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Sample records for brain injury protects

  1. Brain injury requires lung protection

    PubMed Central

    Lopez-Aguilar, Josefina

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is one of the organs most vulnerable to the inflammatory cascade triggered by TBI. HMGB1 is an alarm in that can be released from activated immune cells in response to tissue injury. Increased systemic HMGB1 concentration correlates with poor lung function before and after lung transplant, confirming its role in acute ALI after TBI. HMGB1 exerts its influence by interacting with several receptors, including the RAGE receptor. RAGE also plays an important role in the onset of innate immune inflammatory responses, and systemic levels of RAGE are strongly associated with ALI and clinical outcomes in ventilator-induced lung injury. RAGE ligation to HMGB1 triggers the amplification of the inflammatory cascade involving nuclear factor-κB (NF-κB) activation. Identifying early biomarkers that mediate pulmonary dysfunction will improve outcomes not only in lung transplantation, but also in other scenarios. These novel findings show that upregulation of the HMGB1-RAGE axis plays an important role in brain-lung crosstalk. PMID:26046092

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

    DTIC Science & Technology

    2014-11-01

    Award Number: W81XWH-08-2-0017 TITLE: " Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...TITLE AND SUBTITLE 5a. CONTRACT NUMBER “ Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...traumatic brain injury (bTBI) is largely undefined. Along with reducing mortality, in preliminary experiments Kevlar vests significantly protected

  3. Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke

    PubMed Central

    Szalay, Gergely; Martinecz, Bernadett; Lénárt, Nikolett; Környei, Zsuzsanna; Orsolits, Barbara; Judák, Linda; Császár, Eszter; Fekete, Rebeka; West, Brian L.; Katona, Gergely; Rózsa, Balázs; Dénes, Ádám

    2016-01-01

    Microglia are the main immune cells of the brain and contribute to common brain diseases. However, it is unclear how microglia influence neuronal activity and survival in the injured brain in vivo. Here we develop a precisely controlled model of brain injury induced by cerebral ischaemia combined with fast in vivo two-photon calcium imaging and selective microglial manipulation. We show that selective elimination of microglia leads to a striking, 60% increase in infarct size, which is reversed by microglial repopulation. Microglia-mediated protection includes reduction of excitotoxic injury, since an absence of microglia leads to dysregulated neuronal calcium responses, calcium overload and increased neuronal death. Furthermore, the incidence of spreading depolarization (SD) is markedly reduced in the absence of microglia. Thus, microglia are involved in changes in neuronal network activity and SD after brain injury in vivo that could have important implications for common brain diseases. PMID:27139776

  4. Resveratrol post-treatment protects against neonatal brain injury after hypoxia-ischemia

    PubMed Central

    Hu, Yingying; Zhang, Hao; Liu, Yanlong; Jiang, Huai; Fang, Mingchu; Li, Zhengmao; Xu, Kebin; Zhang, Hongyu; Lin, Zhenlang; Xiao, Jian

    2016-01-01

    Neonatal hypoxic-ischemic brain injury is a devastating disease with limited treatment options. Preventive treatment with resveratrol has indicated to be well tolerated and has lower toxicity in both experimental models and human patients. However, whether resveratrol administration post-hypoxic-ischemic protects against neonatal hypoxic-ischemic injury is not known. Here we reported that post-treatment with resveratrol significantly reduced brain damage at 7-day after the injury. We found that resveratrol reduced the expression levels of key inflammatory factors at the mRNA and protein levels, and at least partially via inhibiting microglia activation. Moreover, resveratrol exerted an anti-apoptotic effect, as assessed by TUNEL staining, and altered the expression of the apoptosis-related genes Bax, Bcl-2 and caspase3. Our data indicate that post-treatment with resveratrol protects against neonatal hypoxic-ischemic brain injury and suggest a promising therapeutic strategy to this disease. PMID:27811363

  5. Protective effects of shikonin on brain injury induced by carbon ion beam irradiation in mice.

    PubMed

    Gan, Lu; Wang, Zhen Hua; Zhang, Hong; Zhou, Rong; Sun, Chao; Liu, Yang; Si, Jing; Liu, Yuan Yuan; Wang, Zhen Guo

    2015-02-01

    Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group (P<0.01), while obviously reduced the MDA and PCO contents and the ROS levels derived from of the brain mitochondria. The shikonin also noticeably improved the spatial memory deficits caused by carbon ion beam irradiation. All results demonstrated that shikonin could improve the irradiated brain injury which might resulted from its modulation effects on the oxidative stress induced by the 12C6+ ion beam.

  6. PHLPP1 gene deletion protects the brain from ischemic injury

    PubMed Central

    Chen, Bo; Van Winkle, Jessica A; Lyden, Patrick D; Brown, Joan H; Purcell, Nicole H

    2013-01-01

    A recently discovered protein phosphatase PHLPP (PH domain Leucine-rich repeat Protein Phosphatase) has been shown to dephosphorylate Akt on its hydrophobic motif (Ser473) thereby decreasing Akt kinase activity. We generated PHLPP1 knockout (KO) mice and used them to explore the ability of enhanced in vivo Akt signaling to protect the brain against ischemic insult. Brains from KO mice subjected to middle cerebral artery occlusion (MCAO) for 2 hours showed significantly greater increases in Akt activity and less neurovascular damage after reperfusion than wild-type (WT) mice. Remarkably, infarct volume in the PHLPP1 KO was significantly reduced compared with WT (12.7±2.7% versus 22.9±3.1%) and this was prevented by Akt inhibition. Astrocytes from KO mice and neurons in which PHLPP1 was downregulated showed enhanced Akt activation and diminished cell death in response to oxygen-glucose deprivation. Thus, deletion of PHLPP1 can enhance Akt activation in neurons and astrocytes, and can significantly increase cell survival and diminish infarct size after MCAO. Inhibition of PHLPP could be a therapeutic approach to minimize damage after focal ischemia. PMID:23072745

  7. Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

    PubMed Central

    Lee, Chao Yu; Wang, Liang-Fei; Wu, Chun-Hu; Ke, Chia-Hua; Chen, Szu-Fu

    2014-01-01

    Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg−1) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect. PMID:25546475

  8. Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: after-stroke-effect.

    PubMed

    Dobrota, Dusan; Fedorova, Tatiana; Stvolinsky, Sergey; Babusikova, Eva; Likavcanova, Katarina; Drgova, Anna; Strapkova, Adriana; Boldyrev, Alexander

    2005-10-01

    Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

  9. Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury.

    PubMed

    Menzel, Lutz; Kleber, Lisa; Friedrich, Carina; Hummel, Regina; Dangel, Larissa; Winter, Jennifer; Schmitz, Katja; Tegeder, Irmgard; Schäfer, Michael K E

    2017-02-01

    In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI. Grn(-/-) mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was elevated in Grn(-/-) mice as reflected by increased transcription of pro-inflammatory cytokines TNFα, IL-1β, IL-6, and decreased transcription of the anti-inflammatory cytokine IL-10. However, numbers of Iba1(+) microglia/macrophages and immigrated CD45(+) leukocytes were similar at perilesional sites while determination of IgG extravasation suggested stronger impairment of blood brain barrier integrity in Grn(-/-) compared to wild-type mice. Most strikingly, Grn(-/-) mice displayed exaggerated astrogliosis 5 days after TBI as demonstrated by anti-GFAP immunohistochemistry and immunoblot. GFAP(+) astrocytes at perilesional sites were immunolabelled for iNOS and TNFα suggesting that pro-inflammatory activation of astrocytes was attenuated by PGRN. Accordingly, recombinant PGRN (rPGRN) attenuated LPS- and cytokine-evoked iNOS and TNFα mRNA expression in cultured astrocytes. Moreover, intracerebroventricular administration of rPGRN immediately before trauma reduced brain damage and neurological deficits, and restored normal levels of cytokine transcription, axonal injury and astrogliosis 5 days after TBI in Grn(-/-) mice. Our results show that endogenous and recombinant PGRN limit axonal injury and astrogliosis and suggest therapeutic potential of PGRN in TBI. GLIA 2017

  10. Protection in Animal Models of Brain and Spinal Cord Injury with Mild to Moderate Hypothermia

    PubMed Central

    Atkins, Coleen M.; Bramlett, Helen M.

    2009-01-01

    Abstract For the past 20 years, various laboratories throughout the world have shown that mild to moderate levels of hypothermia lead to neuroprotection and improved functional outcome in various models of brain and spinal cord injury (SCI). Although the potential neuroprotective effects of profound hypothermia during and following central nervous system (CNS) injury have long been recognized, more recent studies have described clinically feasible strategies for protecting the brain and spinal cord using hypothermia following a variety of CNS insults. In some cases, only a one or two degree decrease in brain or core temperature can be effective in protecting the CNS from injury. Alternatively, raising brain temperature only a couple of degrees above normothermia levels worsens outcome in a variety of injury models. Based on these data, resurgence has occurred in the potential use of therapeutic hypothermia in experimental and clinical settings. The study of therapeutic hypothermia is now an international area of investigation with scientists and clinicians from every part of the world contributing to this important, promising therapeutic intervention. This paper reviews the experimental data obtained in animal models of brain and SCI demonstrating the benefits of mild to moderate hypothermia. These studies have provided critical data for the translation of this therapy to the clinical arena. The mechanisms underlying the beneficial effects of mild hypothermia are also summarized. PMID:19245308

  11. Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude.

    PubMed

    Hu, S L; Hu, R; Li, F; Liu, Z; Xia, Y Z; Cui, G Y; Feng, H

    2008-01-01

    Recent studies have shown that preconditioning with hyperbaric oxygen (HBO) can reduce ischemic and hemorrhagic brain injury. We investigated effects of HBO preconditioning on traumatic brain injury (TBI) at high altitude and examined the role of matrix metalloproteinase-9 (MMP-9) in such protection. Rats were randomly divided into 3 groups: HBO preconditioning group (HBOP; n = 13), high-altitude group (HA; n = 13), and high-altitude sham operation group (HASO; n = 13). All groups were subjected to head trauma by weight-drop device, except for HASO group. HBOP rats received 5 sessions of HBO preconditioning (2.5 ATA, 100% oxygen, 1 h daily) and then were kept in hypobaric chamber at 0.6 ATA (to simulate pressure at 4000m altitude) for 3 days before operation. HA rats received control pretreatment (1 ATA, room air, 1 h daily), then followed the same procedures as HBOP group. HASO rats were subjected to skull opening only without brain injury. Twenty-four hours after TBI, 7 rats from each group were examined for neurological function and brain water content; 6 rats from each group were killed for analysis by H&E staining and immunohistochemistry. Neurological outcome in HBOP group (0.71 +/- 0.49) was better than HA group (1.57 +/- 0.53; p < 0.05). Preconditioning with HBO significantly reduced percentage of brain water content (86.24 +/- 0.52 vs. 84.60 +/- 0.37; p < 0.01). Brain morphology and structure seen by light microscopy was diminished in HA group, while fewer pathological injuries occurred in HBOP group. Compared to HA group, pretreatment with HBO significantly reduced the number of MMP-9-positive cells (92.25 +/- 8.85 vs. 74.42 +/- 6.27; p < 0.01). HBO preconditioning attenuates TBI in rats at high altitude. Decline in MMP-9 expression may contribute to HBO preconditioning-induced protection of brain tissue against TBI.

  12. Heme oxygenase-1 mediated memorial and revivable protective effect of ischemic preconditioning on brain injury.

    PubMed

    Le, Li-Li; Li, Xue-Yi; Meng, Dan; Liang, Qiu-Jun; Wang, Xin-Hong; Li, Ning; Quan, Jing; Xiang, Meng; Jiang, Mei; Sun, Jian; Chen, Si-Feng

    2013-12-01

    Ischemic preconditioning (IPC) has short-term benefits for stroke patients. However, if IPC protective effect is memorial and the role of the intracellular protective protein heme oxygenase-1 (HO-1) is not known. Ischemic preconditioning and the corresponding sham control were achieved by blocking the blood flow of the left internal carotid artery for 20 min and 2 second, respectively, in rats. Both IPC and sham-operated animals were divided into three groups and treated with PBS, the HO-1 inducer hemin, and the HO-1 inhibitor Znpp. Three weeks after IPC, brain ischemia-reperfusion injury was achieved by left middle cerebral artery obstruction for 45 min followed by 24-h reperfusion. 2,3,5-triphenyltetrazolium chloride staining and neurological dysfunction scoring showed IPC significantly reduced brain infarct area and improved neurological function occurred 3 weeks after IPC. Hemin treatment promoted whereas ZnPP blocked the benefits of IPC. Immunohistochemical analysis and Western blotting showed that the expression of HO-1 was higher in the border zone than in the necrotic core zone. The memorial IPC protection is independent of adenosine receptor A1R and A2aR expressions. We found for the first time that the protective effect of IPC can be remembered to protect brain injury occurred after acute response disappear. The results indicate that interventional treatment can achieve protective effect for future cerebral injury not only through interventional treatment itself but also through the memorial and revivable IPC, eliminating the concern that temporary ischemia caused by interventional treatment may leave harmful effect in the brain. © 2013 John Wiley & Sons Ltd.

  13. Bone marrow-derived endothelial progenitor cells protect postischemic axons after traumatic brain injury.

    PubMed

    Park, Katya J; Park, Eugene; Liu, Elaine; Baker, Andrew J

    2014-02-01

    White matter sparing after traumatic brain injury (TBI) is an important predictor of survival and outcome. Blood vessels and axons are intimately associated anatomically and developmentally. Neural input is required for appropriate vascular patterning, and vascular signaling is important for neuron development and axon growth. Owing to this codependence between endothelial cells and axons during development and the contribution of endothelial progenitor cells (EPCs) in ischemic injury, we hypothesized that EPCs are important in axonal survival after TBI. We examined the effects of allogenic-cultured EPCs on white matter protection and microvascular maintenance after midline fluid percussion injury in adult Sprague-Dawley rats. We used two in vitro models of injury, mechanical stretch and oxygen-glucose deprivation (OGD), to examine the effects of EPCs on the mechanical and ischemic components of brain trauma, respectively. Our results indicate that EPCs improve the white matter integrity and decrease capillary breakdown after injury. Cultured cortical neurons exposed to OGD had less axon degeneration when treated with EPC-conditioned media, whereas no effect was seen in axons injured by mechanical stretch. The results indicate that EPCs are important for the protection of the white matter after trauma and represent a potential avenue for therapy.

