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Sample records for focal brain injury

  1. Delayed Postconditioning Protects against Focal Ischemic Brain Injury in Rats

    PubMed Central

    Ren, Chuancheng; Gao, Xuwen; Niu, Gang; Yan, Zhimin; Chen, Xiaoyuan; Zhao, Heng

    2008-01-01

    Background We and others have reported that rapid ischemic postconditioning, interrupting early reperfusion after stroke, reduces infarction in rats. However, its extremely short therapeutic time windows, from a few seconds to minutes after reperfusion, may hinder its clinical translation. Thus, in this study we explored if delayed postconditioning, which is conducted a few hours after reperfusion, offers protection against stroke. Methods and Results Focal ischemia was generated by 30 min occlusion of bilateral common carotid artery (CCA) combined with permanent occlusion of middle cerebral artery (MCA); delayed postconditioning was performed by repetitive, brief occlusion and release of the bilateral CCAs, or of the ipsilateral CCA alone. As a result, delayed postconditioning performed at 3h and 6h after stroke robustly reduced infarct size, with the strongest protection achieved by delayed postconditioning with 6 cycles of 15 min occlusion/15 min release of the ipsilateral CCA executed from 6h. We found that this delayed postconditioning provided long-term protection for up to two months by reducing infarction and improving outcomes of the behavioral tests; it also attenuated reduction in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-uptake therefore improving metabolism, and reduced edema and blood brain barrier leakage. Reperfusion in ischemic stroke patients is usually achieved by tissue plasminogen activator (tPA) application, however, t-PA's side effect may worsen ischemic injury. Thus, we tested whether delayed postconditioning counteracts the exacerbating effect of t-PA. The results showed that delayed postconditioning mitigated the worsening effect of t-PA on infarction. Conclusion Delayed postconditioning reduced ischemic injury after focal ischemia, which opens a new research avenue for stroke therapy and its underlying protective mechanisms. PMID:19066627

  2. Spontaneous gesture and spatial language: Evidence from focal brain injury.

    PubMed

    Göksun, Tilbe; Lehet, Matthew; Malykhina, Katsiaryna; Chatterjee, Anjan

    2015-11-01

    People often use spontaneous gestures when communicating spatial information. We investigated focal brain-injured individuals to test the hypotheses that (1) naming motion event components of manner-path (represented by verbs-prepositions in English) are impaired selectively, (2) gestures compensate for impaired naming. Patients with left or right hemisphere damage (LHD or RHD) and elderly control participants were asked to describe motion events (e.g., running across) depicted in brief videos. Damage to the left posterior middle frontal gyrus, left inferior frontal gyrus, and left anterior superior temporal gyrus (aSTG) produced impairments in naming paths of motion; lesions to the left caudate and adjacent white matter produced impairments in naming manners of motion. While the frequency of spontaneous gestures were low, lesions to the left aSTG significantly correlated with greater production of path gestures. These suggest that producing prepositions-verbs can be separately impaired and gesture production compensates for naming impairments when damage involves left aSTG. PMID:26283001

  3. Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models

    PubMed Central

    Manganozzi, Lucilla; Moretti, Raffaella; Vexler, Zinaida S.; Gressens, Pierre

    2016-01-01

    BACKGROUND Arterial ischemic stroke occurs most frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared to childhood. This concept was recently challenged by clinical studies showing marked motor disabilities after stroke in neonates, with the severity of motor and cortical sensory deficits similar in both perinatal and childhood ischemic stroke. The understanding of the triggers and the pathophysiological mechanisms of perinatal stroke has greatly improved in recent years, but many aspects remain still unclear. METHODS In this review, we will focus on the pathophysiology of perinatal stroke and on therapeutic strategies that can protect the immature brain from the consequences of stroke by targeting inflammation and brain microenvironment. RESULTS Studies in neonatal rodent models of cerebral ischemia have shown a potential role for soluble inflammatory molecules as important modulators of injury and recovery. A great effort has been made and is still in act to try neuroprotective molecules based on the new physiopatological acquisition. CONCLUSION In this review we aim to give a comprehensive view of new insights concerning pathophysiological mechanism of focal and global perinatal brain injury and its new therapeutic approaches. PMID:26002050

  4. Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury.

    PubMed

    Olson, Emily; Badder, Carlie; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Margulies, Susan S

    2016-04-15

    We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention. PMID:26414329

  5. Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats.

    PubMed

    Günther, Mattias; Davidsson, Johan; Plantman, Stefan; Norgren, Svante; Mathiesen, Tiit; Risling, Mårten

    2015-09-01

    We examined the effects of N-acetylcysteine amide (NACA) in the secondary inflammatory response following a novel method of focal penetrating traumatic brain injury (TBI) in rats. N-acetylcysteine (NAC) has limited but well-documented neuroprotective effects after experimental central nervous system ischemia and TBI, but its bioavailability is very low. We tested NACA, a modified form of NAC with higher membrane and blood-brain barrier permeability. Focal penetrating TBI was produced in male Sprague-Dawley rats randomly selected for NACA treatment (n=5) and no treatment (n=5). In addition, four animals were submitted to sham surgery. After 2 hours or 24 hours the brains were removed, fresh frozen, cut in 14 μm coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. All treated animals were given 300 mg/kg NACA intraperitoneally (IP) 2 minutes post trauma. The 24 hour survival group was given an additional bolus of 300 mg/kg IP after 4 hours. NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24 hours with a mean change of 35.0% (p<0.05) and decreased TUNEL staining indicative of apoptosis at 2 hours with a mean change of 38.7% (p<0.05). Manganese superoxide dismutase (MnSOD) increased in the NACA treatment group at 24 hours with a mean change of 35.9% (p<0.05). Levels of migrating macrophages and activated microglia (Ox-42/CD11b), nitric oxide-producing inflammatory enzyme iNOS, peroxynitrite marker 3-nitrotyrosine, NFκB translocated to the nuclei, cytochrome C and Bcl-2 were not affected. NACA treatment decreased neuronal degeneration and apoptosis and increased levels of antioxidative enzyme MnSOD. The antiapoptotic effect was likely regulated by pathways other than cytochrome C. Therefore, NACA prevents brain tissue damage after focal penetrating TBI, warranting further studies towards a clinical application. PMID:26100161

  6. Diosgenin attenuates the brain injury induced by transient focal cerebral ischemia-reperfusion in rats.

    PubMed

    Zhang, Xinxin; Xue, Xuanji; Zhao, Jing; Qian, Chunxiang; Guo, Zengjun; Ito, Yoichiro; Sun, Wenji

    2016-09-01

    The aim of the present study is to explore the potential cerebroprotection of diosgenin against the transient focal cerebral ischemia-reperfusion (I/R) injury and its possible underlying mechanisms. The diosgenin at two dose levels, namely 100 and 200mgkg(-1), was intragastrically administrated once daily for 7-day period prior to the surgery. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) using the intraluminal thread for 90min. After 24h reperfusion, several diagnostic indicators were evaluated and all animals were sacrificed to harvest their brains and blood for subsequent biochemical analyses. The results indicated that diosgenin treatment significantly inhibited the death rate and improved the impaired neurological functions along with neurological deficit scores and cerebral infarct size as compared with the rats exposed to I/R insult without agents administration. The increase in the number of apoptotic cells determined by TUNEL in the hippocampus CA1 and cortex was also apparently attenuated in the diosgenin treatment group, which was closely correlated with suppression of Caspase-3 activity and Bax/Bcl-2 ratio. In addition the elevated concentrations of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in blood serum of the I/R treated rats were reduced almost to their normal level. Further results obtained from the Western blotting analysis revealed that the protein expression of IκBα in the injured brain was up-regulated, while the p65 subunit of NF-κB was down-regulated in nucleus after the treatment. Collectively, this neuroprotection of diosgenin against I/R injury may be attained through its anti-apoptosis, anti-inflammation and intervening the NF-κB signal pathway properties. Due to the satisfactory findings, diosgenin might be a powerful therapeutic agent to combat the similar disease in future clinic. PMID:27425638

  7. Study the efficacy of neuroprotective drugs on brain physiological properties during focal head injury using optical spectroscopy data analysis

    NASA Astrophysics Data System (ADS)

    Abookasis, David; Shochat, Ariel

    2016-03-01

    We present a comparative evaluation of five different neuroprotective drugs in the early phase following focal traumatic brain injury (TBI) in mouse intact head. The effectiveness of these drugs in terms of changes in brain tissue morphology and hemodynamic properties was experimentally evaluated through analysis of the optical absorption coefficient and spectral reduced scattering parameters in the range of 650-1000 nm. Anesthetized male mice (n=50 and n=10 control) were subjected to weight drop model mimics real life focal head trauma. Monitoring the effect of injury and neuroprotective drugs was obtained by using a diffuse reflectance spectroscopy system utilizing independent source-detector separation and location. Result indicates that administration of minocycline improve hemodynamic and reduced the level of tissue injury at an early phase post-injury while hypertonic saline treatment decrease brain water content. These findings highlight the heterogeneity between neuroprotective drugs and the ongoing controversy among researchers regarding which drug therapy is preferred for treatment of TBI. On the other hand, our results show the capability of optical spectroscopy technique to noninvasively study brain function following injury and drug therapy.

  8. 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

  9. 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. PMID:20466762

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

    PubMed Central

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

    2010-01-01

    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. PMID:20466762

  11. Development of a Human Head FE Model and Impact Simulation on the Focal Brain Injury

    NASA Astrophysics Data System (ADS)

    Watanabe, Dai; Yuge, Kohei; Nishimoto, Tetsuya; Murakami, Shigeyuki; Takao, Hiroyuki

    In this paper, a three-dimensional digital human-head model was developed and several dynamic analyses on the head trauma were conducted. This model was built up by the VOXEL approach using 433 slice CT images (512×512 pixels) and made of 1.22 million parallelepiped finite elements with 10 anatomical tissue properties such as scalp, CSF, skull, brain, dura mater and so on. The numerical analyses were conducted using a finite element code the authors have developed. The main features of the code are 1) it is based on the explicit time integration method and 2) it uses the one point integration method to evaluate the equivalent nodal forces with the hourglass control proposed by Flanagan and Belytschko(1) and 3) it utilizes the parallel computation system based on MPI. In order to verify the developed model, the head impact experiment for a cadaver by Nahum et al.(2) was simulated. The calculated results showed good agreement with the experimental ones. A front and rear impact analyses were also performed to discuss on the characteristic measure of the brain injury, in which the von-Mises stress was high in the frontal lobe in both of the analyses because of the large deformations of a frontal cranial base. This result suggests that the von-Mises stress can be a good measure of the brain injury since it is empirically well known that the frontal lobe tends to get injured regardless of the impact positions.

  12. 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

  13. Inosine promotes recovery of skilled motor function in a model of focal brain injury.

    PubMed

    Smith, Justin M; Lunga, Precious; Story, David; Harris, Neil; Le Belle, Janel; James, Michael F; Pickard, John D; Fawcett, James W

    2007-04-01

    Recovery of function following traumatic brain injury (TBI) is partly through neuronal plasticity. However plasticity is limited in the adult CNS compared with young animals. In order to test whether treatments that enhance CNS plasticity might improve functional recovery after TBI, a new rat head injury model was developed, in which a computer-controlled impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex. Behavioural deficits were seen in several sensorimotor tasks, most of which recovered spontaneously by 21 days. However, skilled paw reaching behaviour, a task that requires corticospinal function, was only approximately 40% recovered by 28 days. In order to promote plasticity inosine was infused into the lateral ventricles for 28 days. This treatment produced an almost complete recovery of skilled paw reaching ability, associated with sprouting of the uninjured corticospinal axons across the midline into the territory of the lesioned pathway. In the cervical spinal cord the number of corticospinal axons originating from the uninjured cortex that innervated the contralateral cervical cord was five times that of controls, and in the red nucleus the number of contralaterally projecting axons was four times control values. Inosine treatment did not affect recovery in unskilled behavioural tasks, most of which recovered to normal levels by 28 days without treatment. Animals were placed in an enriched environment as an alternative method to promote plasticity. This resulted in more rapid recovery in several tasks including skilled paw function, but by 28 days normally housed animals had caught up to the same level of improvement. PMID:17293357

  14. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    PubMed

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that

  15. Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats.

    PubMed

    Dietrich, W D; Alonso, O; Busto, R; Prado, R; Dewanjee, S; Dewanjee, M K; Ginsberg, M D

    1996-05-01

    Cerebrovascular damage leading to subsequent reductions in local cerebral blood flow (lCBF) may represent an important secondary injury mechanism following traumatic brain injury (TBI). We determined whether patterns of 111-indium-labeled platelet accumulation were spatially related to alterations in lCBF determined autoradiographically 30 min after TBI. Sprague-Dawley rats (n = 8), anesthetized with halothane and maintained on a 70:30 (vol/vol) mixture of nitrous oxide/oxygen and 0.5% halothane, underwent parasagittal fluid percussion brain injury (1.7-2.2 atm). 111-Indium-tropolone-labeled platelets were injected 30 min prior to TBI while [14C]-iodoantipyrine was infused 30 min after trauma. Sham-operated animals (n = 7) underwent similar surgical procedures but were not injured. In autoradiographic images of the indium-labeled platelets, focal sites of platelet accumulation within the traumatized hemisphere were restricted to the pial surface (five of eight rats), the external capsule underlying the lateral parietal cortex (five of eight rats), and within cerebrospinal fluid (CSF) compartments (six of eight rats). In contrast, mild-to-moderate reductions in lCBF, not restricted to sites of platelet accumulation, were seen throughout the traumatized hemisphere. Flow reductions were most severe in coronal sections underlying the impact site. For example, within the lateral parietal cortex and hippocampus, lCBF was significantly reduced [p <0.01; analysis of variance (ANOVA)] from 1.71 +/- 0.34 (mean +/- SD) and 0.78 +/- 0.12 ml/g/min, respectively, versus 0.72 +/- 0.17 and 0.41 +/- 0.06 ml/g/min within the traumatized hemisphere. Significant flow reductions were also seen in remote cortical and subcortical areas, including the right frontal cortex and striatum. These results indicate that focal platelet accumulation and widespread hemodynamic depression are both early consequences of TBI. Therapeutic strategies directed at these early microvascular consequences of

  16. YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia–reperfusion injury in mice

    PubMed Central

    Cao, Guosheng; Ye, Xinyi; Xu, Yingqiong; Yin, Mingzhu; Chen, Honglin; Kou, Junping; Yu, Boyang

    2016-01-01

    YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB) dysfunction induced by cerebral ischemia–reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. PMID:26834461

  17. 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…

  18. Bone marrow derived mesenchymal stem cells alleviated brain injury via down-regulation of interleukin-1β in focal cerebral ischemic rats

    PubMed Central

    Zhao, Yansong; Wang, Xiaoli; Dong, Peng; Xu, Qinyan; Ma, Ze; Mu, Qingjie; Sun, Xihe; Jiang, Zhengchen; Wang, Xin

    2016-01-01

    Interleukin-1β (IL-1β) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1β, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1β. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1β). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1β was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1β. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1β expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1β expression, thus repair the injured brain in focal cerebral ischemic rats.

  19. Early effects of high-fat diet on neurovascular function and focal ischemic brain injury.

    PubMed

    Li, Weiguo; Prakash, Roshini; Chawla, Dhruv; Du, Wenting; Didion, Sean P; Filosa, Jessica A; Zhang, Quanguang; Brann, Darrell W; Lima, Victor V; Tostes, Rita C; Ergul, Adviye

    2013-06-01

    Obesity is a risk factor for stroke, but the early effects of high-fat diet (HFD) on neurovascular function and ischemic stroke outcomes remain unclear. The goal of this study was to test the hypotheses that HFD beginning early in life 1) impairs neurovascular coupling, 2) causes cerebrovascular dysfunction, and 3) worsens short-term outcomes after cerebral ischemia. Functional hyperemia and parenchymal arteriole (PA) reactivity were measured in rats after 8 wk of HFD. The effect of HFD on basilar artery function after middle cerebral artery occlusion (MCAO) and associated O-GlcNAcylation were assessed. Neuronal cell death, infarct size, hemorrhagic transformation (HT) frequency/severity, and neurological deficit were evaluated after global ischemia and transient MCAO. HFD caused a 10% increase in body weight and doubled adiposity without a change in lipid profile, blood glucose, and blood pressure. Functional hyperemia and PA relaxation were decreased with HFD. Basilar arteries from stroked HFD rats were more sensitive to contractile factors, and acetylcholine-mediated relaxation was impaired. Vascular O-GlcNAcylated protein content was increased with HFD. This group also showed greater mortality rate, infarct volume, HT occurrence rate, and HT severity and poor functional outcome compared with the control diet group. These results indicate that HFD negatively affects neurovascular coupling and cerebrovascular function even in the absence of dyslipidemia. These early cerebrovascular changes may be the cause of greater cerebral injury and poor outcomes of stroke in these animals. PMID:23576615

  20. Early effects of high-fat diet on neurovascular function and focal ischemic brain injury

    PubMed Central

    Li, Weiguo; Prakash, Roshini; Chawla, Dhruv; Du, Wenting; Didion, Sean P.; Filosa, Jessica A.; Zhang, Quanguang; Brann, Darrell W.; Lima, Victor V.; Tostes, Rita C.

    2013-01-01

    Obesity is a risk factor for stroke, but the early effects of high-fat diet (HFD) on neurovascular function and ischemic stroke outcomes remain unclear. The goal of this study was to test the hypotheses that HFD beginning early in life 1) impairs neurovascular coupling, 2) causes cerebrovascular dysfunction, and 3) worsens short-term outcomes after cerebral ischemia. Functional hyperemia and parenchymal arteriole (PA) reactivity were measured in rats after 8 wk of HFD. The effect of HFD on basilar artery function after middle cerebral artery occlusion (MCAO) and associated O-GlcNAcylation were assessed. Neuronal cell death, infarct size, hemorrhagic transformation (HT) frequency/severity, and neurological deficit were evaluated after global ischemia and transient MCAO. HFD caused a 10% increase in body weight and doubled adiposity without a change in lipid profile, blood glucose, and blood pressure. Functional hyperemia and PA relaxation were decreased with HFD. Basilar arteries from stroked HFD rats were more sensitive to contractile factors, and acetylcholine-mediated relaxation was impaired. Vascular O-GlcNAcylated protein content was increased with HFD. This group also showed greater mortality rate, infarct volume, HT occurrence rate, and HT severity and poor functional outcome compared with the control diet group. These results indicate that HFD negatively affects neurovascular coupling and cerebrovascular function even in the absence of dyslipidemia. These early cerebrovascular changes may be the cause of greater cerebral injury and poor outcomes of stroke in these animals. PMID:23576615

  1. A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice.

    PubMed

    Guley, Natalie H; Rogers, Joshua T; Del Mar, Nobel A; Deng, Yunping; Islam, Rafiqul M; D'Surney, Lauren; Ferrell, Jessica; Deng, Bowei; Hines-Beard, Jessica; Bu, Wei; Ren, Huiling; Elberger, Andrea J; Marchetta, Jeffrey G; Rex, Tonia S; Honig, Marcia G; Reiner, Anton

    2016-02-15

    Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits. PMID:26414413

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

    PubMed Central

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

    2009-01-01

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

  3. Indices of impaired self-awareness in traumatic brain injury patients with focal frontal lesions and executive deficits: implications for outcome measurement.

    PubMed

    Spikman, Jacoba M; van der Naalt, Joukje

    2010-07-01

    In patients with moderate to severe traumatic brain injury (TBI), impairments of self-awareness are frequently found and associated with worse functional outcome and poor compliance with rehabilitation. The aim of this study was to investigate whether indications of impaired self-awareness could be found in TBI patients with frontal lesions and executive function deficits. Twenty-two TBI patients with focal frontal injuries were compared to 29 TBI patients without focal frontal injuries visible on neuroimaging. No differences were found on several outcome measures, including the Glasgow Outcome Scale-Extended (GOS-E), the Differential Outcome Scale (DOS), and return to work (RTW), although the frontal injury patients were more severely injured as indicated by the Glasgow Coma Scale (GCS) and duration of post-traumatic amnesia (PTA), and had impaired performance on a neuropsychological test of executive functioning. Even more so, the frontal injury group had a significantly lower score on the Sickness Impact Profile (SIP), indicating that they had fewer complaints than the patients without frontal injury, and scored significantly higher on the percentage of recovery (PoR) score, which expresses the extent of recovery as a percentage of their previous level of functioning. In contrast to the non-frontal-injury group, their PoR scores were not related to RTW, reflecting an erroneous perception of their actual working status. The positive results on these different outcome measures, which are partly or entirely self-reported, were seen as an indication of an impaired self-evaluative ability in the frontal injury patients. To determine outcome in a patient with frontal injuries and executive dysfunction, the judgment of several relevant other persons in the patient's life (e.g., partners, therapists, and employers) of the patient's daily life functioning should be sought. PMID:20380551

  4. Failure of Intravenous or Intracardiac Delivery of Mesenchymal Stromal Cells to Improve Outcomes after Focal Traumatic Brain Injury in the Female Rat

    PubMed Central

    Turtzo, L. Christine; Budde, Matthew D.; Dean, Dana D.; Gold, Eric M.; Lewis, Bobbi K.; Janes, Lindsay; Lescher, Jacob; Coppola, Tiziana; Yarnell, Angela; Grunberg, Neil E.; Frank, Joseph A.

    2015-01-01

    Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model. PMID:25946089

  5. Brain injury in sports.

    PubMed

    Lloyd, John; Conidi, Frank

    2016-03-01

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

  6. Traumatic Brain Injury

    MedlinePlus

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

  7. 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 ...

  8. Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice.

    PubMed

    Ng, Si Yun; Semple, Bridgette D; Morganti-Kossmann, M Cristina; Bye, Nicole

    2012-05-01

    Neurogenesis is stimulated following injury to the adult brain and could potentially contribute to tissue repair. However, evidence suggests that microglia activated in response to injury are detrimental to the survival of new neurons, thus limiting the neurogenic response. The aim of this study was to determine the effect of the anti-inflammatory drug minocycline on neurogenesis and functional recovery after a closed head injury model of focal traumatic brain injury (TBI). Beginning 30 min after trauma, minocycline was administered for up to 2 weeks and bromodeoxyuridine was given on days 1-4 to label proliferating cells. Neurological outcome and motor function were evaluated over 6 weeks using the Neurological Severity Score (NSS) and ledged beam task. Microglial activation was assessed in the pericontusional cortex and hippocampus at 1 week post-trauma, using immunohistochemistry to detect F4/80. Following immunolabeling of bromodeoxyuridine, double-cortin, and NeuN, cells undergoing distinct stages of neurogenesis, including proliferation, neuronal differentiation, neuroblast migration, and long-term survival, were quantified at 1 and 6 weeks in the hippocampal dentate gyrus, as well as in the subventricular zone of the lateral ventricles and the pericontusional cortex. Our results show that minocycline successfully reduced microglial activation and promoted early neurological recovery that was sustained over 6 weeks. We also show for the first time in the closed head injury model, that early stages of neurogenesis were stimulated in the hippocampus and subventricular zone; however, no increase in new mature neurons occurred. Contrary to our hypothesis, despite the attenuation of activated microglia, minocycline did not support neurogenesis in the hippocampus, lateral ventricles, or pericontusional cortex, with none of the neurogenic stages being affected by treatment. These data provide evidence that a general suppression of microglial activation is

  9. Traumatic brain injury-induced sleep disorders.

    PubMed

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%-70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  10. Traumatic brain injury-induced sleep disorders

    PubMed Central

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  11. Induction of Nerve Injury-Induced Protein 1 (Ninjurin 1) in Myeloid Cells in Rat Brain after Transient Focal Cerebral Ischemia

    PubMed Central

    Lee, Hye-Kyung; Lee, Hahnbie; Luo, Lidan

    2016-01-01

    Nerve injury-induced protein-1 (Ninjurin-1, Ninj1) was initially identified as a novel adhesion molecule in rat sciatic nerve and to be up-regulated in neurons and Schwann cells of distal nerve segments after nerve transection or crush injury. Recently, Ninj1 was found to act as a modulator of cell migration, angiogenesis, and apoptosis. Accumulating evidence indicates that innate immune response plays beneficial and deleterious roles in brain ischemia, and the trans-endothelial migration of blood-derived immune cells is key initiator of this response. In the present study, we examined the expression profile and cellular distribution of Ninj1 in rat brain after transient focal cerebral ischemia. Ninj1 expression was found to be significantly induced in cortical penumbras 1 day after 60 min of middle cerebral artery occlusion (MCAO) and to increase gradually for 8 days and then declined. In infarction cores of cortices, patterns of Ninj1 expression were similar to those observed in cortical penumbras, except induction was maintained for 10 days. At 1 day post-MCAO, Ninj1 inductions were detected mainly in neutrophils and endothelial cells in both infarction cores and penumbras, but reactive macrophages were the major cellular expressers of Ninj1 at 4 days post-MCAO. Expressional induction in reactive macrophages was maintained in infarction cores after 12 days post-MCAO but not in penumbras. These dynamic expressions of Ninj1 in different immune cells at different times suggest that this protein performs various, critical roles in the modulation of acute and delayed immune responses in the postischemic brain. PMID:27122992

  12. Induction of Nerve Injury-Induced Protein 1 (Ninjurin 1) in Myeloid Cells in Rat Brain after Transient Focal Cerebral Ischemia.

    PubMed

    Lee, Hye-Kyung; Lee, Hahnbie; Luo, Lidan; Lee, Ja-Kyeong

    2016-04-01

    Nerve injury-induced protein-1 (Ninjurin-1, Ninj1) was initially identified as a novel adhesion molecule in rat sciatic nerve and to be up-regulated in neurons and Schwann cells of distal nerve segments after nerve transection or crush injury. Recently, Ninj1 was found to act as a modulator of cell migration, angiogenesis, and apoptosis. Accumulating evidence indicates that innate immune response plays beneficial and deleterious roles in brain ischemia, and the trans-endothelial migration of blood-derived immune cells is key initiator of this response. In the present study, we examined the expression profile and cellular distribution of Ninj1 in rat brain after transient focal cerebral ischemia. Ninj1 expression was found to be significantly induced in cortical penumbras 1 day after 60 min of middle cerebral artery occlusion (MCAO) and to increase gradually for 8 days and then declined. In infarction cores of cortices, patterns of Ninj1 expression were similar to those observed in cortical penumbras, except induction was maintained for 10 days. At 1 day post-MCAO, Ninj1 inductions were detected mainly in neutrophils and endothelial cells in both infarction cores and penumbras, but reactive macrophages were the major cellular expressers of Ninj1 at 4 days post-MCAO. Expressional induction in reactive macrophages was maintained in infarction cores after 12 days post-MCAO but not in penumbras. These dynamic expressions of Ninj1 in different immune cells at different times suggest that this protein performs various, critical roles in the modulation of acute and delayed immune responses in the postischemic brain. PMID:27122992

  13. Brain injury - discharge

    MedlinePlus

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

  14. Neuropathophysiology of Brain Injury.

    PubMed

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

    2016-09-01

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

  15. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

    Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. PMID:20707892

  16. Traumatic Brain Injury

    MedlinePlus

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

  17. Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

    PubMed Central

    Filippidis, Aristotelis S.; Liang, Xiuyin; Wang, Weili; Parveen, Shanaaz; Baumgarten, Clive M.

    2014-01-01

    Abstract Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na+ and K+ concentrations ([Na+]e; [K+]e). Ion-selective Na+ and K+ electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na+]e, [K+]e, and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na+]e to 80.1±15 and 87.9±7.9 mM and increase in [K+]e to 20.9±3.8 and 13.4±3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p<0.001 vs. baseline; ns between groups). Importantly, [Na+]e in CCI-SR49059-ISE was reduced 5–20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na+]e recovery. In contrast, [K+]e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na+]e recovery and reduced ICP. By augmenting the [Na+]e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI. PMID:24635833

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

    ERIC Educational Resources Information Center

    Nordlund, Marcia R.

    There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…

  19. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury.

    PubMed

    Larsen, Agnete; Kolind, Kristian; Pedersen, Dan Sonne; Doering, Peter; Pedersen, Mie Ostergaard; Danscher, Gorm; Penkowa, Milena; Stoltenberg, Meredin

    2008-10-01

    Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process is limited by their number and activity. We injected 20-45 mum gold particles into the neocortex of mice before generating a cryo-injury. Comparing gold-treated and untreated cryolesions, the release of gold reduced microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and an increased neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue. PMID:18542984

  20. Differential effects of rapamycin treatment on tonic and phasic GABAergic inhibition in dentate granule cells after focal brain injury in mice.

    PubMed

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

    2016-06-01

    The cascade of events leading to post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) remains unclear. Altered inhibition in the hippocampal formation and dentate gyrus is a hallmark of several neurological disorders, including TBI and PTE. Inhibitory synaptic signaling in the hippocampus is predominately driven by γ-aminobutyric acid (GABA) neurotransmission, and is prominently mediated by postsynaptic type A GABA receptors (GABAAR's). Subsets of these receptors involved in tonic inhibition of neuronal membranes serve a fundamental role in maintenance of inhibitory state, and GABAAR-mediated tonic inhibition is altered functionally in animal models of both TBI and epilepsy. In this study, we assessed the effect of mTOR inhibition on hippocampal hilar inhibitory interneuron loss and synaptic and tonic GABAergic inhibition of dentate gyrus granule cells (DGCs) after controlled cortical impact (CCI) to determine if mTOR activation after TBI modulates GABAAR function. Hilar inhibitory interneuron density was significantly reduced 72h after CCI injury in the dorsal two-thirds of the hemisphere ipsilateral to injury compared with the contralateral hemisphere and sham controls. Rapamycin treatment did not alter this reduction in cell density. Synaptic and tonic current measurements made in DGCs at both 1-2 and 8-13weeks post-injury indicated reduced synaptic inhibition and THIP-induced tonic current density in DGCs ipsilateral to CCI injury at both time points post-injury, with no change in resting tonic GABAAR-mediated currents. Rapamycin treatment did not alter the reduced synaptic inhibition observed in ipsilateral DGCs 1-2weeks post-CCI injury, but further reduced synaptic inhibition of ipsilateral DGCs at 8-13weeks post-injury. The reduction in THIP-induced tonic current after injury, however, was prevented by rapamycin treatment at both time points. Rapamycin treatment thus differentially modifies CCI-induced changes in synaptic and tonic GABAAR

  1. Traumatic Brain Injury

    MedlinePlus

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

  2. 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

  3. Pediatric Traumatic Brain Injury.

    PubMed

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

    2015-10-01

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

  4. Unilateral brain oedema related to focal status epilepticus

    PubMed Central

    Ali, Noura Abdulwahid; Palat Chirakkara, Sudhir Kumar; Reddy, Jagan Jinna; Sinha, Shobhit

    2013-01-01

    We present a female patient in her late 30s, with baseline vegetative state following prior traumatic brain injury, who presented with prolonged right hemispheric status epilepticus. The neuroimaging revealed a striking right-sided pancortical oedema with left (crossed) cerebellar diaschisis and dilation of right hemispheric arteries. EEG was concordant and showed nearly continuous right hemispheric seizure discharges with suppressed background. Infective and vascular aetiologies were ruled out. The patient showed clinical and electrographic improvement following treatment with antiepileptic drugs. Unilateral cerebral oedema is a rare presentation of focal status epilepticus, and should be considered as a differential diagnosis in the appropriate clinical scenario. PMID:24334523

  5. Radiation Injury to the Brain

    MedlinePlus

    ... Hits since January 2003 RADIATION INJURY TO THE BRAIN Radiation treatments affect all cells that are targeted. ... fractions, duration of therapy, and volume of [healthy brain] nervous tissue irradiated influence the likelihood of injury. ...

  6. TRAUMATIC BRAIN INJURY (TBI) DATABASE

    EPA Science Inventory

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

  7. Traumatic Brain Injury and Sleep Disorders

    PubMed Central

    Viola-Saltzman, Mari; Watson, Nathaniel F.

