To determine the influence of victim/plaintiff sex, occupation and intoxication status at the time of injury on potential jurors' judgement about the presence of brain damage in mild traumatic brain injury (MTBI). Survey. One of eight scenarios describing a MTBI from a motor vehicle accident was presented to 460 participants at a Department of Motor Vehicles. Victim sex, occupation (accountant or cafeteria worker) and alcohol intoxication status at the time of injury (sober or intoxicated) were manipulated across eight scenarios. Participants rated whether the victim's complaints at 6 months post-injury were the result of brain damage. Ratings were influenced by victim occupation and intoxication status (chi2>5.3, p<0.03), but not the sex of the victim. The occupational and intoxication status of MTBI victims may influence potential jurors' decision about the presence of brain damage.

Changes in SWB following injury to different brain lobes.

PubMed