  14. Mild Traumatic Brain Injury

    MedlinePlus

    ... Questions Glossary Contact Us Visitor Feedback mild Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity ... most common deployment injuries is a mild Traumatic Brain Injury (TBI). A mild TBI is an injury ...

  15. Mechanism of brain protection by nitroxide radicals in experimental model of closed-head injury.

    PubMed

    Zhang, R; Shohami, E; Beit-Yannai, E; Bass, R; Trembovler, V; Samuni, A

    1998-01-15

    Reactive oxygen-derived species were previously implicated in mediation of post-traumatic brain damage; however, the efficacy of traditional antioxidants in preventing/reversing the damage is sometimes limited. The present work focused on the mechanisms underlying the neuroprotective activity of cell permeable, nontoxic, antioxidants, namely stable nitroxide radicals in an experimental model of rat closed-head injury. Brain damage was induced by the weight-drop method and the clinical status was evaluated according to a neurological severity score at 1 h and 24 h, where the difference between these scores reflects the extent of recovery. The metal chelator deferoxamine as well as three nitroxide derivatives, differing in hydrophilicity and charge, and one hydroxylamine (a reduced nitroxide) facilitated the clinical recovery and decreased the brain edema. The nitroxides, but neither the hydroxylamine nor deferoxamine, protected the integrity of the blood-brain barrier. Superoxide dismutase also improved the clinical recovery but did not affect brain edema or the blood-brain barrier. The results suggest that by switching back and forth between themselves, the nitroxide and hydroxylamine act catalytically as self-replenishing antioxidants, and protect brain tissue by terminating radical-chain reactions, oxidizing deleterious metal ions, and by removal of intracellular superoxide.

  16. [Protective effect of salidroside against high altitude hypoxia-induced brain injury in rats].

    PubMed

    Dong, Xiaoru; Zhang, Xiangnan; Li, Dan; Li, Bin; Wang, Jiye; Meng, Shanshan; Luo, Wenjing; Zhang, Wenbin

    2015-10-01

    To observe the protective effect of salidroside against brain injury in rats exposed to hypobaric hypoxia, and investigate the molecular mechanism of salidroside in the prevention of hypobaric hypoxia-induced brain injury. Rats were placed in experiment module simulating 6000 m altitude to establish acute hypobaric hypoxia-induced brain injury models. Their respiratory frequency was observed and recorded. Cell apoptosis in the hippocampal dentate gyrus (DG) was detected by TUNEL assay; the expressions of Ras homolog family member A (RhoA), phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by Western blotting. After acute exposure to 6000 m altitude, the respiratory frequency of the rats increased remarkably. The simulation of hypobaric hypoxia induced cell apoptosis in hippocampal DG region, and salidroside intervention inhibited the process of cell apoptosis. The expressions of RhoA, p-ERK, p-JNK decreased after hypobaric hypoxia exposure. Salidroside intervention reversed RhoA expression and raised the levels of p-ERK and p-JNK. Acute exposure to hypobaric hypoxia can induce cell apoptosis in rat hippocampal DG, and salidroside can protect the cells from the exposure-induced apoptosis.

  17. Therapeutic Inducers of the HSP70/HSP110 Protect Mice Against Traumatic Brain Injury

    PubMed Central

    Eroglu, Binnur; Kimbler, Donald E.; Pang, Junfeng; Choi, Justin; Moskophidis, Demetrius; Yanasak, Nathan; Dhandapani, Krishnan M.; Mivechi, Nahid F.

    2014-01-01

    Traumatic brain injury (TBI) induces severe harm and disability in many accident victims and combat-related activities. The heat shock proteins Hsp70/Hsp110 protect cells against death and ischemic damage. In this study, we used mice deficient in Hsp110 or Hsp70 to examine their potential requirement following TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death of neurons. One of the mechanisms underlying the increased cell death observed in the absence of Hsp110 and Hsp70 following TBI is the increased expression of ROS-induced p53 target genes Pig1, Pig8 and Pig12. To examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells against TBI, we subjected mice to TBI and administered Celastrol or BGP-15. In contrast to Hsp110 or Hsp70i-deficient mice that were not protected following TBI and Celastrol treatment, there was a significant improvement of wild-type mice following administration of these drugs during the first week following TBI. In addition, assessment of neurological injury shows significant improvement of Contextual and Cued Fear Conditioning tests and beam balance in wild-type mice that were treated with Celastrol or BGP-15 following TBI compared to TBI-treated mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward reducing the pathological consequences of TBI. PMID:24903326

  18. IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury

    PubMed Central

    Thaney, Victoria E.; O’Neill, Alan M.; Hoefer, Melanie M.; Maung, Ricky; Sanchez, Ana B.; Kaul, Marcus

    2017-01-01

    Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury. PMID:28425451

  19. IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

    PubMed

    Thaney, Victoria E; O'Neill, Alan M; Hoefer, Melanie M; Maung, Ricky; Sanchez, Ana B; Kaul, Marcus

    2017-04-20

    Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury.

  20. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    SciTech Connect

    Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M. )

    1990-05-01

    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.

  1. Brain injury in sports.

    PubMed

    Lloyd, John; Conidi, Frank

    2016-03-01

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

  2. Treadmill Exercise Protects Against Pentylenetetrazol-Induced Seizures and Oxidative Stress after Traumatic Brain Injury

    PubMed Central

    Silva, Luiz Fernando Almeida; Hoffmann, Maurício Scopel; Gerbatin, Rogério da Rosa; Fiorin, Fernando da Silva; Dobrachinski, Fernando; Mota, Bibiana Castagna; Wouters, Angelica Terezinha Barth; Pavarini, Saulo Petinatti; Soares, Félix Alexandre Antunes; Fighera, Michele Rechia

    2013-01-01

    Abstract Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG recordings also revealed that physical exercise prevented PTZ-induced amplitude increase in TBI animals. Neurochemical analysis showed that exercise training increased glutathione/oxidized glutathione ratio and glutathione levels per se. Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na+,K+-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na+/K+-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility. PMID:23530735

  3. Hydroxysafflor yellow A protects methylglyoxal-induced injury in the cultured human brain microvascular endothelial cells.

    PubMed

    Li, Wenlu; Liu, Jie; He, Ping; Ni, Zhenzhen; Hu, Yangmin; Xu, Huimin; Dai, Haibin

    2013-08-09

    Individuals with diabetes have high concentration of methylglyoxal (MGO) and have advanced glycation end-products (AGEs) which play an important role in vascular complications, such as stroke. Our previous data demonstrated that hydroxysafflor yellow A (HSYA), a major active chemical component of the safflower yellow pigment, had antiglycation effect on the AGEs formation in vitro. It is not known whether HSYA can protect against MGO-induced injury in cultured human brain microvascular endothelial cells (HBMEC). Using cultured HBMEC, cell injury was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, lactate dehydrogenase (LDH) release and AnnexinV/PI staining. Advanced glycogen end-products and caspase-3 formation were measured by Western blotting. Incubation of MGO for 24h concentration-dependently induced HBMEC injury, which was protected by HSYA from 10 to 100 μmol/l. Caspase-3 expression and AnnexinV/PI staining illustrated that the protection of HSYA was probably associated with inhibiting cell apoptosis. What's more, MGO promoted AGEs accumulation in the cultured HBMEC, which was also inhibited by 100 μmol/l HSYA. Thus, our results proved that HSYA could inhibit MGO-induced injury in the cultured HBMEC, which was associated with its antiglycation effect.

  4. Exercise pre-conditioning reduces brain inflammation and protects against toxicity induced by traumatic brain injury: behavioral and neurochemical approach.

    PubMed

    Mota, Bibiana Castagna; Pereira, Leticia; Souza, Mauren Assis; Silva, Luiz Fernando Almeida; Magni, Danieli Valnes; Ferreira, Ana Paula Oliveira; Oliveira, Mauro Schneider; Furian, Ana Flávia; Mazzardo-Martins, Leidiane; Silva, Morgana Duarte da; Santos, Adair Roberto Soares; Ferreira, Juliano; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

    2012-02-01

    Although the favorable effects of physical exercise in neurorehabilitation after traumatic brain injury (TBI) are well known, detailed pathologic and functional alterations exerted by previous physical exercise on post-traumatic cerebral inflammation have been limited. In the present study, it is showed that fluid percussion brain injury (FPI) induced motor function impairment, followed by increased plasma fluorescein extravasation and cerebral inflammation characterized by interleukin-1β, tumor necrosis factor-α (TNF-α) increase, and decreased IL-10. In addition, myeloperoxidase (MPO) increase and Na⁺,K⁺-ATPase activity inhibition after FPI suggest that the opening of blood-brain barrier (BBB) followed by neurtrophils infiltration and cerebral inflammation may contribute to the failure of selected targets leading to secondary damage. In fact, Pearson's correlation analysis revealed strong correlation of MPO activity increase with Na⁺,K⁺-ATPase activity inhibition in sedentary rats. Statistical analysis also revealed that previous running exercise (4 weeks) protected against FPI-induced motor function impairment and fluorescein extravasation. Previous physical training also induced IL-10 increase per se and protected against cerebral IL-1β, and TNF-α increase and IL-10 decrease induced by FPI. This protocol of physical training was effective against MPO activity increase and Na⁺,K⁺-ATPase activity inhibition after FPI. The present protection correlated with MPO activity decrease suggests that the alteration of cerebral inflammatory status profile elicited by previous physical training reduces initial damage and limits long-term secondary degeneration after TBI. This prophylactic effect may facilitate functional recovery in patients suffering from brain injury induced by TBI.

  5. Protective effect of tert-butylhydroquinone on cerebral inflammatory response following traumatic brain injury in mice.

    PubMed

    Jin, Wei; Kong, Jie; Wang, Handong; Wu, Jun; Lu, Tianyu; Jiang, Jian; Ni, Hongbin; Liang, Weibang

    2011-07-01

    Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play a crucial role in protection against TBI induced inflammatory response in the brain. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect mice brain against TBI-induced inflammatory damage. Adult male ICR mice were randomly divided into three groups: (1) sham+vehicle group; (2) TBI+vehicle group; and (3) TBI+tBHQ group (n=12 per group). Closed head injury was adopted using Hall's weight-dropping method. We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay (EMSA), concentrations of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), brain oedema by wet/dry weight method, and cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis. Induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokine production in the injured brain. Administration of tBHQ also significantly attenuated TBI-induced brain oedema and cortical apoptosis. Pre-treatment with tBHQ could attenuate the cerebral inflammatory response after TBI. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid

    PubMed Central

    Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R.; Masliah, Eliezer; Lipton, Stuart A.

    2015-01-01

    Cyanide is a life threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species (ROS). This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain-barrier to upregulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human induced pluripotent stem cell (hiPSC)-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino (NSA) mouse model of cyanide poisoning that simulates damage observed in the human brain. PMID:25692407

  7. Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice.

    PubMed

    Zhao, Jin-Jing; Song, Jin-Qing; Pan, Shu-Yi; Wang, Kai

    2016-08-01

    Ischemic stroke is a major cause of morbidity and mortality, yet lacks effective neuroprotective treatments. The aim of this work was to investigate whether treatment with isorhamnetin protected the brain against ischemic injury in mice. Experimental stroke mice underwent the filament model of middle cerebral artery occlusion with reperfusion. Treatment with isorhamnetin or vehicle was initiated immediately at the onset of reperfusion. It was found that treatment of experimental stroke mice with isorhamnetin reduced infarct volume and caspase-3 activity (a biomarker of apoptosis), and improved neurological function recovery. Treatment of experimental stroke mice with isorhamnetin attenuated cerebral edema, improved blood-brain barrier function, and upregulated gene expression of tight junction proteins including occludin, ZO-1, and claudin-5. Treatment of experimental stroke mice with isorhamnetin activated Nrf2/HO-1, suppressed iNOS/NO, and led to reduced formation of MDA and 3-NT in ipsilateral cortex. In addition, treatment of experimental stroke mice with isorhamnetin suppressed activity of MPO (a biomarker of neutrophil infiltration) and reduced protein levels of IL-1β, IL-6, and TNF-α in ipsilateral cortex. Furthermore, it was found that treatment of experimental stroke mice with isorhamnetin reduced mRNA and protein expression of NMDA receptor subunit NR1 in ipsilateral cortex. In conclusion, treatment with isorhamnetin protected the brain against ischemic injury in mice. Isorhamnetin could thus be envisaged as a countermeasure for ischemic stroke but remains to be tested in humans.

  8. Manganese Superoxide Dismutase Protects against 6-Hydroxydopamine Injury in Mouse Brains*

    PubMed Central

    Callio, Jason; Oury, Tim D.; Chu, Charleen T.

    2007-01-01

    Dopaminergic neurons of the substantia nigra are susceptible to toxin-based insults. Intrastriatal injection of 6-hydroxydopamine results in selective toxicity to these neurons. A mechanistic role for reactive oxygen species is supported by observations that antioxidants confer protection from 6-hydroxydopamine. Although cell culture studies have suggested extracellular or nonmitochondrial mechanisms in 6-hydroxydopamine toxicity, the compartmentalization of oxidative injury mechanisms is incompletely defined in vivo. Transgenic mice overexpressing mitochondrial manganese superoxide dismutase or extracellular superoxide dismutase received unilateral intrastriatal injections of 6-hydroxydopamine. Mice that overexpress manganese superoxide dismutase showed significantly smaller striatal lesions than littermate controls. There were no differences in nonspecific striatal injury associated with contralateral vehicle injection. Manganese superoxide dismutase overexpression also protected against loss of neuronal cell bodies in the substantia nigra. In contrast, mice overexpressing extracellular superoxide dismutase showed no protection from 6-hydroxydopamine toxicity in either brain region. Protection of the nigrostriatal system by overexpression of manganese super-oxide dismutase supports a role for mitochondrially derived superoxide in 6-hydroxydopamine toxicity. Mitochondrial oxidative stress appears to be a common mechanism among diverse models of Parkinson disease, whether involving toxins, mutated genes, or cybrid cells containing patient mitochondria. Antioxidant therapies that target this subcellular compartment may prove promising. PMID:15755737

  9. Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury.