    2012-01-01

    SYNOPSIS Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. Two types of TBI negatively impact sleep: contact injuries causing focal brain damage and acceleration/deceleration injuries causing more generalized brain damage. Diagnosis of sleep disorders after TBI may involve polysomnography, multiple sleep latency testing and/or actigraphy. Treatment is disorder specific and may include the use of medications, continuous positive airway pressure (or similar device) and/or behavioral modifications. Unfortunately, treatment of sleep disorders associated with TBI often does not improve sleepiness or neuropsychological function. PMID:23099139

  8. Traumatic Brain Injury (TBI)

    MedlinePlus

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

  9. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  10. 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 ...

  11. Weight Drop Models in Traumatic Brain Injury.

    PubMed

    Kalish, Brian T; Whalen, Michael J

    2016-01-01

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

  12. Subacute to chronic mild traumatic brain injury.

    PubMed

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

    2012-12-01

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

  13. 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. PMID:24933327

  14. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  15. Traumatic brain injury

    PubMed Central

    Risdall, Jane E.; Menon, David K.

    2011-01-01

    There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilcian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad. PMID:21149359

  16. [Focal connatal acquired brain damage--sonographic study of the course of healing].

    PubMed

    Franek, A

    1985-06-01

    A case of a perinatal acquired focal brain lesion is reported, and the process of resorption and healing demonstrated by ultrasound. Within four weeks a cortical area of increased echogenicity was resorbed. After two months, the resulting porencephalic cyst had been transformed into glial tissue of very high echogenicity. The neurologic development of two children with such glial focus was good. These cases demonstrate that porencephalic cysts are not always the final state after resorption of a focal brain lesion. They are no reliable prognostic indicator of poor neurological outcome. Traumatic and complicated delivery, asphyxia and coagulopathy are conditions which have been found several times in connection with a focal brain lesion. In contrast to periventricular injury, prematurity does not seem to be a factor of higher risk. PMID:3895372

  17. 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…

  18. Brain Injury: A Manual For Educators.

    ERIC Educational Resources Information Center

    Connor, Karen; Dettmer, Judy; Dise-lewis, Jeanne E.; Murphy, Mary; Santistevan, Barbette; Seckinger, Barbara

    This manual provides Colorado educators with guidelines for serving students with brain injuries. Following an introductory chapter, chapter 2 provides basic information on the brain including definitions of brain injury and its severity, incidence of brain injury, and characteristics of students with brain injury. Chapter 3 considers…

  19. Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury

    PubMed Central

    ZHANG, YUQIN; ZHANG, SHENGNAN; LI, HUANG; HUANG, MEI; XU, WEI; CHU, KEDAN; CHEN, LIDIAN; CHEN, XIANWEN

    2015-01-01

    Gualou Guizhi decoction (GLGZD) is a well-established Traditional Chinese Medicinal formulation which has long been used to treat stroke in a clinical setting in China. The present study investigated the ameliorative effects of GLGZD on inflammation in focal cerebral ischemic-reperfusion injury. A rat model of middle cerebral artery occlusion (MCAO) was employed. Rats were administrated GLGZD (7.2 and 14.4 g/kg per day) or saline as control 2 h after reperfusion and daily over the following seven days. Neurological deficit score and screen test were evaluated at 1, 3, 5 and 7 days after MCAO. Brain infarct size and brain histological changes were observed via 2,3,5-triphenyltetrazolium chloride staining and regular hematoxylin & eosin staining. Furthermore, inflammation mediators and nuclear factor-κB (NF-κB) were investigated using ELISA and immunohistochemistry. GLGZD treatment significantly improved neurological function, ameliorated histological changes to the brain and decreased infarct size in focal cerebral ischemic-reperfusion injury. GLGZD was found to significantly reduce interleukin (IL)-1, tumor necrosis factor-α and NF-κB levels, while increasing levels of IL-10. In conclusion, the present study suggested that GLGZD has a neuroprotective effect on focal cerebral ischemic-reperfusion injury and this effect is likely to be associated with the anti-inflammatory function of GLGZD. PMID:25815894

  20. Controversies in preterm brain injury.

    PubMed

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

    2016-08-01

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

  1. Neuropathology of explosive blast traumatic brain injury.

    PubMed

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

    2012-10-01

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

  2. Sleep in traumatic brain injury.

    PubMed

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

    2015-07-01

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

  3. 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…

  4. Opiate withdrawal behavior after focal brain stimulation.

    PubMed

    Williams, D A; Thorn, B E

    1984-11-01

    Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal. PMID:6542676

  5. Effects of non-focal brain dysfunction on visual memory.

    PubMed

    King, M C

    1981-07-01

    Investigated the effects of non-focal brain damage on visual memory abilities with a sample of 114 Ss with confirmed brain-dysfunction and 71 controls who completed the Rey-Osterrieth Complex Figure Test. In contrast, to the findings of earlier studies of patients with focal brain-damage, right-hemisphere lesioned Ss could not be discriminated from left-hemisphere lesioned Ss on the basis of impaired visual recall. All three brain-damaged groups, however, performed more poorly than the control group in both the copy and recall phases of the task. Age and intelligence also were found to be related inversely to task performance. Implications of these data for clinical neuropsychological assessment are discussed. PMID:7263889

  6. NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

    PubMed Central

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

    2012-01-01

    Brain stimulation techniques have evolved in the last few decades with more novel methods capable of painless, noninvasive brain stimulation. While the number of clinical trials employing noninvasive brain stimulation continues to increase in a variety of medication-resistant neurological and psychiatric diseases, studies evaluating their diagnostic and therapeutic potential in traumatic brain injury (TBI) are largely lacking. This review introduces different techniques of noninvasive brain stimulation, which may find potential use in TBI. We cover transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), low-level laser therapy (LLLT) and transcranial doppler sonography (TCD) techniques. We provide a brief overview of studies to date, discuss possible mechanisms of action, and raise a number of considerations when thinking about translating these methods to clinical use. PMID:21691215

  7. Language and focal brain lesion in childhood.

    PubMed

    Avila, Lia; Riesgo, Rudimar; Pedroso, Fleming; Goldani, Marcelo; Danesi, Marlene; Ranzan, Josiane; Sleifer, Pricila

    2010-07-01

    Childhood ischemic strokes can lead to problems like hemiplegias, epilepsies, cognitive changes (memory and mathematical solutions), and language ability (reading, writing, and aphasias). The purpose of this study was to evaluate language and its aspects in children with unilateral ischemic stroke and associate them with the age during the event, injured side, and occurrence of epilepsy. Thirty-two children between 8 months and 19 years of age were evaluated. Among them, 21 (65%) had a change in their language skills, there being a connection between age and the time of injury (P < .05). The most impaired aspects were their phonology, semantics, and syntax. In this sample, there was a persistent change in the semantic aspect, which is an alert for the early detection of learning and future development problems. PMID:20110218

  8. Secondary Focal Segmental Glomerulosclerosis: From Podocyte Injury to Glomerulosclerosis

    PubMed Central

    Kim, Jae Seok; Han, Byoung Geun; Choi, Seung Ok; Cha, Seung-Kuy

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is a common cause of proteinuria and nephrotic syndrome leading to end stage renal disease (ESRD). There are two types of FSGS, primary (idiopathic) and secondary forms. Secondary FSGS shows less severe clinical features compared to those of the primary one. However, secondary FSGS has an important clinical significance because a variety of renal diseases progress to ESRD thorough the form of secondary FSGS. The defining feature of FSGS is proteinuria. The key event of FSGS is podocyte injury which is caused by multiple factors. Unanswered questions about how these factors act on podocytes to cause secondary FSGS are various and ill-defined. In this review, we provide brief overview and new insights into FSGS, podocyte injury, and their potential linkage suggesting clues to answer for treatment of the disease. PMID:27088082

  9. Traumatic Brain Injury

    MedlinePlus

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

  10. Bullet injuries of the brain

    PubMed Central

    Crockard, H Alan

    1974-01-01

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

  11. Traumatic Brain Injury: FDA Research and Actions

    MedlinePlus

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

  12. Neurological consequences of traumatic brain injuries in sports.

    PubMed

    Ling, Helen; Hardy, John; Zetterberg, Henrik

    2015-05-01

    Traumatic brain injury (TBI) is common in boxing and other contact sports. The long term irreversible and progressive aftermath of TBI in boxers depicted as punch drunk syndrome was described almost a century ago and is now widely referred as chronic traumatic encephalopathy (CTE). The short term sequelae of acute brain injury including subdural haematoma and catastrophic brain injury may lead to death, whereas mild TBI, or concussion, causes functional disturbance and axonal injury rather than gross structural brain damage. Following concussion, symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend to develop acutely but usually resolve within a week or two. Severe concussion can also lead to loss of consciousness. Despite the transient nature of the clinical symptoms, functional neuroimaging, electrophysiological, neuropsychological and neurochemical assessments indicate that the disturbance of concussion takes over a month to return to baseline and neuropathological evaluation shows that concussion-induced axonopathy may persist for years. The developing brains in children and adolescents are more susceptible to concussion than adult brain. The mechanism by which acute TBI may lead to the neurodegenerative process of CTE associated with tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) remains speculative. Focal tau-positive NFTs and neurites in close proximity to focal axonal injury and foci of microhaemorrhage and the predilection of CTE-tau pathology for perivascular and subcortical regions suggest that acute TBI-related axonal injury, loss of microvascular integrity, breach of the blood brain barrier, resulting inflammatory cascade and microglia and astrocyte activation are likely to be the basis of the mechanistic link of TBI and CTE. This article provides an overview of the acute and long-term neurological consequences of TBI in sports. Clinical, neuropathological and the possible pathophysiological

  13. Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

    PubMed Central

    Redell, John B.; Moore, Anthony N.; Grill, Raymond J.; Johnson, Daniel; Zhao, Jing; Liu, Yin

    2013-01-01

    Abstract Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated Gene Ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1α (CCL3), GRO-KC (CXCL1), interleukin (IL)-1α, IL-1β, and IL-6. Immunohistochemical localization of MIP-1α and IL-1β showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions

  14. Time Dysperception Perspective for Acquired Brain Injury

    PubMed Central

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

    2014-01-01

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

  15. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

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

    2016-01-01

    Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. PMID:26048614

  16. Diagnostic criteria and differential diagnosis of mild traumatic brain injury.

    PubMed

    De Kruijk, J R; Twijnstra, A; Leffers, P

    2001-02-01

    Brain injury is classified clinically as severe, moderate or mild brain injury characteristics, including admission Glasgow coma score, duration of unconsciousness and post-traumatic amnesia and any focal neurological findings. Most traumatic brain injuries are classified as mild traumatic brain injury (MTBI). Headache, nausea and dizziness are frequent symptoms after MTBI and may continue for weeks to months after the trauma. MTBI may also be complicated by intracranial injuries. Experimental animal models and post-mortem studies have shown axonal damage and dysfunction in MTBI. This damage is mostly localized in the frontal lobes. Serum S-100 and NSE have been reported to be markers for the seventy of brain damage. In the literature, indications for radiodiagnostic evaluation following MTBI have been the subject of debate. Radiographs of the skull are used to exclude skull fractures, but are not useful for an evaluation of brain injury. Computed tomography of the brain seems to be the best way to exclude the development of relevant intracranial lesions. MTBI has a good clinical outcome, although a substantial group of patients develop post-concussional complaints (PCC). There is little information on the effectiveness of various methods suggested for reducing the frequency of PCC. PMID:11260760

  17. Pathology of traumatic brain injury.

    PubMed

    Finnie, John W

    2014-12-01

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

  18. 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…

  19. 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…

  20. Autophagy in acute brain injury.

    PubMed

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

    2016-08-01

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

  1. Impact Acceleration Model of Diffuse Traumatic Brain Injury.

    PubMed

    Hellewell, Sarah C; Ziebell, Jenna M; Lifshitz, Jonathan; Morganti-Kossmann, M Cristina

    2016-01-01

    The impact acceleration (I/A) model of traumatic brain injury (TBI) was developed to reliably induce diffuse traumatic axonal injury in rats in the absence of skull fractures and parenchymal focal lesions. This model replicates a pathophysiology that is commonly observed in humans with diffuse axonal injury (DAI) caused by acceleration-deceleration forces. Such injuries are typical consequences of motor vehicle accidents and falls, which do not necessarily require a direct impact to the closed skull. There are several desirable characteristics of the I/A model, including the extensive axonal injury produced in the absence of a focal contusion, the suitability for secondary insult modeling, and the adaptability for mild/moderate injury through alteration of height and/or weight. Furthermore, the trauma device is inexpensive and readily manufactured in any laboratory, and the induction of injury is rapid (~45 min per animal from weighing to post-injury recovery) allowing multiple animal experiments per day. In this chapter, we describe in detail the methodology and materials required to produce the rat model of I/A in the laboratory. We also review current adaptations to the model to alter injury severity, discuss frequent complications and technical issues encountered using this model, and provide recommendations to ensure technically sound injury induction. PMID:27604723

  2. 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

  3. Neurostimulation for traumatic brain injury.

    PubMed

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

    2014-11-01

    Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI. PMID:25170668

  4. Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4

    PubMed Central

    Lu, Lin; Li, Hui-qin; Li, Ji-huang; Liu, Ai-ju

    2015-01-01

    Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4. PMID:26089944

  5. Brain somatic mutations in MTOR leading to focal cortical dysplasia.

    PubMed

    Lim, Jae Seok; Lee, Jeong Ho

    2016-02-01

    Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients. [BMB Reports 2016; 49(2): 71-72]. PMID:26779999

  6. SYSTEMATIC ANALYSIS OF REAL-WORLD DRIVING BEHAVIOR FOLLOWING FOCAL BRAIN LESIONS

    PubMed Central

    Thompson, Kelsey; Read, Katherine; Anderson, Steven; Rizzo, Matthew

    2012-01-01

    Summary Many patients with circumscribed brain injuries, such as those caused by stroke or focal trauma, return to driving after a period of acute recovery. These persons often have chronic residual cognitive deficits that may impact on driving safety, but little is known about their driving behavior in the real world. Extant studies tend to rely on driving simulators or controlled on-road drives. These methods of observation are not able to capture the complexities of the typical driving environment, and may not accurately represent a driver’s usual behavior on the road. The current study used a video event-activated data recorder (VEADR) system to observe drivers with focal brain lesions in their normal daily driving environment over a three-month period. In the context of primarily safe driving behavior, we were able to document a number of relatively infrequent and hitherto unobserved high risk behaviors and traffic violations. These findings demonstrate the feasibility and value of sampling real-world driving in neurologic patient populations such as those with focal brain lesions, and highlight the critical importance of evaluating unsafe driving behaviors which may occur with insufficient frequency to be captured by relatively brief simulator or controlled on-road evaluations. PMID:25309966

  7. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    PubMed Central

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases. PMID:27533766

  8. Epileptogenesis after traumatic brain injury in Plau-deficient mice.

    PubMed

    Bolkvadze, Tamuna; Rantala, Jukka; Puhakka, Noora; Andrade, Pedro; Pitkänen, Asla

    2015-10-01

    Several components of the urokinase-type plasminogen activator receptor (uPAR)-interactome, including uPAR and its ligand sushi-repeat protein 2, X-linked (SRPX2), are linked to susceptibility to epileptogenesis in animal models and/or humans. Recent evidence indicates that urokinase-type plasminogen activator (uPA), a uPAR ligand with focal proteinase activity in the extracellular matrix, contributes to recovery-enhancing brain plasticity after various epileptogenic insults such as traumatic brain injury (TBI) and status epilepticus. Here, we examined whether deficiency of the uPA-encoding gene Plau augments epileptogenesis after TBI. Traumatic brain injury was induced by controlled cortical impact in the somatosensory cortex of adult male wild-type and Plau-deficient mice. Development of epilepsy and seizure susceptibility were assessed with a 3-week continuous video-electroencephalography monitoring and a pentylenetetrazol test, respectively. Traumatic brain injury-induced cortical or hippocampal pathology did not differ between genotypes. The pentylenetetrazol test revealed increased seizure susceptibility after TBI (p<0.05) in injured mice. Epileptogenesis was not exacerbated, however, in Plau-deficient mice. Taken together, Plau deficiency did not worsen controlled cortical impact-induced brain pathology or epileptogenesis caused by TBI when assessed at chronic timepoints. These data expand previous observations on Plau deficiency in models of status epilepticus and suggest that inhibition of focal extracellular proteinase activity resulting from uPA-uPAR interactions does not modify epileptogenesis after TBI. PMID:26253597

  9. TRAUMATIC BRAIN INJURY SURVEILLANCE SYSTEM (TBISS)

    EPA Science Inventory

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

  10. Traumatic brain injury among Indiana state prisoners.

    PubMed

    Ray, Bradley; Sapp, Dona; Kincaid, Ashley

    2014-09-01

    Research on traumatic brain injury among inmates has focused on comparing the rate of traumatic brain injury among offenders to the general population, but also how best to screen for traumatic brain injury among this population. This study administered the short version of the Ohio State University Traumatic Brain Injury Identification Method to all male inmates admitted into Indiana state prisons were screened for a month (N = 831). Results indicate that 35.7% of the inmates reported experiencing a traumatic brain injury during their lifetime and that these inmates were more likely to have a psychiatric disorder and a prior period of incarceration than those without. Logistic regression analysis finds that a traumatic brain injury predicts the likelihood of prior incarceration net of age, race, education, and psychiatric disorder. This study suggests that brief instruments can be successfully implemented into prison screenings to help divert inmates into needed treatment. PMID:24588316

  11. How woodpecker avoids brain injury?

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

    It has long been recognized that woodpecker is an excellent anti-shock organism, as its head and brain can bear high deceleration up to 1500 g under fast pecking. To investigate the mechanism of brain protection of woodpecker, we built a finite element model of a whole woodpecker using computed topography scanning technique and geometry modeling. Numerical results show that the periodical changing Young's modulus around the skull affects the stress wave propagation in head and makes the stress lowest at the position of the brain. Modal analysis reveals the application of pre-tension force to the hyoid bone can increase the natural frequency of woodpecker's head. The large gap between the natural and working frequencies enable the woodpecker to effectively protect its brain from the resonance injury. Energy analyses indicate the majority of the impact energy (99.7%) is stored in the bulk of body and is utilized in the next pecking. There is only a small fraction of it enters into the head (0.3%). The whole body of the woodpecker gets involved in the energy conversion and forms an efficient anti-shock protection system for the brain.

  12. [Mild brain injuries in emergency medicine].

    PubMed

    Liimatainen, Suvi; Niskakangas, Tero; Ohman, Juha

    2011-01-01

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

  13. 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:…

  14. Brain plasticity and recovery from early cortical injury.

    PubMed

    Kolb, Bryan; Mychasiuk, Richelle; Williams, Preston; Gibb, Robbin

    2011-09-01

    Neocortical development represents more than a simple unfolding of a genetic blueprint: rather, it represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Most cortical regions are sensitive to a wide range of experiential factors during development and later in life, but the injured cortex appears to be unusually sensitive to perinatal experiences. This paper reviews the factors that influence how normal and injured brains (both focal and ischemic injuries) develop and adapt into adulthood. Such factors include prenatal experiences in utero as well as postnatal experiences throughout life. Examples include the effects of sensory and motor stimulation, psychoactive drugs (including illicit and prescription drugs), maternal and postnatal stress, neurotrophic factors, and pre- and postnatal diet. All these factors influence cerebral development and influence recovery from brain injury during development. PMID:21950386

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

    ERIC Educational Resources Information Center

    Bigler, Erin D.

    1996-01-01

    This review explores the cellular pathology associated with traumatic brain injury (TBI) and its relation to neurobehavioral outcomes, the relationship of brain imaging findings to underlying pathology, brain imaging techniques, various image analysis procedures and how they relate to neuropsychological testing, and the importance of brain imaging…

  16. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications

    PubMed Central

    Simard, J Marc; Kent, Thomas A; Chen, Mingkui; Tarasov, Kirill V; Gerzanich, Volodymyr

    2009-01-01

    Focal cerebral ischaemia and post-ischaemic reperfusion cause cerebral capillary dysfunction, resulting in oedema formation and haemorrhagic conversion. There are substantial gaps in understanding the pathophysiology, especially regarding early molecular participants. Here, we review physiological and molecular mechanisms involved. We reaffirm the central role of Starling's principle, which states that oedema formation is determined by the driving force and the capillary “permeability pore”. We emphasise that the movement of fluids is largely driven without new expenditure of energy by the ischaemic brain. We organise the progressive changes in osmotic and hydrostatic conductivity of abnormal capillaries into three phases: formation of ionic oedema, formation of vasogenic oedema, and catastrophic failure with haemorrhagic conversion. We suggest a new theory suggesting that ischaemia-induced capillary dysfunction can be attributed to de novo synthesis of a specific ensemble of proteins that determine osmotic and hydraulic conductivity in Starling's equation, and whose expression is driven by a distinct transcriptional program. PMID:17303532

  17. Behavioral Considerations Associated with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Mayfield, Joan; Homack, Susan

    2005-01-01

    Children who sustain traumatic brain injury (TBI) can experience significant cognitive deficits. These deficits may significantly impair their functioning in the classroom, resulting in the need for academic and behavioral modifications. Behavior and social problems can be the direct or indirect result of brain injury. Difficulties in paying…

  18. Traumatic Brain Injury. Fact Sheet Number 18.

    ERIC Educational Resources Information Center

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This fact sheet describes traumatic brain injury (TBI), an injury of the brain caused by the head being hit by something or being shaken violently. It discusses the incidence of TBI, and describes its symptoms as changes in thinking and reasoning, understanding words, remembering things, paying attention, solving problems, thinking abstractly,…

  19. Resource Guide on Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Monfore, Dorothea

    2005-01-01

    The purpose of this resource guide on traumatic brain injury (TBI) is to provide assistance to educators, families, and professionals who may be striving to increase their knowledge and understanding of brain injury. This guide will hopefully become an initial resource. It provides: a glossary of TBI Terms; contact information for and brief…

  20. 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…

  1. 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…

  2. 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.

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

    PubMed

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

    2011-01-01

    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. PMID:21876530

  4. 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

  5. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    PubMed

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation. PMID:26342279

  6. 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

  7. Defining sleep disturbance after brain injury.

    PubMed

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

    1998-01-01

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

  8. Clinimetric measurement in traumatic brain injuries

    PubMed Central

    Opara, N; Małecka, I; Szczygiel, M

    2014-01-01

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

  9. Mitochondrial specific therapeutic targets following brain injury.

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    1996-04-01

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

  11. Traumatic brain injury and forensic neuropsychology.

    PubMed

    Bigler, Erin D; Brooks, Michael

    2009-01-01

    As part of a special issue of The Journal of Head Trauma Rehabilitation, forensic neuropsychology is reviewed as it applies to traumatic brain injury (TBI) and other types of acquired brain injury in which clinical neuropsychologists and rehabilitation psychologists may be asked to render professional opinions about the neurobehavioral effects and outcome of a brain injury. The article introduces and overviews the topic focusing on the process of forensic neuropsychological consultation and practice as it applies to patients with TBI or other types of acquired brain injury. The emphasis is on the application of scientist-practitioner standards as they apply to legal questions about the status of a TBI patient and how best that may be achieved. This article introduces each topic area covered in this special edition. PMID:19333063

  12. Traumatic brain injury: pathophysiology for neurocritical care.

    PubMed

    Kinoshita, Kosaku

    2016-01-01

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

  13. PROGESTERONE EXERTS NEUROPROTECTIVE EFFECTS AFTER BRAIN INJURY

    PubMed Central

    Stein, Donald G.

    2009-01-01

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

  14. 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

  15. Microglia toxicity in preterm brain injury

    PubMed Central

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

    2014-01-01

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

  16. 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,…

  17. Traumatic Brain Injury: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

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

    2011-01-01

    This article is the eighth of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received limited national attention and support. However, since it is the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained attention of elected officials, military leaders, policymakers, and the public. The…

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

    MedlinePlus

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

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

    SciTech Connect

    Nagle, C.E.

    1986-07-01

    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.

  20. Purines: forgotten mediators in traumatic brain injury.

    PubMed

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

    2016-04-01

    Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. PMID:26809224

  1. Mapping the Connectome Following Traumatic Brain Injury.

    PubMed

    Hannawi, Yousef; Stevens, Robert D

    2016-05-01

    There is a paucity of accurate and reliable biomarkers to detect traumatic brain injury, grade its severity, and model post-traumatic brain injury (TBI) recovery. This gap could be addressed via advances in brain mapping which define injury signatures and enable tracking of post-injury trajectories at the individual level. Mapping of molecular and anatomical changes and of modifications in functional activation supports the conceptual paradigm of TBI as a disorder of large-scale neural connectivity. Imaging approaches with particular relevance are magnetic resonance techniques (diffusion weighted imaging, diffusion tensor imaging, susceptibility weighted imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, and positron emission tomographic methods including molecular neuroimaging). Inferences from mapping represent unique endophenotypes which have the potential to transform classification and treatment of patients with TBI. Limitations of these methods, as well as future research directions, are highlighted. PMID:27021773

  2. Neurobiological consequences of traumatic brain injury

    PubMed Central

    McAllister, Thomas W.

    2011-01-01

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

  3. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

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

  4. Structural Neuroimaging Findings in Mild Traumatic Brain Injury.

    PubMed

    Bigler, Erin D; Abildskov, Tracy J; Goodrich-Hunsaker, Naomi J; Black, Garrett; Christensen, Zachary P; Huff, Trevor; Wood, Dawn-Marie G; Hesselink, John R; Wilde, Elisabeth A; Max, Jeffrey E

    2016-09-01

    Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI. PMID:27482782

  5. Catecholamines and cognition after traumatic brain injury.

    PubMed

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

    2016-09-01

    Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

  6. Catecholamines and cognition after traumatic brain injury

    PubMed Central

    Jenkins, Peter O.; Mehta, Mitul A.

    2016-01-01

    Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

  7. Driving, brain injury and assistive technology.

    PubMed

    Lane, Amy K; Benoit, Dana

    2011-01-01

    Individuals with brain injury often present with cognitive, physical and emotional impairments which impact their ability to resume independence in activities of daily living. Of those activities, the resumption of driving privileges is cited as one of the greatest concerns by survivors of brain injury. The integration of driving fundamentals within the hierarchical model proposed by Keskinen represents the complexity of skills and behaviors necessary for driving. This paper provides a brief review of specific considerations concerning the driver with TBI and highlights current vehicle technology which has been developed by the automotive industry and by manufacturers of adaptive driving equipment that may facilitate the driving task. Adaptive equipment technology allows for compensation of a variety of operational deficits, whereas technological advances within the automotive industry provide drivers with improved safety and information systems. However, research has not yet supported the use of such intelligent transportation systems or advanced driving systems for drivers with brain injury. Although technologies are intended to improve the safety of drivers within the general population, the potential of negative consequences for drivers with brain injury must be considered. Ultimately, a comprehensive driving evaluation and training by a driving rehabilitation specialist is recommended for individuals with brain injury. An understanding of the potential impact of TBI on driving-related skills and knowledge of current adaptive equipment and technology is imperative to determine whether return-to-driving is a realistic and achievable goal for the individual with TBI. PMID:21558628

  8. Minocycline Attenuates Iron-Induced Brain Injury.

    PubMed

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

    2016-01-01

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

  9. Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

    PubMed Central

    Wolf, John A.; Koch, Paul F.

    2016-01-01

    Traumatic brain injury (TBI) is a heterogeneous disorder with many factors contributing to a spectrum of severity, leading to cognitive dysfunction that may last for many years after injury. Injury to axons in the white matter, which are preferentially vulnerable to biomechanical forces, is prevalent in many TBIs. Unlike focal injury to a discrete brain region, axonal injury is fundamentally an injury to the substrate by which networks of the brain communicate with one another. The brain is envisioned as a series of dynamic, interconnected networks that communicate via long axonal conduits termed the “connectome”. Ensembles of neurons communicate via these pathways and encode information within and between brain regions in ways that are timing dependent. Our central hypothesis is that traumatic injury to axons may disrupt the exquisite timing of neuronal communication within and between brain networks, and that this may underlie aspects of post-TBI cognitive dysfunction. With a better understanding of how highly interconnected networks of neurons communicate with one another in important cognitive regions such as the limbic system, and how disruption of this communication occurs during injury, we can identify new therapeutic targets to restore lost function. This requires the tools of systems neuroscience, including electrophysiological analysis of ensemble neuronal activity and circuitry changes in awake animals after TBI, as well as computational modeling of the effects of TBI on these networks. As more is revealed about how inter-regional neuronal interactions are disrupted, treatments directly targeting these dysfunctional pathways using neuromodulation can be developed. PMID:27242454

  10. Epidemiology of traumatic brain injuries: Indian scenario.

    PubMed

    Gururaj, G

    2002-01-01

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

  11. Molecular Mechanisms of Neonatal Brain Injury

    PubMed Central

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

    2012-01-01

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

  12. Traumatic Brain Injury and Dystonia

    MedlinePlus

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

  13. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

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

    2016-01-01

    Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children. PMID:27604726

  14. Managing traumatic brain injury secondary to explosions

    PubMed Central

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

    2010-01-01

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

  15. Severe Traumatic Brain Injury: A Case Report

    PubMed Central

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

    2016-01-01

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

  16. Paclitaxel improves outcome from traumatic brain injury

    PubMed Central

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

    2016-01-01

    Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2 mm3 for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury. PMID:26086366

  17. Acquired Focal Brain Lesions in Childhood: Effects on Development and Reorganization of Language

    ERIC Educational Resources Information Center

    Chilosi, A. M.; Cipriani, P.; Pecini, C.; Brizzolara, D.; Biagi, L.; Montanaro, D.; Tosetti, M.; Cioni, G.

    2008-01-01

    In the present paper, we address brain-behaviour relationships in children with acquired aphasia, by reviewing some recent studies on the effects of focal brain lesions on language development. Timing of the lesion, in terms of its occurrence, before or after the onset of speech and language acquisition, may be a major factor determining language…

  18. Neuropsychiatry of Pediatric Traumatic Brain Injury

    PubMed Central

    Max, Jeffrey E.

    2014-01-01

    Synopsis Pediatric traumatic brain injury (TBI) is a major public health problem. Psychiatric disorders with onset before the injury appear to be more common than population base rates. Novel (postinjury onset) psychiatric disorders (NPD) are also common and complicate child function after injury. Novel disorders include personality change due to TBI, secondary attention-deficit/hyperactivity disorder (SADHD), as well as other disruptive behavior disorders, and internalizing disorders. This article reviews preinjury psychiatric disorders as well as biopsychosocial risk factors and treatments for NPD. PMID:24529428

  19. Biomarkers in traumatic brain injury: a review.

    PubMed

    Toman, Emma; Harrisson, S; Belli, T

    2016-04-01

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

  20. Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke.