    PubMed

    Eroglu, Binnur; Kimbler, Donald E; Pang, Junfeng; Choi, Justin; Moskophidis, Demetrius; Yanasak, Nathan; Dhandapani, Krishnan M; Mivechi, Nahid F

    2014-09-01

    Traumatic brain injury (TBI) induces severe harm and disability in many accident victims and combat-related activities. The heat-shock proteins Hsp70/Hsp110 protect cells against death and ischemic damage. In this study, we used mice deficient in Hsp110 or Hsp70 to examine their potential requirement following TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death of neurons. One of the mechanisms underlying the increased cell death observed in the absence of Hsp110 and Hsp70 following TBI is the increased expression of reactive oxygen species-induced p53 target genes Pig1, Pig8, and Pig12. To examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells against TBI, we subjected mice to TBI and administered Celastrol or BGP-15. In contrast to Hsp110- or Hsp70i-deficient mice that were not protected following TBI and Celastrol treatment, there was a significant improvement of wild-type mice following administration of these drugs during the first week following TBI. In addition, assessment of neurological injury shows significant improvement in contextual and cued fear conditioning tests and beam balance in wild-type mice that were treated with Celastrol or BGP-15 following TBI compared to TBI-treated mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward reducing the pathological consequences of TBI. Our data indicate that loss of Hsp110 or Hsp70 in mice increases brain injury following TBI. (a) One of the mechanisms underlying the increased cell death observed in the absence of these Hsps following TBI is the increased expression of ROS-induced p53 target genes known as Pigs. In addition, (b) using drugs (Celastrol or BGP-15) to increase Hsp70/Hsp110 levels protect cells against TBI, suggesting the beneficial effects of Hsp70/Hsp110 inducers to reduce the pathological consequences of TBI. © 2014 International Society

  10. Magnesium gluconate offers no more protection than magnesium sulphate following diffuse traumatic brain injury in rats.

    PubMed

    Turner, Renee J; Dasilva, K W; O'Connor, C; van den Heuvel, Corinna; Vink, Robert

    2004-10-01

    Previous studies have demonstrated that magnesium salts, including the sulphate and chloride forms, are neuroprotective following traumatic brain injury (TBI). Recently, studies in cardiac ischaemia/reperfusion injury have demonstrated that the gluconate salt of magnesium may provide superior protection against oxidative damage and postischaemic dysfunction than MgSO(4). We have therefore compared the efficacy of both MgSO(4) and magnesium gluconate (MgGl(2)) on outcome following diffuse TBI in rats. Adult male Sprague-Dawley rats were injured using the 2-metre impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered with either 250 micromoles/kg i.v. MgSO(4), MgGl(2), or equal volume saline vehicle. Thereafter, animals were assessed for motor and cognitive outcome using the rotarod and Barnes maze, respectively, or their brains removed at 3 days after TBI and used for histological examination. Treatment with either magnesium salt significantly improved functional outcome as compared to vehicle treated controls. Similarly, treatment with either magnesium salt attenuated the degree of histological dark cell change at 3 days after TBI relative to the vehicle treated animals. There were no significant differences between the magnesium treated groups. We conclude that MgSO(4) and MgGl(2) are equally neuroprotective following TBI. Our results suggest that MgGl(2) may only be more effective in conditions that produce ischaemia, where high concentrations of reactive oxygen species are generated.

  11. Ischemic preconditioning protects the brain against injury via inhibiting CaMKII-nNOS signaling pathway.

    PubMed

    Wang, Mei; Qi, Da-Shi; Zhou, Cui; Han, Dong; Li, Pei-Pei; Zhang, Fang; Zhou, Xiao-Yan; Han, Meng; Di, Jie-Hui; Ye, Jun-Song; Yu, Hong-Min; Song, Yuan-Jian; Zhang, Guang-Yi

    2016-03-01

    Although studies have shown that cerebral ischemic preconditioning (IPC) can ameliorate ischemia/reperfusion (I/R) induced brain damage, but its precise mechanisms remain unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of IPC against ischemic brain damage induced by cerebral I/R and to explore whether the Calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway contributed to the protection provided by IPC. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with 3 min of IPC alone or KN62 (selective antagonist of CaMKII) treatment before IPC, after reperfusion for 3 days, 6 min ischemia was induced. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting was performed to measure the phosphorylation of CaMKII, nNOS, c-Jun and the expression of FasL. Immunoprecipitation was used to examine the binding between PSD95 and nNOS. The results showed that IPC could significantly protect neurons against cerebral I/R injury, furthermore, the combination of PSD95 and nNOS was increased, coinstantaneously the phosphorylation of CaMKII and nNOS (ser847) were up-regulated, however the activation of c-Jun and FasL were reduced. Conversely, KN62 treatment before IPC reversed all these effects of IPC. Taken together, the results suggest that IPC could diminish ischemic brain injury through CaMKII-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway.

  12. Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow.

    PubMed

    Wang, Qin; Fan, Weijia; Cai, Ying; Wu, Qiaoli; Mo, Lidong; Huang, Zhenwu; Huang, Huiling

    2016-09-01

    In mammalian tissues, taurine is an important natural component and the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. This study is to examine the taurine's protective effects on neuronal ultrastructure, the function of the mitochondrial respiratory chain complex, and on cerebral blood flow (CBF). The model of traumatic brain injury (TBI) was made for SD rats by a fluid percussion device, with taurine (200 mg/kg) administered by tail intravenous injection once daily for 7 days after TBI. It was found that CBF was improved for both left and right brain at 30 min and 7 days post-injury by taurine. Reaction time was prolonged relative to the TBI-only group. Neuronal damage was prevented by 7 days taurine. Mitochondrial electron transport chain complexes I and II showed greater activity with the taurine group. The improvement by taurine of CBF may alleviate edema and elevation in intracranial pressure. Importantly taurine improved the hypercoagulable state.

  13. 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 ...

  14. Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI)

    PubMed Central

    Baratz-Goldstein, Renana; Deselms, Hanna; Heim, Leore Raphael; Khomski, Lena; Hoffer, Barry J.

    2016-01-01

    Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries. PMID:27285176

  15. Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI).

    PubMed

    Baratz-Goldstein, Renana; Deselms, Hanna; Heim, Leore Raphael; Khomski, Lena; Hoffer, Barry J; Atlas, Daphne; Pick, Chaim G

    2016-01-01

    Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries.

  16. The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis.

    PubMed

    Jiang, Lianxiang; Hu, Meizhu; Lu, Yan; Cao, Ya; Chang, Yan; Dai, Zeping

    2017-08-01

    Intracranial lesions, trauma or surgery-related damage activate immune inflammation and neuroendocrine responses, causing ischemic brain injury. Studies have shown that inflammatory cascade mediated by neuroendocrine hormones and proinflammatory mediators is implicated in the pathophysiology of ischemic brain injury. Alpha2-adrenoceptor agonists, dexmedetomidine, is widely used as neuroprotectants in anesthesia practice. However, it is still lack of a comprehensive meta-analysis to evaluate the neuroprotection of dexmedetomidine against ischemic brain injury via suppressing these two physiological responses. Searched the Cochrane Library, Pub-Med, EMBASE, EBSCO, Ovid, Chinese biological and medical database (CBM). Related literatures published in English or Chinese before January 2017 were enrolled. We assessed the quality of eligible studies and synthesized predefined outcomes with a random-effects model or fixed-effects model. Nineteen Randomized Controlled Trials including 879 patients were included. Findings for meta-analysis of various outcomes were summarised. Primary results shown that compared with placebo, dexmedetomidine reduced a surge of TNF-α [SMD=-2.34, 95%CI (-3.25, -1.44)], IL-6 [SMD=-2.44, 95%CI (-3.40, -1.47)], S100-β [SMD=-2.73, 95%CI (-3.65, -1.82)], NSE [SMD=-1.69, 95%CI (-2.77, -0.61)], cortisol [SMD=-2.48, 95%CI (-3.38, -1.58)] and glucose [SMD=-1.44, 95%CI (-1.85, -1.04)]; maintained the level of SOD [SMD=1.36, 95%CI (0.62, 2.10)]; decreased the rise in CRP level at postoperative one day. In response to stress reaction, dexmedetomidine attenuated the stress-related increasing of MAP, HR and intracranial pressure without significant effects on cerebral oxygen metabolism. Alpha2-adrenoceptor agonists, dexmedetomidine, could reduce the release of inflammatory mediators and neuroendocrine hormones as well as maintain intracranial homoeostasis, alleviating ischemic brain injury and exerting an effect on brain protection. Copyright © 2017

  17. Injectable caltrop fruit saponin protects against ischemia-reperfusion injury in rat brain.

    PubMed

    Yan, Ling-Geng; Lu, Yin; Zheng, Shi-Zhong; Wang, Ai-Yun; Li, Meng-Qiu; Ruan, Jun-Shan; Zhang, Lei

    2011-01-01

    The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

  18. Up-regulation of heme oxygenase-1 protects against cold injury-induced brain damage: a laboratory-based study.

    PubMed

    Shih, Ruey-Horng; Cheng, Shin-Ei; Tung, Wei-Hsuan; Yang, Chuen-Mao

    2010-08-01

    Heme oxygenase-1 (HO-1), a kind of stress protein, is critical for the protection against ischemic stroke and cerebrovascular endothelium damage. However, the effects of HO-1 on trauma-induced brain injury are still unknown. Hence, we attempted to use a cold injury-induced brain trauma (CIBT) model in mice, which provides for a well-established approach for assessing brain edema and blood-brain barrier breakdown. Additionally, we explored cultured mouse brain endothelial cells (bEnd.3) to investigate the protective effects of HO-1. HO-1 was induced by infection with a recombinant adenovirus carrying the human HO-1 gene or an inducer of HO-1 activity, cobalt protoporphyrin IX (CoPP). The recombinant adenovirus (3.5 x 10(7) PFU/mouse, i.v.) or CoPP (10 mg/kg, i.v.) significantly increased HO-1 protein expression and HO-1 enzyme activity in the cerebral cortex of the mice. We found that overexpression of HO-1 protected against cold injury-induced secondary damage and behavioral impairment. Up-regulation of HO-1 decreased brain edema and neutrophil infiltration induced by cold injury. These HO-1-dependent protecting effects were abrogated by pretreatment with the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP; 3 mg/kg, i.v.). HO-1 expression in the cerebral endothelium was observed by immunofluorescent staining. CoPP-induced (1 muM, 24 h) HO-1 protein expression was determined by western blotting in bEnd.3 cells. Enhanced HO-1 also protected against cold injury-induced cell loss and damage, which were respectively determined by GAPDH leakage into the cell medium and XTT assay in bEnd.3 cells. In summary, HO-1 overexpression appears to offer an effective neuroprotection against cold-induced secondary brain injury.

  19. Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

    PubMed

    Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

    2015-06-01

    Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2).

  20. Fermented Chinese Formula Shuan-Tong-Ling Protects Brain Microvascular Endothelial Cells against Oxidative Stress Injury

    PubMed Central

    Tan, Lingjing; Zhang, Xiang; Wang, Jinfeng; Li, Xiaoli; Huang, Weifeng; Yang, Songbai

    2016-01-01

    Fermented Chinese formula Shuan-Tong-Ling (STL), composed of fourteen medicinal herbs, was an experiential formula by Dr. Zhigang Mei for treating vascular encephalopathy, but the underlying mechanisms remained unknown. In this study, we aimed to investigate the protective effects of fermented STL on hydrogen peroxide- (H2O2-) induced injury in rat brain microvascular endothelial cells (BMECs) and the possible mechanisms. Cultured BMECs were treated with H2O2, STL, or nicotinamide (NAM, a SIRT1 inhibitor). Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was employed to detect cell proliferation and senescence-associated beta-galactosidase (SA-β-gal) was used to examine cell senescence. Cell nuclei were observed by 4′,6-diamidino-2-phenylindole. Additionally, changes in reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) levels were measured. Expression of SIRT1, p21, and PGC-1α was determined by western blot. Cell proliferation significantly increased with STL treatment in a dose-dependent manner. H2O2 treatment could intensify cell senescence and nuclei splitting or pyknosis. With STL treatment, the reduced ROS level was accompanied by increased SOD and GSH activity. Further assays showed upregulation of SIRT1 and PGC-1α and downregulation of p21 after STL treatment. The results revealed that STL could protect BMECs against oxidative stress injury at least partially through the SIRT1 pathway. PMID:28096886

  1. Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury.

    PubMed

    Shee, Kevin; Lucas, Alexandra; Flashman, Laura A; Nho, Kwangsik; Tsongalis, Gregory J; McDonald, Brenna C; Saykin, Andrew J; McAllister, Thomas W; Rhodes, C Harker

    2016-09-06

    Problems with attention and short-term learning and memory are commonly reported after mild traumatic brain injury (mTBI). Due to the known relationships between α-synuclein (SNCA), dopaminergic transmission, and neurologic deficits, we hypothesized that SNCA polymorphisms might be associated with cognitive outcome after mTBI. A cohort of 91 mTBI patients one month after injury and 86 healthy controls completed a series of cognitive tests assessing baseline intellectual function, attentional function, and memory, and was genotyped at 13 common single nucleotide polymorphisms (SNPs) in the SNCA gene. Significant differences in two memory measures (p=0.001 and 0.002), but not baseline intellectual function or attentional function tasks, were found between the mTBI group and controls. A highly significant protective association between memory performance and SNCA promoter SNP rs1372525 was observed in the mTBI patients (p=0.006 and 0.029 for the long and short delay conditions of the California Verbal Learning Tests, respectively), where the presence of at least one copy of the A (minor) allele was protective after mTBI. These results may help elucidate the pathophysiology of cognitive alterations after mTBI, and thus warrant further investigation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Heat Acclimation Regulates the Autophagy-Lysosome Function to Protect Against Heat Stroke-Induced Brain Injury in Mice.

    PubMed

    Yi, Junfeng; He, Genlin; Yang, Ju; Luo, Zhen; Yang, Xuesen; Luo, Xue

    2017-01-01

    The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear. The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS. The effects of HA on autophagy and lysosomes were assessed in the presence of the autophagy inhibitor 3-methyladenine (3MA). Autophagy and lysosome-associated proteins were analysed by Western blotting. We found that HA protected against HS-induced death and brain injury. HS can robustly induce autophagy and impair lysosome function. HA pre-conditioning significantly modulated the autophagy level, and improved lysosome function in HS mice. Furthermore, 3MA completely abolished the neuroprotective effect of HA on HS. HS may induce brain injury through lysosomal dysfunction and impaired autophagic flux. HA protected against HS-induced brain injury via a mechanism involving the autophagy-lysosome pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats

    PubMed Central

    Zhang, Xiang-Sheng; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Jiang, Tian-Wei; Li, Wei; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH. PMID:27735947

  4. Brain injuries from blast.

    PubMed

    Bass, Cameron R; Panzer, Matthew B; Rafaels, Karen A; Wood, Garrett; Shridharani, Jay; Capehart, Bruce

    2012-01-01

    Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is

  5. Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke.

    PubMed

    Yang, Wenjie; Chen, Xiang; Pan, Jie; Ge, Huiming; Yin, Kailin; Wu, Zhengzheng; Li, Xiaoxi; Sha, Dujuan; Xu, Yun

    2015-01-01

    Ischemic stroke is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunction. Malibatol A (MA), a novel resveratrol oligomer, has shown potential antioxidant property in vitro. But little is known about its effect on central nervous system (CNS) in vivo. In the present study, the effect of MA was evaluated in focal cerebral ischemia induced by right middle cerebral artery occlusion (MCAO) in mice. MA at the dose of 20 mg/kg was administered by caudal-vein injection within 15 min after reperfusion. At 24 h after cerebral ischemia/reperfusion (I/R) injury, ameliorated neurological scores and reduced infarct volume was observed in MA treated group. Also, MA treatment restored the increased levels of reactive oxygen species (ROS), 3-Nitrotyrosine (3-NT), and 4-Hydroxynonenal (4-HNE) induced by MCAO. The activities of respiratory enzyme complex I, III and mitochondrial transmembrane potential (Δm) were effectively preserved compared with MCAO group through MA treatment. Western blot analysis showed a marked increase in Bcl-2 and decrease in Bax expression after MA treatment as compared with MCAO group. Moreover, MA treatment prevented release of cytochrome c from mitochondria into cytoplasm and blunted activities of caspase-9 and caspase-3. Collectively, the present study indicates that MA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 h of I/R injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Kelvar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology

    DTIC Science & Technology

    2013-05-01

    brain results from pressure surges transmitted through the vasculature that elicit intracranial disruptions, and 2) Kevlar vests are neuroprotective...vascular), and central (e.g. intracranial pressure ) BOP-induced pressure changes, and assess the impact of Kevlar vests on these changes. We seek to...and venous), and central (e.g. intracranial pressure ) BOP-induced pressure changes, and assess the impact of Kevlar vests on these changes. In

  7. Sphingosine kinase 2 mediates cerebral preconditioning and protects mouse brain against ischemic injury

    PubMed Central

    Yung, Lai Ming; Wei, Ying; Qin, Tao; Wang, Yumei; Smith, Charles; Waeber, Christian

    2011-01-01

    Background and purpose Cerebral preconditioning provides insights into endogenous mechanisms that protect the brain from ischemic injury. Hypoxia and the anesthetic isoflurane are powerful preconditioning agents. Recent data show that sphingosine 1-phosphate (S1P) receptor stimulation improves outcome in rodent models of stroke. Endogenous S1P levels are controlled by the expression and activity of sphingosine kinases (SPK). We hypothesize that SPK up-regulation mediates preconditioning induced by isoflurane and hypoxia and reduces ischemic injury. Methods Male wild-type C57BL/J, SPK1−/− and SPK2−/− mice were exposed to isoflurane (IsoPC) or hypoxia preconditioning (HPC) before transient middle cerebral artery occlusion. Infarct volume and neurological outcome were measured 24 hours later. SPK inhibitors (SKI-II and ABC294640) were used to test the involvement of SPK2. Expressions of SPK1, SPK2 and HIF1α were determined. Primary cultures of mouse cortical neurons were exposed to isoflurane before glutamate- or hydrogen peroxide-induced cell death. Results IsoPC and HPC significantly reduced infarct volume and improved neurological outcome in wild-type and SPK1−/− mice, but not in SPK2−/− mice. Pretreatment with SKI-II or ABC294640 abolished the IsoPC-induced tolerance. Western blot showed a rapid and sustained increase in SPK2 level, whereas SPK1 level was similar between preconditioned mice and controls. HIF1α was up-regulated in wild-type IsoPC mice, but not in SPK2−/−. IsoPC protected primary neurons against cell death, which was abolished in ABC294640-treated cells. Conclusions Applying genetic and pharmacological approaches, we demonstrate that neuronal SPK2 isoform plays an important role in cerebral preconditioning. PMID:21980199

  8. Stachys sieboldii (Labiatae, Chorogi) Protects against Learning and Memory Dysfunction Associated with Ischemic Brain Injury.

    PubMed

    Harada, Shinichi; Tsujita, Tsukasa; Ono, Akiko; Miyagi, Kei; Mori, Takaharu; Tokuyama, Shogo

    2015-01-01

    Stachys sieboldii (Labiatae; Chinese artichoke, a tuber), "chorogi" in Japanese, has been extensively used in folk medicine, and has a number of pharmacological properties, including antioxidative activity. However, few studies have examined the neuroprotective effects of S. sieboldii tuber extract (chorogi extract), and it remains unknown whether the extract can alleviate learning and memory dysfunction associated with vascular dementia or Alzheimer's disease. Therefore, in this study, we investigated the neuroprotective effects of chorogi extract, and examined its protection against learning and memory dysfunction using Ginkgo biloba leaf extract (ginkgo extract) as a positive control. Mice were subjected to bilateral carotid artery occlusion (BCAO) for 30 min. Oral administration of chorogi extract or ginkgo extract significantly reduced post-ischemic glucose intolerance on day 1 and neuronal damage including memory impairment on day 3 after BCAO, compared with the vehicle-treated group. Neither herbal medicine affected locomotor activity. Furthermore, neither significantly alleviated scopolamine-induced learning and memory impairment. In primary neurons, neuronal survival rate was significantly reduced by hydrogen peroxide treatment. This hydrogen peroxide-induced neurotoxicity was significantly suppressed by chorogi extract and ginkgo extract. Taken together, our findings suggest that chorogi extract as well as ginkgo extract can protect against learning and memory dysfunction associated with ischemic brain injury through an antioxidative mechanism.

  9. Protective effects of perfluorooctyl-bromide nanoparticles on early brain injuries following subarachnoid hemorrhage in rats

    PubMed Central

    Zhang, Huan; Xu, Rui; Xie, Fei; Xu, Wei; Zeng, Meng-Fei; Wang, Xin; Zhu, Ji

    2015-01-01

    To investigate the protective effects of perfluorooctyl-bromide (PFOB) nanoparticles on early brain injury (EBI) following subarachnoid hemorrhage (SAH), a total of 120 rats were randomly assigned to the following groups: Sham operation group (n = 40), SAH group (n = 40), and SAH + PFOB group (n = 40). Endovascular perforation was performed to induce subarachnoid hemorrhage. Brain water content was measured 24 h after surgery. Meanwhile, morphological changes in the rat hippocampal CA1 region were examined using light and transmission electron microscopy. The rate of neuronal apoptosis in rat hippocampal CA1 region was determined using TUNEL assay. Protein and mRNA expression levels of Caspase-3, Bax, and Bcl-2 were measured using western blot and RT-PCR assays 12, 24, 48, and 72 h after surgery. Compared to the SAH group, the SAH + PFOB group had significantly lower brain water content (P<0.01), with alleviated morphological abnormalities in HE-stained neurons and significantly decreased neurons with karyopyknosis and hyperchromatism in the hippocampal CA1 region. Electron microscopy revealed reduction of neuronal apoptosis, alleviation of glial cell swelling, and mitigation of perivascular edema in the hippocampal region. Immunohistochemical analysis showed that the expression of apoptosis-related factors Caspase-3 and Bax was significantly reduced, while that of the anti-apoptotic factor Bcl-2 was significantly increased. TUNEL staining showed that neuronal apoptosis was significantly reduced in the hippocampal CA1 region (P<0.01). RT-PCR and Western-blot data indicated that expressions of Caspase-3 and Bax were both significantly reduced, while bcl-2 expression was increased significantly at 12, 24, 48, and 72 h after SAH (P<0.01). Together, our data support that PFOB nanoparticles with high oxygen content could counteract ischemia and hypoxia, block neuronal apoptotic pathways, reduce neuronal apoptosis, and therefore, achieve neuroprotective effects in EBI

  10. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant

    PubMed Central

    Kelpke, Stacey S.; Chen, Bo; Bradley, Kelley M.; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A.; Crossman, David K.; Bray, Molly S.; Eckhoff, Devin E.; Agarwal, Anupam; Patel, Rakesh P.

    2012-01-01

    Renal injury induced by brain death is characterized by ischemia and inflammation and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 hours of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 hours of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain dead rats showed significant improvement in function over the first 2 to 4 days post transplantation compared to untreated brain dead animals. Gene microarray analysis after 2 hours of brain death without or with nitrite therapy showed the latter significantly altered the expression of about 400 genes. Ingenuity Pathway analysis indicated multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription and genes related to humoral immune responses. Thus, nitrite-therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function. PMID:22534964

  11. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    PubMed

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  12. Guanosine Protects Against Traumatic Brain Injury-Induced Functional Impairments and Neuronal Loss by Modulating Excitotoxicity, Mitochondrial Dysfunction, and Inflammation.

    PubMed

    Gerbatin, Rogério da Rosa; Cassol, Gustavo; Dobrachinski, Fernando; Ferreira, Ana Paula O; Quines, Caroline B; Pace, Iuri D Della; Busanello, Guilherme L; Gutierres, Jessié M; Nogueira, Cristina W; Oliveira, Mauro S; Soares, Félix A; Morsch, Vera M; Fighera, Michele R; Royes, Luiz Fernando F

    2016-11-09

    Traumatic brain injury (TBI) is one of the most common types of brain injuries that cause death or persistent neurological disturbances in survivors. Most of the promising experimental drugs were not effective in clinical trials; therefore, the development of TBI drugs represents a huge unmet need. Guanosine, an endogenous neuroprotective nucleoside, has not been evaluated in TBI to the best of our knowledge. Therefore, the present study evaluated the effect of guanosine on TBI-induced neurological damage. Our findings showed that a single dose of guanosine (7.5 mg/kg, intraperitoneally (i.p.) injected 40 min after fluid percussion injury (FPI) in rats protected against locomotor and exploratory impairments 8 h after injury. The treatment also protected against neurochemical damage to the ipsilateral cortex, glutamate uptake, Na(+)/K(+)-ATPase, glutamine synthetase activity, and alterations in mitochondrial function. The inflammatory response and brain edema were also reduced by this nucleoside. In addition, guanosine protected against neuronal death and caspase 3 activation. Therefore, this study suggests that guanosine plays a neuroprotective role in TBI and can be exploited as a new pharmacological strategy.

  13. Brain-derived neurotrophic factor administration after traumatic brain injury in the rat does not protect against behavioral or histological deficits.

    PubMed

    Blaha, G R; Raghupathi, R; Saatman, K E; McIntosh, T K

    2000-01-01

    Brain-derived neurotrophic factor has been shown to be neuroprotective in models of excitotoxicity, axotomy and cerebral ischemia. The present study evaluated the therapeutic potential of brain-derived neurotrophic factor following traumatic brain injury in the rat. Male Sprague-Dawley rats (N=99) were anesthetized and subjected to lateral fluid percussion brain injury of moderate severity (2.4-2.8 atm) or sham injury. Four hours after injury, the animals were reanesthetized, an indwelling, intraparenchymal cannula was implanted, and infusion of brain-derived neurotrophic factor or phosphate-buffered saline vehicle was initiated from a mini-osmotic pump and continued for two weeks. In Study 1 (N=48), vehicle or 12 microg/day of brain-derived neurotrophic factor was infused into the dorsal hippocampus. In Study 2 (N=51), vehicle or brain-derived neurotrophic factor at a high (12 microg/day) or low dose (1.2 microg/day) was infused into the injured parietal cortex. All animals were evaluated for neurological motor function at two days, one week and two weeks post-injury. Cognitive function (learning and memory) was assessed at two weeks post-injury using a Morris Water Maze. At two weeks post-injury, neuronal loss in the hippocampal CA3 and dentate hilus and in the injured cortex was evaluated. In Study 2, neuronal loss was also quantified in the thalamic medial geniculate nucleus. All of the above outcome measures demonstrated significant deleterious effects of brain injury (P<0.05 compared to sham). However, post-traumatic brain-derived neurotrophic factor infusion did not significantly affect neuromotor function, learning, memory or neuronal loss in the hippocampus, cortex or thalamus when compared to vehicle infusion in brain-injured animals, regardless of the infusion site or infusion dose (P>0.05 for each). In contrast to previous studies of axotomy, ischemia and excitotoxicity, our data indicate that brain-derived neurotrophic factor is not protective against

  14. Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury

    PubMed Central

    2012-01-01

    Background An increase in intracellular calcium concentration [Ca2+]i is one of the first events to take place after brain ischemia. A key [Ca2+]i-regulated signaling molecule is the phosphatase calcineurin (CN), which plays important roles in the modulation of inflammatory cascades. Here, we have analyzed the role of endogenous regulator of CN 1 (Rcan1) in response to experimental ischemic stroke induced by middle cerebral artery occlusion. Methods Animals were subjected to focal cerebral ischemia with reperfusion. To assess the role of Rcan1 after stroke, we measured infarct volume after 48 h of reperfusion in Rcan1 knockout (KO) and wild-type (WT) mice. In vitro studies were performed in astrocyte-enriched cortical primary cultures subjected to 3% oxygen (hypoxia) and glucose deprivation (HGD). Adenoviral vectors were used to analyze the effect of overexpression of Rcan1-4 protein. Protein expression was examined by immunohistochemistry and immunoblotting and expression of mRNA by quantitative real-time Reverse-Transcription Polymerase Chain Reaction (real time qRT-PCR). Results Brain ischemia/reperfusion (I/R) injury in vivo increased mRNA and protein expression of the calcium-inducible Rcan1 isoform (Rcan1-4). I/R-inducible expression of Rcan1 protein occurred mainly in astroglial cells, and in an in vitro model of ischemia, HGD treatment of primary murine astrocyte cultures induced Rcan1-4 mRNA and protein expression. Exogenous Rcan1-4 overexpression inhibited production of the inflammatory marker cyclo-oxygenase 2. Mice lacking Rcan1 had higher expression of inflammation associated genes, resulting in larger infarct volumes. Conclusions Our results support a protective role for Rcan1 during the inflammatory response to stroke, and underline the importance of the glial compartment in the inflammatory reaction that takes place after ischemia. Improved understanding of non-neuronal mechanisms in ischemic injury promises novel approaches to the treatment of

  15. Mice Brain Tissue Injury Induced by Diisononyl Phthalate Exposure and the Protective Application of Vitamin E.

    PubMed

    Peng, Ling

    2015-07-01

    As a widely used plasticizer in plastic industry, the data of diisononyl phthalate (DINP) toxicity due to exposure are insufficient. This work investigated the brain tissue injury induced by DINP exposure. Through oral exposure to DINP, oxidative stress, inflammatory responses, apoptosis, and hippocampus pathological alterations were found in the mice brain. And through the Morris water maze test, cognitive deficits were tested. Our data also showed that these exacerbations were counteracted by vitamin E. These results above indicated that oral exposure of mice to DINP induced brain damage, and oxidative stress, inflammation, and the consequential apoptosis jointly constituted the potential mechanisms of such induced toxicity. © 2015 Wiley Periodicals, Inc.