    PubMed

    Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D; Liu, Cuimei; Li, Yonggang; Stovall, Kyndra C; Cannon, Virginetta S; Tewolde, Teclemichael; Moreno, Carlos S; Ford, Byron D

    2013-02-01

    Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology. The CONserved transcription FACtor binding site (CONFAC) software package was used to identify over-represented TFBS in the upstream promoter regions of ischemia-induced genes compared to control datasets. CONFAC identified 12 TFBS that were statistically over-represented from our dataset of ischemia-induced genes, including three members of the Ets-1 family of transcription factors (TFs). Microarray results showed that mRNA for Ets-1 was increased following tMCAO but not pMCAO. Immunohistochemical analysis of Ets-1 protein in rat brains following MCAO showed that Ets-1 was highly expressed in neurons in the brain of sham control animals. Ets-1 protein expression was virtually abolished in injured neurons of the ischemic brain but was unchanged in peri-infarct brain areas. These data indicate that TFs, including Ets-1, may influence neuronal injury following ischemia. These findings could provide important insights into the mechanisms that lead to brain injury and could provide avenues for the development of novel therapies. PMID:23246490

  1. Interleukin-1 and acute brain injury

    PubMed Central

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

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

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

    MedlinePlus

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

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

    MedlinePlus

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

  4. 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

  5. Lateral (Parasagittal) Fluid Percussion Model of Traumatic Brain Injury.

    PubMed

    Van, Ken C; Lyeth, Bruce G

    2016-01-01

    Fluid percussion was first conceptualized in the 1940s and has evolved into one of the leading laboratory methods for studying experimental traumatic brain injury (TBI). Over the decades, fluid percussion has been used in numerous species and today is predominantly applied to the rat. The fluid percussion technique rapidly injects a small volume of fluid, such as isotonic saline, through a circular craniotomy onto the intact dura overlying the brain cortex. In brief, the methods involve surgical production of a circular craniotomy, attachment of a fluid-filled conduit between the dura overlying the cortex and the outlet port of the fluid percussion device. A fluid pulse is then generated by the free-fall of a pendulum striking a piston on the fluid-filled cylinder of the device. The fluid enters the cranium, producing a compression and displacement of the brain parenchyma resulting in a sharp, high magnitude elevation of intracranial pressure that is propagated diffusely through the brain. This results in an immediate and transient period of traumatic unconsciousness as well as a combination of focal and diffuse damage to the brain, which is evident upon histological and behavioral analysis. Numerous studies have demonstrated that the rat fluid percussion model reproduces a wide range of pathological features associated with human TBI. PMID:27604722

  6. Traumatic Brain Injury: Empirical Family Assessment Techniques.

    ERIC Educational Resources Information Center

    Bishop, Duane S.; Miller, Ivan W.

    1988-01-01

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

  7. Academic Placement after Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Donders, Jacques

    The acadmic placement of 87 children (ages 6 to 16 years) who had sustained brain injuries was determined within 1 year after initial psychological assessment. Forty-five children had returned full time to regular academic programs, 21 children received special education support for less than half of their classes, and 21 children were enrolled in…

  8. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

    Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in the United States for individuals below the age of 45. Current estimates from the Center for Disease Control (CDC) indicate that at least 1.4 million Americans sustain a TBI annually. TBI affects 475,000 children under age 14 each year in the United States alone.…

  9. Traumatic Brain Injury and Vocational Rehabilitation.

    ERIC Educational Resources Information Center

    Corthell, David W., Ed.

    Intended to serve as a resource guide on traumatic brain injury for rehabilitation practitioners, the book's 10 chapters are grouped into sections which provide an introduction and examine aspects of evaluation, treatment and placement planning, and unresolved issues. Chapters have the following titles and authors: "Scope of the Problem" (Marilyn…

  10. School Reentry Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2005-01-01

    Successful school reentry following traumatic brain injury (TBI) is critical to recovery. Physical, cognitive, behavioral, academic, and social problems can affect a child's school performance after a TBI. However, early intervention has the potential to improve child academic outcomes and promote effective coping with any persistent changes in…

  11. Reality Lessons in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2008-01-01

    This article goes beyond the typical guidance on how to address the educational needs of students with traumatic brain injury (TBI). A survivor of TBI and his parent advocate describe real-life encounters in the education arena and offer ways to respond to the problems depicted in the situations. Their candor enhances educator awareness of the…

  12. Traumatic Brain Injury: Perspectives from Educational Professionals

    ERIC Educational Resources Information Center

    Mohr, J. Darrell; Bullock, Lyndal M.

    2005-01-01

    This article reports the outcomes from 2 focus groups conducted to ascertain professional educators' perceptions regarding their (a) level of preparedness for working with students with traumatic brain injury (TBI), (b) ideas regarding ways to improve support to students and families, and (c) concerns about meeting the diverse needs of children…

  13. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

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

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  14. Psychiatric disorders and traumatic brain injury

    PubMed Central

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

    2008-01-01

    Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed. PMID:19043523

  15. Defense and Veterans Brain Injury Center

    MedlinePlus

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

  16. Mild Traumatic Brain Injury: Facilitating School Success.

    ERIC Educational Resources Information Center

    Hux, Karen; Hacksley, Carolyn

    1996-01-01

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

  17. Narrative Language in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2011-01-01

    Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS less than 8) in the phase of neurological stability and 14 neurologically intact participants…

  18. Working with Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

    The participation of a student with Traumatic Brain Injury (TBI) in general physical education can often be challenging and rewarding for the student and physical education teacher. This article addresses common characteristics of students with TBI and presents basic solutions to improve the education of students with TBI in the general physical…

  19. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  20. Discriminating military and civilian traumatic brain injuries.

    PubMed

    Reid, Matthew W; Velez, Carmen S

    2015-05-01

    Traumatic brain injury (TBI) occurs at higher rates among service members than civilians. Explosions from improvised explosive devices and mines are the leading cause of TBI in the military. As such, TBI is frequently accompanied by other injuries, which makes its diagnosis and treatment difficult. In addition to postconcussion symptoms, those who sustain a TBI commonly report chronic pain and posttraumatic stress symptoms. This combination of symptoms is so typical they have been referred to as the "polytrauma clinical triad" among injured service members. We explore whether these symptoms discriminate civilian occurrences of TBI from those of service members, as well as the possibility that repeated blast exposure contributes to the development of chronic traumatic encephalopathy (CTE). This article is part of a Special Issue entitled 'Traumatic Brain Injury'. PMID:25827093

  1. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

    Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244

  2. [Actovegin in the treatment of brain injuries of mild and moderate severity].

    PubMed

    Talypov, A E; Ioffe, Iu S; Miatchin, M Iu; Kuksova, N S

    2008-01-01

    Sixty-eight patients, including 32 patients of the main group who received aktovegin in addition to standard therapy and 36 patients of the control group with standard therapy only, have been studied. In both groups, various traumatic injuries (small focal injuries, subdural and epidural hematomas, traumatic subarachnoid hemorrhages, a combination of covering hematoma and small focal injuries) have been found. Aktovegin has been used in drops in dosage 400 mg per 200 ml physiological solution for 10 days. A comparative analysis of clinical data and results of instrumental studies (EEG, CT etc) in the main and control groups gives grounds to conclude that the use of aktovegin in the complex with standard therapy improves the course of brain injuries thus promoting the earlier compensation of disturbed functions and shortening the terms of treatment. The regress of asthenic symptoms as well as positive EEG changes are most pronounced. PMID:18833103

  3. 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

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2012-01-01

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

  6. Chronic cerebrovascular dysfunction after traumatic brain injury.

    PubMed

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

    2016-07-01

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

  7. Clinical Outcomes after Traumatic Brain Injury.

    PubMed

    Sandsmark, Danielle K

    2016-06-01

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

  8. Forensic Pathology of Traumatic Brain Injury.

    PubMed

    Finnie, J W

    2016-09-01

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

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

    PubMed

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

    2016-03-15

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

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

    PubMed Central

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

    2015-01-01

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

  11. Mast cells promote blood brain barrier breakdown and neutrophil infiltration in a mouse model of focal cerebral ischemia

    PubMed Central

    McKittrick, Craig M; Lawrence, Catherine E; Carswell, Hilary V O

    2015-01-01

    Blood brain barrier (BBB) breakdown and neuroinflammation are key events in ischemic stroke morbidity and mortality. The present study investigated the effects of mast cell deficiency and stabilization on BBB breakdown and neutrophil infiltration in mice after transient middle cerebral artery occlusion (tMCAo). Adult male C57BL6/J wild type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tMCAo and BBB breakdown, brain edema and neutrophil infiltration were examined after 4 hours of reperfusion. Blood brain barrier breakdown, brain edema, and neutrophil infiltration were significantly reduced in Wsh versus WT mice (P<0.05). These results were reproduced pharmacologically using mast cell stabilizer, cromoglycate. Wild-type mice administered cromoglycate intraventricularly exhibited reduced BBB breakdown, brain edema, and neutrophil infiltration versus vehicle (P<0.05). There was no effect of cromoglycate versus vehicle in Wsh mice, validating specificity of cromoglycate on brain mast cells. Proteomic analysis in Wsh versus WT indicated that effects may be via expression of endoglin, endothelin-1, and matrix metalloproteinase-9. Using an in vivo model of mast cell deficiency, this is the first study showing that mast cells promote BBB breakdown in focal ischemia in mice, and opens up future opportunities for using mice to identify specific mechanisms of mast cell-related BBB injury. PMID:25564235

  12. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats

    PubMed Central

    Kim, Gyeyeop; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV included rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10) as well as treadmill exercise after ischemia. At different time points (1, 7, 14, and 21 days) Garcia’s score, and the hippocampal expressions level of BDNF were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (Garcia’s score) were observed and hippocampal BDNF protein expression levels increased. [Conclusion] These results indicate that antecedent treadmill exercise, before permanent brain ischemia exerts a neuroprotective effect against ischemia brain injury by improving motor performance and increasing the level of BDNF expression. Furthermore, the antecedent treadmill exercise of appropriate intensity is critical for post-stroke rehabilitation. PMID:24259800

  13. Respiratory mechanics in brain injury: A review.

    PubMed

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

    2016-02-01

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

  14. Respiratory mechanics in brain injury: A review

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-15

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

  17. Diagnosing pseudobulbar affect in traumatic brain injury

    PubMed Central

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

    2014-01-01

    Pseudobulbar affect (PBA) is defined by episodes of involuntary crying and/or laughing as a result of brain injury or other neurological disease. Epidemiology studies show that 5.3%–48.2% of people with traumatic brain injury (TBI) may have symptoms consistent with (or suggestive of) PBA. Yet it is a difficult and often overlooked condition in individuals with TBI, and is easily confused with depression or other mood disorders. As a result, it may be undertreated and persist for longer than it should. This review presents the signs and symptoms of PBA in patients with existing TBI and outlines how to distinguish PBA from other similar conditions. It also compares and contrasts the different diagnostic criteria found in the literature and briefly mentions appropriate treatments. This review follows a composite case with respect to the clinical course and treatment for PBA and presents typical challenges posed to a provider when diagnosing PBA. PMID:25336956

  18. Mild Traumatic Brain Injury in Translation

    PubMed Central

    Robertson, Claudia S.

    2013-01-01

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

  19. Mild traumatic brain injury in a gymnast.

    PubMed

    Knight, Debra; Dewitt, Rachel; Moser, Sharon

    2016-07-01

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

  20. Psychotic disorder caused by traumatic brain injury.

    PubMed

    Fujii, Daryl E; Ahmed, Iqbal

    2014-03-01

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

  1. Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI.

    PubMed

    Pedersen, Mangor; Curwood, Evan K; Vaughan, David N; Omidvarnia, Amir H; Jackson, Graeme D

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy. PMID:26537783

  2. Inflammatory neuroprotection following traumatic brain injury.

    PubMed

    Russo, Matthew V; McGavern, Dorian B

    2016-08-19

    Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed. PMID:27540166

  3. Emerging Therapies in Traumatic Brain Injury

    PubMed Central

    Kochanek, Patrick M.; Jackson, Travis C.; Ferguson, Nikki Miller; Carlson, Shaun W.; Simon, Dennis W.; Brockman, Erik C.; Ji, Jing; Bayir, Hülya; Poloyac, Samuel M.; Wagner, Amy K.; Kline, Anthony E.; Empey, Philip E.; Clark, Robert S.B.; Jackson, Edwin K.; Dixon, C. Edward

    2015-01-01

    Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discuss TBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field. PMID:25714870

  4. 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.

  5. Cerebral Lactate Metabolism After Traumatic Brain Injury.

    PubMed

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

    2016-04-01

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

  6. Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.

    PubMed

    Clark, Darren L; Penner, Mark; Wowk, Shannon; Orellana-Jordan, Ian; Colbourne, Frederick

    2009-12-01

    Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. In comparison to normothermic controls, 12- and 48-h bouts of hypothermia significantly lessened functional impairment, such as skilled reaching ability, and lesion volume out to a 1-month survival. In the second experiment, brain-selective cooling was induced in awake rats via a water-cooled metal strip implanted underneath the temporalis muscle overlying the ischemic territory. Use of a 48-h cooling treatment significantly mitigated injury and behavioral impairment whereas a 12-h treatment did not. These findings show that while systemic and focal techniques are effective when initiated after the onset of pMCAO, they differ in efficacy depending upon the treatment duration. A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method. PMID:19833128

  7. 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

  8. Mechanisms of blast induced brain injuries, experimental studies in rats.

    PubMed

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. PMID:20493951

  9. 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

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

    PubMed

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

    2011-01-01

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

  11. Neurocomputational models of the remote effects of focal brain damage.

    PubMed

    Reggia, James A

    2004-11-01

    Sudden localized brain damage, such as occurs in stroke, produces neurological deficits directly attributable to the damaged site. In addition, other clinical deficits occur due to secondary "remote" effects that functionally impair the remaining intact brain regions (e.g., due to their sudden disconnection from the damaged area), a phenomenon known as diaschisis. The underlying mechanisms of these remote effects, particularly those involving interactions between the left and right cerebral hemispheres, have proven somewhat difficult to understand in the context of current theories of hemispheric specialization. This article describes some recent neurocomputational models done in the author's research group that try to explain diaschisis qualitatively. These studies show that both specialization and diaschisis can be accounted for with a single model of hemispheric interactions. Further, the results suggest that left-right subcortical influences may be much more important in influencing hemispheric specialization than is generally recognized. PMID:15564108

  12. Microglia in ischemic brain injury

    PubMed Central

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

    2010-01-01

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

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

    ERIC Educational Resources Information Center

    Carter, Susanne

    This guide is an introduction to head injury and to educational resources in the field. An introductory section describes traumatic brain injury (TBI) as a federally recognized disability category and provides its federal and Idaho definitions. The following section introduces the unique characteristics of students with brain injuries. A section…

  14. Traumatic brain injury: Does gender influence outcomes?

    PubMed Central

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

    2016-01-01

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

  15. Imaging assessment of traumatic brain injury.

    PubMed

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

    2016-01-01

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

  16. 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…

  17. 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

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

    PubMed Central

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

    2016-01-01

    It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

  19. Concussive brain injury from explosive blast

    PubMed Central

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

    2014-01-01

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

  20. [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. PMID:6659781

  1. miR-200c Contributes to Injury From Transient Focal Cerebral Ischemia by Targeting Reelin

    PubMed Central

    Stary, Creed M.; Xu, Lijun; Sun, Xiaoyun; Ouyang, Yi-Bing; White, Robin E.; Leong, Jason; Li, John; Xiong, Xiaoxing; Giffard, Rona G.

    2015-01-01

    Background and Purpose miR-200c increases rapidly in the brain following transient cerebral ischemia but its role in post-stroke brain injury is unclear. Reelin, a regulator of neuronal migration and synaptogenesis, is a predicted target of miR-200c. We hypothesized that miR-200c contributes to injury from transient cerebral ischemia by targeting reelin. Methods Brain infarct volume, neurological score and levels of miR-200c, reelin mRNA and reelin protein were assessed in mice subjected to 1 hr of middle cerebral artery occlusion (MCAO) with/without intracerebroventricular infusion of miR-200c antagomir, mimic or mismatch control. Direct targeting of reelin by miR-200c was assessed in vitro by dual luciferase assay and immunoblot. Results Pre-treatment with miR-200c antagomir decreased post-MCAO brain levels of miR-200c, resulting in a significant reduction in infarct volume and neurologic deficit. Changes in brain levels of miR-200c inversely correlated with reelin protein expression. Direct targeting of the Reln 3’UTR by miR-200c was verified with dual luciferase assay. Inhibition of miR-200c resulted in an increase in cell survival subsequent to in vitro oxidative injury. This effect was blocked by knockdown of reelin mRNA, while application of reelin protein afforded protection. Conclusions These findings suggest that the post-stroke increase in miR-200c contributes to brain cell death by inhibiting reelin expression, and that reducing post-stroke miR-200c is a potential target to mitigate stroke induced brain injury. PMID:25604249

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

    PubMed

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

    2013-01-01

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

  3. N-Acetylcysteine and Ceftriaxone as Preconditioning Strategies in Focal Brain Ischemia: Influence on Glutamate Transporters Expression.

    PubMed

    Krzyzanowska, Weronika; Pomierny, Bartosz; Budziszewska, Boguslawa; Filip, Malgorzata; Pera, Joanna

    2016-05-01

    Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia. PMID:26861954

  4. Anti-inflammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury

    PubMed Central

    Han, Jiang-quan; Liu, Cheng-ling; Wang, Zheng-yuan; Liu, Ling; Cheng, Ling; Fan, Ya-dan

    2016-01-01

    Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4 via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4. PMID:27212926

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

    PubMed

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

    2007-05-01

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

  6. Pathophysiology of battlefield associated traumatic brain injury.

    PubMed

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

    2013-02-01

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

  7. Electrophysiologic monitoring in acute brain injury.

    PubMed

    Claassen, Jan; Vespa, Paul

    2014-12-01

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

  8. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

  12. Aggression after Traumatic Brain Injury: Prevalence & Correlates

    PubMed Central

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

    2010-01-01

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

  13. Neuroprotective effects of total steroid saponins on cerebral ischemia injuries in animal model of focal ischemia/reperfusion

    PubMed Central

    Zhang, Xinxin; Chen, Lin; Dang, Xuan; Liu, Jianli; Ito, Yoichiro; Sun, Wenji

    2014-01-01

    Total steroid saponins (TSSN) isolated from Dioscorea zingiberensis C.H.Wright (DZW), a unique Traditional Chinese Medicine, is known for its potential usage in various types of diseases. However, there are a little evidences about its neuroprotective effect in transient focal ischemia-reperfusion (I/R) cerebral injury. Therefore, the current study was carried out to investigate the effect of TSSN on neuroprotection and its potential mechanisms in the rat I/R model by middle cerebral artery occlusion (MCAO) for 90 min. The rats were each treated with TSSN (30 mg/kg, 10 mg/kg, and 3 mg/kg) or Nimodipine (20 mg/kg) daily for 6 days before MCAO. Then, the neurological deficit score, cerebral infarct volume, and brain water content were measured at 24 h after reperfusion. Meanwhile, the histopathological changes and AQP-4 protein activities were examined in hippocampal CA1 and the cortex of ipsilateral ischemic cerebral hemisphere by hematoxylin & eosin staining and immunohistochemistry, respectively. The indices of oxidative stress in the serum were also obtained, and NF-κB and ERK 1/2 protein expressions in the injured brain were evaluated by western blotting. The results indicated that the pre-treatment with these drugs not only significantly reduced cerebral infarct volume, brain water content and improved neurological deficit score, but also restored neuronal morphology and decreased the AQP-4 positive cells in CA1 and the cortex. Moreover, it markedly restored the level of oxidant stress makers (CAT, SOD, MDA, NO and iNOS) to their normal range in serum. In addition, the increased NF-κB and ERK 1/2 protein expressions were alleviated as compared with the I/R group. These findings demonstrate that TSSN exhibits promising neuroprotection effects against the transient focal ischemia-reperfusion (I/R) cerebral injury in the rat experimental model, where the underlying mechanisms might be mediated through inhibition of anti-edema as well as anti-oxidative effects by

  14. Inosine improves functional recovery after experimental traumatic brain injury.

    PubMed

    Dachir, Shlomit; Shabashov, Dalia; Trembovler, Victoria; Alexandrovich, Alexander G; Benowitz, Larry I; Shohami, Esther

    2014-03-25

    Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100 mg/kg i.p. at 1, 24 and 48 h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score (NSS, p<0.04 vs. saline), an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance (object recognition, p<0.016 vs. saline) but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze). Inosine did not affect CST sprouting in the lumbar spinal cord but did restore levels of the growth-associated protein GAP-43 in the hippocampus, though not in the cerebral cortex. Our results suggest that inosine may improve functional outcome after TBI. PMID:24502983

  15. Crosstalk in the measurement of focal brain activation by near-infrared topography

    NASA Astrophysics Data System (ADS)

    Okui, N.; Okada, E.

    2005-08-01

    Crosstalk between oxy- and deoxy-haemoglobin observed in near-infrared topography is investigated. The light propagation in an adult head model is predicted by Monte Carlo simulation to obtain the change in intensity detected with source-detector pairs on the scalp caused by a focal absorption change in the brain. The topographic images of changes in oxy- and deoxy-haemoglobin are obtained from the changes in intensity detected with source-detector pairs on the scalp. The crosstalk depends on the relative position of the focal absorption change to source-detector pairs. The crosstalk is minimised when the focal absorption change is located below a measurement point that is the midpoint between a source and a detector. Appropriate selection of wavelength pair is effective to reduce the crosstalk in the topographic image.

  16. [Changes in epidural pulse pressure in brain edema following experimental focal ischemia].

    PubMed

    Mase, M

    1990-07-01

    It is well known that epidural pulse pressure (PP) increases with rising intracranial pressure (ICP). However, PP at the same ICP is not always identical in various intracranial pathologies. Many authors have investigated PP at increased states of ICP, but few studies related to brain edema have been done. This study was carried out in order to clarify the changes of PP in brain edema following focal ischemia. ICP and PP were measured in two groups of anesthetized dogs; 1) increased volume of CSF by cisternal saline injection (control, n = 5), 2) brain edema caused by focal ischemia (edema, n = 11). Ischemia was induced by electro-coagulation of the right anterior cerebral artery and by clipping the right middle cerebral artery and right internal carotid artery transorbitaly. The brain was recirculated for 6 hours after 2 hours of ischemia. The ischemic areas were identified by Evans blue, triphenyl tetrazolium chloride (TTC) or histological examination. Water content of the brain was measured by the wet-dry weight method. The canine focal ischemic model showed consistent ischemic damage in the caudate nucleus and produced brain edema successfully. PP increased linearly with rising ICP to 35 mmHg, and PP in the edema group was significantly smaller than that in the control group at the same ICP value. The slopes of the regression equation of ICP and PP were significantly different between the edema and control group (edema: 0.061 +/- 0.030, control: 0.107 +/- 0.015, mean +/- SD, p less than 0.01). These results suggest that PP is easily affected by ischemic brain edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2223260

  17. Radiation-induced brain injury: A review

    PubMed Central

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

    2012-01-01

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

  18. Leukocyte Recruitment and Ischemic Brain Injury

    PubMed Central

    Yilmaz, Gokhan

    2010-01-01

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

  19. A study of rotational brain injury.

    PubMed

    Misra, J C; Chakravarty, S

    1984-01-01

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

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

    PubMed

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

    2016-03-15

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

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

    PubMed

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

    2016-03-15

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

  2. Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury.

    PubMed

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

    2016-07-15

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

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

    PubMed

    Povlishock, John

    2016-01-01

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

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

    PubMed

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

    2015-04-01

    We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to

  5. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.

    PubMed

    Jacobson, Else; 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 3 cm 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

  6. 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

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

    PubMed Central

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

    2014-01-01

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

  8. Ischemic preconditioning protects against ischemic brain injury.

    PubMed

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

    2016-05-01

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

  9. Altered Calcium Signaling Following Traumatic Brain Injury

    PubMed Central

    Weber, John T.

    2012-01-01

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

  10. MRI of radiation injury to the brain

    SciTech Connect

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

    1986-07-01

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

  11. ANTIOXIDANT THERAPIES FOR TRAUMATIC BRAIN INJURY

    PubMed Central

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

    2010-01-01

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

  12. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

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

  13. Neuropsychological rehabilitation for traumatic brain injury patients.

    PubMed

    Chantsoulis, Marzena; Mirski, Andrzej; Rasmus, Anna; Kropotov, Juri D; Pachalska, Maria

    2015-01-01

    The aim of this review is to discuss the basic forms of neuropsychological rehabilitation for patients with traumatic brain injury (TBI). More broadly, we discussed cognitive rehabilitation therapy (CRT) which constitutes a fundamental component in therapeutic interaction at many centres worldwide. Equally presented is a comprehensive model of rehabilitation, the fundamental component of which is CRT. It should be noted that the principles of this approach first arose in Poland in the 1970s, in other words, several decades before their appearance in other programmemes. Taken into consideration are four factors conditioning the effectiveness of such a process: comprehensiveness, earlier interaction, universality and its individualized character. A comprehensive programmeme of rehabilitation covers: cognitive rehabilitation, individual and group rehabilitation with the application of a therapeutic environment, specialist vocational rehabilitation, as well as family psychotherapy. These training programmemes are conducted within the scope of the 'Academy of Life,' which provides support for the patients in their efforts and shows them the means by which they can overcome existing difficulties. Equally emphasized is the close cooperation of the whole team of specialists, as well as the active participation of the family as an essential condition for the effectiveness of rehabilitation and, in effect, a return of the patient to a relatively normal life. Also presented are newly developing neurothechnologies and the neuromarkers of brain injuries. This enables a correct diagnosis to be made and, as a result, the selection of appropriate methods for neuropsychological rehabilitation, including neurotherapy. PMID:26094541

  14. Ethics of neuroimaging after serious brain injury

    PubMed Central

    2014-01-01

    Background Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Methods/Design Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients’ interests, and we

  15. Brain injury, neuroinflammation and Alzheimer's disease

    PubMed Central

    Breunig, Joshua J.; Guillot-Sestier, Marie-Victoire; Town, Terrence

    2013-01-01

    With as many as 300,000 United States troops in Iraq and Afghanistan having suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered much recent attention. While the cause and severity of these injuries is variable, severe cases can lead to lifelong disability or even death. While aging is the greatest risk factor for Alzheimer's disease (AD), it is now becoming clear that a history of TBI predisposes the individual to AD later in life (Sivanandam and Thakur, 2012). In this review article, we begin by defining hallmark pathological features of AD and the various forms of TBI. Putative mechanisms underlying the risk relationship between these two neurological disorders are then critically considered. Such mechanisms include precipitation and ‘spreading’ of cerebral amyloid pathology and the role of neuroinflammation. The combined problems of TBI and AD represent significant burdens to public health. A thorough, mechanistic understanding of the precise relationship between TBI and AD is of utmost importance in order to illuminate new therapeutic targets. Mechanistic investigations and the development of preclinical therapeutics are reliant upon a clearer understanding of these human diseases and accurate modeling of pathological hallmarks in animal systems. PMID:23874297

  16. Traumatic brain injury brief outcome interview.

    PubMed

    Burton, Leslie A; Leahy, Derek M; Volpe, Bruce

    2003-01-01

    There is much evidence that deficits in physical and psychological functioning persist long after traumatic brain injury occurs. This paper presents a brief outcome interview (BOI) that can be administered in person or over the telephone, with evaluation of change in functioning in three areas: (a). occupational status, (b). mobility/activities of daily living (ADL), and (c). social relationships. Forty-four traumatic brain injury participants were evaluated at an average of 6.2 years postinjury with the present BOI as well as with the Glasgow Outcome Scale and Karnofsky Performance Scale (KPS). The BOI demonstrated strong concurrent validity with both scales, as well as strong test-retest reliability. IQ and memory scores obtained at an average of 4.1 months postinjury suggested that the injury was moderately severe. The average score on the GPS suggested "good recovery" and the average score on the KPS suggested "normal activity with effort, some signs or symptoms." These descriptions matched the BOI for the mobility/ADL dimension, for which all respondents reported some form of independent mobility, and 88.6% of the respondents reported no need for any kind of assistance in daily life functioning. However, significant long-term issues were seen for social and occupational functioning. Fifty-four percent said that they did not socialize as much as before their injury, and half of the participants reported not being involved in a romantic relationship in spite of an average age of 32 years. In terms of occupational status, 40.9% reported not working at all at any kind of job. Compared to before their injury, 47.7% said this was less time, 40.9% said that it was for a lower salary, and 54.5% said that their responsibilities were less. The stability of these social and occupational changes was indicated by high test-test reliabilities for the overall BOI score and the three subscale scores (r's ranged from.97 to 1.0). These stable long-term changes are consistent

  17. 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…

  18. Depression After Brain Injury: A Guide for Patients and Their Caregivers

    MedlinePlus

    ... a> Consumer Summary – Apr. 13, 2011 Depression After Brain Injury: A Guide for Patients and Their Caregivers ... productID=658 . Understanding Your Condition What is traumatic brain injury? Traumatic brain injury (TBI) is the medical ...

  19. Components of Traumatic Brain Injury Severity Indices

    PubMed Central

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

    2015-01-01

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

  20. Brain Injury among Children and Adolescents. Tip Cards.

    ERIC Educational Resources Information Center

    Lash, Marilyn; Savage, Ron; DePompei, Roberta; Blosser, Jean

    These eight brochures for parents provide practical information and suggestions regarding various aspects of managing a child with a brain injury. The brochures are: (1) "Back to School after a Mild Brain Injury or Concussion," which covers helping the student in the classroom and changes that occur in school and knowing when extra help is needed…

  1. Community-Based Employment Following Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Thomas, Dale F., Ed.; And Others

    This collection of papers on vocational rehabilitation of persons impaired as a result of traumatic brain injury is designed to provide a resource for individuals concerned with community-based employment. The 11 papers include: "Training Persons with Traumatic Brain Injury for Complex Computer Jobs: The Domain-Specific Learning Approach"…

  2. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  3. Students with Acquired Brain Injury. The School's Response.

    ERIC Educational Resources Information Center

    Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.

    Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…

  4. 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,…

  5. Traumatic Brain Injury - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Traumatic Brain Injury URL of this page: https://www.nlm. ... W XYZ List of All Topics All Traumatic Brain Injury - Multiple Languages To use the sharing features on this page, ...

  6. Rehabilitation outcome after traumatic brain injury.

    PubMed

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

    2007-02-01

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

  7. 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.,…

  8. Training to Optimize Learning after Traumatic Brain Injury

    PubMed Central

    Skidmore, Elizabeth R.

    2015-01-01

    One of the major foci of rehabilitation after traumatic brain injury is the design and implementation of interventions to train individuals to learn new knowledge and skills or new ways to access and execute previously acquired knowledge and skills. To optimize these interventions, rehabilitation professionals require a clear understanding of how traumatic brain injury impacts learning, and how specific approaches may enhance learning after traumatic brain injury. This brief conceptual review provides an overview of learning, the impact of traumatic brain injury on explicit and implicit learning, and the current state of the science examining selected training approaches designed to advance learning after traumatic brain injury. Potential directions for future scientific inquiry are discussed throughout the review. PMID:26217546

  9. Comparison of cerebral blood flow pattern by transcranial Doppler in patients with diffuse and focal causes of brain death

    PubMed Central

    Vakilian, Alireza; Iranmanesh, Farhad

    2012-01-01

    Background: This study aims to assess the cerebral vessels flow in brain death patients with different causes, including focal and diffuse lesions and comparison of flows according to the underlying causes. Materials and Methods: Two groups of 15 brain-dead patients one with focal and the other with diffuse brain lesions were compared according to their cerebral blood flow pattern 48 h passed brain death certification. Results: Bilateral absence of flow in middle cerebral artery (MCA) was found in 54.5% of brain-dead patients with diffuse lesion and 50.33% of those with focal lesions. Systolic spike pattern in MCA flow was found in 46.2% of patients with focal lesion and 16.65% of patients with diffuse lesion. Diastole–systole separation pattern in MCA was seen in 16.65% of patients with the diffuse lesions. This pattern in MCA was not seen in patients with the focal lesion group. In carotid arteries, we did not find the absence of flow in any cases. Thirty percent of all patients in both groups had a normal flow pattern (36.6% of patients with focal lesions and 23.3% of patients with diffuse lesion). Patients with focal lesion had 33.3% systolic spike pattern flow and had 23.35% diastole–systole separation flow pattern. In intra-cranial vessels, systolic spike pattern was more common among patients with focal lesions than patients with diffuse lesion, however, this difference was not statistically significant (46.2% of patients with focal lesion and 16.65% of patients with diffuse lesion) (P value = 0.244-0.09). Diastole–systole separation flow was more common in patients with diffuse lesions than those with the focal lesions although this could not reach the significant level as the previous pattern (20% of patients with diffuse lesion versus no case in patients with focal lesion) (P value = 0.181). Conclusion: Absence of flow was the most common brain flow pattern in the focal and diffuse group lesions. There was no difference in flow pattern between the

  10. Evaluation of Autophagy Using Mouse Models of Brain Injury

    PubMed Central

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

    2009-01-01

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

  11. Brain SPECT with short focal-length cone-beam collimation

    SciTech Connect

    Park, Mi-Ae; Moore, Stephen C.; Kijewski, Marie Foley

    2005-07-15

    Single-photon emission-computed tomography (SPECT) imaging of deep brain structures is compromised by loss of photons due to attenuation. We have previously shown that a centrally peaked collimator sensitivity function can compensate for this phenomenon, increasing sensitivity over most of the brain. For dual-head instruments, parallel-hole collimators cannot provide variable sensitivity without simultaneously degrading spatial resolution near the center of the brain; this suggests the use of converging collimators. We have designed collimator pairs for dual-head SPECT systems to increase sensitivity, particularly in the center of the brain, and compared the new collimation approach to existing approaches on the basis of performance in estimating activity concentration of small structures at various locations in the brain. The collimator pairs we evaluated included a cone-beam collimator, for increased sensitivity, and a fan-beam collimator, for data sufficiency. We calculated projections of an ellipsoidal uniform background, with 0.9-cm-radius spherical lesions at several locations in the background. From these, we determined ideal signal-to-noise ratios (SNR{sub CRB}) for estimation of activity concentration within the spheres, based on the Cramer-Rao lower bound on variance. We also reconstructed, by an ordered-subset expectation-maximization (OS-EM) procedure, images of this phantom, as well as of the Zubal brain phantom, to allow visual assessment and to ensure that they were free of artifacts. The best of the collimator pairs evaluated comprised a cone-beam collimator with 20 cm focal length, for which the focal point is inside the brain, and a fan-beam collimator with 40 cm focal length. This pair yielded increased SNR{sub CRB}, compared to the parallel-parallel pair, throughout the imaging volume. The factor by which SNR{sub CRB} increased ranged from 1.1 at the most axially extreme location to 3.5 at the center. The gains in SNR{sub CRB} were relatively

  12. The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

    PubMed Central

    Sun, Dong

    2016-01-01

    Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent development in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury. PMID:26981070

  13. Brain Network Organization in Focal Epilepsy: A Systematic Review and Meta-Analysis

    PubMed Central

    Jansen, Floor E.; Stam, Cornelis J.; Braun, Kees P. J.; Otte, Willem M.

    2014-01-01

    Normal brain functioning is presumed to depend upon interacting regions within large-scale neuronal networks. Increasing evidence exists that interictal network alterations in focal epilepsy are associated with cognitive and behavioral deficits. Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes. We therefore systematically reviewed the existing literature and conducted a meta-analysis to characterize the changes in whole-brain interictal focal epilepsy networks at sufficient power levels. We focused on the two most commonly used metrics in whole-brain networks: average path length and average clustering coefficient. Twelve studies were included that reported whole-brain network average path length and average clustering coefficient characteristics in patients and controls. The overall group difference, quantified as the standardized mean average path length difference between epilepsy and control groups, corresponded to a significantly increased average path length of 0.29 (95% confidence interval (CI): 0.12 to 0.45, p = 0.0007) in the epilepsy group. This suggests a less integrated interictal whole-brain network. Similarly, a significantly increased standardized mean average clustering coefficient of 0.35 (CI: 0.05 to 0.65, p = 0.02) was found in the epilepsy group in comparison with controls, pointing towards a more segregated interictal network. Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics. In addition, we found individual network studies to be prone to low power due to the relatively small group differences in average path length and average clustering coefficient in combination with small sample sizes. The pooled network characteristics support the hypothesis that focal epilepsy has widespread detrimental effects, that is, reduced integration and increased

  14. Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

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

    2016-03-15

    Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C-terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT. PMID:26671550

  15. Traumatic Brain Injury Models in Animals.

    PubMed

    Rostami, Elham

    2016-01-01

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

  16. Hyperbaric oxygen therapy for traumatic brain injury

    PubMed Central

    2011-01-01

    Traumatic brain injury (TBI) is a major public health issue. The complexity of TBI has precluded the use of effective therapies. Hyperbaric oxygen therapy (HBOT) has been shown to be neuroprotective in multiple neurological disorders, but its efficacy in the management of TBI remains controversial. This review focuses on HBOT applications within the context of experimental and clinical TBI. We also discuss its potential neuroprotective mechanisms. Early or delayed multiple sessions of low atmospheric pressure HBOT can reduce intracranial pressure, improve mortality, as well as promote neurobehavioral recovery. The complimentary, synergistic actions of HBOT include improved tissue oxygenation and cellular metabolism, anti-apoptotic, and anti-inflammatory mechanisms. Thus HBOT may serve as a promising neuroprotective strategy that when combined with other therapeutic targets for TBI patients which could improve long-term outcomes. PMID:22146562

  17. 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

  18. Iatrogenic traumatic brain injury during tooth extraction.

    PubMed

    Troxel, Mark

    2015-01-01

    An 8 yr old spayed female Yorkshire terrier was referred for evaluation of progressive neurological signs after a routine dental prophylaxis with tooth extractions. The patient was circling to the left and blind in the right eye with right hemiparesis. Neurolocalization was to the left forebrain. MRI revealed a linear tract extending from the caudal oropharynx, through the left retrobulbar space and frontal lobe, into the left parietal lobe. A small skull fracture was identified in the frontal bone through which the linear tract passed. Those findings were consistent with iatrogenic trauma from slippage of a dental elevator during extraction of tooth 210. The dog was treated empirically with clindamycin. The patient regained most of its normal neurological function within the first 4 mo after the initial injury. Although still not normal, the dog has a good quality of life. Traumatic brain injury is a rarely reported complication of extraction. Care must be taken while performing dental cleaning and tooth extraction, especially of the maxillary premolar and molar teeth to avoid iatrogenic damage to surrounding structures. PMID:25695556

  19. Diabetes Insipidus after Traumatic Brain Injury

    PubMed Central

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

    2015-01-01

    Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685

  20. Sexual changes associated with traumatic brain injury.

    PubMed

    Ponsford, Jennie

    2003-01-01

    Findings from numerous outcome studies have suggested that people with traumatic brain injuries (TBI) experience relationship difficulties and changes in sexuality. However, there have been few investigations of these problems. This paper reports the results of a study of sexuality following TBI, which aimed to identify changes in sexual behaviour, affect, self-esteem, and relationship quality, and their inter-relationships. Two hundred and eight participants with moderate-to-severe TBI (69% males) completed a questionnaire 1-5 years post-injury. Their responses were compared with those of 150 controls, matched for age, gender, and education. Of TBI participants 36-54% reported: (1) A decrease in the importance of sexuality, opportunities, and frequency of engaging in sexual activities; (2) reduced sex drive; (3) a decline in their ability to give their partner sexual satisfaction and to engage in sexual intercourse; and (4) decreased enjoyment of sexual activity and ability to stay aroused and to climax. The frequencies of such negative changes were significantly higher than those reported by controls and far outweighed the frequency of increases on these dimensions. A significant proportion of TBI participants also reported decreased self-confidence, sex appeal, higher levels of depression, and decreased communication levels and relationship quality with their sexual partner. Factors associated with sexual problems in the TBI group are explored and implications of all findings discussed. PMID:21854338

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

    PubMed

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

    2014-01-01

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

  2. 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…

  3. Sports-related brain injuries: connecting pathology to diagnosis.

    PubMed

    Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

    2016-04-01

    Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery. PMID:27032917

  4. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury.

    PubMed

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

    2016-05-23

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article. PMID:26772317

  5. Erythropoietin as a Neuroprotectant for Neonatal Brain Injury: Animal Models

    PubMed Central

    Traudt, Christopher M.; Juul, Sandra E.

    2016-01-01

    Prematurity and perinatal hypoxia-ischemia are common problems that result in significant neurodevelopmental morbidity and high mortality worldwide. The Vannucci model of unilateral brain injury was developed to model perinatal brain injury due to hypoxia-ischemia. Because the rodent brain is altricial, i.e., it develops postnatally, investigators can model either preterm or term brain injury by varying the age at which injury is induced. This model has allowed investigators to better understand developmental changes that occur in susceptibility of the brain to injury, evolution of brain injury over time, and response to potential neuroprotective treatments. The Vannucci model combines unilateral common carotid artery ligation with a hypoxic insult. This produces injury of the cerebral cortex, basal ganglia, hippocampus, and periventricular white matter ipsilateral to the ligated artery. Varying degrees of injury can be obtained by varying the depth and duration of the hypoxic insult. This chapter details one approach to the Vannucci model and also reviews the neuroprotective effects of erythropoietin (Epo), a neuroprotective treatment that has been extensively investigated using this model and others. PMID:23456865

  6. Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

    PubMed Central

    Ma, H.; Sinha, B.; Pandya, R.S.; Lin, N.; Popp, A.J.; Li, J.; Yao, J.; Wang, X.

    2014-01-01

    Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury. PMID:22834830

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

    PubMed Central

    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.

    2012-01-01

    OBJECTIVE 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). MATERIALS AND METHODS 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 SWs at 120 or 60 SWs/min) using an unmodified Dornier HM3 lithotriptor. RESULTS Treatment with the SLX produced a highly focused lesion running from cortex to medulla and often spanning the full thickness of the kidney. Unlike the diffuse interstitial haemorrhage observed with the HM3, the SLX lesion bore a blood-filled core of near-complete tissue disruption devoid of histologically recognizable kidney structure. Despite the intensity of tissue destruction at the core of the lesion, measures of lesion size based on macroscopic determination of haemorrhage in the parenchyma were not significantly different from kidneys treated using the HM3 (2000 SWs, 120 SWs/min: SLX, 1.86 ± 0.52% FRV; HM3, 3.93 ± 1.29% FRV). Doubling the SW dose of the SLX from 2000 to 4000 SWs did not significantly increase lesion size. In addition, slowing the firing rate of the SLX to 60 SWs/min did not reduce the size of the lesion (2.16 ± 0.96% FRV) compared with treatment at 120 SWs/min, as was the case with the HM3 (0.42 ± 0.23% FRV vs 3

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

    PubMed

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

    2012-01-01

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

  9. Motor Vehicle Crash Brain Injury in Infants and Toddlers: A Suitable Model for Inflicted Head Injury?

    ERIC Educational Resources Information Center

    Shah, Mahim; Vavilala, Monica S.; Feldman, Kenneth W.; Hallam, Daniel K.

    2005-01-01

    Objective: Children involved in motor vehicle crash (MVC) events might experience angular accelerations similar to those experienced by children with inflicted traumatic brain injury (iTBI). This is a pilot study to determine whether the progression of signs and symptoms and radiographic findings of MVC brain injury (mvcTBI) in children of the age…

  10. 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.

  11. Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

    PubMed Central

    Bernabeu, Montse; Demirtas-Tatlidede, Asli; Opisso, Eloy; Lopez, Raquel; Tormos, Jose Mª

    2009-01-01

    Abstract This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (SP) duration. The patient group overall revealed a higher MT, smaller MEP areas, and narrower recruitment curves compared to normal controls (p < 0.05). The alterations in excitability were more pronounced with an increase in DAI severity (p < 0.005) and the presence of motor impairment (p < 0.05), while co-existence of focal lesions did not affect the degree of MEP changes. MEP variability was significantly lower in the group with motor impairment only (p < 0.05). The intracortical inhibition, as revealed by SP duration, did not exhibit any significant differences in any of the patient groups. In conclusion, our findings expand the concept that impairment of the excitatory and inhibitory phenomena in the motor cortex does not proceed in parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore, these data suggest that alterations in the corticospinal excitatory mechanisms are determined predominantly by the severity of DAI, and show a significant relationship with clinical motor dysfunction following severe trauma diffusely affecting the motor cortical connections. In severe TBI, motor and functional recovery might be linked to restitution of normal corticospinal mechanisms, indexed by normalization of the cortical excitability parameters. PMID:19604100

  12. Driving after traumatic brain injury: evaluation and rehabilitation interventions

    PubMed Central

    Schultheis, Maria T.; Whipple, Elizabeth

    2014-01-01

    The ability to return to driving is a common goal for individuals who have sustained a traumatic brain injury. However, specific and empirically validated guidelines for clinicians who make the return-to-drive decision are sparse. In this article, we attempt to integrate previous findings on driving after brain injury and detail the cognitive, motor, and sensory factors necessary for safe driving that may be affected by brain injury. Various forms of evaluation (both in clinic and behind-the-wheel) are discussed, as well as driver retraining and modifications that may be necessary. PMID:25436178

  13. [Graphical recording of the state of the basal cerebral vessels and focal changes in the brain].

    PubMed

    Shuvaeva, L N

    1976-01-01

    A method of graphic registration of the length and diameter of vessels of basis cerebri is suggested. The registration is carried out on special cards--punch cards with due account of the structure of the circle of Willis, with subsequent collation of these indices with focal changes in the brain. The method is graphically clear and may be used in research work, as well as in the practice of a pathoanatomist in documentation of an autopsy report and for demonstrations in clinico-anatomical conferences. PMID:985143

  14. Non-Invasive Brain Stimulation for Treatment of Focal Hand Dystonia: Update and Future Direction

    PubMed Central

    Cho, Hyun Joo; Hallett, Mark

    2016-01-01

    Focal hand dystonia (FHD) is characterized by excessive and unwanted muscle activation in both the hand and arm resulting in impaired performance in particular tasks. Understanding the pathophysiology of FHD has progressed significantly for several decades and this has led to consideration of other potential therapies such as non-invasive brain stimulation (NIBS). A number of studies have been conducted to develop new therapy for FHD using transcranial magnetic stimulation and transcranial direct current stimulation. In this paper, we review previous studies and describe the potential therapeutic use of NIBS for FHD. We also discuss the future direction of NIBS to treat FHD. PMID:27240806

  15. Identification and Functional Analysis of MicroRNAs in Mice following Focal Cerebral Ischemia Injury

    PubMed Central

    Liu, Cuiying; Zhao, Lei; Han, Song; Li, Junfa; Li, Dongguo

    2015-01-01

    Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs) are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims of this study were to quantify the altered expression levels of miRNAs in the infarct region 6 h after middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in mice using a large-scale miRNAs microarray. Firstly, MCAO-induced cerebral ischemic injuries were investigated by observing the changes of neurological deficits, infarct volume and edema ratio. One hundred and eighteen differentially expressed miRNAs were identified in the infarct region of mice following the MCAOs compared with sham group (p < 0.05 was considered as significant). Among these 118 significantly expressed microRNAs, we found that 12 miRNAs were up-regulated with fold changes lager than two, and 18 miRNAs were down-regulated with fold changes less than 0.5 in the infarct region of mice following the 6 h MCAOs, compared with the sham group. Then, these 30 miRNAs with expression in fold change larger than two or less than 0.5 was predicted, and the functions of the target genes of 30 miRNAs were analyzed using a bioinformatics method. Finally, the miRNA-gene network was established and the functional miRNA-mRNA pairs were identified, which provided insight into the roles of the specific miRNAs that regulated specified genes in the ischemic injuries. The miRNAs identified in this study may represent effective therapeutic targets for stroke, and further study of the role of these targets may increase our understanding of the mechanisms underlying ischemic injuries. PMID:26473853

  16. Traumatic brain injury, axonal injury and shaking in New Zealand sea lion pups.

    PubMed

    Roe, W D; Mayhew, I G; Jolly, R D; Marshall, J; Chilvers, B L

    2014-04-01

    Trauma is a common cause of death in neonatal New Zealand sea lion pups, and subadult male sea lions have been observed picking up and violently shaking some pups. In humans, axonal injury is a common result of traumatic brain injury, and can be due to direct trauma to axons or to ischaemic damage secondary to trauma. 'Shaken baby syndrome', which has been described in human infants, is characterised by retinal and intracranial subdural haemorrhages, and has been associated with axonal injury to the brain, spinal cord and optic nerve. This study identifies mechanisms of traumatic brain injury in New Zealand sea lion pups, including impact injuries and shaking-type injuries, and identifies gross lesions of head trauma in 22/36 sea lion pups found dead at a breeding site in the Auckland Islands. Despite the high frequency of such gross lesions, only three of the pups had died of traumatic brain injury. Observational studies confirmed that shaking of pups occurred, but none were shown to die as a direct result of these shaking events. Axonal injury was evaluated in all 36 pup brains using β-amyloid precursor protein immunohistochemistry. Immunoreactive axons were present in the brains of all pups examined including seven with vascular axonal injury and two with diffuse axonal injury, but the severity and pattern of injury was not reliably associated with death due to traumatic brain injury. No dead pups had the typical combination of gross lesions and immunohistochemical findings that would conform to descriptions of 'shaken baby syndrome'. Axonal injury was present in the optic nerves of most pups, irrespective of cause of death, but was associated with ischaemia rather than trauma. PMID:24565687

  17. Brain injury causes loss of cardiovascular response to hemorrhagic shock.

    PubMed

    Fulton, R L; Flynn, W J; Mancino, M; Bowles, D; Cryer, H M

    1993-01-01

    The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective. PMID:8512886

  18. Brain injury tolerance limit based on computation of axonal strain.

    PubMed

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy

    2016-07-01

    Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI. PMID:27038501

  19. The King's Outcome Scale for Childhood Head Injury and Injury Severity and Outcome Measures in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Calvert, Sophie; Miller, Helen E.; Curran, Andrew; Hameed, Biju; McCarter, Renee; Edwards, Richard J.; Hunt, Linda; Sharples, Peta Mary

    2008-01-01

    The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The…

  20. Structural and functional connectivity in traumatic brain injury

    PubMed Central

    Xiao, Hui; Yang, Yang; Xi, Ji-hui; Chen, Zi-qian

    2015-01-01

    Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID:26889200

  1. Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study

    PubMed Central

    Carpenter, Keri L.H.; Helmy, Adel; Pickard, John D.; Menon, David K.; Hutchinson, Peter J.A.

    2015-01-01

    Abstract Matrix metalloproteinases (MMPs) are extracellular enzymes that have been implicated in the pathophysiology of blood–brain barrier (BBB) breakdown, contusion expansion, and vasogenic edema after traumatic brain injury (TBI). Specifically, in focal injury models, increased MMP-9 expression has been observed in pericontusional brain, and MMP-9 inhibitors reduce brain swelling and final lesion volume. The aim of this study was to examine whether there is a similarly localized increase of MMP concentrations in patients with contusional TBI. Paired microdialysis catheters were inserted into 12 patients with contusional TBI (with or without associated mass lesion) targeting pericontusional and radiologically normal brain defined on admission computed tomography scan. Microdialysate was pooled every 8 h and analyzed for MMP-1, -2, -7, -9, and -10 using a multiplex immunoassay. Concentrations of MMP-1, -2, and -10 were similar at both monitoring sites and did not show discernible temporal trends. Overall, there was a gradual increase in MMP-7 concentrations in both normal and injured brain over the monitoring period, although this was not consistent in every patient. MMP-9 concentrations were elevated in pericontusional, compared to normal, brain, with the maximal difference at the earliest monitoring times (i.e., <24 h postinjury). Repeated-measures analysis of variance showed that MMP-9 concentrations were significantly higher in pericontusional brain (p=0.03) and within the first 72 h of injury, compared with later in the monitoring period (p=0.04). No significant differences were found for the other MMPs assayed. MMP-9 concentrations are increased in pericontusional brain early post-TBI and may represent a potential therapeutic target to reduce hemorrhagic progression and vasogenic edema. PMID:25858502

  2. Predicting outcome after traumatic brain injury.

    PubMed

    Maas, Andrew I R; Lingsma, Hester F; Roozenbeek, Bob

    2015-01-01

    Developing insight into which factors determine prognosis after traumatic brain injury (TBI) is useful for clinical practice, research, and policy making. Several steps can be identified in prediction research: univariate analysis, multivariable analysis, and the development of prediction models. For each step, several methodological issues should be considered, such as selection/coding of predictors and dealing with missing data. "Traditional" predictors include demographic factors (age), type of injury, clinical severity, second insults, and the presence of structural abnormalities on neuroimaging. In combination, these predictors can explain approximately 35% of the variance in outcome in populations with severe and moderate TBI. Novel and emerging predictors include genetic constitution, biomarkers, and advanced magnetic resonance (MR) imaging. To estimate prognosis for individual patients reliably, multiple predictors need to be considered jointly in prognostic models. Two prognostic models for use in TBI, developed upon large patient numbers, have been extensively validated externally: the IMPACT and CRASH prediction models. Both models showed good performance in validations across a wide range of settings. Importantly, these models were developed not only for mortality but also for functional outcome. Prognostic models can be used for providing information to relatives of individual patients, for resource allocation, and to support decisions on treatment. At the group level, prognostic models aid in the characterization of patient populations, are important to clinical trial design and analysis, and importantly, can serve as benchmarks for assessing quality of care. Continued development, refinement, and validation of prognostic models for TBI is required and this should become an ongoing process. PMID:25701901

  3. Dementia Resulting From Traumatic Brain Injury

    PubMed Central

    Shively, Sharon; Scher, Ann I.; Perl, Daniel P.; Diaz-Arrastia, Ramon

    2013-01-01

    Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2-and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed. PMID:22776913

  4. 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

  5. A clinical study on closing-in in focal brain-damaged individuals.

    PubMed

    De Lucia, Natascia; Grossi, Dario; Trojano, Luigi

    2016-04-15

    In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis". PMID:27000246

  6. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

    PubMed Central

    Su, Enming J.; Fredriksson, Linda; Kanzawa, Mia; Moore, Shannon; Folestad, Erika; Stevenson, Tamara K.; Nilsson, Ingrid; Sashindranath, Maithili; Schielke, Gerald P.; Warnock, Mark; Ragsdale, Margaret; Mann, Kris; Lawrence, Anna-Lisa E.; Medcalf, Robert L.; Eriksson, Ulf; Murphy, Geoffrey G.; Lawrence, Daniel A.

    2015-01-01

    Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor α (PDGFRα) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα. PMID:26500491

  7. Expression of aquaporin-4 and pathological characteristics of brain injury in a rat model of traumatic brain injury

    PubMed Central

    ZHANG, CHENGCHENG; CHEN, JIANQIANG; LU, HONG

    2015-01-01

    Aquaporin 4 (AQP4) is a widely distributed membrane protein, which is found in glial cells, ependymocytes and capillary endothelial cells in the brain, and particularly in the choroid plexus. AQP4 is a key regulator of water metabolism, and changes in its expression following brain injury are associated with pathological changes in the damaged side of the brain; however, the effects of brain injury on AQP4 and injury-induced pathological changes in the contralateral non-damaged side of the brain remain to be fully elucidated. In the present study, male Sprague-Dawley rats were subjected to traumatic brain injury (TBI) and changes in brain water content, the expression of AQP4 expression and pathological characteristics in the damaged and contralateral non-damaged sides of the brain were examined. In the damaged side of the brain, vasogenic edema appeared first, followed by cellular edema. The aggravated cellular edema in the damaged side of the brain resulted in two periods of peak edema severity. Pathological changes in the contralateral non-damaged side of the brain occurred later than those in the damaged side; cellular edema appeared first, followed by vasogenic edema, which was alleviated earlier than the cellular edema. AQP4 was downregulated during vasogenic edema, and upregulated during cellular edema. Taken together, these results suggested that the downregulation of AQP4 was a result of vasogenic edema and that the upregulation of AQP4 may have induced cellular edema. PMID:26459070

  8. Common astrocytic programs during brain development, injury and cancer

    PubMed Central

    Silver, Daniel J.; Steindler, Dennis A.

    2011-01-01

    In addition to radial glial cells of neurohistogenesis, immature astrocytes with stem-cell-like properties cordon off emerging functional patterns in the developing brain. Astrocytes also can be stem cells during adult neurogenesis, and a proposed potency of injury-associated reactive astrocytes has recently been substantiated. Astrocytic cells might additionally be involved in cancer stem cell-associated gliomagenesis. Thus, there are distinguishing roles for stem-cell-like astrocytes during brain development, in neurogenic niches in the adult, during attempted reactive neurogenesis after brain injury or disease and during brain tumorigenesis. PMID:19398132

  9. Controversies in the Management of Traumatic Brain Injury.

    PubMed

    Jinadasa, Sayuri; Boone, M Dustin

    2016-09-01

    Traumatic brain injury (TBI) is a physical insult (a bump, jolt, or blow) to the brain that results in temporary or permanent impairment of normal brain function. TBI describes a heterogeneous group of disorders. The resulting secondary injury, namely brain swelling and its sequelae, is the reason why patients with these vastly different initial insults are homogenously treated. Much of the evidence for the management of TBI is poor or conflicting, and thus definitive guidelines are largely unavailable for clinicians at this time. A substantial portion of this article focuses on discussing the controversies in the management of TBI. PMID:27521198

  10. Patterns of Brain Injury in Inborn Errors of Metabolism

    PubMed Central

    Gropman, Andrea L.

    2013-01-01

    Many inborn errors of metabolism (IEMs) are associated with irreversible brain injury. For many, it is unclear how metabolite intoxication or substrate depletion accounts for the specific neurologic findings observed. IEM-associated brain injury patterns are characterized by whether the process involves gray matter, white matter, or both, and beyond that, whether subcortical or cortical gray matter nuclei are involved. Despite global insults, IEMs may result in selective injury to deep gray matter nuclei or white matter. This manuscript reviews the neuro-imaging patterns of neural injury in selected disorders of metabolism involving small molecule and macromolecular disorders (ie, Phenylketonuria, urea cycle disorders, and maple syrup urine disease) and discusses the contribution of diet and nutrition to the prevention or exacerbation of injury in selected inborn metabolic disorders. Where known, a review of the roles of individual differences in blood–brain permeability and transport mechanisms in the etiology of these disorders will be discussed. PMID:23245553

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

    PubMed

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

    2016-01-01

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

  12. What Can I Do to Help Prevent Traumatic Brain Injury?

    MedlinePlus

    ... to Congress: Epidemiology and Rehabilitation Report to Congress: Military Personnel TBI in the US: Emergency Department Visits, Hospitalizations ... sustaining a traumatic brain injury, including: Buckling your child in the car using a child safety seat, ...

  13. How Do Health Care Providers Diagnose Traumatic Brain Injury (TBI)?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose traumatic brain injury (TBI)? Skip sharing ... links Share this: Page Content To diagnose TBI, health care providers may use one or more tests that ...

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

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159124.html Money, Language Barriers Can Affect Kids' Brain Injury Care Those ... included providers of physical and occupational therapy; speech, language and cognitive therapy; and mental health services. The ...

  15. Psychiatric treatment in severe brain injury: a case report.

    PubMed

    Kaplan De-Nour, A; Bauman, A

    1980-03-01

    A patient with severe, penetrating brain injury is presented. The patient was in psychiatric treatment for four years, starting two months after the injury; psychological tests were administered four times. By most criteria, the patient recovered completely. The case confirmed earlier observations that intelligence measured by verbal subtests, recovers faster than that measured by performance subtests. The latter continued to improve during the two to four year period after injury. The case clearly indicates the emotional and psychological problems that arise in the presence of severe brain damage. These reactions may hamper rehabilitation, although the gross psychological disabilities caused by the brain injury have improved. It is suggested, therefore, that brain damaged patients should receive psychiatric treatment. Some of the problems of such psychotherapeutic treatment are briefly discussed. PMID:7380245

  16. Defense Centers of Excellence for Psychological Health & Traumatic Brain Injury

    MedlinePlus

    ... brain injury may make sleep more difficult. Simple changes to your behavior and environment - sleep schedule, bedtime habits and daily lifestyle choices - ... for the 2016 DCoE Summit is Open Register today for the ...

  17. Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury.

    PubMed

    Lee, Seunghoon; Shin, Jinhee; Lee, Minkyung; Hong, Yunkyung; Lee, Sang-Kil; Lee, Youngjeon; Lkhagvasuren, Tserentogtokh; Kim, Dong-Wook; Yang, Young-Ae; Chang, Kyu-Tae; Hong, Yonggeun

    2012-05-01

    Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor 1α mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 (NG2) mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage. PMID:25722687

  18. Ventral frontal cortex functions and quantified MRI in traumatic brain injury

    PubMed Central

    Fujiwara, Esther; Schwartz, Michael L.; Gao, Fuqiang; Black, Sandra E.; Levine, Brian

    2008-01-01

    Ventral frontal cortex is commonly involved in traumatic brain injury (TBI). The Smell Identification Test (SIT), Object Alternation (OA), and the Iowa Gambling Task (IGT) are associated with this brain region in experimental and neuropsychological research. We examined the relationship of performance on these tests to residual structural brain integrity quantified from MRI in 58 TBI patients, including 18 patients with focal cortical contusions and 40 patients with diffuse injury only. Image analysis yielded regional volumetric measures of gray matter, white matter and cerebrospinal fluid. Multivariate analyses identified distributed patterns of regional volume loss associated with test performance across all three behavioral measures. The tasks were sensitive to effects of TBI. In multivariate analyses, performance in all three tasks was related to gray matter loss including ventral frontal cortex, but the SIT was most sensitive to ventral frontal cortex damage, even in patients without focal lesions. The SIT was further related to temporal lobe and posterior cingulate/retrosplenial volumes. OA and the IGT were associated with superior medial frontal volumes. Complex tasks, such as OA and the IGT, do not consistently localize to a single cortical region. The SIT is associated with the integrity of ventral frontal regions, but it is also affected by distributed damage, although the contribution of undetected olfactory tract or bulb damage could not be ruled out. This study illustrates the scope and limitations of functional localization in human ventral frontal cortex. PMID:17976665

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

    PubMed Central

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

    2016-01-01

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

  20. Cooking breakfast after a brain injury

    PubMed Central

    Tanguay, Annick N.; Davidson, Patrick S. R.; Guerrero Nuñez, Karla V.; Ferland, Mark B.

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik and Bialystok, 2006) as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task. Patients also completed the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003) and prepared actual meals that were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on) relative to controls. Surprisingly, however, patients' Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency. PMID:25228863

  1. Narrative language in traumatic brain injury.

    PubMed

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

    2011-08-01

    Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS<8) in the phase of neurological stability and 14 neurologically intact participants were recruited for the experiment. Their cognitive, linguistic and narrative skills were thoroughly assessed. The group of non-aphasic individuals with TBI had normal lexical and grammatical skills. However, they produced narratives with increased errors of cohesion and coherence due to the frequent interruption of ongoing utterances, derailments and extraneous utterances that made their discourse vague and ambiguous. They produced a normal amount of thematic units (i.e. concepts) in their narratives. However, this information was not correctly organized at micro- and macrolinguistic levels of processing. A Principal Component Analysis showed that a single factor accounted for the production of global coherence errors, and the reduction of both propositional density at the utterance level and proportion of words that conveyed information. It is hypothesized that the linguistic deficits observed in the participants with TBI may reflect a deficit at the interface between cognitive and linguistic processing rather than a specific linguistic disturbance. PMID:21723304

  2. Advanced Neuroimaging in Traumatic Brain Injury

    PubMed Central

    Edlow, Brian L.; Wu, Ona

    2013-01-01

    Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

  3. Adenosine Neuromodulation and Traumatic Brain Injury

    PubMed Central

    Lusardi, T.A

    2009-01-01

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

  4. Cooking breakfast after a brain injury.

    PubMed

    Tanguay, Annick N; Davidson, Patrick S R; Guerrero Nuñez, Karla V; Ferland, Mark B

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik and Bialystok, 2006) as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task. Patients also completed the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003) and prepared actual meals that were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on) relative to controls. Surprisingly, however, patients' Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency. PMID:25228863

  5. Ceruloplasmin and β-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron.

    PubMed

    Ayton, Scott; Zhang, Moses; Roberts, Blaine R; Lam, Linh Q; Lind, Monica; McLean, Catriona; Bush, Ashley I; Frugier, Tony; Crack, Peter J; Duce, James A

    2014-04-01

    Traumatic brain injury (TBI) is in part complicated by pro-oxidant iron elevation independent of brain hemorrhage. Ceruloplasmin (CP) and β-amyloid protein precursor (APP) are known neuroprotective proteins that reduce oxidative damage through iron regulation. We surveyed iron, CP, and APP in brain tissue from control and TBI-affected patients who were stratified according to time of death following injury. We observed CP and APP induction after TBI accompanying iron accumulation. Elevated APP and CP expression was also observed in a mouse model of focal cortical contusion injury concomitant with iron elevation. To determine if changes in APP or CP were neuroprotective we employed the same TBI model on APP(-/-) and CP(-/-) mice and found that both exhibited exaggerated infarct volume and iron accumulation postinjury. Evidence supports a regulatory role of both proteins in defence against iron-induced oxidative damage after TBI, which presents as a tractable therapeutic target. PMID:24509156

  6. 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

  7. 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.