  16. Inhibition of microglial activation contributes to propofol-induced protection against post-cardiac arrest brain injury in rats.

    PubMed

    Wang, Wei; Lu, Rui; Feng, Da-Yun; Liang, Li-Rong; Liu, Bing; Zhang, Hui

    2015-09-01

    It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post-cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre-treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p-p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre-treatment inhibited ATP-induced microglial activation and release of tumor necrosis factor-α and interleukin-1β. In addition, propofol protected neurons from injury when co-culturing with ATP-treated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function. We proposed a possible mechanism of propofol-mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF-α and IL-1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol-induced anti-inflammatory treatment as a plausible strategy for therapeutic intervention in post-CA brain injury.

  17. Inhibiting HMGB1 with Glycyrrhizic Acid Protects Brain Injury after DAI via Its Anti-Inflammatory Effect

    PubMed Central

    Pang, Honggang; Huang, Tinqin; Li, Dandong; Zhao, Yonglin; Ma, Xudong

    2016-01-01

    High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in several neurological diseases by mediating inflammatory response. In this study, a lateral head rotation device was used to establish a rat diffuse axonal injury (DAI) model. The dynamic expression of HMGB1, apoptosis-associated proteins, and proinflammatory cytokines were detected by Western blot, and neuronal apoptosis was observed by TUNEL staining. The extracellular release of HMGB1 and the accumulation of β-APP were observed by immunofluorescence and immunohistochemistry, respectively. The brain injury was indicated by modified neurological severity score (mNSS), brain water content (BWC), and the extravasation of Evans blue. We showed that HMGB1 level obviously decreased within 48 h after DAI, accompanied by neuronal apoptosis, the activation of caspases 3 and 9, and the phosphorylation of BCL-2. Inhibiting HMGB1 with glycyrrhizic acid (GL) can suppress the activation of apoptosis-associated proteins and inhibit the expression of proinflammatory cytokines, which ameliorated motor and cognitive deficits, reduced neuronal apoptosis, and protected the integrity of blood brain barrier (BBB) and axonal injury after experimental DAI in rats. Thus, HMGB1 may be involved in the inflammatory response after DAI, and inhibition of HMGB1 release with GL can notably alleviate the brain injury after DAI. PMID:27041825

  18. Inhibiting HMGB1 with Glycyrrhizic Acid Protects Brain Injury after DAI via Its Anti-Inflammatory Effect.

    PubMed

    Pang, Honggang; Huang, Tinqin; Song, Jinning; Li, Dandong; Zhao, Yonglin; Ma, Xudong

    2016-01-01

    High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in several neurological diseases by mediating inflammatory response. In this study, a lateral head rotation device was used to establish a rat diffuse axonal injury (DAI) model. The dynamic expression of HMGB1, apoptosis-associated proteins, and proinflammatory cytokines were detected by Western blot, and neuronal apoptosis was observed by TUNEL staining. The extracellular release of HMGB1 and the accumulation of β-APP were observed by immunofluorescence and immunohistochemistry, respectively. The brain injury was indicated by modified neurological severity score (mNSS), brain water content (BWC), and the extravasation of Evans blue. We showed that HMGB1 level obviously decreased within 48 h after DAI, accompanied by neuronal apoptosis, the activation of caspases 3 and 9, and the phosphorylation of BCL-2. Inhibiting HMGB1 with glycyrrhizic acid (GL) can suppress the activation of apoptosis-associated proteins and inhibit the expression of proinflammatory cytokines, which ameliorated motor and cognitive deficits, reduced neuronal apoptosis, and protected the integrity of blood brain barrier (BBB) and axonal injury after experimental DAI in rats. Thus, HMGB1 may be involved in the inflammatory response after DAI, and inhibition of HMGB1 release with GL can notably alleviate the brain injury after DAI.

  19. 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

  20. Citicoline protects brain against closed head injury in rats through suppressing oxidative stress and calpain over-activation.

    PubMed

    Qian, Ke; Gu, Yi; Zhao, Yumei; Li, Zhenzong; Sun, Ming

    2014-07-01

    Citicoline, a natural compound that functions as an intermediate in the biosynthesis of cell membrane phospholipids, is essential for membrane integrity and repair. It has been reported to protect brain against trauma. This study was designed to investigate the protective effects of citicoline on closed head injury (CHI) in rats. Citicoline (250 mg/kg i.v. 30 min and 4 h after CHI) lessened body weight loss, and improved neurological functions significantly at 7 days after CHI. It markedly lowered brain edema and blood-brain barrier permeability, enhanced the activities of superoxide dismutase and the levels of glutathione, reduced the levels of malondialdehyde and lactic acid. Moreover, citicoline suppressed the activities of calpain, and enhanced the levels of calpastatin, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. Also, it attenuated the axonal and myelin sheath damage in corpus callosum and the neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. These data demonstrate the protection of citicoline against white matter and grey matter damage due to CHI through suppressing oxidative stress and calpain over-activation, providing additional support to the application of citicoline for the treatment of traumatic brain injury.

  1. Lung Protective Ventilation (ARDSNet) versus APRV: Ventilatory Management in a Combined Model of Acute Lung and Brain Injury

    PubMed Central

    Davies, Stephen W.; Leonard, Kenji L.; Falls, Randall K.; Mageau, Ronald P.; Efird, Jimmy T.; Hollowell, Joseph P.; Trainor, Wayne E.; Kanaan, Hilal A.; Hickner, Robert C.; Sawyer, Robert G.; Poulin, Nathaniel R.; Waibel, Brett H.; Toschlog, Eric A.

    2014-01-01

    Background Concomitant lung/brain traumatic injury, results in significant morbidity and mortality. Lung protective ventilation (ARDSNet) has become the standard for managing acute respiratory distress syndrome (ARDS); however, the resulting permissive hypercapnea may compound traumatic brain injury (TBI). Airway pressure release ventilation (APRV) offers an alternative strategy for management of this patient population. APRV was hypothesized to retard the progression of acute lung/brain injury to a greater degree than ARDSNet in a swine model. Methods Yorkshire swine were randomized to ARDSNet, APRV, or sham. Ventilatory settings and pulmonary parameters, vitals, blood gases, quantitative histopathology, and cerebral microdialysis were compared between groups using chi-square, Fisher’s exact, Student’s t-test, Wilcoxon rank-sum, and mixed effects repeated measures modeling. Results 22 swine (17 male, 5 female), weighing 25±6.0kg, were randomized to APRV (n=9), ARDSNet (n=12), or sham (n=1). PaO2/FiO2 (P/F) ratio dropped significantly while intracranial pressure increased significantly for all three groups immediately following lung and brain injury. Over time, peak inspiratory pressure, mean airway pressure, and P/F ratio significantly increased, while total respiratory rate significantly decreased within the APRV group compared to the ARDSNet group. Histopathology did not show significant differences between groups in overall brain or lung tissue injury; however, cerebral microdialysis trends suggested increased ischemia within the APRV group compared to ARDSNet over time. Conclusion Previous studies have not evaluated the effects of APRV in this population. While our macroscopic parameters and histopathology did not observe a significant difference between groups, microdialysis data suggest a trend toward increased cerebral ischemia associated with APRV over time. Additional and future studies should focus on extending the time interval for observation to

  2. A Fluid Helmet Liner for Protection Against Blast Induced Traumatic Brain Injury

    DTIC Science & Technology

    2010-05-01

    Induced Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER N00014-08-1-0261 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Young, Laurence, R...NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge...MA 02139 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) Office of Naval Research 875 North

  3. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.

    PubMed

    Li, Wenlu; Xu, Hongjiao; Hu, Yangmin; He, Ping; Ni, Zhenzhen; Xu, Huimin; Zhang, Zhongmiao; Dai, Haibin

    2013-01-01

    Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

  4. Brain injury - discharge

    MedlinePlus

    Head injury - discharge; Head trauma - discharge; Contusion - discharge; Shaken baby syndrome - discharge ... done to help them recover from the brain injury. The person may have stayed in a special ...

  5. Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice.

    PubMed

    Ahmad, Akbar; Crupi, Rosalia; Impellizzeri, Daniela; Campolo, Michela; Marino, Angela; Esposito, Emanuela; Cuzzocrea, Salvatore

    2012-11-01

    Traumatic brain injury (TBI) is a major cause of preventable death and morbidity in young adults. This complex condition is characterized by significant blood brain barrier leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Recovery of function after TBI is partly through neuronal plasticity. In order to test whether treatments that enhance plasticity might improve functional recovery, a controlled cortical impact (CCI) in adult mice, as a model of TBI, in which a controlled cortical impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex, was performed. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family that maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether PEA shows efficacy in a mice model of experimental TBI. PEA treatment is able to reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level further support the efficacy of PEA therapy. The PEA treatment blocked infiltration of astrocytes and restored CCI-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, CD11b and GFAP. PEA inhibited the TBI-mediated decrease in the expression of pJNK and NF-κB. PEA-treated injured animals improved neurobehavioral functions as evaluated by behavioral tests.

  6. Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway

    PubMed Central

    Xiao, Xiaolan

    2017-01-01

    This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH. PMID:28337226

  7. Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Zhou, Yuan; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway. PMID:27780244

  8. Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway.

    PubMed

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Zhou, Yuan; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway.

  9. Bexarotene protects against traumatic brain injury in mice partially through apolipoprotein E.

    PubMed

    Zhong, Jianjun; Cheng, Chongjie; Liu, Han; Huang, Zhijian; Wu, Yue; Teng, Zhipeng; He, Junchi; Zhang, Hongrong; Wu, Jinchuan; Cao, Fang; Jiang, Li; Sun, Xiaochuan

    2017-02-20

    Bexarotene has been proved to have neuroprotective effects in many animal models of neurological diseases. However, its neuroprotection in traumatic brain injury (TBI) is still unknown. This study aims to explore the neuroprotective effects of bexarotene on TBI and its possible mechanism. Controlled cortical impact (CCI) model was used to simulate TBI in C57BL/6 mice as well as APOE gene knockout (APOE-KO) mice. After CCI, mice were daily dosed with bexarotene or vehicle solution intraperitoneally. The motor function, learning and memory, inflammatory factors, microglia amount, apoptosis condition around injury site and main side-effects were all measured. The results showed that, after CCI, bexarotene treatment markedly improved the motor function and spatial memory in C57BL/6 compare to APOE-KO mice which showed no improvement. The inflammatory cytokines, microglia amount, cell apoptosis rate, and protein of cleaved caspase-3 around the injury site were markedly upregulated after TBI in both C57BL/6 and APOE-KO mice, and all these upregulation were significantly mitigated by bexarotene treatment in C57BL/6 mice, but not in APOE-KO mice. No side-effects were detected after consecutive administration. Taken together, bexarotene inhibits the inflammatory response as well as cell apoptosis and improves the neurological function of mice after TBI partially through apolipoprotein E. This may make it a promising candidate for the therapeutic treatment after TBI.

  10. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.

    PubMed

    Norris, Christopher M; Sompol, Pradoldej; Roberts, Kelly N; Ansari, Mubeen; Scheff, Stephen W

    2016-02-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague-Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10 mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma.

  11. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury

    PubMed Central

    Sompol, Pradoldej; Roberts, Kelly N.; Ansari, Mubeen

    2015-01-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma. PMID:26607913

  12. Ischemic postconditioning as a novel avenue to protect against brain injury after stroke

    PubMed Central

    Zhao, Heng

    2009-01-01

    Ischemic postconditioning initially referred to a stuttering reperfusion performed immediately after reperfusion, for preventing ischemia/reperfusion injury in both myocardial and cerebral infarction. It has evolved into a concept that can be induced by a broad range of stimuli or triggers, and may even be performed as late as 6 h after focal ischemia and 2 days after transient global ischemia. The concept is thought to be derived from ischemic preconditioning or partial/gradual reperfusion, but in fact the first experiment for postconditioning was carried out much earlier than that of preconditioning or partial/gradual reperfusion, in the research on myocardial ischemia. This review first examines the protective effects and parameters of postconditioning in various cerebral ischemic models. Thereafter, it provides insights into the protective mechanisms of postconditioning associated with reperfusion injury and the Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive K+ (KATP) channel cell signaling pathways. Finally, some open issues and future challenges regarding clinical translation of postconditioning are discussed. PMID:19240739

  13. Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission.

    PubMed

    Guan, Y-F; Wu, C-Y; Fang, Y-Y; Zeng, Y-N; Luo, Z-Y; Li, S-J; Li, X-W; Zhu, X-H; Mei, L; Gao, T-M

    2015-10-29

    Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.

  14. Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats

    PubMed Central

    Pérez-Asensio, Fernando J; de la Rosa, Xavier; Jiménez-Altayó, Francesc; Gorina, Roser; Martínez, Emili; Messeguer, Àngel; Vila, Elisabet; Chamorro, Àngel; Planas, Anna M

    2010-01-01

    Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague–Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser–Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline (±20%) in several animals, whereas others showed hyper-perfusion (>20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury. PMID:19904289

  15. Biphalin protects against cognitive deficits in a mouse model of mild traumatic brain injury (mTBI).

    PubMed

    Lesniak, Anna; Pick, Chaim G; Misicka, Aleksandra; Lipkowski, Andrzej W; Sacharczuk, Mariusz

    2016-02-01

    Traumatic brain injury (TBI) is often a result of traffic accidents, contact sports or battlefield explosions. A mild form of traumatic brain injury (mTBI) is frequently underestimated, as the immediate physical symptoms decrease rapidly and conventional neuroimaging studies often do not show visible evidence of brain lesions. However, cognitive impairments persist for weeks, months or even years after the incident. Endogenous opioids were documented to play a role in thmodulation of mTBI pathology, whereas exogenous opioids were shown to possess neuroprotective properties. In the present study, biphalin, a dimeric enkephalin analog, improved cognitive performance in the Morris Water Maze and Novel Object Recognition tests in a mouse weight-drop model of mTBI. The effect of a single systemic injection of 10 mg/kg biphalin immediately after trauma was reversed by naltrexone, suggesting an opioid receptor-mediated mechanism. Biphalin also reduced cortical and hippocampal neurodegeneration, as shown by silver staining. Our data indicates that opioid receptor activation by biphalin may provide neuroprotection of post-traumatic neurodegeneration processes and may protect against memory impairments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients[S

    PubMed Central

    Fellows, Kelly; Uher, Tomas; Browne, Richard W.; Weinstock-Guttman, Bianca; Horakova, Dana; Posova, Helena; Vaneckova, Manuela; Seidl, Zdenek; Krasensky, Jan; Tyblova, Michaela; Havrdova, Eva; Zivadinov, Robert; Ramanathan, Murali

    2015-01-01

    The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS inflammation following the first clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 ± 8.2 years (mean ± SD)] enrolled in a multi-center study of interferon β1-a treatment following the first demyelinating event. Blood and cerebrospinal fluid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profile and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P ≤ 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ (P < 0.001) and with CSF CD80+CD19+ (P = 0.007) cell frequencies. Higher serum HDL is associated with lower levels of BBB injury and decreased CD80+ and CD80+CD19+ cell extravasation into the CSF. HDL may potentially inhibit the initiation and/or maintenance of pathogenic BBB injury following the first demyelinating event. PMID:26243484

  17. Quercitrin offers protection against brain injury in mice by inhibiting oxidative stress and inflammation.

    PubMed

    Ma, Jie-Qiong; Luo, Rong-Zhen; Jiang, Hai-Xia; Liu, Chan-Min

    2016-01-01

    Quercitrin is one of the primary flavonoid compounds present in vegetables and fruits. The aim of the present study was to evaluate the effects of quercitrin against carbon tetrachloride (CCl4) induced brain injury and further to elucidate its probable mechanisms. ICR mice received CCl4 intraperitoneally with or without quercitrin co-administration for 4 weeks. Our data showed that quercitrin significantly suppressed the elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) content, reduced tissue plasminogen activator (t-PA) activity, enhanced the antioxidant enzyme activities and abrogated cytochrome P450 2E1 (CYP2E1) induction in mouse brains. Quercitrin also prevented CCl4 induced cerebral function disorders associated with its ability to inhibit the activities of monoamine oxidase (MAO), acetylcholine esterase (AChE) and the N-methyl-d-aspartate receptor 2B subunit (NR2B). In addition, western blot analysis showed that quercitrin suppressed the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Taken together, our findings suggested that quercitrin may be a potential candidate to be developed as a neuroprotective agent.

  18. Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury.

    PubMed

    Karve, Ila P; Zhang, Moses; Habgood, Mark; Frugier, Tony; Brody, Kate M; Sashindranath, Maithili; Ek, C Joakim; Chappaz, Stephane; Kile, Ben T; Wright, David; Wang, Hong; Johnston, Leigh; Daglas, Maria; Ates, Robert C; Medcalf, Robert L; Taylor, Juliet M; Crack, Peter J

    2016-01-01

    Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type-1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in disorders of the CNS. In this study, we have investigated the role of type-1 IFNs in neuroinflammation following traumatic brain injury (TBI). Using a controlled cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and IFNAR1(-/-) mice and brains were excised to study infarct volume, inflammatory mediator release via quantitative PCR analysis and immune cell profile via immunohistochemistry. IFNAR1(-/-) mice displayed smaller infarcts compared with WT mice after TBI. IFNAR1(-/-) mice exhibited an altered anti-inflammatory environment compared with WT mice, with significantly reduced levels of the proinflammatory mediators TNFα, IL-1β and IL-6, an up-regulation of the anti-inflammatory mediator IL-10 and an increased activation of resident and peripheral immune cells after TBI. WT mice injected intravenously with an anti-IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and 2 d after TBI displayed significantly improved histological and behavioral outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in human postmortem TBI brains. Together, these data demonstrate that type-1 IFN signaling is a critical pathway in the progression of neuroinflammation and presents a viable therapeutic target for the treatment of TBI.

  19. Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury123

    PubMed Central

    Karve, Ila P.; Zhang, Moses; Habgood, Mark; Frugier, Tony; Brody, Kate M.; Sashindranath, Maithili; Ek, C. Joakim; Kile, Ben T.; Wright, David; Wang, Hong; Johnston, Leigh; Daglas, Maria; Ates, Robert C.; Medcalf, Robert L.; Taylor, Juliet M.

    2016-01-01

    Abstract Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type-1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in disorders of the CNS. In this study, we have investigated the role of type-1 IFNs in neuroinflammation following traumatic brain injury (TBI). Using a controlled cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and IFNAR1−/− mice and brains were excised to study infarct volume, inflammatory mediator release via quantitative PCR analysis and immune cell profile via immunohistochemistry. IFNAR1−/− mice displayed smaller infarcts compared with WT mice after TBI. IFNAR1−/− mice exhibited an altered anti-inflammatory environment compared with WT mice, with significantly reduced levels of the proinflammatory mediators TNFα, IL-1β and IL-6, an up-regulation of the anti-inflammatory mediator IL-10 and an increased activation of resident and peripheral immune cells after TBI. WT mice injected intravenously with an anti-IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and 2 d after TBI displayed significantly improved histological and behavioral outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in human postmortem TBI brains. Together, these data demonstrate that type-1 IFN signaling is a critical pathway in the progression of neuroinflammation and presents a viable therapeutic target for the treatment of TBI. PMID:27022620

  20. [Protective effect of mitochondria-targeted antioxidant SS31 on early brain injury following subarachnoid hemorrhage in rats].

    PubMed

    Zhou, Jian; Li, Zhengzheng; Chen, Zhenggang; Yang, Kun

    2017-09-28

    To evaluate protective effects of SS31 on early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) in rats.
 Methods: A total of 96 Sprague-Dawley rats were randomly divided into 4 groups: A sham group, an SAH group, an SAH+vehicle group (SAH+V), and an SAH+SS31 group. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological deficit scores were evaluated at 24 h after SAH. The SS31 (5 mg/kg) as well as equal volume of vehicle were administrated intraperitoneally at 2 h after SAH. The neurological scores, brain edema, blood-brain barrier (BBB) permeability, apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, superoride dismutase (SOD) activity, and the expression of cytosolic cytochrome c (Cyt C) and Bax were analyzed at 24 h after SAH.
 Results: Treatment with SS31 could significantly reduce MDA levels, and restored the activities of GPx and SOD in the cortex following SAH when compared with the SAH+V group. In addition, Bax SS31 trearment increased or decreased the levels of mitochondrial Cyt C or Bax, respectively. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH.
 Conclusion: SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibition of neuronal apoptosis.

  1. Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

    PubMed Central

    Luo, Xu-Ying; Hu, Ying-Hong; Cao, Xiang-Yuan; Kang, Yan; Liu, Li-Ping; Wang, Shou-Hong; Yu, Rong-Guo; Yu, Xiang-You; Zhang, Xia; Li, Bao-Shan; Ma, Zeng-Xiang; Weng, Yi-Bing; Zhang, Heng; Chen, De-Chang; Chen, Wei; Chen, Wen-Jin; Chen, Xiu-Mei; Du, Bin; Duan, Mei-Li; Hu, Jin; Huang, Yun-Feng; Jia, Gui-Jun; Li, Li-Hong; Liang, Yu-Min; Qin, Bing-Yu; Wang, Xian-Dong; Xiong, Jian; Yan, Li-Mei; Yang, Zheng-Ping; Dong, Chen-Ming; Wang, Dong-Xin; Zhan, Qing-Yuan; Fu, Shuang-Lin; Zhao, Lin; Huang, Qi-Bing; Xie, Ying-Guang; Huang, Xiao-Bo; Zhang, Guo-Bin; Xu, Wang-Bin; Xu, Yuan; Liu, Ya-Ling; Zhao, He-Ling; Sun, Rong-Qing; Sun, Ming; Cheng, Qing-Hong; Qu, Xin; Yang, Xiao-Feng; Xu, Ming; Shi, Zhong-Hua; Chen, Han; He, Xuan; Yang, Yan-Lin; Chen, Guang-Qiang; Sun, Xiu-Mei; Zhou, Jian-Xin

    2016-01-01

    Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: Clinical

  2. Traumatic Brain Injuries. Guidelines Paper.

    ERIC Educational Resources Information Center

    Colorado State Dept. of Education, Denver. Special Education Services Unit.

    This paper on traumatic brain injuries begins with statistics on the incidence of the disorder, especially as they relate to Colorado. Traumatic brain injury is then defined, and problems caused by traumatic brain injury are discussed. The components of effective programming for students with traumatic brain injuries are described, followed by the…

  3. [Traumatic brain injury].

    PubMed

    Hackenberg, K; Unterberg, A

    2016-02-01

    Since traumatic brain injury is the most common cause of long-term disability and death among young adults, it represents an enormous socio-economic and healthcare burden. As a consequence of the primary lesion, a perifocal brain edema develops causing an elevation of the intracranial pressure due to the limited intracranial space. This entails a reduction of the cerebral perfusion pressure and the cerebral blood flow. A cerebral perfusion deficit below the threshold for ischemia leads to further ischemic lesions and to a progression of the contusion. As the irreversible primary lesion can only be inhibited by primary prevention, the therapy of traumatic brain injury focuses on the secondary injuries. The treatment consists of surgical therapy evacuating the space-occupying intracranial lesion and conservative intensive medical care. Due to the complex pathophysiology the therapy of traumatic brain injury should be rapidly performed in a neurosurgical unit.

  4. Rhubarb extract has a protective role against radiation-induced brain injury and neuronal cell apoptosis.

    PubMed

    Lu, Kui; Zhang, Cheng; Wu, Wenjun; Zhou, Min; Tang, Yamei; Peng, Ying

    2015-08-01

    Oxidative stress caused by ionizing radiation is involved in neuronal damage in a number of disorders, including trauma, stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Ionizing radiation can lead to the formation of free radicals, which cause neuronal apoptosis and have important roles in the development of some types of chronic brain disease. The present study evaluated the effects of varying concentrations (2, 5 and 10 µg/ml) of ethanolic rhubarb extract on the neuronal damage caused by irradiation in primary neuronal cultures obtained from the cortices of rat embryos aged 20 days. Brain damage was induced with a single dose of γ-irradiation that induced DNA fragmentation, increased lactate dehydrogenase release in neuronal cells and acted as a trigger for microglial cell proliferation. Treatment with rhubarb extract significantly decreased radiation-induced lactate dehydrogenase release and DNA fragmentation, which are important in the process of cell apoptosis. The rhubarb extract exhibited dose-dependent inhibition of lactate dehydrogenase release and neuronal cell apoptosis that were induced by the administration of ionizing radiation. The effect of a 10 µg/ml dose of rhubarb extract on the generation of reactive oxygen species (ROS) induced by radiation was also investigated. This dose led to significant inhibition of ROS generation. In conclusion, the present study showed a protective role of rhubarb extract against irradiation-induced apoptotic neuronal cell death and ROS generation.

  5. Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

    PubMed

    Dohi, Kenji; Kraemer, Brian C; Erickson, Michelle A; McMillan, Pamela J; Kovac, Andrej; Flachbartova, Zuzana; Hansen, Kim M; Shah, Gul N; Sheibani, Nader; Salameh, Therese; Banks, William A

    2014-01-01

    Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

  6. Inhibition of cytoskeletal protein carbonylation may protect against oxidative damage in traumatic brain injury

    PubMed Central

    Zhang, Qiusheng; Zhang, Meng; Huang, Xianjian; Liu, Xiaojia; Li, Weiping

    2016-01-01

    Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates protracted neuronal dysfunction and remodeling. Cytoskeletal proteins are known to be carbonylated under oxidative stress; however, the complex molecular and cellular mechanisms of cytoskeletal protein carbonylation remain poorly understood. In the present study, the expression levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were investigated in PC12 cells treated with H2O2. Western blot analysis was used to monitor the carbonylation levels of β-actin and β-tubulin. The results indicated that oxidative stress was increased in PC12 cells that were treated with H2O2 for 24 or 48 h. In addition, increased carbonylation levels of β-actin and β-tubulin were detected in H2O2-treated cells. However, these carbonylation levels were reduced by pretreatment with aminoguanidine, a type of reactive carbonyl species chelating agent, and a similar trend was observed following overexpression of proteasome β5 via transgenic technology. In conclusion, the present study results suggested that the development of TBI may cause carbonylation of cytoskeletal proteins, which would then undermine the stability of cytoskeletal proteins. Thus, the development of TBI may be improved via the inhibition of cytoskeletal protein carbonylation. PMID:28101189

  7. Molecular Hydrogen in Drinking Water Protects against Neurodegenerative Changes Induced by Traumatic Brain Injury

    PubMed Central

    Dohi, Kenji; Kraemer, Brian C.; Erickson, Michelle A.; McMillan, Pamela J.; Kovac, Andrej; Flachbartova, Zuzana; Hansen, Kim M.; Shah, Gul N.; Sheibani, Nader; Salameh, Therese; Banks, William A.