  8. Intravenous Fluid Therapy in Traumatic Brain Injury and Decompressive Craniectomy

    PubMed Central

    Alvis-Miranda, Hernando Raphael; Castellar-Leones, Sandra Milena; Moscote-Salazar, Luis Rafael

    2014-01-01

    The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various supportive therapeutic strategies in the pre-hospital and pre-operative stages is essential for optimal care. The immediate rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure is now the standard treatment of patients with combined traumatic brain injury (TBI) and hemorrhagic shock (HS). The fluid in patients with brain trauma and especially in patients with brain injur y is a critical issue. In this context we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regarding the use of fluid therapy in traumatic brain injury and decompressive craniectomy. PMID:27162857

  9. Memory Strategies to Use With Students Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Pershelli, Andi

    2007-01-01

    Following a traumatic brain injury, including a mild concussion, most students will have some degree of memory impairment. It can take 1-3 years for a child's memory to improve to its maximum capability following injury. Children cannot wait that long before returning to school. Teachers need to know how to diversify their instruction in order to…

  10. Traumatic Brain Injury: Persistent Misconceptions and Knowledge Gaps among Educators

    ERIC Educational Resources Information Center

    Ettel, Deborah; Glang, Ann E.; Todis, Bonnie; Davies, Susan C.

    2016-01-01

    Each year approximately 700,000 U.S. children aged 0-19 years sustain a traumatic brain injury (TBI) placing them at risk for academic, cognitive, and behavioural challenges. Although TBI has been a special education disability category for 25 years, prevalence studies show that of the 145,000 students each year who sustain long-term injury from…

  11. Development of an Ontology for Rehabilitation: Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Grove, Michael J.

    2013-01-01

    Traumatic Brain Injury (TBI) rehabilitation interventions are very heterogeneous due to injury characteristics and pathology, patient demographics, healthcare settings, caregiver variability, and individualized, multi-discipline treatment plans. Consequently, comparing and generalizing the effectiveness of interventions is limited largely due to…

  12. Traumatic Brain Injury (TBI): Moderate or Severe

    MedlinePlus

    ... know? There are two types of TBIs: Closed Head Injury Caused by a blow or jolt to the head that does not penetrate the skull Penetrating Head Injury Occurs when an object goes through the skull ...

  13. A vascular injury model using focal heat-induced activation of endothelial cells

    PubMed Central

    Sylman, J.L.; Artzer, D.T.; Rana, K.; Neeves, K.B.

    2015-01-01

    Endothelial cells (EC) both inhibit and promote platelet function depending on their activation state. Quiescent EC inhibit platelet activation by constitutive secretion of platelet inhibitors. Activated EC promote platelet adhesion by secretion of von Willebrand factor (vWF). EC also secrete an extracellular matrix that support platelet adhesion when exposed following vascular injury. Previous studies of EC-platelet interactions under flow activate entire monolayers of cells by chemical activation. In this study, EC cultured in microfluidic channels were focally activated by heat from an underlying microelectrode. Based on finite element modeling, microelectrodes induced peak temperature increases of 10–40 °C above 37 °C after applying 5–9 V for 30 s resulting in three zones: (1) A quiescent zone corresponded to peak temperatures of less than 15 °C characterized by no EC activation or platelet accumulation. (2) An activation zone corresponding to an increase of 16–22 °C yielded EC that were viable, secreted elevated levels of vWF, and were P-selectin positive. Platelets accumulated in the retracted spaces between EC in the activation zone at a wall shear rate of 150 s−1. Experiments with blocking antibodies show that platelets adhere via GPIbα-vWF and α6β1-laminin interactions. (3) A kill zone corresponded to peak temperatures of greater than 23 °C where EC were not viable and did not support platelet adhesion. These data define heating conditions for the activation of EC, causing the secretion of vWF and the exposure of a subendothelial matrix that support platelet adhesion and aggregation. This model provides for spatially defined zones of EC activation that could be a useful tool for measuring the relative roles of anti- and prothrombotic roles of EC at the site of vascular injury. PMID:26087748

  14. Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

    PubMed Central

    Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

    2012-01-01

    Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

  15. [Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options)].

    PubMed

    Potapov, A A; Krylov, V V; Gavrilov, A G; Kravchuk, A D; Likhterman, L B; Petrikov, S S; Talypov, A E; Zakharova, N E; Solodov, A A

    2016-01-01

    Traumatic brain injury (TBI) is one of the main causes of mortality and severe disability in young and middle age patients. Patients with severe TBI, who are in coma, are of particular concern. Adequate diagnosis of primary brain injuries and timely prevention and treatment of secondary injury mechanisms markedly affect the possibility of reducing mortality and severe disability. The present guidelines are based on the authors' experience in developing international and national recommendations for the diagnosis and treatment of mild TBI, penetrating gunshot wounds of the skull and brain, severe TBI, and severe consequences of brain injury, including a vegetative state. In addition, we used the materials of international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe TBI, which were published in recent years. The proposed recommendations for surgical treatment of severe TBI in adults are addressed primarily to neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in treating these patients. PMID:27070263

  16. The neuroprotective roles of BDNF in hypoxic ischemic brain injury.

    PubMed

    Chen, Ai; Xiong, Li-Jing; Tong, Yu; Mao, Meng

    2013-03-01

    Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury. PMID:24648914

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

    PubMed

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

    1993-07-01

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

  18. Focal brain damage protects against post-traumatic stress disorder in combat veterans.

    PubMed

    Koenigs, Michael; Huey, Edward D; Raymont, Vanessa; Cheon, Bobby; Solomon, Jeffrey; Wassermann, Eric M; Grafman, Jordan

    2008-02-01

    Post-traumatic stress disorder (PTSD) is an often debilitating mental illness that is characterized by recurrent distressing memories of traumatic events. PTSD is associated with hypoactivity in the ventromedial prefrontal cortex (vmPFC), hyperactivity in the amygdala and reduced volume in the hippocampus, but it is unknown whether these neuroimaging findings reflect the underlying cause or a secondary effect of the disorder. To investigate the causal contribution of specific brain areas to PTSD symptoms, we studied a unique sample of Vietnam War veterans who suffered brain injury and emotionally traumatic events. We found a substantially reduced occurrence of PTSD among those individuals with damage to one of two regions of the brain: the vmPFC and an anterior temporal area that included the amygdala. These results suggest that the vmPFC and amygdala are critically involved in the pathogenesis of PTSD. PMID:18157125

  19. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    PubMed

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  20. Day of Injury CT and Late MRI Findings: Cognitive Outcome in a Pediatric Sample with Complicated Mild Traumatic Brain Injury

    PubMed Central

    Jantz, Paul B; Farrer, Thomas J.; Abildskov, Tracy J.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn; Yeates, Keith Owen

    2016-01-01

    Objectives Complicated mild traumatic brain injury (mTBI) or cmTBI is based on the presence of visibly identifiable brain pathology on the day-of-injury computed tomography (CT) scan. In a pediatric sample the relation of DOI CT to late MRI findings and neuropsychological outcome was examined. Methods MRI (> 12 months) was obtained in pediatric cmTBI patients and a sample of orthopedically injured (OI) children. Those children with positive imaging findings (MRI+) were quantitatively compared to those without (MRI-) or with the OI sample. Groups were also compared in neurocognitive outcome from WASI subtests and the WISC-IV Processing Speed Index (PSI), along with the Test of Everyday Attention for Children (TEA-Ch) and a parent-rated behavioral functioning measure (ABAS-II). Results Despite the MRI+ group having significantly more DOI CT findings than the MRI-group, no quantitative differences were found. WASI Vocabulary and Matrix Reasoning scores were significantly lower, but not PSI, TEA-Ch or ABAS-II scores. MRI+ and MRI-groups did not differ on these measures. Conclusions Heterogeneity in the occurrence of MRI-identified focal pathology was not associated with uniform changes in quantitative analyses of brain structure in cmTBI. Increased number of DOI CT abnormalities was associated with lowered neuropsychological performance. PMID:26186038

  1. Classification of Traumatic Brain Injury for Targeted Therapies

    PubMed Central

    Saatman, Kathryn E.; Duhaime, Ann-Christine; Bullock, Ross; Maas, Andrew I.R.; Valadka, Alex

    2008-01-01

    Abstract The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. While the GCS is extremely useful in the clinical management and prognosis of TBI, it does not provide specific information about the pathophysiologic mechanisms which are responsible for neurological deficits and targeted by interventions. On the premise that brain injuries with similar pathoanatomic features are likely to share common pathophysiologic mechanisms, participants proposed that a new, multidimensional classification system should be developed for TBI clinical trials. It was agreed that preclinical models were vital in establishing pathophysiologic mechanisms relevant to specific pathoanatomic types of TBI and verifying that a given therapeutic approach improves outcome in these targeted TBI types. In a clinical trial, patients with the targeted pathoanatomic injury type would be selected using an initial diagnostic entry criterion, including their severity of injury. Coexisting brain injury types would be identified and multivariate prognostic modeling used for refinement of inclusion/exclusion criteria and patient stratification. Outcome assessment would utilize endpoints relevant to the targeted injury type. Advantages and disadvantages of currently available diagnostic, monitoring, and

  2. Cyclosporin A Preserves Mitochondrial Function after Traumatic Brain Injury in the Immature Rat and Piglet

    PubMed Central

    Kilbaugh, Todd J.; Bhandare, Sunita; Lorom, David H.; Saraswati, Manda; Robertson, Courtney L.

    2011-01-01

    Abstract Cyclosporin A (CsA) has been shown to be neuroprotective in mature animal models of traumatic brain injury (TBI), but its effects on immature animal models of TBI are unknown. In mature animal models, CsA inhibits the opening of the mitochondrial permeability transition pore (MPTP), thereby maintaining mitochondrial homeostasis following injury by inhibiting calcium influx and preserving mitochondrial membrane potential. The aim of the present study was to evaluate CsA's ability to preserve mitochondrial bioenergetic function following TBI (as measured by mitochondrial respiration and cerebral microdialysis), in two immature models (focal and diffuse), and in two different species (rat and piglet). Three groups were studied: injured+CsA, injured+saline vehicle, and uninjured shams. In addition, we evaluated CsA's effects on cerebral hemodynamics as measured by a novel thermal diffusion probe. The results demonstrate that post-injury administration of CsA ameliorates mitochondrial dysfunction, preserves cerebral blood flow (CBF), and limits neuropathology in immature animals 24 h post-TBI. Mitochondria were isolated 24 h after controlled cortical impact (CCI) in rats and rapid non-impact rotational injury (RNR) in piglets, and CsA ameliorated cerebral bioenergetic crisis with preservation of the respiratory control ratio (RCR) to sham levels. Results were more dramatic in RNR piglets than in CCI rats. In piglets, CsA also preserved lactate pyruvate ratios (LPR), as measured by cerebral microdialysis and CBF at sham levels 24 h after injury, in contrast to the significant alterations seen in injured piglets compared to shams (p<0.01). The administration of CsA to piglets following RNR promoted a 42% decrease in injured brain volume (p<0.01). We conclude that CsA exhibits significant neuroprotective activity in immature models of focal and diffuse TBI, and has exciting translational potential as a therapeutic agent for neuroprotection in children. PMID

  3. 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. PMID:26956452

  4. The influence of anisotropy on brain injury prediction.

    PubMed

    Giordano, C; Cloots, R J H; van Dommelen, J A W; Kleiven, S

    2014-03-21

    Traumatic Brain Injury (TBI) occurs when a mechanical insult produces damage to the brain and disrupts its normal function. Numerical head models are often used as tools to analyze TBIs and to measure injury based on mechanical parameters. However, the reliability of such models depends on the incorporation of an appropriate level of structural detail and accurate representation of the material behavior. Since recent studies have shown that several brain regions are characterized by a marked anisotropy, constitutive equations should account for the orientation-dependence within the brain. Nevertheless, in most of the current models brain tissue is considered as completely isotropic. To study the influence of the anisotropy on the mechanical response of the brain, a head model that incorporates the orientation of neural fibers is used and compared with a fully isotropic model. A simulation of a concussive impact based on a sport accident illustrates that significantly lowered strains in the axonal direction as well as increased maximum principal strains are detected for anisotropic regions of the brain. Thus, the orientation-dependence strongly affects the response of the brain tissue. When anisotropy of the whole brain is taken into account, deformation spreads out and white matter is particularly affected. The introduction of local axonal orientations and fiber distribution into the material model is crucial to reliably address the strains occurring during an impact and should be considered in numerical head models for potentially more accurate predictions of brain injury. PMID:24462379

  5. IQ Decline Following Early Unilateral Brain Injury: A Longitudinal Study

    ERIC Educational Resources Information Center

    Levine, Susan C.; Kraus, Ruth; Alexander, Erin; Suriyakham, Linda Whealton; Huttenlocher, Peter R.

    2005-01-01

    We examine whether children with early unilateral brain injury show an IQ decline over the course of development. Fifteen brain injured children were administered an IQ test once before age 7 and again several years later. Post-7 IQ scores were significantly lower than pre-7 IQ scores. In addition, pre-7 IQ scores were lower for children with…

  6. In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury

    NASA Astrophysics Data System (ADS)

    Alt, Clemens; Lin, Charles P.

    2012-03-01

    Microglia are the resident immune cells of the central nervous system and play a crucial role in maintaining neuronal health and function. Their dynamic behavior, that is, the constant extension and retraction of microglia processes, is thought to be critical for communication between microglia and their cellular neighbors, such as neurons, astrocytes and vascular endothelial cells. Here, we investigated the morphology and dynamics of retinal microglia in vivo under normal conditions and in response to focal laser injury of blood vessel endothelial wall, using a scanning laser ophthalmoscope (SLO) designed specifically for imaging the retina of live mice. The multichannel confocal imaging system allows retinal microstructure, such as the processes of microglia and retinal vasculature, to be visualized simultaneously. In order to generate focal laser injury, a photocoagulator based on a continuous wave (cw) laser was coupled into the SLO. An acousto-optic modulator chopped pulses from the cw laser. A tip-tilt-scanner was used to direct the laser beam into a blood vessel of interest under SLO image guidance. Mild coagulation was produced using millisecond-long pulses. Microglia react dynamically to focal laser injury of blood vessel endothelial walls. Under normal conditions, microglia somas remain stationary and the processes probe a territory of their immediate environment. In response to local injury, process movement velocity approximately doubles within minutes after injury. Moreover, the previously unpolarized process movement assumes a distinct directionality towards the injury site, indicating signaling between the injured tissue and the microglia. In vivo retinal imaging is a powerful tool for understanding the dynamic behavior of retinal cells.

  7. Standardizing Data Collection in Traumatic Brain Injury

    PubMed Central

    Harrison-Felix, Cynthia L.; Menon, David; Adelson, P. David; Balkin, Tom; Bullock, Ross; Engel, Doortje C.; Gordon, Wayne; Langlois-Orman, Jean; Lew, Henry L.; Robertson, Claudia; Temkin, Nancy; Valadka, Alex; Verfaellie, Mieke; Wainwright, Mark; Wright, David W.; Schwab, Karen

    2011-01-01

    Abstract Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we “speak the same language.” Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies. Randomized controlled trials can never address the many uncertainties concerning treatment approaches in TBI. Pooling data from different clinical studies and high-quality observational studies combined with comparative effectiveness research may provide excellent alternatives in a cost-efficient way. Standardization of data collection and coding is essential to this end. Common data elements (CDEs) are presented for demographics and clinical variables applicable across the broad spectrum of TBI. Most recommendations represent a consensus derived from clinical practice. Some recommendations concern novel approaches, for example assessment of the intensity of therapy in severely injured patients. Up to three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail attained in the advanced version. More detailed codings can be collapsed into the basic version. Templates were produced to summarize coding formats, explanation of choices, and recommendations for procedures. Endorsement of the recommendations has been obtained from many authoritative organizations. The development of CDEs for TBI should be viewed as a continuing process; as more experience is gained, refinement and amendments will be required. This proposed process of standardization will facilitate comparative effectiveness research and encourage high-quality meta-analysis of individual patient data. PMID:21162610

  8. Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury.

    PubMed

    Song, Yu; Pimentel, Corrin; Walters, Katherine; Boller, Lauren; Ghiasvand, Shabnam; Liu, Jing; Staley, Kevin J; Berdichevsky, Yevgeny

    2016-01-01

    Exogenous Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective in animal models of brain injury, and has been considered as a potential therapeutic. Akt-mTOR and MAPK are downstream targets of IGF-1 signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-1 may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after brain injury, using the organotypic hippocampal culture model of post-traumatic epileptogenesis. We found that IGF-1 was neuroprotective within a few days of injury but that long-term IGF-1 treatment was pro-epileptic. Pro-epileptic effects of IGF-1 were mediated by Akt-mTOR signaling. We also found that IGF-1 - mediated increase in epileptic activity led to neurotoxicity. The dualistic nature of effects of IGF-1 treatment demonstrates that anabolic enhancement through IGF-1 activation of mTOR cascade can be beneficial or harmful depending on the stage of the disease. Our findings suggest that epilepsy risk may need to be considered in the design of neuroprotective treatments for brain injury. PMID:27561791

  9. Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury

    PubMed Central

    Song, Yu; Pimentel, Corrin; Walters, Katherine; Boller, Lauren; Ghiasvand, Shabnam; Liu, Jing; Staley, Kevin J.; Berdichevsky, Yevgeny

    2016-01-01

    Exogenous Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective in animal models of brain injury, and has been considered as a potential therapeutic. Akt-mTOR and MAPK are downstream targets of IGF-1 signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-1 may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after brain injury, using the organotypic hippocampal culture model of post-traumatic epileptogenesis. We found that IGF-1 was neuroprotective within a few days of injury but that long-term IGF-1 treatment was pro-epileptic. Pro-epileptic effects of IGF-1 were mediated by Akt-mTOR signaling. We also found that IGF-1 – mediated increase in epileptic activity led to neurotoxicity. The dualistic nature of effects of IGF-1 treatment demonstrates that anabolic enhancement through IGF-1 activation of mTOR cascade can be beneficial or harmful depending on the stage of the disease. Our findings suggest that epilepsy risk may need to be considered in the design of neuroprotective treatments for brain injury. PMID:27561791

  10. 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.

  11. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    PubMed Central

    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

    2014-01-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (<32 weeks gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments1,2. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI3. In a previous study, we demonstrated that epidermal growth factor receptor (EGFR) plays an important role in oligodendrocyte development4. Here, we examine whether enhanced epidermal growth factor receptor (EGFR) signaling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioral recovery in the developing brain. Using an established model of very preterm brain injury, we demonstrate that selective overexpression of human (h)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 (OPCs) and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioral deficits on white matter-specific paradigms. Inhibition of EGFR signaling 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 OPCs at a specific time after injury is clinically feasible and applicable for the treatment of premature children with white matter injury. PMID:24390343

  12. Magnetic Resonance Imaging in Experimental Traumatic Brain Injury.

    PubMed

    Shen, Qiang; Watts, Lora Tally; Li, Wei; Duong, Timothy Q

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. Common causes of TBI include falls, violence, injuries from wars, and vehicular and sporting accidents. The initial direct mechanical damage in TBI is followed by progressive secondary injuries such as brain swelling, perturbed cerebral blood flow (CBF), abnormal cerebrovascular reactivity (CR), metabolic dysfunction, blood-brain-barrier disruption, inflammation, oxidative stress, and excitotoxicity, among others. Magnetic resonance imaging (MRI) offers the means to noninvasively probe many of these secondary injuries. MRI has been used to image anatomical, physiological, and functional changes associated with TBI in a longitudinal manner. This chapter describes controlled cortical impact (CCI) TBI surgical procedures, a few common MRI protocols used in TBI imaging, and, finally, image analysis pertaining to experimental TBI imaging in rats. PMID:27604743

  13. Finite Element Analysis of Brain Injury due to Head Impact

    NASA Astrophysics Data System (ADS)

    Suh, Chang Min; Kim, Sung Ho; Goldsmith, Werner

    Traumatic Brain Injury (TBI) due to head impact by external impactor was analyzed using Finite Element Method (FEM). Two-dimensiona modeling was performed according to Magnetic Resonance Imaging (MRI) data of Mongolian subject. Pressure variation in a cranium due to external impact was analyzed in order to simulate Nahum et al.'s cadaver test.6 And, analyzed results were compared with Nahum et al.'s experimental data.6 As results, stress and strain behaviors of the brain during impact were accorded with experimental data qualitatively even though there were some differences in quantitative values. In addition, they were accorded with other references about brain injury as well.

  14. Biomarkers and acute brain injuries: interest and limits

    PubMed Central

    2014-01-01

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

  15. Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study

    PubMed Central

    Idris, Zamzuri; Zenian, Mohd Sofan; Muzaimi, Mustapha; Hamid, Wan Zuraida Wan Abdul

    2014-01-01

    Background: Induced hypothermia for treatment of traumatic brain injury is controversial. Since many pathways involved in the pathophysiology of secondary brain injury are temperature dependent, regional brain hypothermia is thought capable to mitigate those processes. The objectives of this study are to assess the therapeutic effects and complications of regional brain cooling in severe head injury with Glasgow coma scale (GCS) 6-7. Materials and Methods: A prospective randomized controlled pilot study involving patients with severe traumatic brain injury with GCS 6 and 7 who required decompressive craniectomy. Patients were randomized into two groups: Cooling and no cooling. For the cooling group, analysis was made by dividing the group into mild and deep cooling. Brain was cooled by irrigating the brain continuously with cold Hartmann solution for 24-48 h. Main outcome assessments were a dichotomized Glasgow outcome score (GOS) at 6 months posttrauma. Results: A total of 32 patients were recruited. The cooling-treated patients did better than no cooling. There were 63.2% of patients in cooling group attained good GOS at 6 months compared to only 15.4% in noncooling group (P = 0.007). Interestingly, the analysis at 6 months post-trauma disclosed mild-cooling-treated patients did better than no cooling (70% vs. 15.4% attained good GOS, P = 0.013) and apparently, the deep-cooling-treated patients failed to be better than either no cooling (P = 0.074) or mild cooling group (P = 0.650). Conclusion: Data from this pilot study imply direct regional brain hypothermia appears safe, feasible and maybe beneficial in treating severely head-injured patients. PMID:25685201

  16. Emergency treatment options for pediatric traumatic brain injury

    PubMed Central

    Exo, J; Smith, C; Smith, R; Bell, MJ

    2010-01-01

    Traumatic brain injury is a leading killer of children and is a major public health problem around the world. Using general principles of neurocritical care, various treatment strategies have been developed to attempt to restore homeostasis to the brain and allow brain healing, including mechanical factors, cerebrospinal fluid diversion, hyperventilation, hyperosmolar therapies, barbiturates and hypothermia. Careful application of these therapies, normally in a step-wise fashion as intracranial injuries evolve, is necessary in order to attain maximal neurological outcome for these children. It is hopeful that new therapies, such as early hypothermia or others currently in preclinical trials, will ultimately improve outcome and quality of life for children after traumatic brain injury. PMID:20191093

  17. Recovery of consciousness after brain injury: a mesocircuit hypothesis

    PubMed Central

    Schiff, Nicholas D.

    2009-01-01

    Recovery of consciousness following severe brain injuries may occur over long time intervals. Importantly, evolving cognitive recovery can be strongly dissociated from motor recovery in some individuals, resulting in underestimation of cognitive capacities. Common mechanisms of cerebral dysfunction that arise at the neuronal population level may explain slow functional recoveries from severe brain injuries. This review proposes a “mesocircuit” model that predicts specific roles for different structural and dynamic changes that may occur gradually during recovery. Recent functional neuroimaging studies that operationally identify varying levels of awareness, memory and other higher brain functions in patients with no behavioral evidence of these cognitive capacities are discussed. Measuring evolving changes in underlying brain function and dynamics post-injury and post-treatment frames future investigative work. PMID:19954851

  18. Toll-Like Receptors and Ischemic Brain Injury

    PubMed Central

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

    2014-01-01

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

  19. Translational Research for Blast-Induced Traumatic Brain Injury: Injury Mechanism to Development of Medical Instruments

    NASA Astrophysics Data System (ADS)

    Nakagawa, A.; Ohtani, K.; Arafune, T.; Washio, T.; Iwasaki, M.; Endo, T.; Ogawa, Y.; Kumabe, T.; Takayama, K.; Tominaga, T.

    1. Investigation of shock wave-induced phenomenon: blast-induced traumatic brain injury Blast wave (BW) is generated by explosion and is comprised of lead shock wave (SE) followed by subsequent supersonic flow.

  20. Noninvasive Imaging of the High Frequency Brain Activity in Focal Epilepsy Patients

    PubMed Central

    Lu, Yunfeng; Worrell, Gregory A.; Zhang, Huishi Clara; Yang, Lin; Brinkmann, Benjamin; Nelson, Cindy

    2014-01-01

    High frequency (HF) activity represents a potential biomarker of the epileptogenic zone in epilepsy patients, the removal of which is considered to be crucial for seizure-free surgical outcome. We proposed a high frequency source imaging (HFSI) approach to noninvasively image the brain sources of scalp recorded high frequency EEG activity. Both computer simulation and clinical patient data analysis were performed to investigate the feasibility of using the HFSI approach to image the sources of HF activity from noninvasive scalp EEG recordings. The HF activity was identified from high-density scalp recordings after high-pass filtering the EEG data and the EEG segments with HF activity were concatenated together to form repetitive HF activity. Independent component analysis was utilized to extract the components corresponding to the HF activity. Noninvasive EEG source imaging using realistic geometric boundary element head modeling was then applied to image the sources of the pathological HF brain activity. Five medically intractable focal epilepsy patients were studied and the estimated sources were found to be concordant with the surgical resection or intracranial recordings of the patients. The present study demonstrates, for the first time, that source imaging from the scalp HF activity could help to localize the seizure onset zone (SOZ) and provide a novel noninvasive way of studying the epileptic brain in humans. This study also indicates the potential application of studying HF activity in the pre-surgical planning of medically intractable epilepsy patients. PMID:24845275

  1. The effects of focal anterior and posterior brain lesions on verbal fluency.

    PubMed

    Stuss, D T; Alexander, M P; Hamer, L; Palumbo, C; Dempster, R; Binns, M; Levine, B; Izukawa, D

    1998-05-01

    Seventy-four patients with focal brain lesions were compared to a neurologically normal control group on tasks of letter-based and category-based list generation. When patients were divided only by right frontal, left frontal, or nonfrontal lesion sites, the pattern of fluency impairments confirmed prior claims. When more precise lesion sites within the frontal lobes were compared between groups classified based on their fluency performance, much more specific brain-behavior relations were uncovered. Damage to the right dorsolateral cortical or connecting striatal regions, the right posterior area, or the medial inferior frontal lobe of either hemisphere did not significantly affect letter-based fluency performance. Superior medial frontal damage, right or left, resulted in moderate impairment. Patients with left dorsolateral and/or striatal lesions were most impaired. Left parietal damage led to performance relatively equivalent to the superior medial and left dorsolateral groups. The same lesion sites produced impairments in category based fluency, but so did lesions of right dorsolateral and inferior medial regions. Task analysis and correlations with other measures revealed that different cognitive processes related to different brain regions underlie performance on verbal fluency tests. PMID:9623001

  2. Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays

    SciTech Connect

    Anschell,D.; Romanelli, P.; Benveniste, H.; Foerster, B.; Kalef-Ezra, J.; Zhong, Z.; Dilmanian, F.

    2007-01-01

    Stereotactic radiosurgery has led to advances in the treatment of central nervous system disease. It relies upon the principle of delivering relatively high dose irradiation to a precise target, while exposing surrounding tissues to extremely low doses. We describe a novel radiosurgical approach using interlaced microplanar X-rays which we have termed 'microradiosurgery.' The use of microbeams allows for 1000-times greater precision than current clinically employed techniques. As a demonstration of this new method, we produced a -3.8 mm{sup 3} lesion in the rat brain. The lesion was followed over a period of 216 days using 9.4 Tesla magnetic resonance imaging. Our results show a gradually developing lesion at the site of the interlaced beams. The lesion began as a high T2 signal only, but advanced to include a central area of low T1 and mixed T2 signal within 2 months. No lesion was observed in the other side of the brain which was exposed to non-interlaced microbeams only. Interlaced microbeams is an effective method to create focal brain microlesions. This technique may allow the future treatment of pathology not accessible by surgical or more traditional radiosurgical means.

  3. Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia.

    PubMed Central

    Botchkina, G. I.; Meistrell, M. E.; Botchkina, I. L.; Tracey, K. J.

    1997-01-01

    Cerebral ischemia induces a rapid and dramatic up-regulation of tumor necrosis factor (TNF) protein and mRNA, but the cellular sources of TNF in the ischemic brain have not been defined. The diverse activities of TNF are mediated via ligand interaction with two distinct receptors, p55 and p75, which activate separate intracellular signal transduction pathways, leading to distinct biological effects. Since the effects of cerebral ischemia on TNF receptor (TNFR) expression are unknown, we examined the cellular localization and protein expression of TNF and its two receptors in the rat cerebral cortex in response to permanent middle cerebral artery (MCA) occlusion. The results indicate that focal. cerebral ischemia up-regulates expression of TNF and both TNFRs within the ischemic cortex. The most abundant type of TNF immunoreactivity (IR) was a punctate and filamentous pattern of transected cellular processes; however, cell bodies of neurons, astrocytes, and microglia, as well as infiltrating polymorphonuclear (PMN) leukocytes also showed TNF IR. Brain vasculature displayed TNF IR not only within endothelial cells but also in the perivascular space. MCA occlusion induced significant up-regulation of TNF receptors, with p55 IR appearing within 6 hr, significantly before the appearance of p75 IR at 24 hr after the onset of ischemia. Since p55 has been implicated in transducing cytotoxic signalling of TNF, these results support the proposed injurious role of excessive TNF produced during the acute response to cerebral ischemia. Images FIG. 7 FIG. 3 FIG. 1 FIG. 2 FIG. 4 FIG. 5 FIG. 6 FIG. 8 FIG. 9 PMID:9407552

  4. Effects of traumatic brain injury on intestinal contractility

    PubMed Central

    OLSEN, A. B.; HETZ, R. A.; XUE, H.; AROOM, K. R.; BHATTARAI, D.; JOHNSON, E.; BEDI, S.; COX, C. S.; URAY, K.