    2014-01-01

    Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1–40 or 1–42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI. PMID:25251220

  8. Guanosine protects against reperfusion injury in rat brains after ischemic stroke.

    PubMed

    Connell, Barry J; Di Iorio, Patrizia; Sayeed, Iqbal; Ballerini, Patrizia; Saleh, Monique C; Giuliani, Patricia; Saleh, Tarek M; Rathbone, Michel P; Su, Caixin; Jiang, Shucui

    2013-02-01

    After ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion improves outcome but triggers a cascade of deleterious cellular and molecular events. Using a collaborative approach, our groups examined the effects of guanosine (Guo) in response to ischemic reperfusion injury in vitro and in vivo. In a transient middle cerebral artery occlusion (MCAO) in rats, Guo significantly reduced infarct volume in a dose-dependent manner when given systemically either immediately before or 30 min, but not 60 min, after the onset of the 5.5-hr reperfusion period. In a separate experiment, Guo significantly reduced infarct volume after 24 hr of reperfusion when administered 5 min before reperfusion. Western blot analysis did not reveal any significant changes either in endoplasmic reticulum (ER) stress proteins (GRP 78 and 94) or HSP 70 or in levels of m-calpain. In vitro oxygen and glucose deprivation (OGD) significantly increased production of both reactive oxygen species (ROS) and interleukin-8 (IL-8) in the primary astrocytes. Guo did not alter ROS or IL-8 production when given to the astrocytes before OGD. However, Guo when added to the cells prior to or 30 min after reperfusion significantly reduced IL-8 release but not ROS formation. Our study revealed a dose- and time-dependent protective effect of Guo on reperfusion injury in vitro and vivo. The mechanisms by which Guo exerts its effect are independent of unfolded proteins in ER or the level of intracellular calcium or ROS formation. However, the effect may be induced, at least partially, by inhibiting IL-8, a marker of reperfusion-triggered proinflammatory events.

  9. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    PubMed

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-05

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death.

  10. Omega-3 Fatty Acids Protect the Brain against Ischemic Injury by Activating Nrf2 and Upregulating Heme Oxygenase 1

    PubMed Central

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K.; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun

    2014-01-01

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. PMID:24478369

  11. Caffeine protects neuronal cells against injury caused by hyperoxia in the immature brain.

    PubMed

    Endesfelder, Stefanie; Zaak, Irina; Weichelt, Ulrike; Bührer, Christoph; Schmitz, Thomas

    2014-02-01

    Caffeine administered to preterm infants has been shown to reduce rates of cerebral palsy and cognitive delay, compared to placebo. We investigated the neuroprotective potential of caffeine for the developing brain in a neonatal rat model featuring transient systemic hyperoxia. Using 6-day-old rat pups, we found that after 24 and 48h of 80% oxygen exposure, apoptotic (TUNEL(+)) cell numbers increased in the cortex, hippocampus, and central gray matter, but not in the hippocampus or dentate gyrus. In the dentate gyrus, high oxygen exposure led to a decrease in the number of proliferating (Ki67(+)) cells and the number of Ki67(+) cells double staining for nestin (immature neurons), doublecortin (progenitors), and NeuN (mature neurons). Absolute numbers of nestin(+), doublecortin(+), and NeuN(+) cells also decreased after hyperoxia. This was mirrored in a decline of transcription factors expressed in immature neurons (Pax6, Sox2), progenitors (Tbr2), and mature neurons (Prox1, Tbr1). Administration of a single dose of caffeine (10mg/kg) before high oxygen exposure almost completely prevented these effects. Our findings suggest that caffeine exerts protection for neonatal neurons exposed to high oxygen, possibly via its antioxidant capacity. © 2013 Elsevier Inc. All rights reserved.

  12. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    PubMed Central

    Duanmu, Wang-sheng; Cao, Liu; Chen, Jing-yu; Ge, Hong-fei; Hu, Rong; Feng, Hua

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury. PMID:27212927

  13. Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

    PubMed

    Zhang, Tingting; Su, Jingyuan; Guo, Bingyu; Wang, Kaiwen; Li, Xiaoming; Liang, Guobiao

    2015-09-01

    Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption.

  14. Protective effect of polydatin on learning and memory impairments in neonatal rats with hypoxic‑ischemic brain injury by up‑regulating brain‑derived neurotrophic factor.

    PubMed

    Sun, Jin; Qu, Yunxia; He, Huiming; Fan, Xiaolei; Qin, Yuanhua; Mao, Weifeng; Xu, Lixin

    2014-12-01

    Polydatin is a key component of Polygonum cuspidatum, a herb with medical and nutritional value. The present study investigated the protective effect of polydatin against learning and memory impairment in neonatal rats with hypoxic‑ischemic brain injury (HIBI). The unilateral common carotid artery ligation method was used to generate neonatal HIBI rats. Y‑maze testing revealed that rats with HIBI exhibited memory impairment, while rats with HIBI treated with polydatin displayed enhanced long‑term learning and memory. Of note, polydatin was found to upregulate the expression of hippocampal brain‑derived neurotrophic factor (BDNF) in rats with HIBI. BDNF has a role in protecting HIBI‑induced brain tissue injury and alleviating memory impairment. These findings showed that polydatin had a protective effect against learning and memory impairment in neonatal rats with HIBI and that the protective effect may be mediated through the upregulation of BDNF.

  15. Protective effects of total flavonoids in Caragana against hypoxia/reoxygenation-induced injury in human brain microvascular endothelial cells.

    PubMed

    He, Qian-Song; Zhang, Li; Fan, Zi-Yuan; Feng, Guo; Wang, Fu-Jiang; Liu, Zheng-Qi; Tang, Ting; Kuang, Shi-Xiang

    2017-02-22

    This study aimed to explore the protective effect of total flavonoids in Caragana against hypoxia/reoxygenation (H/R)-induced injury in human brain microvascular endothelial cells (BMECs). Human BMECs were selected and assigned into control, H/R, H/R+NMP, H/R+Low dose, H/R+Moderate dose, H/R+High dose groups. MTT and Transwell assays were used to detect cell viability and migration, respectively. Cell adhesion rate and tube formation were also detected. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to test HIF-1α, VEGF and Notch1 mRNA and protein expressions. Compared with the H/R group, the cell viability rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were increased. The cell adhesion rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were significantly different from those in the H/R group. As compared to the H/R group, the cell migration abilities in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were enhanced. Compared with the H/R group, the number and length of tubes of BMECs in the H/R+NMP, H/R+High dose and H/R+Moderate dose groups were increased. HIF-1α, VEGF and Notch1 mRNA and protein expressions were higher in the H/R+Low dose, H/R+Moderate dose and H/R+High dose groups than in the H/R group. These findings revealed that total flavonoids in Caragana can protect BMECs from H/R-induced injury in a dose-dependent manner and it also may promote angiogenesis in BMECs by activating HIF- 1α-VEGF-Notch 1 signaling pathway.

  16. The female advantage: sex as a possible protective factor against emotion recognition impairment following traumatic brain injury.

    PubMed

    Rigon, Arianna; Turkstra, Lyn; Mutlu, Bilge; Duff, Melissa

    2016-10-01

    Although moderate to severe traumatic brain injury (TBI) leads to facial affect recognition impairments in up to 39% of individuals, protective and risk factors for these deficits are unknown. The aim of the current study was to examine the effect of sex on emotion recognition abilities following TBI. We administered two separate emotion recognition tests (one static and one dynamic) to 53 individuals with moderate to severe TBI (females = 28) and 49 demographically matched comparisons (females = 22). We then investigated the presence of a sex-by-group interaction in emotion recognition accuracy. In the comparison group, there were no sex differences. In the TBI group, however, females significantly outperformed males in the dynamic (but not the static) task. Moreover, males (but not females) with TBI performed significantly worse than comparison participants in the dynamic task. Further analysis revealed that sex differences in emotion recognition abilities within the TBI group could not be explained by lesion location, TBI severity, or other neuropsychological variables. These findings suggest that sex may serve as a protective factor for social impairment following TBI and inform clinicians working with TBI as well as research on the neurophysiological correlates of sex differences in social functioning.

  17. 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. ...

  18. Glibenclamide pretreatment protects against chronic memory dysfunction and glial activation in rat cranial blast traumatic brain injury.

    PubMed

    Stokum, Jesse A; Keledjian, Kaspar; Hayman, Erik; Karimy, Jason K; Pampori, Adam; Imran, Ziyan; Woo, Seung Kyoon; Gerzanich, Volodymyr; Simard, J Marc

    2017-08-30

    Blast traumatic brain injury (bTBI) affects both military and civilian populations, and often results in chronic deficits in cognition and memory. Chronic glial activation after bTBI has been linked with cognitive decline. Pharmacological inhibition of sulfonylurea receptor 1 (SUR1) with glibenclamide was shown previously to reduce glial activation and improve cognition in contusive models of CNS trauma, but has not been examined in bTBI. We postulated that glibenclamide would reduce chronic glial activation and improve long-term memory function after bTBI. Using a rat direct cranial model of bTBI (dc-bTBI), we evaluated the efficacy of two glibenclamide treatment paradigms: glibenclamide prophylaxis (pre-treatment), and treatment with glibenclamide starting after dc-bTBI (post-treatment). Our results show that dc-bTBI caused hippocampal astrocyte and microglial/macrophage activation that was associated with hippocampal memory dysfunction (rapid place learning paradigm) at 28days, and that glibenclamide pre-treatment, but not post-treatment, effectively protected against glial activation and memory dysfunction. We also report that a brief transient time-window of blood-brain barrier (BBB) disruption occurs after dc-bTBI, and we speculate that glibenclamide, which is mostly protein bound and does not normally traverse the intact BBB, can undergo CNS delivery only during this brief transient opening of the BBB. Together, our findings indicate that prophylactic glibenclamide treatment may help to protect against chronic cognitive sequelae of bTBI in warfighters and other at-risk populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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…

  20. 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 ...

  1. Environmental Enrichment Protects against Functional Deficits caused by Traumatic Brain Injury

    DTIC Science & Technology

    2012-11-01

    negative outcomes, but its efficacy is limited by the fact that damage has already occurred, and in this usage is palliative , rather than preventative...Bennett, E. L., Hebert, M., and Morimoto, H. (1977). Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures

  2. Ischemic brain injury: New insights on the protective role of melatonin.

    PubMed

    Ramos, Eva; Patiño, Paloma; Reiter, Russel J; Gil-Martín, Emilio; Marco-Contelles, José; Parada, Esther; Los Rios, Cristobal de; Romero, Alejandro; Egea, Javier

    2017-03-01

    Stroke represents one of the most common causes of brain's vulnerability for many millions of people worldwide. The plethora of physiopathological events associated with brain ischemia are regulate through multiple signaling pathways leading to the activation of oxidative stress process, Ca(2+) dyshomeostasis, mitochondrial dysfunction, proinflammatory mediators, excitotoxicity and/or programmed neuronal cell death. Understanding this cascade of molecular events is mandatory in order to develop new therapeutic strategies for stroke. In this review article, we have highlighted the pleiotropic effects of melatonin to counteract the multiple processes of the ischemic cascade. Additionally, experimental evidence supports its actions to ameliorate ischemic long-term behavioural and neuronal deficits, preserving the functional integrity of the blood-brain barrier, inducing neurogenesis and cell proliferation through receptor-dependent mechanism, as well as improving synaptic transmission. Consequently, the synthesis of melatonin derivatives designed as new multitarget-directed products has focused a great interest in this area. This latter has been reinforced by the low cost of melatonin and its reduced toxicity. Furthermore, its spectrum of usages seems to be wide and with the potential for improving human health. Nevertheless, the molecular and cellular mechanisms underlying melatonin´s actions need to be further exploration and accordingly, new clinical studies should be conducted in human patients with ischemic brain pathologies.

  3. Phenolic alkaloids from Menispermum dauricum rhizome protect against brain ischemia injury via regulation of GLT-1, EAAC1 and ROS generation.

    PubMed

    Zhao, Bo; Chen, Yang; Sun, Xi; Zhou, Mei; Ding, Jie; Zhan, Jin-Jin; Guo, Lian-Jun

    2012-03-06

    Menispermum dauricum rhizome has been widely used in China to treat various cardiovascular and thrombosis disorders. Some studies have reported that the phenolic alkaloids of Menispermum dauricum rhizome (PAM) have protective effects against brain ischemia injury, but the mechanism of this action remains to be clarified. In the present study, we investigated the possible mechanisms of action of PAM on experimental brain ischemia injury. Oxygen and glucose deprivation (OGD) in rat primary cortical cultures and middle cerebral artery occlusion in rats were used to mimic ischemia-reperfusion injury, respectively. The results suggested that PAM protected rat primary cortical cultures against OGD-reoxygenation induced cytotoxicity. PAM decreased extracellular glutamate content and markedly prevented the effects induced by OGD on protein level of GLT-1 and EAAC1 glutamate transporters. In addition, it reduced intracellular ROS generation. In vivo, PAM significantly reduced cerebral infarct area and ameliorated neurological functional deficits at different time points. Our findings revealed that the possible mechanism of action of PAM protected against brain ischemia injury involves regulation of GLT-1, EAAC1 and ROS generation.

  4. 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

  5. Preconditioning for traumatic brain injury.

    PubMed

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

    2013-02-01

    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 preconditioning studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible future clinical situations, in which pre-TBI preconditioning could be considered.

  6. 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.

  7. Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

    PubMed Central

    Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

    2011-01-01

    Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8−/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8−/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional

  8. PERSONALITY CHANGES IN BRAIN INJURY

    PubMed Central

    Garcia, Patricia Gracia; Mielke, Michelle M.; Rosenberg, Paul; Bergey, Alyssa; Rao, Vani

    2011-01-01

    Traumatic brain injury (TBI) is frequently complicated by alterations in mood and behaviour and changes in personality. We report mild personality changes post-TBI as a possible indicator of traumatic brain injury, but not of injury severity or psychiatric complications. PMID:21677207

  9. Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.