    2014-01-01

    Background Patients with traumatic brain injury (TBI) often suffer from gastrointestinal dysfunction including intolerance to enteral feedings. However, it is unclear how TBI affects small intestinal contractile activity. The purpose of this study was to determine if TBI affects intestinal smooth muscle function. Methods Sprague–Dawley rats were subjected to controlled cortical impact injury (TBI). Sham animals underwent a similar surgery but no injury (SHAM). Animals were sacrificed 1, 3, and 7 days after TBI and intestinal smooth muscle tissue was collected for measurement of contractile activity and transit, NF-kB activity, and cytokine levels. Brains were collected after sacrifice to determine volume loss due to injury. Key Results Contractile activity decreased significantly in ileum, but not jejunum, in the TBI group 7 days after injury compared with SHAM. Brain volume loss increased significantly 7 days after injury compared with 3 days and correlated significantly with the contractile activity 1 day after injury. In the intestinal smooth muscle, NF-kB activity increased significantly in the TBI group 3 and 7 days after injury vs SHAM. Wet to dry weight ratio, indicating edema, also increased significantly in the TBI group. Interleukin- 1α, -1β, and -17 increased significantly in the TBI group compared with SHAM. Conclusions & Inferences Traumatic brain injury causes a delayed but significant decrease in intestinal contractile activity in the ileum leading to delayed transit. The decreased intestinal contractile activity is attributed to secondary inflammatory injury as evidenced by increased NF-kB activity, increased edema, and increased inflammatory cytokines in the intestinal smooth muscle. PMID:23551971

  5. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

    PubMed

    Garzon-Muvdi, Tomas; Schiapparelli, Paula; ap Rhys, Colette; Guerrero-Cazares, Hugo; Smith, Christopher; Kim, Deok-Ho; Kone, Lyonell; Farber, Harrison; Lee, Danielle Y; An, Steven S; Levchenko, Andre; Quiñones-Hinojosa, Alfredo

    2012-01-01

    Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF), which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1) through the regulation of focal adhesion dynamics and cell contractility and (2) through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms. PMID:22570591

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

    PubMed Central

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

    2015-01-01

    Objectives: Traumatic brain injury is a poly-pathology characterized by changes in the cerebral blood flow, inflammation, diffuse axonal, cellular, and vascular injuries. However, studies related to understanding the temporal changes in the cerebral blood flow following traumatic brain injury extending to sub-acute periods are limited. In addition, knowledge related to microhemorrhages, such as their detection, localization, and temporal progression, is important in the evaluation of traumatic brain injury. Materials and Methods: Cerebral blood flow changes and microhemorrhages in male Sprague Dawley rats at 4 h, 24 h, 3 days, and 7 days were assessed following a closed head injury induced by the Marmarou impact acceleration device (2 m height, 450 g brass weight). Cerebral blood flow was measured by arterial spin labeling. Microhemorrhages were assessed by susceptibility-weighted imaging and Prussian blue histology. Results: Traumatic brain injury rats showed reduced regional and global cerebral blood flow at 4 h and 7 days post-injury. Injured rats showed hemorrhagic lesions in the cortex, corpus callosum, hippocampus, and brainstem in susceptibility-weighted imaging. Injured rats also showed Prussian blue reaction products in both the white and gray matter regions up to 7 days after the injury. These lesions were observed in various areas of the cortex, corpus callosum, hippocampus, thalamus, and midbrain. Conclusions: These results suggest that changes in cerebral blood flow and hemorrhagic lesions can persist for sub-acute periods after the initial traumatic insult in an animal model. In addition, microhemorrhages otherwise not seen by susceptibility-weighted imaging are present in diverse regions of the brain. The combination of altered cerebral blood flow and microhemorrhages can potentially be a source of secondary injury changes following traumatic brain injury and may need to be taken into consideration in the long-term care of these cases. PMID:26605126

  7. 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

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

    PubMed Central

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

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  9. Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor.

    PubMed

    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

  10. 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

  11. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    PubMed

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  12. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats.

    PubMed

    Ren, Xiaoyan; Ma, Hong; Zuo, Zhiyi

    2016-06-01

    Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues. PMID:26932203

  13. Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

    PubMed Central

    Naseem, Mehar; Parvez, Suhel

    2014-01-01

    Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it. PMID:25587567

  14. Return to Work for Persons with Traumatic Brain Injury and Spinal Cord Injury: Three Case Studies.

    ERIC Educational Resources Information Center

    Wehman, Paul; And Others

    1994-01-01

    Supported employment was utilized in the vocational rehabilitation of two people with traumatic brain injury and one with a traumatic spinal cord injury. Supported employment was found to yield real work outcomes, though it required substantial amounts of money to return the three patients to relatively low-paying jobs. Funding issues are…

  15. Enduring changes in tonic GABAA receptor signaling in dentate granule cells after controlled cortical impact brain injury in mice.

    PubMed

    Boychuk, Jeffery A; Butler, Corwin R; Halmos, Katalin Cs; Smith, Bret N

    2016-03-01

    Changes in functional GABAAR signaling in hippocampus have previously been evaluated using pre-clinical animal models of either diffuse brain injury or extreme focal brain injury that precludes measurement of cells located ipsilateral to injury. As a result, there is little information about the status of functional GABAAR signaling in dentate granule cells (DGCs) located ipsilateral to focal brain injury, where significant cellular changes have been documented. We used whole-cell patch-clamp recordings from hippocampal slices to measure changes in GABAARs in dentate granule cells (DGCs) at 1-2, 3-5, and 8-13 weeks after controlled cortical impact (CCI) brain injury. Synaptic and tonic GABAAR currents (ITonicGABA) were measured in DGCs at baseline conditions and during application of the GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol hydrochloride (THIP) to assess in the function of δ subunit-containing GABAARs. DGCs ipsilateral to CCI exhibited no changes in the amplitude of resting ITonicGABA relative to DGCs after sham-injury or contralateral to CCI. In contrast, there was a significant reduction in the THIP-evoked ITonicGABA in DGCs ipsilateral to CCI at both time-points. Tonic GABAergic inhibition of DGCs ipsilateral to injury also exhibited reduced responsiveness to the neurosteroid THDOC. ITonicGABA in DGCs ipsilateral to CCI did not exhibit a change in sensitivity to L655,708, an inverse agonist with selectivity for α5 subunit-containing GABAARs, suggesting a lack of functional change in GABAARs containing this subunit. At the 8-13 week time-point, gene expression of GABAAR subunits expected to contribute to ITonicGABA (i.e., α4, α5 and δ) was not significantly altered by CCI injury in isolated dentate gyrus. Collectively, these results demonstrate enduring functional changes in ITonicGABA in DGCs ipsilateral to focal brain injury that occur independent of altered gene expression. PMID:26772635

  16. Patterns of Alcohol Use after Traumatic Brain Injury.

    PubMed

    Pagulayan, Kathleen F; Temkin, Nancy R; Machamer, Joan E; Dikmen, Sureyya S

    2016-07-15

    Alcohol misuse and traumatic brain injury (TBI) frequently co-occur. The negative consequences of this interaction are well documented, but the patterns of long-term post-injury alcohol consumption are less clear. This study examined patterns of alcohol use among 170 adults with a history of complicated mild to severe TBI. Participants were recruited from a Level 1 Trauma Center at the time of their injury and completed evaluations at 1 month, 6 months, 12 months, and 3-5 years post-injury. Pre-injury alcohol use was also assessed at the time of the 1-month assessment. A modified Quantity-Frequency Index of alcohol consumption was then calculated for each time point. The results revealed high levels of pre-injury alcohol consumption, followed by a reduction in consumption at 1-month post-injury. A significant increase in consumption was noted by 6 months post-injury, followed by more gradual increases in alcohol consumption at 1 year. Post-injury alcohol consumption was comparable to the general public at 6 months, 12 months, and 3-5 years post-injury. These results suggest that the first 6 months post-injury may be the critical window of opportunity for alcohol intervention. PMID:26530335

  17. 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. PMID:24326094

  18. Traumatic brain injury: the lag between diagnosis and treatment.

    PubMed

    Retsinas, J

    1993-01-01

    Ogburn described the "culture lag" between technology and attitudes, as people take time to assimilate new technologies, and new facts, into their worldviews. Traumatic brain injury is now a common diagnosis, thanks to neurosurgical expertise. Where thirty years ago mortality from head injuries was high, today mortality rates have improved dramatically; yet even while neurosurgeons spare thousands of people each year, our society struggles to develop appropriate rehabilitation protocols. To date, we are in the lag phase, between diagnosis and treatment. This paper discusses that lag, including reasons for the lack of an effective rehabilitation protocol (the paucity of funds for research, the nature of brain injuries per se), the reluctance of insurers to cover brain injury rehabilitation (the lengthy time involved in rehabilitation, the blurring between rehabilitation and long term care, the nature of experience-rated contracting to businesses for health care insurance, the burgeoning of proprietary brain injury rehabilitation centers), and the prospects for closing the gap in the near future. The paper concludes that preventive measures (seat belt laws, motorcycle helmet laws, laws for helmets in contact sports) allow policy-makers to confront the growing societal problem of the mounting census of head-injured, by avoiding that census and focusing instead on the prevention, or diminution, of future head injuries. PMID:10125462

  19. The Importance of Early Brain Injury after Subarachnoid Hemorrhage

    PubMed Central

    Sehba, Fatima A.; Hou, Jack; Pluta, Ryszard M.; Zhang, John H.

    2012-01-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH. PMID:22414893

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

    PubMed

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

    2014-05-01

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

  1. Does distracting pain justify performing brain computed tomography in multiple traumas with mild head injury?

    PubMed

    Sadeghian, Homa; Motiei-Langroudi, Rouzbeh

    2016-06-01

    Traumatic brain injury (TBI) is a significant health concern classified as mild, moderate, and severe. Although the indications to perform brain computed tomography (CT) are clear in moderate and severe cases, there still exists controversy in mild TBI (mTBI). We designed the study to evaluate the significance of distracting pain in patients with mTBI. The study population included patients with mild traumatic brain injury (GCS ≥13). Moderate and high risk factors including age <18 months or ≥60 years, moderate to severe or progressive headache, ≥2 episodes of vomiting, loss of consciousness (LOC), post-traumatic amnesia, seizure or prior antiepileptic use, alcohol intoxication, previous neurosurgical procedures, uncontrolled hypertension, anticoagulant use, presence of focal neurologic deficits, deformities in craniofacial region, and penetrating injuries were excluded. The patients were then grouped based on presence (DP+) or absence (DP-) of another organ fracture with severe pain (based on VAS). The primary outcome was any abnormal findings on brain CT scans; 330 patients were enrolled (184 DP+ and 146 DP-). Overall, two DP+ and one DP- patients had mild cerebral edema in brain CT (p > 0.99). No patients had any neurologic symptoms or signs in follow-up. Our results show that in the absence of any other risk factors, distracting pain from other organs (limbs, pelvis, and non-cervical spine) cannot be regarded as a brain CT indication in patients with mild TBI, as it is never associated with significant intracranial lesions. PMID:26931118

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

    PubMed

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

    1988-03-01

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

  3. 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

  4. 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

  5. Vampiristic behaviors in a patient with traumatic brain injury induced disinhibition.

    PubMed

    Hervey, William M; Catalano, Glenn; Catalano, Maria C

    2016-06-16

    Vampiristic behaviors are rarely seen clinically and less than 100 cases have been reported in the world literature to date. A distinction is usually made as to whether the patient drinks their own blood or the blood of others. We describe a 38-year-old patient who had vampiristic thoughts and fantasies that began in adolescence, but did not act on these thoughts until after she suffered a traumatic brain injury with a three-week loss of consciousness while serving in the military. Brain imaging showed focal damage to her bilateral frontal lobes. Psychological testing demonstrated impairment of executive function. We review the proposed diagnostic criteria for vampirism and discuss how behavioral disinhibition may have affected the emergence into behavior of her previously inhibited vampiristic thoughts. PMID:27326398

  6. Vampiristic behaviors in a patient with traumatic brain injury induced disinhibition

    PubMed Central

    Hervey, William M; Catalano, Glenn; Catalano, Maria C

    2016-01-01

    Vampiristic behaviors are rarely seen clinically and less than 100 cases have been reported in the world literature to date. A distinction is usually made as to whether the patient drinks their own blood or the blood of others. We describe a 38-year-old patient who had vampiristic thoughts and fantasies that began in adolescence, but did not act on these thoughts until after she suffered a traumatic brain injury with a three-week loss of consciousness while serving in the military. Brain imaging showed focal damage to her bilateral frontal lobes. Psychological testing demonstrated impairment of executive function. We review the proposed diagnostic criteria for vampirism and discuss how behavioral disinhibition may have affected the emergence into behavior of her previously inhibited vampiristic thoughts. PMID:27326398

  7. Network analysis of human fMRI data suggests modular restructuring after simulated acquired brain injury.

    PubMed

    Ruiz Vargas, E; Mitchell, D G V; Greening, S G; Wahl, L M

    2016-01-01

    The pathophysiology underlying neurocognitive dysfunction following mild traumatic brain injury (TBI), or concussion, is poorly understood. In order to shed light on the effects of TBI at the functional network or modular level, our research groups are engaged in the acquisition and analysis of functional magnetic resonance imaging data from subjects post-TBI. Complementary to this effort, in this paper we use mathematical and computational techniques to determine how modular structure changes in response to specific mechanisms of injury. In particular, we examine in detail the potential effects of focal contusions, diffuse axonal degeneration and diffuse microlesions, illustrating the extent to which functional modules are preserved or degenerated by each type of injury. One striking prediction of our study is that the left and right hemispheres show a tendency to become functionally separated post-injury, but only in response to diffuse microlesions. We highlight other key differences among the effects of the three modelled injuries and discuss their clinical implications. These results may help delineate the functional mechanisms underlying several of the cognitive sequelae associated with TBI. PMID:26463519

  8. Synaptic Mechanisms of Blast-Induced Brain Injury.

    PubMed

    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

  9. 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

  10. Atypical language lateralization and early linguistic development in children with focal brain lesions.

    PubMed

    Chilosi, A M; Pecini, C; Cipriani, P; Brovedani, P; Brizzolara, D; Ferretti, G; Pfanner, L; Cioni, G

    2005-11-01

    The effects of congenital, unilateral, focal brain lesions on early linguistic development and hemispheric lateralization for language were investigated longitudinally in 24 preschool children with hemiplegia (14 males, 10 females), 12 with left hemisphere damage (LHD) and 12 with right hemisphere damage (RHD). A comprehensive linguistic assessment was performed at 2 and 3 years of life; cerebral lateralization for language was measured by the Fused Dichotic Words Listening Test. An early left-side specificity for language was indicated by the presence of lexical and grammatical delay in most children with LHD. In the dichotic listening test all 12 children with LHD showed a shift of language lateralization from the left to the right hemisphere. Atypical lateralization coefficients (lambda), i.e. values falling more than two standard deviations from the mean of a normative sample, were associated with a delay in lexical and grammatical development, especially after LHD. In addition, cortical-subcortical-periventricular lesions rather than solely periventricular damage, and larger lesions rather than small, were associated with the most atypical lateralization coefficients, irrespective of lesion side. Results of this study suggest that language and lateralization data are closely related and that reallocation of language functions in alternative regions of the brain has a cost in terms of a slow rate of language acquisition. PMID:16225734

  11. Dimensions of Personality Disturbance After Focal Brain Damage: Investigation with the Iowa Scales of Personality Change

    PubMed Central

    Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W.; Tranel, Daniel

    2011-01-01

    This study employed a multi-step, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (1) Five dimensions were hypothesized based on empirical literature and conceptual grounds. (2) Principal components analysis was performed on the Iowa Scales of Personality Change to determine the pattern of covariance among 30 personality characteristics. (3) When discrepancies existed between principal components analysis results and conceptually-based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions. (4) The fit of data to the refined dimensions was assessed by examination of intercorrelations. (5) Differential predictions concerning the relationship of dimensions to ventromedial prefrontal (vmPFC) damage were tested. This process resulted in specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits, and tended to have more Diminished Motivation/Hypo-emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change. PMID:21500116

  12. Dimensions of personality disturbance after focal brain damage: investigation with the Iowa Scales of Personality Change.

    PubMed

    Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W; Tranel, Daniel

    2011-10-01

    This study employed a multistep, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (a) Five dimensions were hypothesized based on empirical literature and conceptual grounds; (b) principal components analysis was performed on the Iowa Scales of Personality Change (ISPC) to determine the pattern of covariance among 30 personality characteristics; (c) when discrepancies existed between principal components analysis results and conceptually based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions; (d) the fit of data to the refined dimensions was assessed by examination of intercorrelations; (e) differential predictions concerning the relationship of dimensions to ventromedial prefrontal cortex (vmPFC) damage were tested. This process resulted in the specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-Emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits and tended to have more Diminished Motivation/Hypo-Emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change. PMID:21500116

  13. Transorbital brain injury by a metallic fragment: a case report.

    PubMed

    Seçer, Mehmet; Ergüngör, Mehmet Fikret; Dalgiç, Ali; Okay, Hilmi Onder; Dağlioğlu, Ergun; Nacar, Osman Arikan

    2007-04-01

    Because of anatomical configuration of the orbit, the brain can be damaged by penetrating transorbital injuries. At first sight, this type of trauma can be thought of as a solitary eye trauma. In this paper, we report a case who suffered from brain injury by a metallic foreign body which passed into the brain through the orbit. He was operated on urgently at two stages and there was no complication after 14 months of follow-up. Any neurological deficit or deterioration of consciousness would be marked. These types of injuries have to be evaluated systemically. Finally, detailed history, neuroradiological investigations, early surgical exploration and multidisciplinary studies are very important to obtain a good outcome. PMID:17935038

  14. Detecting Behavioral Deficits Post Traumatic Brain Injury in Rats.

    PubMed

    Awwad, Hibah O

    2016-01-01

    Traumatic brain injury (TBI), ranging from mild to severe, almost always elicits an array of behavioral deficits in injured subjects. Some of these TBI-induced behavioral deficits include cognitive and vestibulomotor deficits as well as anxiety and other consequences. Rodent models of TBI have been (and still are) fundamental in establishing many of the pathophysiological mechanisms of TBI. Animal models are also utilized in screening and testing pharmacological effects of potential therapeutic agents for brain injury treatment. This chapter details validated protocols for each of these behavioral deficits post traumatic brain injury in Sprague-Dawley male rats. The elevated plus maze (EPM) protocol is described for assessing anxiety-like behavior; the Morris water maze protocol for assessing cognitive deficits in learning memory and spatial working memory and the rotarod test for assessing vestibulomotor deficits. PMID:27604739

  15. Traumatic Brain Injury (TBI) Data and Statistics

    MedlinePlus

    ... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...

  16. A case of “Borrowed Identity Syndrome” after severe traumatic brain injury

    PubMed Central

    Pachalska, Maria; MacQueen, Bruce Duncan; Kaczmarek, Bozydar L. J.; Wilk-Franczuk, Magdalena; Herman-Sucharska, Izabela

    2011-01-01

    Summary Background It is well known that traumatic brain injury often changes the way the patient perceives reality, which often means a distortion of the perception of self and the world. The purpose of this article is to understand the processes of identity change after traumatic brain injury. Case Report We describe progressive deterioration in personal identity in a former physician who had sustained a serious head injury (1998), resulting in focal injuries to the right frontal and temporal areas. He regained consciousness after 63 days in coma and 98 days of post-traumatic amnesia, but has since displayed a persistent loss of autobiographical memory, self-image, and emotional bonds to family and significant others. Qualitative ‘life-story’ interviewing was undertaken to explore the mental state of a patient whose subjective, “first person” identity has been disengaged, despite the retention of significant amounts of objective, “third person” information about himself and his personal history (though this was also lost at a later stage in the patient’s deterioration). Identity change in our patient was characterized by a dynamic and convoluted process of contraction, expansion and tentative balance. Our patient tends to cling to the self of others, borrowing their identities at least for the period he is able to remember. Identity is closely connected with the processes of memory. Conclusions The results will be examined in relation to the microgenetic theory of brain function. The brain mechanisms that may account for these impairments are discussed. Findings from this study have important implications for the delivery of person-focused rehabilitation. PMID:21278697

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

    PubMed Central

    Yattoo, GH; Tabish, Amin

    2008-01-01

    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 PMID:18570674

  18. Cellular Basis of Anoxic-Ischemic Brain Injury

    PubMed Central

    Bronshvag, Michael M.

    1978-01-01

    Anoxic-ischemic cerebral disease is an important primary cause of morbidity and mortality, and also complicates a number of systemic diseases. Its clinical manifestations, such as hemiparesis and coma, represent cellular injury sustained by the complex, inhomogeneous brain. An understanding of the nature and pattern of anoxic-ischemic cerebral injury, and of the logical basis for avenues of therapy, is necessary to the management of patients with the various anoxic-ischemic disorders. PMID:685270

  19. 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. PMID:23473341

  20. Sawdust for Brains: Definition and Disconfirmation after Mild Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Schell-Word, Charlotte

    1999-01-01

    Offers an account of one person's struggles with the effects of a mild brain injury. Framed within the context of current literature on mild head injuries, this first-person account discusses how the changes in sense of self created feelings of disconfirmation, confusion, and emotional distress. Discusses ways of coping with internal changes when…

  1. The emergence of artistic ability following traumatic brain injury

    PubMed Central

    Midorikawa, Akira; Kawamura, Mitsuru

    2015-01-01

    In this study, the case of a patient who developed artistic ability following a traumatic brain injury is reported. The subject was a 49-year-old male who suffered brain injury at the age of 44 due to an accidental fall. At age 48, he began drawing with great enthusiasm and quickly developed a personal style with his own biomorphic iconography. At first, his drawing was restricted to realistic reproductions of photographs of buildings, but his style of drawing changed and became more personal and expressionistic over the following 6 months. PMID:24417345

  2. 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

  3. Do metals that translocate to the brain exacerbate traumatic brain injury?

    PubMed

    Kalinich, John F; Kasper, Christine E

    2014-05-01

    Metal translocation to the brain is strictly controlled and often prevented by the blood-brain barrier. For the most part, only those metals required to maintain normal function are transported into the brain where they are under tight metabolic control. From the literature, there are reports that traumatic brain injury disrupts the blood-brain barrier. This could allow the influx of metals that would normally have been excluded from the brain. We also have preliminary data showing that metal pellets, surgically-implanted into the leg muscle of a rat to simulate a shrapnel wound, solubilize and the metals comprising the pellet can enter the brain. Surprisingly, rats implanted with a military-grade tungsten alloy composed of tungsten, nickel, and cobalt also showed significantly elevated uranium levels in their brains as early as 1 month after pellet implantation. The only source of uranium was low levels that are naturally found in food and water. Conversely, rats implanted with depleted uranium pellets demonstrated elevated uranium levels in brain resulting from degradation of the implanted pellets. However, when cobalt levels were measured, there were no significant increases in the brain until the rats had reached old age. The only source of cobalt for these rats was the low levels found in their food and water. These data suggest that some metals or metal mixtures (i.e., tungsten alloy), when embedded into muscle, can enhance the translocation of other, endogenous metals (e.g., uranium) across the blood-brain barrier. For other embedded metals (i.e., depleted uranium), this effect is not observed until the animal is of advanced age. This raises the possibility that metal body-burdens can affect blood-brain barrier permeability in a metal-specific and age-dependent manner. This possibility is disconcerting when traumatic brain injury is considered. Traumatic brain injury has been called the "signature" wound of the conflicts in Iraq and Afghanistan, often, an

  4. Hyperbaric oxygen therapy improves cognitive functioning after brain injury

    PubMed Central

    Liu, Su; Shen, Guangyu; Deng, Shukun; Wang, Xiubin; Wu, Qinfeng; Guo, Aisong

    2013-01-01

    Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney's free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats’ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was significantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly improves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is mediated by metabolic changes and nerve cell restoration in the hippocampal CA3 region. PMID:25206655

  5. Traumatic Brain Injury Detection Using Electrophysiological Methods

    PubMed Central

    Rapp, Paul E.; Keyser, David O.; Albano, Alfonso; Hernandez, Rene; Gibson, Douglas B.; Zambon, Robert A.; Hairston, W. David; Hughes, John D.; Krystal, Andrew; Nichols, Andrew S.

    2015-01-01

    Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3) The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in q

  6. Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

    PubMed Central

    2014-01-01

    Background Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. Findings Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction. PMID:24576351

  7. Brain-computer interface after nervous system injury.

    PubMed

    Burns, Alexis; Adeli, Hojjat; Buford, John A

    2014-12-01

    Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders. PMID:25193343

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  9. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    PubMed

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID:26556240

  10. Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy.

    PubMed

    Wong, Victor S; Langley, Brett

    2016-06-20

    Traumatic brain injury (TBI) contributes to nearly a third of all injury-related deaths in the United States. For survivors of TBI, depending on severity, patients can be left with devastating neurological disabilities that include impaired cognition or memory, movement, sensation, or emotional function. Despite the efforts to identify novel therapeutics, the only strategy to combat TBI is risk reduction (helmets, seatbelts, removal of fall hazards, etc.). Enormous heterogeneity exists within TBI, and it depends on the severity, the location, and whether the injury was focal or diffuse. Evidence from recent studies support the involvement of epigenetic mechanisms such as DNA methylation, chromatin post-translational modification, and miRNA regulation of gene expression in the post-injured brain. In this review, we discuss studies that have assessed epigenetic changes and mechanisms following TBI, how epigenetic changes might not only be limited to the nucleus but also impact the mitochondria, and the implications of these changes with regard to TBI recovery. PMID:27155457

  11. Sleep Doesn't Come Easy to Those with Brain Injuries

    MedlinePlus

    ... Sleep Doesn't Come Easy to Those With Brain Injuries And that may affect daytime performance at ... HealthDay News) -- Many people who suffer a traumatic brain injury struggle with sleep problems they may not ...

  12. 78 FR 37834 - Submission for OMB review; 30-Day Comment Request; Federal Interagency Traumatic Brain Injury...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... HUMAN SERVICES National Institutes of Health Submission for OMB review; 30-Day Comment Request; Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data Access Request SUMMARY: Under the... Collection: Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data...

  13. 78 FR 12334 - Proposed Collection; Comment Request: Federal Interagency Traumatic Brain Injury Research (FITBIR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request: Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data Access Request SUMMARY: In compliance with.... Proposed Collection: Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System...

  14. Traumatic Brain Injury: Hope through Research

    MedlinePlus

    ... with TBI visited an emergency department [1] . This computer-generated graphic shows how, in 1848, a 3- ... carry electrical impulses). Like the wires in a computer, axons connect various areas of the brain to ...

  15. Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury.

    PubMed

    Clayton, E; Kinley-Cooper, S K; Weber, R A; Adkins, D L

    2016-06-01

    There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26855256

  16. Updating memory after mild traumatic brain injury and orthopedic injuries.

    PubMed

    Hanten, Gerri; Li, Xiaoqi; Ibarra, Alyssa; Wilde, Elisabeth A; Barnes, Amanda; McCauley, Stephen R; McCarthy, James; Hoxhaj, Shkelzen; Mendez, Donna; Hunter, Jill V; Levin, Harvey S; Smith, Douglas H

    2013-04-15

    Few studies have examined the trajectory of recovery of executive function (EF) after mild TBI (mTBI). Therefore, consensus has not been reached on the incidence and extent of EF impairment after mTBI. The present study investigated trajectory of change in executive memory over 3 months after mTBI on 59 right-handed participants with mTBI, as defined by Centers for Disease Control criteria, ages 14-30 years, recruited within 96 hours post-injury and tested <1 week (baseline), 1 month, and 3 months after injury. Also included were 58 participants with orthopedic injury (OI) and 27 typically developing (TD) non-injured participants with similar age, socioeconomic status, sex, and ethnicity. MRI data were acquired at baseline and 3 months. Although criteria included a normal CT scan, lesions were detected by MRI in 19 mTBI patients. Participants completed the KeepTrack task, a verbal recall task placing demands on goal maintenance, semantic memory, and memory updating. Scores reflected items recalled and semantic categories maintained. The mTBI group was divided into two groups: high (score ≥12) or low (score <12) symptoms based on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Mixed model analyses revealed the trajectory of change in mTBI patients (high and low RPQ), OI patients, and TD subjects were similar over time (although the TD group differed from other groups at baseline), suggesting no recovery from mTBI up to 90 days. For categories maintained, differences in trajectory of recovery were discovered, with the OI comparison group surprisingly performing similar to those in the mTBI group with high RPQ symptoms, and different from low RPQ and the TD groups, bringing up questions about utility of OIs as a comparison group for mTBI. Patients with frontal lesions (on MRI) were also found to perform worse than those without lesions, a pattern that became more pronounced with time. PMID:23227898

  17. Regional Differences in Susceptibility to Hypoxic-Ischemic Injury in the Preterm Brain: Exploring the Spectrum from White Matter Loss to Selective Grey Matter Injury in a Rat Model

    PubMed Central

    Selip, D. B.; Jantzie, L. L.; Chang, M.; Jackson, M. C.; Fitzgerald, E. C.; Boll, G.; Murphy, A.; Jensen, F. E.

    2012-01-01

    Models of premature brain injury have largely focused on the white matter injury thought to underlie periventricular leukomalacia (PVL). However, with increased survival of very low birth weight infants, injury patterns involving grey matter are now recognized. We aimed to determine how grey matter lesions relate to hypoxic-ischemic- (HI) mediated white matter injury by modifying our rat model of PVL. Following HI, microglial infiltration, astrocytosis, and neuronal and axonal degeneration increased in a region-specific manner dependent on the severity of myelin loss in pericallosal white matter. The spectrum of injury ranged from mild, where diffuse white matter abnormalities were dominant and were associated with mild axonal injury and local microglial activation, to severe HI injury characterized by focal MBP loss, widespread neuronal degeneration, axonal damage, and gliosis throughout the neocortex, caudate putamen, and thalamus. In sum, selective regional white matter loss occurs in the preterm rat concomitantly with a clinically relevant spectrum of grey matter injury. These data demonstrate an interspecies similarity of brain injury patterns and further substantiates the reliable use of this model for the study of preterm brain injury. PMID:22530125

  18. Transcranial vibro-acoustography can detect traumatic brain injury, in-vivo: Preliminary studies.

    PubMed

    Suarez, Martin W; Dever, David D; Gu, Xiaohan; Ray Illian, P; McClintic, Abbi M; Mehic, Edin; Mourad, Pierre D

    2015-08-01

    Vibro-acoustography (VA) uses two or more beams of confocal ultrasound to generate local vibrations within their target tissue through induction of a time-dependent radiation force whose frequency equals that of the difference of the applied frequencies. While VA has proven effective for assaying the mechanical properties of clinically relevant tissue such as breast lesions and tissue calcifications, its application to brain remains unexplored. Here we investigate the ability of VA to detect acute and focal traumatic brain injury (TBI) in-vivo through the use of transcranially delivered high-frequency (2 MHz) diagnostic focused ultrasound to rat brain capable of generating measurable low-frequency (200-270 kHz) acoustic emissions from outside of the brain. We applied VA to acute sham-control and TBI model rats (sham N=6; TBI N=6) and observed that acoustic emissions, captured away from the site of TBI, had lower amplitudes for TBI as compared to sham-TBI animals. The sensitivity of VA to acute brain damage at frequencies currently transmittable across human skulls, as demonstrated in this preliminary study, supports the possibility that the VA methodology may one day serve as a technique for detecting TBI. PMID:25964238

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

    PubMed

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

    2016-04-01

    Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptorSarm1(sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model.Sarm1(-/-)mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared toSarm1(+/+)mice. Furthermore, mice lackingSarm1had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function inSarm1(-/-)animals. Finally, usingin vivoproton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism inSarm1(-/-)mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. PMID:26912636

  20. Correlation between astrocyte activity and recovery from blood-brain barrier breakdown caused by brain injury.

    PubMed

    Ikeshima-Kataoka, Hiroko; Yasui, Masato

    2016-08-17

    Glial activation is associated with cell proliferation and upregulation of astrocyte marker expression following traumatic injury in the brain. However, the biological significance of these processes remains unclear. In the present study, astrocyte activation was investigated in a murine brain injury model. Brain injury induces blood-brain barrier (BBB) breakdown and immunoglobulin G (IgG) leak into the brain parenchyma. The recovery of BBB breakdown was evaluated by analyzing immunofluorescent staining with mouse IgG antibody. IgG leakage was greatest at 1 day after stab wound injury and decreased thereafter, and almost diminished after 7 days. Bromodeoxy uridine incorporation was used, and astrocyte proliferation rates were examined by coimmunostaining with anti-bromodeoxy uridine and anti-glial fibrillary acid protein antibodies. Consistent with IgG leakage assays, astrocyte activation was the highest at day 3 and decreased after 7 days. Moreover, in reverse transcriptase-quantitative-PCR experiments, genes associated with BBB integrity were downregulated immediately after BBB breakdown and recovered to basal expression levels within 7 days. These data indicated that astrocyte activation correlated with BBB recovery from breakdown following brain injury. PMID:27362437

  1. 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

  2. Crash Simulator: Brain-and-Spine Injury Mechanics

    NASA Astrophysics Data System (ADS)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    Recently, the first author has proposed a new coupled loading-rate hypothesis as a unique cause of both brain and spinal injuries, which states that they are both caused by a Euclidean jolt, an impulsive loading that strikes head and spine (or, any other part of the human body)- in several coupled degrees-of-freedom simultaneously. Injury never happens in a single direction only, nor is it ever caused by a static force. It is always an impulsive translational plus rotational force. The Euclidean jolt causes two basic forms of brain, spine and other musculo-skeletal injuries: (i) localized translational dislocations; and (ii) localized rotational disclinations. In the present Chapter, we first review this unique mechanics of a general human mechanical injury, and then describe how it can be predicted and controlled by a crash simulator toolbox. This rigorous Matlab toolbox has been developed using an existing thirdparty toolbox DiffMan, for accurately solving differential equations on smooth manifolds and mechanical Lie groups. The present crash simulator toolbox performs prediction/control of brain and spinal injuries within the framework of the Euclidean group SE(3) of rigid motions in our natural 3-dimensional space.

  3. Early community outreach intervention in children with acquired brain injury.

    PubMed

    Emanuelson, I; Wendt, L V; Hagberg, I; Marchioni-Johansson, M; Ekberg, G; Olsson, U; Larsson, J; Egerlund, H; Lindgren, K; Pestat, C

    2003-12-01

    Ten patients with acquired brain injury were recruited over an 18 month period in the south-western health care region of Sweden in order to evaluate the costs and effectiveness of a multidisciplinary community outreach intervention programme. An experienced multidisciplinary project team was involved and patients underwent detailed functional, cognitive and motor assessments following initial contact within two weeks of injury, within six weeks of injury and at a 12-month follow-up. An individualized counselling programme was also offered. Of an expected recruitment number of 50 patients (based on epidemiological and population based figures) 10 children were reached, evaluated and followed; eight patients with traumatic brain injury (five severe, two moderate and one mild), and two patients with non-traumatic brain injury (both severe). At follow-up there was a significant improvement in motor function. No significant changes were seen in other areas of functional assessment or on neuropsychological measures although there were mild improvements in communication and behaviour functions. The financial costs per patient in the programme were deemed relatively modest compared with cost estimates of shorter-term in-patient rehabilitation. Time intensive interventions included supporting caregivers and school staff and the direct and indirect patient interventions were shown to enhance support and promote active involvement of local services. PMID:14634359

  4. Traumatic Brain Injury: What the Teacher Needs To Know.

    ERIC Educational Resources Information Center

    Pieper, Betty

    Intended for use by the classroom teacher, this guide presents teaching suggestions as well as suggested resources for teaching children with traumatic brain injuries (TBI). Emphasis is placed on working with the injured family and the importance of planning for transition and re-entry into the classroom through a continuum of settings. Teachers…

  5. Spoken Persuasive Discourse Abilities of Adolescents with Acquired Brain Injury

    ERIC Educational Resources Information Center

    Moran, Catherine; Kirk, Cecilia; Powell, Emma

    2012-01-01

    Purpose: The aim of this study was to examine the performance of adolescents with acquired brain injury (ABI) during a spoken persuasive discourse task. Persuasive discourse is frequently used in social and academic settings and is of importance in the study of adolescent language. Method: Participants included 8 adolescents with ABI and 8 peers…

  6. 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. PMID:26804988

  7. Transfer and generalization of cognitive skill after traumatic brain injury.

    PubMed

    Parenté, R; Twum, M; Zoltan, B

    1994-01-01

    The authors discuss the principles of transfer and generalization of learning as they apply to rehabilitation after traumatic brain injury. A general model is provided that predicts the outcome of most rehabilitation therapies. Implications of the model for improving treatment are discussed. Two experimental tests of the model are described and the results are in accord with model predictions. PMID:24526210

  8. Traumatic Brain Injury and Its Effect on Students

    ERIC Educational Resources Information Center

    Rosenthal, Stacy B.

    2012-01-01

    Over one million people suffer a traumatic brain injury every year, many of whom are students between the ages of 5 and 18. Using a qualitative case study approach, I wanted to discover the specific factors that both impede and help the school re-entry process for students in grades kindergarten through twelve so that these students can return to…

  9. Working with Parents of Students with Traumatic Brain Injuries.

    ERIC Educational Resources Information Center

    Rhein, Barbara; And Others

    Intended for educators working with children who have suffered traumatic brain injuries (TBI), this brief paper addresses parent issues, administrative issues, and programmatic issues. Noted are the five stages of adjustment typically experienced by parents: shock, elation, reality, crisis, and mourning. Professionals are encouraged to be informed…

  10. Predictors of Neuropsychological Test Performance After Pediatric Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Donders, Jacobus; Nesbit-Greene, Kelly

    2004-01-01

    The influence of neurological and demographic variables on neuropsychological test performance was examined in 100 9- to 16-year-old children with traumatic brain injury (TBI). Regression analyses were conducted to determine the relative contributions of coma, neuroimaging findings, ethnicity, socioeconomic status, and gender to variance in…

  11. Social dysfunction after pediatric traumatic brain injury: A translational perspective.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J; Shultz, Sandy R; O'Brien, Terence J; Anderson, Vicki; Semple, Bridgette D

    2016-05-01

    Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood and adolescence. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224

  12. Endogenous lipoid pneumonia in a cachectic patient after brain injury.

    PubMed

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618

  13. Endogenous lipoid pneumonia in a cachectic patient after brain injury

    PubMed Central

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618

  14. Students with Acquired Brain Injury: A Legal Analysis

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2011-01-01

    This article provides a comprehensive and current synthesis of the legislation, regulations, policy interpretations, and case law concerning students with traumatic and nontraumatic brain injury from pre-K to grade 12. The primary focus is the Individuals with Disabilities Education Act, but the scope extends to other applicable legal bases. The…

  15. Performance Monitoring in Children following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Ornstein, Tisha J.; Levin, Harvey S.; Chen, Shirley; Hanten, Gerri; Ewing-Cobbs, Linda; Dennis, Maureen; Barnes, Marcia; Max, Jeffrey E.; Logan, Gordon D.; Schachar, Russell

    2009-01-01

    Background: Executive control deficits are common sequelae of childhood traumatic brain injury (TBI). The goal of the current study was to assess a specific executive control function, performance monitoring, in children following TBI. Methods: Thirty-one children with mild-moderate TBI, 18 with severe TBI, and 37 control children without TBI, of…

  16. Communicative Impairment in Traumatic Brain Injury: A Complete Pragmatic Assessment

    ERIC Educational Resources Information Center

    Angeleri, R.; Bosco, F. M.; Zettin, M.; Sacco, K.; Colle, L.; Bara, B. G.

    2008-01-01

    The aim of the present study was to examine the communicative abilities of traumatic brain injury patients (TBI). We wish to provide a complete assessment of their communicative ability/disability using a new experimental protocol, the "Assessment Battery of Communication," ("ABaCo") comprising five scales--linguistic, extralinguistic,…

  17. Blissfully unaware: Anosognosia and anosodiaphoria after acquired brain injury.

    PubMed

    Gasquoine, Philip Gerard

    2016-01-01

    Historically, anosognosia referred to under-report of striking symptoms of acquired brain injury (e.g., hemiplegia) with debilitating functional consequences and was linked with anosodiaphoria, an emotional reaction of indifference. It was later extended to include under-report of all manner of symptoms of acquired brain injury by the patient compared to clinicians, family members, or functional performance. Anosognosia is related to time since onset of brain injury but not consistently to demographic variables, lesion location (except that it is more common after unilateral right than left hemispheric injury), or specific neuropsychological test scores. This review considers all manifestations of anosognosia as a unitary phenomenon with differing clinical characteristics dictated by variability in linked cognitive impairments. It is concluded that anosognosia has three chief contributing factors: (1) procedural: measurement differences across studies in terms of symptom selection and the designation of a "gold standard" of patient symptomatology; (2) psychological: a tendency towards positive self-evaluation and the avoidance of adverse information, that also occurs in neurologically intact individuals; and (3) neuropathological: an increased likelihood of error recognition failure from disconnections that disrupt feedback between injured brain regions governing specific behaviours (symptoms) and anterior cingulate/insular cortex. Anosodiaphoria is considered as an associated symptom, resulting from the same psychological and neuropathological factors. PMID:25686381

  18. Swallowing Disorders in Severe Brain Injury in the Arousal Phase.

    PubMed

    Bremare, A; Rapin, A; Veber, B; Beuret-Blanquart, F; Verin, E

    2016-08-01

    The objective of this study was to determine the clinical characteristics of swallowing disorders in severe brain injury in the arousal phase after coma. Between December 1, 2013 and June 30, 2014, eleven patients with severe acquired brain injury who were admitted to rehabilitation center (Male 81.8 %; 40.7 ± 14.6 years) were included in the study. Evaluation of swallowing included a functional examination, clinical functional swallowing test, and naso-endoscopic swallowing test. All patients had swallowing disorders at admission. The first functional swallowing test showed oral (77.8 %) and pharyngeal (66.7 %) food bolus transport disorders; and alterations in airway protection mechanisms (80 %). Swallowing test under endoscopic control showed a disorder in swallowing coordination in 55.6 % of patients tested. Seven (63.6 %) patients resumed oral feeding within an average of 6 weeks after admission to rehabilitation center and 14 weeks after acquired brain injury. Six (85.7 %) of these seven patients continued to require modified solid and liquid textures. Swallowing disorders are a major concern in severe brain injury in the arousal phase. Early bedside assessment of swallowing is essential for detection of swallowing disorders to propose appropriate medical rehabilitation care to these patients in a state of altered consciousness. PMID:27090424

  19. Intervention Strategies for Serving Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Arroyos-Jurado, Elsa; Savage, Todd A.

    2008-01-01

    As school-age children are at the highest risk for sustaining a traumatic brain injury (TBI), educational professionals working in school settings will encounter students dealing with the after-effects of a TBI. These effects can influence students' ability to navigate the behavioral, social, and academic demands of the classroom. This article…

  20. Classroom Interventions for Students with Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Bowen, Julie M.

    2005-01-01

    Students who have sustained a traumatic brain injury (TBI) return to the school setting with a range of cognitive, psychosocial, and physical deficits that can significantly affect their academic functioning. Successful educational reintegration for students with TBI requires careful assessment of each child's unique needs and abilities and the…

  1. Traumatic Brain Injury and Special Education: An Information Resource Guide.

    ERIC Educational Resources Information Center

    Stevens, Alice M.

    This resource guide of annotated references on traumatic brain injury (TBI) was created to help educators locate information from such disciplines as neurology, neuropsychology, rehabilitation, and pediatric medicine. Twenty-four resources published from 1990 to 1994 are listed, with annotations. The resources include research reports/reviews,…

  2. Integration of Neuropsychology in Educational Planning Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Stavinoha, Peter L.

    2005-01-01

    Traumatic brain injuries (TBIs) have the potential to significantly disrupt a student's cognitive, academic, social, emotional, behavioral, and physical functioning. It is important for educators to appreciate the array of difficulties students with TBI may experience in order to appropriately assess needs and create an educational plan that…

  3. Decompressive Craniectomy and Traumatic Brain Injury: A Review

    PubMed Central

    Alvis-Miranda, Hernando; Castellar-Leones, Sandra Milena; Moscote-Salazar, Luis Rafael

    2013-01-01

    Intracranial hypertension is the largest cause of death in young patients with severe traumatic brain injury. Decompressive craniectomy is part of the second level measures for the management of increased intracranial pressure refractory to medical management as moderate hypothermia and barbiturate coma. The literature lack of concepts is their indications. We present a review on the state of the art. PMID:27162826

  4. School-Based Traumatic Brain Injury and Concussion Management Program

    ERIC Educational Resources Information Center

    Davies, Susan C.

    2016-01-01

    Traumatic brain injuries (TBIs), including concussions, can result in a constellation of physical, cognitive, emotional, and behavioral symptoms that affect students' well-being and performance at school. Despite these effects, school personnel remain underprepared identify, educate, and assist this population of students. This article describes a…

  5. Hemispheric Visual Attentional Imbalance in Patients with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Pavlovskaya, Marina; Groswasser, Zeev; Keren, Ofer; Mordvinov, Eugene; Hochstein, Shaul

    2007-01-01

    We find a spatially asymmetric allocation of attention in patients with traumatic brain injury (TBI) despite the lack of obvious asymmetry in neurological indicators. Identification performance was measured for simple spatial patterns presented briefly to a locus 5 degrees into the left or right hemifield, after precuing attention to the same…

  6. Evaluation of a Health Education Programme about Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Garcia, Jane Mertz; Sellers, Debra M.; Hilgendorf, Amy E.; Burnett, Debra L.

    2014-01-01

    Objective: Our aim was to evaluate a health education programme (TBIoptions: Promoting Knowledge) designed to increase public awareness and understanding about traumatic brain injury (TBI) through in-person (classroom) and computer-based (electronic) learning environments. Design: We used a pre-post survey design with randomization of participants…

  7. 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. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH...

  8. 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. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD...

  9. 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. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH...

  10. 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. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH...

  11. 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. 1308.16 Section 1308.16 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH...

  12. Assisting Students with a Traumatic Brain Injury in School Interventions

    ERIC Educational Resources Information Center

    Aldrich, Erin M.; Obrzut, John E.

    2012-01-01

    Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…

  13. Predictors of Outcome following Acquired Brain Injury in Children

    ERIC Educational Resources Information Center

    Johnson, Abigail R.; DeMatt, Ellen; Salorio, Cynthia F.

    2009-01-01

    Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources,…

  14. Cognitive Rehabilitation for Children with Acquired Brain Injury

    ERIC Educational Resources Information Center

    Slomine, Beth; Locascio, Gianna

    2009-01-01

    Cognitive deficits are frequent consequences of acquired brain injury (ABI) and often require intervention. We review the theoretical and empirical literature on cognitive rehabilitation in a variety of treatment domains including attention, memory, unilateral neglect, speech and language, executive functioning, and family involvement/education.…

  15. Low level laser therapy for traumatic brain injury

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    Low level laser (or light) therapy (LLLT) has been clinically applied for many indications in medicine that require the following processes: protection from cell and tissue death, stimulation of healing and repair of injuries, and reduction of pain, swelling and inflammation. One area that is attracting growing interest is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may have beneficial effects in the acute treatment of brain damage injury by increasing respiration in the mitochondria, causing activation of transcription factors, reducing key inflammatory mediators, and inhibiting apoptosis. We tested LLLT in a mouse model of TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with 660-nm, 810-nm or 980-nm laser (36 J/cm2) four hours post-injury and were followed up by neurological performance testing for 4 weeks. Mice with moderate to severe TBI treated with 660- nm and 810-nm laser had a significant improvement in neurological score over the course of the follow-up and histological examination of the brains at sacrifice revealed less lesion area compared to untreated controls. Further studies are underway.

  16. Children with Acquired Brain Injury: A Silent Voice in the Ontario School System

    ERIC Educational Resources Information Center

    Bennett, Sheila; Good, Dawn; Zinga, Dawn; Kumpf, John

    2004-01-01

    The leading cause of death and injuries in school age children is acquired brain injury (Savage & Wolcott, 1994). Each year approximately 1 in 450 school age children and 1 in 200 adolescents/young adults suffer an injury as a result of some form of acquired brain injury. Approximately 27,000 students in the Ontario school system have acquired…

  17. Signs and Strategies for Educating Students with Brain Injuries: A Practical Guide for Teachers and Schools.

    ERIC Educational Resources Information Center

    Wolcott, Gary; And Others

    This resource guide offers strategies for working with children having mild to severe brain injuries. Chapter 1 corrects common misunderstandings about brain injuries and gives suggestions and illustrative case examples. Chapter 2 discusses 12 common changes in students with brain injuries such as tiredness, irritability, passivity, depression,…

  18. Naming and gesturing spatial relations: Evidence from focal brain-injured individuals

    PubMed Central

    Göksun, Tilbe; Lehet, Matthew; Malykhina, Katsiaryna; Chatterjee, Anjan

    2013-01-01

    Spatial language helps us encode relations between objects and organize our thinking. Little is known about the neural instantiations of spatial language. Using voxel-lesion symptom mapping (VLSM), we tested the hypothesis that focal brain injured patients who had damage to left frontal-parietal peri-Sylvian regions would have difficulty in naming spatial relations between objects. We also investigated the relationship between impaired verbalization of spatial relations and spontaneous gesture production. Patients with left or right hemisphere damage and elderly control participants were asked to name static (e.g., an apple on a book) and dynamic (e.g., a pen moves over a box) locative relations depicted in brief video clips. The correct use of prepositions in each task and gestures that represent the spatial relations were coded. Damage to the left posterior middle frontal gyrus, the left inferior frontal gyrus, and the left anterior superior temporal gyrus were related to impairment in naming spatial relations. Production of spatial gestures negatively correlated with naming accuracy, suggesting that gestures might help or compensate for difficulty with lexical access. Additional analyses suggested that left hemisphere patients who had damage to the left posterior middle frontal gyrus and the left inferior frontal gyrus gestured less than expected, if gestures are used to compensate for impairments in retrieving prepositions. PMID:23685196

  19. Focal adhesion kinase as a mechanotransducer during rapid brain growth of the chick embryo.

    PubMed

    Desmond, Mary E; Knepper, Janice E; DiBenedetto, Angela J; Malaugh, Elizabeth; Callejo, Sagrario; Carretero, Raquel; Alonso, Maria-Isabel; Gato, Angel

    2014-01-01

    Expansion of the hollow fluid-filled embryonic brain occurs by an increase in intraluminal pressure created by accumulation of cerebrospinal fluid (CSF). Experiments have shown a direct correlation between cavity pressure and cell proliferation within the neuroepithelium. These findings lead us to ask how mechanistically this might come about. Are there perhaps molecules on the luminal surface of the embryonic neuroepithelium, such as focal adhesion kinases (FAKs) known to respond to tension in other epithelial cells? Immunodetection using antibodies to total FAK and p-FAK was performed with subsequent confocal analysis of the pattern of their activation under normal intraluminal pressure and induced chronic pressure. Western analysis was also done to look at the amount of FAK expression, as well as its activation under these same conditions. Using immunolocalization, we have shown that FAK is present and activated on both apical and basolateral surfaces and within the cytoplasm of the neuroepithelial cells. This pattern changed profoundly when the neuroepithelium was under pressure. By Western blot, we have shown that FAK was upregulated and activated in the neuroepithelium of the embryos just after the neural tube becomes a closed pressurized system, with phosphorylation detected on the luminal instead of the basal surface, along with an increase in cell proliferation. Chronic hyper-pressure does not induce an increase in phosphorylation of FAK. In conclusion, here we show that neuroepithelial cells respond to intraluminal pressure via FAK phosphorylation on the luminal surface. PMID:24860993

  20. The experience of traumatic brain injury in Botswana.

    PubMed

    Mbakile-Mahlanza, Lingani; Manderson, Lenore; Ponsford, Jennie

    2015-01-01

    Whilst the consequences of traumatic brain injury (TBI) are understood in Western countries, it is not known how cultural background and beliefs affect response and outcome following TBI in low and middle income countries. This study aimed to explore the experiences of TBI in Botswana. Participants included 21 individuals with moderate to severe TBI (68% males, mean age 35.2 years), 18 caregivers and 25 healthcare workers. Qualitative semi-structured interviews were transcribed, translated and thematically coded. Thematic analysis indicated several themes: Injury-related changes, attributions and beliefs about the cause of the injury, family reactions, attitudes, and resources. Participants described the common injury-related effects of TBI. Many participants attributed their injury to supernatural causes. Immediate family members of participants with TBI expressed a sense of love and devotion towards the injured person. Communication was characterised by inadequate information given to those injured and their caregivers. Provision of care was impeded by insufficient staff, limited supplies and lack of training of nurses. The current healthcare system would therefore appear to be ill-equipped to meet the needs of TBI survivors in Botswana. This study will improve understanding of cultural responses and approaches to brain injuries in Botswana which may, in turn, inform improved practice. PMID:25558888

  1. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice

    PubMed Central

    ZHAO, PENG; ZHOU, RU; ZHU, XIAO-YUN; HAO, YIN-JU; LI, NAN; WANG, JIE; NIU, YANG; SUN, TAO; LI, YU-XIANG; YU, JIAN-QIANG

    2015-01-01

    Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl-2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against

  2. Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse

    PubMed Central

    Pozner, Amir; Xu, Ben; Palumbos, Sierra; Gee, J. Michael; Tvrdik, Petr; Capecchi, Mario R.

    2015-01-01

    Microglia, the resident immune cells of the brain parenchyma, are highly responsive to tissue injury. Following cell damage, microglial processes redirect their motility from randomly scouting the extracellular space to specifically reaching toward the compromised tissue. While the cell morphology aspects of this defense mechanism have been characterized, the intracellular events underlying these responses remain largely unknown. Specifically, the role of intracellular Ca2+ dynamics has not been systematically investigated in acutely activated microglia due to technical difficulty. Here we used live two-photon imaging of the mouse cortex ubiquitously expressing the genetically encoded Ca2+ indicator GCaMP5G and fluorescent marker tdTomato in central nervous system microglia. We found that spontaneous Ca2+ transients in microglial somas and processes were generally low (only 4% of all microglia showing transients within 20 min), but baseline activity increased about 8-fold when the animals were treated with LPS 12 h before imaging. When challenged with focal laser injury, an additional surge in Ca2+ activity was observed in the somas and protruding processes. Notably, coherent and simultaneous Ca2+ rises in multiple microglial cells were occasionally detected in LPS-treated animals. We show that Ca2+ transients were pre-dominantly mediated via purinergic receptors. This work demonstrates the usefulness of genetically encoded Ca2+ indicators for investigation of microglial physiology. PMID:26005403

  3. Injury biomechanics, neuropathology, and simplified physics of explosive blast and impact mild traumatic brain injury.

    PubMed

    Bandak, F A; Ling, G; Bandak, A; De Lanerolle, N C

    2015-01-01

    Explosive blast shock waves and blunt impact to the head are two types of loading shown to result in mild traumatic brain injury (mTBI). While mTBI from these two causes shares some common features behaviorally, there are distinct differences in the pathophysiology of the underlying injury mechanisms. Various elucidations have been offered in the literature to explain the organic damage associated with mTBI resulting from both types of loading. The current state of understanding in this field is somewhat limited by the degree of appreciation of the physics and biomechanics governing the effects of explosive blast shock waves and blunt impact on the head, which has resulted in the various approaches to the investigation of the operative brain injury "wounding mechanisms". In this chapter we provide a simplified description of terminology associated with forces on the head from explosive blast shock waves and blunt impact, to assist readers in the field in evaluating interpretations of brain injury "wounding" processes. Remarkably, mTBI from either loading is shown generally to result in only a small loss of neurons, with hippocampal neurons appearing to be particularly vulnerable to explosive blast shock waves. Explosive blast studies in large animal models show a unique pattern of periventricular injury, which is different from the classic diffuse axonal injury. Both astrocyte and microglial activation are also seen in explosive blast as well as impact trauma, but this may be a general secondary brain injury response, nonspecific to explosive blast or blunt trauma. Additionally, while moderate to severe impact closed head injuries sometimes result in petechial hemorrhages or hematomas, they do not appear to be associated with explosive blast mTBI even with repeated exposure to blasts. PMID:25702211

  4. MR of brain radiation injury: experimental studies in cats

    SciTech Connect

    Hecht-Leavitt, C.; Grossman, R.I.; Curran, W.J. Jr.; McGrath, J.T.; Biery, D.N.; Joseph, P.M.; Nelson, D.F.

    1987-05-01

    Two of six cats receiving small-field, single-dose, brain irradiation of 35 Gy with 6 MeV photons developed brain abnormalities in the irradiated area on MR images at 6 and 8 months, respectively, after treatment. The lesions were of high intensity on T2-weighted images and did not enhance after IV administration of gadolinium-DTPA. An additional lesion in one of these cats displayed high signal on T2-weighted images and enhanced on T1-weighted images after IV gadolinium-DTPA. Pathologic correlation revealed that the nonenhancing T2-weighted lesions consisted of edema or demyelinated regions without inflammation while the gadolinium-enhanced lesion demonstrated necrosis with inflammatory infiltrate. Focal brain irradiation may produce noninflammatory demyelination and necrosis. These histologic entities may be potentially distinguished on MR with IV gadolinium-DTPA.

  5. Episodic disorders of behaviour and affect after acquired brain injury.

    PubMed

    Eames, Peter Eames; Wood, Rodger Ll

    2003-01-01

    Psychological disorders that follow traumatic brain injury are possibly more complex and diverse than those associated with other forms of "brain damage". These may include organic aggressive, or organic affective syndromes that are episodic in nature and therefore require a more specific diagnosis, a different classification, and a different approach to treatment. Consequently, it is necessary for clinicians to learn to distinguish between "primary" psychiatric illnesses and those disorders of behavioural control and mood that stem specifically from brain injury. There is relatively little in the clinical literature that explains the relationship between variable states of behaviour, mood or temperament, and clinical disorders that may have long-term implications for patient management. This concept paper therefore addresses abnormalities of mood and behaviour that are episodic in character and are not recognisably included in the DSM and ICD classifications of psychological or psychiatric disorders. PMID:21854336

  6. Does Caspase-6 Have a Role in Perinatal Brain Injury?

    PubMed Central

    Baburamani, Ana A.; Miyakuni, Yasuka; Vontell, Regina; Supramaniam, Veena G.; Svedin, Pernilla; Rutherford, Mary; Gressens, Pierre; Mallard, Carina; Takeda, Satoru; Thornton, Claire; Hagberg, Henrik

    2015-01-01

    Apoptotic mechanisms are centre stage for the development of injury in the immature brain, and caspases have been shown to play a pivotal role during brain development and in response to injury. The inhibition of caspases using broad-spectrum agents such as Q-VD-OPh is neuroprotective in the immature brain. Caspase-6, an effector caspase, has been widely researched in neurodevelopmental disorders and found to be important following adult stroke, but its function in the neonatal brain has yet to be detailed. Furthermore, caspases may be important in microglial activation; microglia are required for optimal brain development and following injury, and their close involvement during neuronal cell death suggests that apoptotic cues such as caspase activation may be important in microglial activation. Therefore, in this study we aimed to investigate the possible apoptotic and non-apoptotic functions caspase-6 may have in the immature brain in response to hypoxia-ischaemia. We examined whether caspases are involved in microglial activation. We assessed cleaved caspase-6 expression following hypoxia-ischaemia and conducted primary microglial cultures to assess whether the broad-spectrum inhibitor Q-VD-OPh or caspase-6 gene deletion affected lipopolysaccharide (LPS)-mediated microglial activation and phenotype. We observed cleaved caspase-6 expression to be low but present in the cell body and cell processes in both a human case of white matter injury and 72 h following hypoxia-ischaemia in the rat. Gene deletion of caspase-6 did not affect the outcome of brain injury following mild (50 min) or severe (60 min) hypoxia-ischaemia. Interestingly, we did note that cleaved caspase-6 was co-localised with microglia that were not of apoptotic morphology. We observed that mRNA of a number of caspases was modulated by low-dose LPS stimulation of primary microglia. Q-VD-OPh treatment and caspase-6 gene deletion did not affect microglial activation but modified slightly the M2b

  7. Neural Bases of Recovery after Brain Injury

    ERIC Educational Resources Information Center

    Nudo, Randolph J.

    2011-01-01

    Substantial data have accumulated over the past decade indicating that the adult brain is capable of substantial structural and functional reorganization after stroke. While some limited recovery is known to occur spontaneously, especially within the first month post-stroke, there is currently significant optimism that new interventions based on…

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

    PubMed

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

    2016-09-01

    Head injuries are relatively common in ice hockey, with the majority represented by concussions, a form of mild traumatic brain injury. More severe head injuries are rare since the implementation of mandatory helmet use in the 1960s. We present a case of a 27 year-old male who sustained a traumatic intraparenchymal hemorrhage with an associated subdural hematoma resulting after being struck by a puck shot at high velocity. The patient presented with expressive aphasia, with no other apparent neurologic deficits. Acutely, he was successfully treated with observation and serial neuroimaging studies ensuring an absence of hematoma expansion. After a stable clinical picture following 24 hours of observation, the patient was discharged and managed with outpatient speech therapy with full resolution of symptoms and return to play 3 months later. We will outline the patient presentation and pertinent points in the management of acute head injuries in athletes. PMID:27074595

  9. Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals.

    PubMed

    Chen, Po-Ching; Castillo, Eduardo M; Baumgartner, James; Seo, Joo Hee; Korostenskaja, Milena; Lee, Ki Hyeong

    2016-09-01

    Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures. PMID:27142358

  10. Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury

    PubMed Central

    Eakin, Katharine; Baratz-Goldstein, Renana; Pick, Chiam G.; Zindel, Ofra; Balaban, Carey D.; Hoffer, Michael E.; Lockwood, Megan; Miller, Jonathan; Hoffer, Barry J.

    2014-01-01

    In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30–60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man. PMID:24740427

  11. Brain Injury After Intracerebral Hemorrhage in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Gang; Bao, Xuhui; Xi, Guohua; Keep, Richard; Thompson, B. Gregory; Hua, Ya

    2011-01-01

    Object Hypertension is the main cause of spontaneous intracerebral hemorrhages (ICH), but the effects of hypertension on ICH-induced brain injury have not been well studied. In this study, we examined ICH-induced brain injury in spontaneously hypertensive rats (SHR). Methods This two-part study was performed on 12 weeks old male SHR and Wistar Kyoto (WKY) rats. First, rats received an intracaudate injection of 0.3 units collagenase and hematoma sizes were determined at 24 hours. Second, rats were injected with 100-μL autologous whole blood into the right basal ganglia. Brain edema, neuronal death, ferritin expression, microglia activation, and neurological deficits were examined. Results Hematoma sizes were the same in SHR and WKY rats 24 hours after collagenase injection. SHR had greater neuronal death and neurological deficits after blood injection. ICH also resulted in higher brain ferritin levels and stronger activation of microglia in SHR. However, perihematomal brain edema was same in the SHR and WKY rats. Conclusion Moderate chronic hypertension resulted in more severe ICH-induced neuronal death and neurological deficits, but did not exaggerate hematoma enlargement and perihematomal brain edema in the rat ICH models. PMID:21294617

  12. Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

    ERIC Educational Resources Information Center

    Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

    2010-01-01

    Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

  13. 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. PMID:26130959

  14. Characterization of Pressure Distribution in Penetrating Traumatic Brain Injuries

    PubMed Central

    Davidsson, Johan; Risling, Mårten

    2015-01-01

    Severe impacts to the head commonly lead to localized brain damage. Such impacts may also give rise to temporary pressure changes that produce secondary injuries in brain volumes distal to the impact site. Monitoring pressure changes in a clinical setting is difficult; detailed studies into the effect of pressure changes in the brain call for the development and use of animal models. The aim of this study is to characterize the pressure distribution in an animal model of penetrating traumatic brain injuries (pTBI). This data may be used to validate mathematical models of the animal model and to facilitate correlation studies between pressure changes and pathology. Pressure changes were measured in rat brains while subjected to pTBI for a variety of different probe velocities and shapes; pointy, blunt, and flat. Experiments on ballistic gel samples were carried out to study the formation of any temporary cavities. In addition, pressure recordings from the gel experiments were compared to values recorded in the animal experiments. The pTBI generated short lasting pressure changes in the brain tissue; the pressure in the contralateral ventricle (CLV) increased to 8 bar followed by a drop to 0.4 bar when applying flat probes. The pressure changes in the periphery of the probe, in the Cisterna Magna, and the spinal canal, were significantly less than those recorded in the CLV or the vicinity of the skull base. High-speed videos of the gel samples revealed the formation of spherically shaped cavities when flat and spherical probes were applied. Pressure changes in the gel were similar to those recorded in the animals, although amplitudes were lower in the gel samples. We concluded cavity expansion rate rather than cavity size correlated with pressure changes in the gel or brain secondary to probe impact. The new data can serve as validation data for finite element models of the trauma model and the animal and to correlate physical measurements with secondary injuries

  15. Characterization of pressure distribution in penetrating traumatic brain injuries.

    PubMed

    Davidsson, Johan; Risling, Mårten

    2015-01-01

    Severe impacts to the head commonly lead to localized brain damage. Such impacts may also give rise to temporary pressure changes that produce secondary injuries in brain volumes distal to the impact site. Monitoring pressure changes in a clinical setting is difficult; detailed studies into the effect of pressure changes in the brain call for the development and use of animal models. The aim of this study is to characterize the pressure distribution in an animal model of penetrating traumatic brain injuries (pTBI). This data may be used to validate mathematical models of the animal model and to facilitate correlation studies between pressure changes and pathology. Pressure changes were measured in rat brains while subjected to pTBI for a variety of different probe velocities and shapes; pointy, blunt, and flat. Experiments on ballistic gel samples were carried out to study the formation of any temporary cavities. In addition, pressure recordings from the gel experiments were compared to values recorded in the animal experiments. The pTBI generated short lasting pressure changes in the brain tissue; the pressure in the contralateral ventricle (CLV) increased to 8 bar followed by a drop to 0.4 bar when applying flat probes. The pressure changes in the periphery of the probe, in the Cisterna Magna, and the spinal canal, were significantly less than those recorded in the CLV or the vicinity of the skull base. High-speed videos of the gel samples revealed the formation of spherically shaped cavities when flat and spherical probes were applied. Pressure changes in the gel were similar to those recorded in the animals, although amplitudes were lower in the gel samples. We concluded cavity expansion rate rather than cavity size correlated with pressure changes in the gel or brain secondary to probe impact. The new data can serve as validation data for finite element models of the trauma model and the animal and to correlate physical measurements with secondary injuries

  16. Experimental Models Combining Traumatic Brain Injury and Hypoxia.

    PubMed

    Thelin, Eric P

    2016-01-01

    Traumatic brain injury (TBI) is one of the most common causes of death and disability, and cerebral hypoxia is a frequently occurring harmful secondary event in TBI patients. The hypoxic conditions that occur on the scene of accident, where the airways are often obstructed or breathing is in other ways impaired, could be reproduced using animal TBI models where oxygen delivery is strictly controlled throughout the entire experimental procedure. Monitoring physiological parameters of the animal is of utmost importance in order to maintain an adequate quality of the experiment. Peripheral oxygen saturation, O2 pressure (pO2) in the blood, or fraction of inhaled O2 (FiO2) could be used as goals to validate the hypoxic conditions. Different models of traumatic brain injury could be used to inflict desired injury type, whereas effects then could be studied using radiological, physiological and functional tests. In order to confirm that the brain has been affected by a hypoxic injury, appropriate substances in the affected cerebral tissue, cerebrospinal fluid, or serum should be analyzed. PMID:27604734

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. An examination of co-occurring conditions and management of psychotropic medication use in soldiers with traumatic brain injury.

    PubMed

    Farinde, Abimbola

    2014-01-01

    There are approximately 1.4 million cases of traumatic brain injury (TBI) per year in the United States, with about 23 000 survivors requiring hospitalization. The incidence of TBI has increased in the patient population of the Department of Defense and Veterans Healthcare Administration as a result of injuries suffered during recent military and combat operations. Within the past few years, TBI has emerged as a common form of injury in service members with a subset of patients experiencing postinjury symptoms that greatly affect their quality of life. Traumatic brain injury can occur when sudden trauma (ie, penetration blast or blunt) causes damage to the brain. Traumatic brain injury produces a cascade of potentially injurious processes that include focal contusions and cytotoxic damage. The results of TBI can include impaired physical, cognitive, emotional, and behavioral functioning, which may or may not require the initiation of pharmacological and nonpharmacological interventions when deemed appropriate. Associated outcomes of TBI include alterations in mental state at the time of injury (confusion, disorientation, slowed thinking, and alteration of consciousness). Neurological deficits include loss of balance, praxis, aphasia, change in vision that may or may not be transient. Individuals who sustain a TBI are more likely to have or developed co-occurring conditions (ie, sleep problems, headaches, depression, anxiety, and posttraumatic stress disorder) that may require the administration of multiple medications. It has been identified that veterans being discharged on central nervous system and muscular skeletal drug classes can develop addiction and experience medication misadventures. With the severity of TBI being highly variable but typically categorized as either mild, moderate, or severe, it can assist health care providers in determining which patients are more susceptible to medication misadventures compared with others. The unique development of

  20. Microglia activation as a biomarker for traumatic brain injury.

    PubMed

    Hernandez-Ontiveros, Diana G; Tajiri, Naoki; Acosta, Sandra; Giunta, Brian; Tan, Jun; Borlongan, Cesar V

    2013-01-01

    Traumatic brain injury (TBI) has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells' detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation, and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation, and accurate handling of all data (Landis et al., 2012). A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer's disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI. PMID:23531681

  1. Microglia Activation as a Biomarker for Traumatic Brain Injury

    PubMed Central

    Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Acosta, Sandra; Giunta, Brian; Tan, Jun; Borlongan, Cesar V.

    2013-01-01

    Traumatic brain injury (TBI) has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells’ detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation, and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation, and accurate handling of all data (Landis et al., 2012). A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer’s disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI. PMID:23531681

  2. Complexity Analysis of Resting State Magnetoencephalography Activity in Traumatic Brain Injury Patients

    PubMed Central

    Xu, Duo; Roskos, Tyler; Stout, Jeff; Kull, Lynda; Cheng, Xi; Whitson, Diane; Boomgarden, Erich; Gfeller, Jeffrey; Bucholz, Richard D.

    2013-01-01

    Abstract Diagnosis of mild traumatic brain injuries (TBIs) has been difficult because of the absence of obvious focal brain lesions, using conventional computed tomography (CT) or magnetic resonance imaging (MRI) scans, in a large percentage of TBIs. One useful measure that can characterize potential tissue and neural network damage objectively is Lempel–Ziv complexity (LZC) applied to magnetoencephalography (MEG) signals. LZC is a model-independent estimator of system complexity that estimates the number of different patterns in a sequence. We hypothesized that because of the potential network damage, TBIs would show a reduced level of complexity in regions that are impaired. We included 18 healthy controls and 18 military veterans with TBI in the study. Resting state MEG data were acquired, and the LZCs were analyzed across the whole brain. Our results indicated reduced complexity in multiple brain areas in TBI patients relative to the healthy controls. In addition, we detected several neuropsychological measures associated with motor responses, visual perception, and memory, correlated with LZC, which likely explains some of the cognitive deficits in TBI patients. PMID:23692211

  3. Systemic progesterone for modulating electrocautery-induced secondary brain injury.

    PubMed

    Un, Ka Chun; Wang, Yue Chun; Wu, Wutian; Leung, Gilberto Ka Kit

    2013-09-01

    Bipolar electrocautery is an effective and commonly used haemostatic technique but it may also cause iatrogenic brain trauma due to thermal injury and secondary inflammatory reactions. Progesterone has anti-inflammatory and neuroprotective actions in traumatic brain injury. However, its potential use in preventing iatrogenic brain trauma has not been explored. We conducted a pilot animal study to investigate the effect of systemic progesterone on brain cellular responses to electrocautery-induced injury. Adult male Sprague-Dawley rats received standardized bipolar electrocautery (40 W for 2 seconds) over the right cerebral cortex. The treatment group received progesterone intraperitoneally 2 hours prior to surgery; the control group received the drug vehicle only. Immunohistochemical studies showed that progesterone could significantly reduce astrocytic hypertrophy on postoperative day 1, 3 and 7, as well as macrophage infiltration on day 3. The number of astrocytes, however, was unaffected. Our findings suggest that progesterone should be further explored as a neuroprotective agent against electrocautery-induced or other forms of iatrogenic trauma during routine neurosurgical procedures. Future studies may focus on different dosing regimens, neuronal survival, functional outcome, and to compare progesterone with other agents such as dexamethasone. PMID:23830688

  4. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  5. Blood biomarkers for brain injury: What are we measuring?

    PubMed Central

    Kawata, Keisuke; Liu, Charles Y.; Merkel, Steven F.; Ramirez, Servio H.; Tierney, Ryan T.; Langford, Dianne

    2016-01-01

    Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID:27181909

  6. Extracellular N-Acetylaspartate in Human Traumatic Brain Injury

    PubMed Central

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

    2016-01-01

    Abstract N-acetylaspartate (NAA) is an amino acid derivative primarily located in the neurons of the adult brain. The function of NAA is incompletely understood. Decrease in brain tissue NAA is presently considered symptomatic and a potential biomarker of acute and chronic neuropathological conditions. The aim of this study was to use microdialysis to investigate the behavior of extracellular NAA (eNAA) levels after traumatic brain injury (TBI). Sampling for this study was performed using cerebral microdialysis catheters (M Dialysis 71) perfused at 0.3 μL/min. Extracellular NAA was measured in microdialysates by high-performance liquid chromatography in 30 patients with severe TBI and for comparison, in radiographically “normal” areas of brain in six non-TBI neurosurgical patients. We established a detailed temporal eNAA profile in eight of the severe TBI patients. Microdialysate concentrations of glucose, lactate, pyruvate, glutamate, and glycerol were measured on an ISCUS clinical microdialysis analyzer. Here, we show that the temporal profile of microdialysate eNAA was characterized by highest levels in the earliest time-points post-injury, followed by a steady decline; beyond 70 h post-injury, average levels were 40% lower than those measured in non-TBI patients. There was a significant inverse correlation between concentrations of eNAA and pyruvate; eNAA showed significant positive correlations with glycerol and the lactate/pyruvate (L/P) ratio measured in microdialysates. The results of this on-going study suggest that changes in eNAA after TBI relate to the release of intracellular components, possibly due to neuronal death or injury, as well as to adverse brain energy metabolism. PMID:26159566

  7. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.

    2009-01-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  8. Scatter imaging of injured brain slices: detection of mitochondrial injury

    NASA Astrophysics Data System (ADS)

    Johnson, Lee J.; Hanley, Daniel F.; Thakor, Nitish V.

    1999-06-01

    Stroke has been shown to cause exitotoxic injury, two of its manifestations being cellular and mitochondrial swelling. In vitro models of stroke attempt to reproduce the effects of stroke by treating brain tissue with excitotoxins or hypotonic solutions. To further resolve the mechanism of stroke injury, we have designed a dual-angle scatter imaging (DASI) system sensitive to particle size. The DASI system has been used with a hippocampal slice preparation to contrast cellular swelling, induced by hypotonicity, and combined cellular and mitochondrial swelling caused by excitotoxicity. We found that both hypotonic end excitotoxic treatments caused changes in light scatter. However, only excitotoxic treatment caused a significant change in DASI.

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

    PubMed

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

    2015-01-01

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

  10. Traumatic Brain Injury in Children and Adolescents: Academic and Intellectual Outcomes Following Injury

    ERIC Educational Resources Information Center

    Arroyos-Jurado, Elsa; Paulsen, Jane S.; Ehly, Stewart; Max, Jeffrey E.

    2006-01-01

    This study was conducted to examine the impact of childhood traumatic brain injury (TBI) on intellectual and academic outcomes postinjury. A comprehensive assessment of cognition, achievement, learning, and memory was administered to 27 children and adolescents 6 to 8 years post-TBI. Findings revealed that parent ratings of premorbid achievement…

  11. Impact of Posttraumatic Stress Disorder and Injury Severity on Recovery in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kenardy, Justin; Le Brocque, Robyne; Hendrikz, Joan; Iselin, Greg; Anderson, Vicki; McKinlay, Lynne

    2012-01-01

    The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a…

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

    PubMed

    Masel, Brent E; Bell, Randy S; Brossart, Shawn; Grill, Raymond J; Hayes, Ronald L; Levin, Harvey S; Rasband, Matthew N; Ritzel, David V; Wade, Charles E; DeWitt, Douglas S

    2012-08-10

    Blast injury is the most prevalent source of mortality and morbidity among combatants in Operations Iraqi and Enduring Freedom. Blast-induced neurotrauma (BINT) is a common cause of mortality, and even mild BINT may be associated with chronic cognitive and emotional deficits. In addition to military personnel, the increasing use of explosives by terrorists has resulted in growing numbers of blast injuries in civilian populations. Since the medical and rehabilitative communities are likely to be faced with increasing numbers of patients suffering from blast injury, the 2010 Galveston Brain Injury Conference focused on topics related to the diagnosis, treatment, and mechanisms of BINT. Although past military actions have resulted in large numbers of blast casualties, BINT is considered the signature injury of the conflicts in Iraq and Afghanistan. The attention focused on BINT has led to increased financial support for research on blast effects, contributing to the development of better experimental models of blast injury and a clearer understanding of the mechanisms of BINT. This more thorough understanding of blast injury mechanisms will result in novel and more effective therapeutic and rehabilitative strategies designed to reduce injury and facilitate recovery, thereby improving long-term outcomes in patients suffering from the devastating and often lasting effects of BINT. The following is a summary of the 2010 Galveston Brain Injury Conference, that included presentations related to the diagnosis and treatment of acute BINT, the evaluation of the long-term neuropsychological effects of BINT, summaries of current experimental models of BINT, and a debate about the relative importance of primary blast effects on the acute and long-term consequences of blast exposure. PMID:22655746

  13. Tau Reduction Diminishes Spatial Learning and Memory Deficits after Mild Repetitive Traumatic Brain Injury in Mice

    PubMed Central

    Cheng, Jason S.; Craft, Ryan; Yu, Gui-Qiu; Ho, Kaitlyn; Wang, Xin; Mohan, Geetha; Mangnitsky, Sergey; Ponnusamy, Ravikumar; Mucke, Lennart

    2014-01-01

    Objective Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI). Methods We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla) and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. Results Repeated (2-hit), but not single (1-hit), mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. Interpretation Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects. PMID:25551452

  14. 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

  15. 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. PMID:19449961

  16. Anemia management after acute brain injury.

    PubMed

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

    2016-01-01

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

  17. Coated-Platelet Levels Increase with Number of Injuries in Patients with Mild Traumatic Brain Injury.

    PubMed

    Prodan, Calin I; Vincent, Andrea S; Dale, George L

    2016-05-01

    Coated-platelets are procoagulant platelets that are elevated in stroke and are associated with stroke recurrence. In a previous study, prompted by data showing an increased risk for stroke following traumatic brain injury (TBI), we found that coated-platelet levels are elevated in patients with combat-related mild TBI (mTBI) several years after the injury, compared with controls. We now investigate in an expanded patient population whether parameters commonly recorded in mTBI are related to increased coated-platelet potential. Coated-platelet levels were assayed in 120 mTBI patients at intervals ranging from 6 months to 10 years from the last injury. Correlations were calculated between coated-platelet levels and age, gender, race/ethnicity, loss of consciousness, alteration in consciousness, post-traumatic amnesia, number of injuries, mechanism of injury, time since first and last injury, smoking, medications that may influence coated-platelet levels, and pertinent comorbid conditions. Significant correlations were detected between coated-platelet levels and number of injuries (p = 0.026), gender (p = 0.01), and time since last injury (p = 0.04). A multi-variable linear model analysis, including these three parameters and an additional three parameters (race/ethnicity, smoking, and mechanism of injury) that reached a p value of <0.2, showed that the number of injuries were predictive of coated-platelet levels (p = 0.004). These results support a mechanistic link between increased coated-platelet levels and repeated injuries in mTBI. Long-term studies will be required to determine the impact of increased prothrombotic potential in mTBI patients. PMID:26414016

  18. Predictors of Driving Avoidance and Exposure Following Traumatic Brain Injury

    PubMed Central

    Labbe, Donald R.; Vance, David E.; Wadley, Virginia; Novack, Thomas A.

    2015-01-01

    Background An estimated 40–60% of individuals who experience a moderate to severe Traumatic Brain Injury (TBI) return to driving. However, little is known about driving behavior post-TBI and how this may be related to demographic, injury, and outcome factors. Methods A total of 184 participants who experienced moderate to severe TBI were included in this study. Participants completed a telephone survey regarding return to driving and current driving behavior. Structural Equation Modeling (SEM) was used to analyze predicted relationships between demographic and injury-related variables with driving exposure and avoidance within 5 years of injury. Results The model indicated that participants who were older and female tended to avoid a greater number of challenging everyday driving scenarios. Participants that had more severe injuries and those with poorer performance on cognitive measures at the time of rehabilitation discharge were likely to drive less frequently and over less distances at follow up, though they did not avoid challenging driving situations. Conclusions Young males and those with more severe injuries may require additional attention regarding their driving behavior following TBI. PMID:23474877

  19. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

    PubMed Central

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

    2015-01-01

    Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

  20. Traumatic brain injury in late adolescent rats: effects on adulthood memory and anxiety.

    PubMed

    Amorós-Aguilar, Laura; Portell-Cortés, Isabel; Costa-Miserachs, David; Torras-Garcia, Meritxell; Coll-Andreu, Margalida

    2015-04-01

    The consequences of traumatic brain injury (TBI) sustained during late adolescence (7 weeks old) on spontaneous object recognition memory and on anxiety-like behaviors in the elevated plus maze were tested in rats during adulthood. Testing took place at 2 different postinjury times, in separate groups: 3 and 6 weeks, when animals were 10 and 13 weeks old, respectively. The rats were either submitted to controlled cortical impact injury, an experimental model of focal TBI with contusion, or were sham-operated. TBI animals failed to remember the familiar object and had a significantly lower performance than sham-operated animals, indicating memory disruption, when the retention delay was 24 hr, but not when it was 3 hr. TBI did not have any significant effect on the main anxiety-related behaviors, but it reduced time in the central platform of the elevated plus maze. The effects of TBI on memory and on anxiety-like behaviors were similar at the 2 postinjury times. In both TBI and sham-operated groups, animals tested 6 weeks after surgery had lower anxiety-related indices than those tested at 3 weeks, an effect that might be indicative of reduced anxiety levels with increasing age. In summary, focal TBI with contusion sustained during late adolescence led to object recognition memory deficits in a 24-hr test during adulthood but did not have a major impact on anxiety-like behaviors. Memory deficits persisted for at least 6 weeks after injury, indicating that spontaneous modifications of these functional disturbances did not take place along this time span. PMID:25730123

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

    PubMed

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

    2013-01-01

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

  2. Fever of central origin in traumatic brain injury controlled with propranolol.

    PubMed

    Meythaler, J M; Stinson, A M

    1994-07-01

    Central fevers are known to develop in traumatic brain injury (TBI) and are believed to be caused by injury involving the hypothalamus. Described are three patients admitted with very severe TBI secondary to motor vehicle accidents. Initial Glasgow Coma Score ratings were 3 or 4. Head computed tomography (CT) scans showed intraventricular hemorrhage in two cases and no focal injury or bleeding in the third. All patients had decorticate posturing and symptoms of autonomic dysfunction, manifested by tachycardia and profuse sweating. Each of these patients developed high fevers ranging from 38.9 degrees C to 40.6 degrees C during their hospitalization course. Centrally mediated fevers were indicated after fever workups failed to show an infectious or inflammatory source. Propranolol 20 to 30 mg every 6 hours reduced the temperatures at least 1.5 degree C within 48 hours. In each case, when weaning from propranolol was attempted, an increase in temperature to greater than 38.0 degrees C reoccurred within 3 days. Repeat workups for infectious or inflammatory causes of fever were negative. The fevers were reduced after a reinstitution of propranolol. The propranolol was continued until all signs of autonomic dysfunction abated. Central fevers after TBI have been reported to have been treated successfully with propranolol in two children with decerebrate posturing. Pharmacological, neurophysiological, and anatomic studies provide evidence of a significant central nervous system role in the regulation of blood pressure and temperature. PMID:8024432

  3. Minding and Caring about Ethics in Brain Injury.

    PubMed

    Gillett, Grant

    2016-05-01

    Joseph Fins's book Rights Come to Mind: Brain Injury, Ethics, and the Struggle for Consciousness (Cambridge UP, 2015) is a considerable addition to the literature on disorders of consciousness and the murky area of minimally conscious states. Fins brings to this fraught area of clinical practice and neuroethical analysis a series of stories and reflections resulting in a pressing and sustained ethical challenge both to clinicians and to health care systems. The challenge is multifaceted, with diagnostic and therapeutic demands to be met by clinicians and a mix of moral, scientific-economic, and political resonances for health care analysts. Everything in the book resonates with my own clinical experience and the often messy and emotionally wrenching business of providing ongoing care for patients with severe brain injuries and disorders, people who frequently resist the categorizations that well-organized health care systems prefer and that can dictate terms of patient management. PMID:27150418

  4. Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship

    PubMed Central

    Prata, Cecilia; Vieceli Dalla Sega, Francesco; Piperno, Roberto; Hrelia, Silvana

    2015-01-01

    Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI. PMID:25918580

  5. Two approaches to behavior disorder after traumatic brain injury.

    PubMed

    Giles, Gordon Muir; Manchester, David

    2006-01-01

    A 3-stage model of intervention is used to contrast the philosophy and treatment practices of 2 behavioral approaches to behavior disorder following traumatic brain injury. The first referred to here as the Operant Neurobehavioral Approach developed from neuropsychology and learning theory. The second referred to as the Relational Neurobehavioral Approach builds on the nonaversive behavioral techniques of the Operant Neurobehavioral Approach. It also incorporates principles of motivational interviewing, places more overt emphasis on the therapeutic relationship, and targets staff attributions for aggression in staff training. The strengths and weaknesses of both approaches are discussed. It is suggested that the Relational Neurobehavioral Approach is more likely to engage and/or reengage clients with traumatic brain injury who are resistant to behavior change. Research implications are discussed including the need to measure the fidelity of all intervention variables. PMID:16569990

  6. Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury.

    PubMed

    Dong, Hui; Ma, Yunfu; Ren, Zengxi; Xu, Bin; Zhang, Yunhe; Chen, Jing; Yang, Bo

    2016-07-01

    Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future. PMID:26228028

  7. Aquaporin-4 Inhibition Mediates Piroxicam-Induced Neuroprotection against Focal Cerebral Ischemia/Reperfusion Injury in Rodents

    PubMed Central

    Paul, Sudip; Patnaik, Ranjana

    2013-01-01

    Background and Purpose Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Methods Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Results Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Conclusions Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in

  8. Influence of exercise training on ischemic brain injury in type 1 diabetic rats.

    PubMed

    Arrick, Denise M; Sun, Hong; Mayhan, William G

    2012-10-01

    While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50 mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we measured infarct volume in all groups of rats following right MCA occlusion for 2 h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy was performed over the parietal cortex, and we measured responses of pial arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)-dependent, and a NOS-independent agonist in all groups of rats. We found that sedentary diabetic rats had significantly larger total, cortical, and subcortical infarct volumes following ischemia-reperfusion than sedentary nondiabetic, nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS-independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened ischemic brain injury following middle cerebral artery occlusion and restored impaired eNOS- and nNOS-dependent vascular function. Since the incidence of ischemic stroke is increased during T1D, we suggest that our finding are significant in that modest ExT may be a viable preventative therapeutic approach to lessen ischemia-induced brain injury that may occur in T1D subjects. PMID:22858624

  9. A rodent model of mild traumatic brain blast injury.

    PubMed

    Perez-Polo, J R; Rea, H C; Johnson, K M; Parsley, M A; Unabia, G C; Xu, G-Y; Prough, D; DeWitt, D S; Spratt, H; Hulsebosch, C E

    2015-04-01

    One of the criteria defining mild traumatic brain injury (mTBI) in humans is a loss of consciousness lasting for less than 30 min. mTBI can result in long-term impairment of cognition and behavior. In rats, the length of time it takes a rat to right itself after injury is considered to be an analog for human return to consciousness. This study characterized a rat mild brain blast injury (mBBI) model defined by a righting response reflex time (RRRT) of more than 4 min but less than 10 min. Assessments of motor coordination relying on beam-balance and foot-fault assays and reference memory showed significant impairment in animals exposed to mBBI. This study's hypothesis is that there are inflammatory outcomes to mTBI over time that cause its deleterious effects. For example, mBBI significantly increased brain levels of interleukin (IL)-1β and tumor necrosis factor-α (TNFα) protein. There were significant inflammatory responses in the cortex, hippocampus, thalamus, and amygdala 6 hr after mBBI, as evidenced by increased levels of the inflammatory markers associated with activation of microglia and macrophages, ionized calcium binding adaptor 1 (IBA1), impairment of the blood-brain barrier, and significant neuronal losses. There were significant increases in phosphorylated Tau (p-Tau) levels, a putative precursor to the development of neuroencephalopathy, as early as 6 hr after mBBI in the cortex and the hippocampus but not in the thalamus or the amygdala. There was an apparent correlation between RRRTs and p-Tau protein levels but not IBA1. These results suggest potential therapies for mild blast injuries via blockade of the IL-1β and TNFα receptors. PMID:25410497

  10. Language functioning and deficits following pediatric traumatic brain injury.

    PubMed

    Sullivan, Jeremy R; Riccio, Cynthia A

    2010-04-01

    The purpose of this article is to provide a current review of language functioning and deficits following traumatic brain injury (TBI), specifically among the pediatric population. This paper will: (a) outline the manner in which these deficits may impede functioning across environments; (b) review methods of assessing language functioning within this population; and (c) discuss empirically supported interventions to address noted language deficits as they present in pediatric TBI. PMID:20467948

  11. Inhibitory Control after Traumatic Brain Injury in Children

    PubMed Central

    Sinopoli, Katia J.; Dennis, Maureen

    2011-01-01

    Inhibitory control describes a number of distinct processes. Effortless inhibition refers to acts of control that are automatic and reflexive. Effortful inhibition refers to voluntary, goal-directed acts of control such as response flexibility, interference control, cancellation inhibition, and restraint inhibition. Disruptions to a number of inhibitory control processes occur as a consequence of childhood traumatic brain injury (TBI). This paper reviews the current knowledge of inhibition deficits following childhood TBI, and includes an overview of the inhibition construct and a discussion of the specific deficits shown by children and adolescents with TBI and the factors that mediate the expression of these deficits, including injury-related variables and the expression of pre- and post-injury attention-deficit/hyperactivity disorder. The review illustrates that inhibitory control processes differ in terms of measurement, assessment, and neurological underpinnings, and also that childhood TBI may selectively disrupt particular forms of inhibition. PMID:22100363

  12. Clinical Traumatic Brain Injury in the Preclinical Setting.

    PubMed

    Berkner, Justin; Mannix, Rebekah; Qiu, Jianhua

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability for people under 45 years of age. Clinical TBI is often the result of disparate forces resulting in heterogeneous injuries. Preclinical modeling of TBI is a vital tool for studying the complex cascade of metabolic, cellular, and molecular post-TBI events collectively termed secondary injury. Preclinical models also provide an important platform for studying therapeutic interventions. However, modeling TBI in the preclinical setting is challenging, and most models replicate only certain aspects of clinical TBI. This chapter details the most widely used models of preclinical TBI, including the controlled cortical impact, fluid percussion, blast, and closed head models. Each of these models replicates particular critical aspects of clinical TBI. Prior to selecting a preclinical TBI model, it is important to address what aspect of human TBI is being sought to evaluate. PMID:27604710

  13. Chapter 2 traumatic brain injury research in military populations.

    PubMed

    Kasper, Christine E

    2015-01-01

    Traumatic brain injury (TBI) in all of its forms--blast, concussive, and penetrating--has been an unfortunate sequela of warfare since ancient times. The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to blast-related TBI whose long-term effects on behavior and cognition are not yet known. Advances in medical care have greatly increased survival from these types of injuries. Therefore, an understanding of the potential health effects of TBI is essential. This review focuses on specific aspects of military-related TBI. There exists a large body of literature reporting the environmental conditions, forces, and staging of injury. Many of these studies are focused on the neuropathology of TBI, due to blast overpressure waves, and the emergence of large numbers of mild blast-related TBI cases. PMID:25946382

  14. Lipid peroxidation in brain or spinal cord mitochondria after injury.

    PubMed

    Hall, Edward D; Wang, Juan A; Bosken, Jeffrey M; Singh, Indrapal N

    2016-04-01

    Extensive evidence has demonstrated an important role of oxygen radical formation (i.e., oxidative stress) as a mediator of the secondary injury process that occurs following primary mechanical injury to the brain or spinal cord. The predominant form of oxygen radical-induced oxidative damage that occurs in injured nervous tissue is lipid peroxidation (LP). Much of the oxidative stress in injured nerve cells initially begins in mitochondria via the generation of the reactive nitrogen species peroxynitrite (PN) which then can generate multiple highly reactive free radicals including nitrogen dioxide (•NO2), hydroxyl radical (•OH) and carbonate radical (•CO3). Each can readily induce LP within the phospholipid membranes of the mitochondrion leading to respiratory dysfunction, calcium buffering impairment, mitochondrial permeability transition and cell death. Validation of the role of LP in central nervous system secondary injury has been provided by the mitochondrial and neuroprotective effects of multiple antioxidant agents which are briefly reviewed. PMID:25595872

  15. Biomechanical Risk Estimates for Mild Traumatic Brain Injury

    PubMed Central

    Funk, J. R.; Duma, S. M.; Manoogian, S. J.; Rowson, S.

    2007-01-01

    The objective of this study was to characterize the risk of mild traumatic brain injury (MTBI) in living humans based on a large set of head impact data taken from American football players at the collegiate level. Real-time head accelerations were recorded from helmet-mounted accelerometers designed to stay in contact with the player’s head. Over 27,000 head impacts were recorded, including four impacts resulting in MTBI. Parametric risk curves were developed by normalizing MTBI incidence data by head impact exposure data. An important finding of this research is that living humans, at least in the setting of collegiate football, sustain much more significant head impacts without apparent injury than previously thought. The following preliminary nominal injury assessment reference values associated with a 10% risk of MTBI are proposed: a peak linear head acceleration of 165 g, a HIC of 400, and a peak angular head acceleration of 9000 rad/s2. PMID:18184501

  16. Predictors of Personality Change Due to Traumatic Brain Injury in Children and Adolescents in the First Six Months after Injury.

    ERIC Educational Resources Information Center

    Max, Jeffrey E.; Levin, Harvey S.; Landis, Julie; Schachar, Russell; Saunders, Ann; Ewing-Cobbs, Linda; Chapman, Sandra B.; Dennis, Maureen

    2005-01-01

    Objective: To assess the phenomenology and predictive factors of personality change due to traumatic brain injury. Method: Children (N = 177), aged 5 to 14 years with traumatic brain injury from consecutive admissions to five trauma centers, were followed prospectively at baseline and 6 months with semistructured psychiatric interviews. Injury…

  17. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    PubMed

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body. PMID:24486465

  18. Exosome platform for diagnosis and monitoring of traumatic brain injury

    PubMed Central

    Taylor, Douglas D.; Gercel-Taylor, Cicek

    2014-01-01

    We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID:25135964

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

    PubMed

    Beauchamp, M H; Anderson, V

    2013-01-01

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

  20. Neuroprotective measures in children with traumatic brain injury

    PubMed Central

    Agrawal, Shruti; Branco, Ricardo Garcia

    2016-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in children. Severe TBI is a leading cause of death and often leads to life changing disabilities in survivors. The modern management of severe TBI in children on intensive care unit focuses on preventing secondary brain injury to improve outcome. Standard neuroprotective measures are based on management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) to optimize the cerebral blood flow and oxygenation, with the intention to avoid and minimise secondary brain injury. In this article, we review the current trends in management of severe TBI in children, detailing the general and specific measures followed to achieve the desired ICP and CPP goals. We discuss the often limited evidence for these therapeutic interventions in children, extrapolation of data from adults, and current recommendation from paediatric guidelines. We also review the recent advances in understanding the intracranial physiology and neuroprotective therapies, the current research focus on advanced and multi-modal neuromonitoring, and potential new therapeutic and prognostic targets. PMID:26855892