    PubMed

    Shi, Hong; Wang, Hai-Lian; Pu, Hong-Jian; Shi, Ye-Jie; Zhang, Jia; Zhang, Wen-Ting; Wang, Guo-Hua; Hu, Xiao-Ming; Leak, Rehana K; Chen, Jun; Gao, Yan-Qin

    2015-04-01

    Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed. Ethyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Ethyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage. © 2014 John Wiley & Sons Ltd.

  10. Ethyl Pyruvate Protects against Blood-Brain Barrier Damage and Improves Long-Term Neurological Outcomes in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Shi, Hong; Wang, Hailian; Pu, Hongjian; Shi, Yejie; Zhang, Jia; Zhang, Wenting; Wang, Guohua; Hu, Xiaoming; Leak, Rehana K.; Chen, Jun; Gao, Yanqin

    2015-01-01

    Aims Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Methods Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity and neuroinflammation were assessed. Results EP improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 d post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent anti-inflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Conclusion EP confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation and long-lasting brain damage. PMID:25533312

  11. Traumatic brain injuries.

    PubMed

    Blennow, Kaj; Brody, David L; Kochanek, Patrick M; Levin, Harvey; McKee, Ann; Ribbers, Gerard M; Yaffe, Kristine; Zetterberg, Henrik

    2016-11-17

    Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury - the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators.

  12. Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats.

    PubMed

    Sharma, Priyanka; Singla, Neha; Dhawan, D K

    2017-03-06

    In the present world, X-rays have been regarded as one of the most efficient tools in medicine, industry and research. On the contrary, extensive human exposure to these rays is responsible for causing detrimental effects on physiological system. The aim of the present study was to investigate the role of zinc (Zn), if any, in mitigating the adverse effects induced by fractionated X-irradiation on rat brain. Female Sprague-Dawley rats weighing 170-200 g were divided into four different groups viz.: (a) normal control, (b) X-irradiated (21Gy), (c) zinc treated (227 mg/L in drinking water) and (d) X-irradiated + zinc treated. The skulls of animals belonging to groups (b) and (d) were exposed to X-rays in 30 fractions. Each fraction delivered a radiation dose of 70 rads, and rats were exposed to two fractions every day for 15 days, consecutively. X-ray treatment resulted in significant alterations in the neurobehavior, neurotransmitter levels and neuro-histoarchitecture of rats, whereas zinc co-treatment with X-rays resulted in significant improvement in these parameters. X-ray exposure also caused a significant increase in the levels of lipid peroxidation as well as activities of catalase and superoxide dismutase, which however were decreased upon simultaneous Zn treatment. On the contrary, X-ray treatment down-regulated the glutathione system, which were found to be up-regulated by zinc co-treatment. Further, protein expressions of p53 and NF-ҚB were found to be significantly elevated after X-irradiation, which were reversed following Zn supplementation. Hence, Zn seems to be an effective agent in mitigating the detrimental effects caused by exposure to X-rays.

  13. [Brain protection by anesthetics].

    PubMed

    Adachi, Naoto

    2006-05-01

    Many investigators have attempted to protect the brain against ischemia by reducing the cerebral metabolic rate using anesthetic agents. However, the magnitude of suppression of the cerebral metabolic rate does not correlate with neuroprotective effects of anesthetics, suggesting that other factors besides reduction in the cerebral metabolic rate contribute to the protection. Facilitation of protein synthesis, GABAergic activity, and anti-oxidant action are likely factors responsible for beneficial effects of barbiturates and propofol. Although the brain is protected during anesthesia, anesthetics cannot provide effects sufficiently enough to recover damage caused by severe ischemia. Further, no desired outcome has been reported by treatments after ischemic events.

  14. Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase.

    PubMed

    Deng, Chang-Bo; Li, Juan; Li, Lu-Yi; Sun, Feng-Jie

    2016-07-01

    In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50=19.4±2.5μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. Autophagy protects human brain microvascular endothelial cells against methylglyoxal-induced injuries, reproducible in a cerebral ischemic model in diabetic rats.

    PubMed

    Fang, Lili; Li, Xue; Zhong, Yinbo; Yu, Jing; Yu, Lina; Dai, Haibin; Yan, Min

    2015-10-01

    Cerebral microvascular endothelial cells (ECs) are crucial for brain vascular repair and maintenance, but their physiological function may be impaired during ischemic stroke and diabetes. Methylglyoxal (MGO), a reactive dicarbonyl produced during glucose metabolism, could exacerbate ischemia-induced EC injury and dysfunction. We investigated the protective effect of autophagy on cultured human brain microvascular endothelial cells (HBMEC) that underwent MGO treatment. A further study was conducted to explore the underlying mechanisms of the protective effect. Autophagic activity was assessed by evaluating protein levels, using western blot. 3-methyladenine (3-MA), bafilomycin A1, ammonium chloride (AC), Beclin 1 siRNA, and chloroquine (CQ) were used to cause autophagy inhibition. Alarmar blue assay and lactate dehydrogenase release assay were used to evaluate cell viability. Streptozotocin was administered to induce type I diabetes in rats and post-permanent middle cerebral artery occlusion was performed to elicit cerebral ischemia. Blood-brain barrier permeability was also assessed. Our study found that MGO reduced HBMEC cell viability in a concentration- and time-dependent manner, and triggered the responsive autophagy activation. Autophagy inhibitors bafilomycin A1, AC, 3-MA, and BECN1 siRNA exacerbated MGO-induced HBMEC injury. FAK phosphorylation inhibitor PF573228 inhibited MGO-triggered autophagy and enhanced lactate dehydrogenase release. Meanwhile, similar autophagy activation in brain vascular ECs was observed during permanent middle cerebral artery occlusion-induced cerebral ischemia in diabetic rats, while chloroquine-induced autophagy inhibition enhanced blood-brain barrier permeability. Taken together, our study indicates that autophagy triggered by MGO defends HBMEC against injuries.

  17. Castanea sativa Mill. Bark Extract Protects U-373 MG Cells and Rat Brain Slices Against Ischemia and Reperfusion Injury.

    PubMed

    Santulli, Chiara; Brizi, Claudia; Micucci, Matteo; Del Genio, Ambra; De Cristofaro, Assunta; Bracco, Federica; Pepe, Giuseppina Lucia; di Perna, Ilaria; Budriesi, Roberta; Chiarini, Alberto; Frosini, Maria

    2017-04-01

    Ischemic brain injury is one of the most important causes of death worldwide. The use of one-drug-multi-target agents based on natural compounds is a promising therapeutic option for cerebral ischemia due to their pleiotropic properties. This study assessed the neuroprotective properties of Castanea sativa Mill. bark extract (ENC) in human astrocytoma U-373 MG cells subjected to oxygen-glucose deprivation and reperfusion and rat cortical slices subjected to ischemia-like conditions or treated with glutamate or hydrogen peroxide. Neuroprotective effects were determined by assessing cells or slices viability (MTT assay), ROS formation (DCFH-DA assay), apoptosis (sub G0/G1 peak), nuclear fragmentation and chromatin condensation (DAPI staining) as well as changes in lysosomes and mitochondria morphology (Acridine Orange and Rhodamine123 staining, respectively). ENC treatment before injury on U-373 MG cells (5-50 μg/ml) and cortical slices (50-100 μg/ml) provided neuroprotection, while lower or higher concentrations (100 μg/ml U-373 MG cells, 200 μg/ml brain slices) were ineffective. ENC addition during reperfusion or after the injury was not found to be effective. The results suggest that ENC might hold potential as preventive neuroprotective agent, and indicate the importance of further studies exploring its mechanism of action. J. Cell. Biochem. 118: 839-850, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. NINDS Traumatic Brain Injury Information Page

    MedlinePlus

    ... Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ... Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ...

  19. Traumatic Brain Injury and Aggression.

    ERIC Educational Resources Information Center

    Miller, Laurence

    1994-01-01

    Persons who have suffered traumatic injury to the brain may subsequently display aggressive behavior. Three main syndromes of aggression following traumatic brain injury are described: (1) episodic dyscontrol; (2) frontal lobe disinhibition; and (3) exacerbation of premorbid antisociality. The neuropsychological substrates of these syndromes are…

  20. Prodigiosin inhibits gp91{sup phox} and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia

    SciTech Connect

    Chang, Chia-Che; Wang, Yea-Hwey; Chern, Chang-Ming; Liou, Kuo-Tong; Hou, Yu-Chang; Peng, Yu-Ta; Shen, Yuh-Chiang

    2011-11-15

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 {mu}g/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91{sup phox}), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood-brain barrier (BBB) by activation of nuclear factor-kappa B (NF-{kappa}B). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91{sup phox} and iNOS via activation of the NF-{kappa}B pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91{sup phox} and iNOS expression possibly by impairing NF-{kappa}B activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: Black-Right-Pointing-Pointer Prodigiosin ameliorated brain infarction and deficits. Black-Right-Pointing-Pointer Prodigiosin protected against hypoxia/reperfusion-induced brain injury. Black-Right-Pointing-Pointer Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. Black-Right-Pointing-Pointer Prodigiosin reduced BBB breakdown. Black

  1. 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…

  2. 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…

  3. Synaptic Mitochondria Sustain More Damage than Non-Synaptic Mitochondria after Traumatic Brain Injury and Are Protected by Cyclosporine A.

    PubMed

    Kulbe, Jacqueline R; Hill, Rachel L; Singh, Indrapal N; Wang, Juan A; Hall, Edward D

    2016-10-13

    Currently, there are no Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of those with traumatic brain injury (TBI). As central mediators of the secondary injury cascade, mitochondria are promising therapeutic targets for prevention of cellular death and dysfunction after TBI. One of the most promising and extensively studied mitochondrial targeted TBI therapies is inhibition of the mitochondrial permeability transition pore (mPTP) by the FDA-approved drug, cyclosporine A (CsA). A number of studies have evaluated the effects of CsA on total brain mitochondria after TBI; however, no study has investigated the effects of CsA on isolated synaptic and non-synaptic mitochondria. Synaptic mitochondria are considered essential for proper neurotransmission and synaptic plasticity, and their dysfunction has been implicated in neurodegeneration. Synaptic and non-synaptic mitochondria have heterogeneous characteristics, but their heterogeneity can be masked in total mitochondrial (synaptic and non-synaptic) preparations. Therefore, it is essential that mitochondria targeted pharmacotherapies, such as CsA, be evaluated in both populations. This is the first study to examine the effects of CsA on isolated synaptic and non-synaptic mitochondria after experimental TBI. We conclude that synaptic mitochondria sustain more damage than non-synaptic mitochondria 24 h after severe controlled cortical impact injury (CCI), and that intraperitoneal administration of CsA (20 mg/kg) 15 min after injury improves synaptic and non-synaptic respiration, with a significant improvement being seen in the more severely impaired synaptic population. As such, CsA remains a promising neuroprotective candidate for the treatment of those with TBI.

  4. 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…

  5. Protective Effects of Calpain Inhibition on Neurovascular Unit Injury through Downregulating Nuclear Factor-κB-related Inflammation during Traumatic Brain Injury in Mice

    PubMed Central

    Tao, Xiao-Gang; Shi, Jing-Hua; Hao, Shu-Yu; Chen, Xue-Tao; Liu, Bai-Yun

    2017-01-01

    Background: In addition to neurons, all components of the neurovascular unit (NVU), such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury (TBI). Previous studies have shown that excessive stimulation of calpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact (CCI). Methods: One hundred and eight mice were divided into three groups: the sham group, the control group, and the MDL28170 group. MDL28170 (20 mg/kg), an efficient calpain inhibitor, was administered intraperitoneally at 5 min, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood–brain barrier (BBB) disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. Results: The MDL28170 treatment significantly reduced the extent of both cerebral contusion (MDL28170 vs. vehicle group, 16.90 ± 1.01 mm3 and 17.20 ± 1.17 mm3 vs. 9.30 ± 1.05 mm3 and 9.90 ± 1.17 mm3, both P < 0.001) and edema (MDL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P < 0.05), improved neurological scores (MDL28170 vs. vehicle group, 7.50 ± 0.45 and 6.33 ± 0.38 vs. 12.33 ± 0.48 and 11.67 ± 0.48, both P < 0.001), and attenuated NVU damage resulting (including tight junction (TJ), basement membrane, BBB, and neuron) from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation (tumor necrosis factor-α [TNF-α]: MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62 ± 0.08 vs. 1.59 ± 0.10 and 2.18 ± 0.10, both P < 0.001; inducible nitric oxide synthase: MDL28170 vs. vehicle group, 4.51 ± 0.23 vs. 6.23 ± 0.12, P < 0.001 at 24 h; intracellular adhesion molecule-1: MDL28170 vs. vehicle group

  6. Analysis of the protective effects of the α2/δ subunit of voltage-gated Ca(2+) channels in brain injury.

    PubMed

    Kim, Tae Yeon; Niimi, Kimie; Takahashi, Eiki

    2017-01-15

    Voltage-gated Ca(2+) channels (VGCCs) are comprised of α1, α2/δ, β, and γ subunits. The pore-forming α1 subunit is essential for the proper functioning of Ca(2+) channels, while the α2/δ subunit interacts with components of the extracellular matrix. The α2/δ subunit is related in many neuropathological symptoms, including epilepsy and cerebellar ataxia. We previously reported that the mutant Cav.2.1α1 subunit has protective effects following brain injury. The present study aimed to investigate the effects of the α2/δ subunit inhibition alone and in combination with the inhibition of the Cav.2.1α1 subunit following brain injury by injecting Gabapentin using Cav.2.1α1 mutant heterozygous rolling Nagoya (rol/+) and wild-type (+/+) mice. Gabapentin binds to the α2/δ subunit and leads to Ca(2+) flow disturbance. A cryogenic method was used to induce brain injury. The mice pretreated with 100mg/kg Gabapentin exhibited a decrease in lesion size, while the 40mg/kg Gabapentin injection was effective in rol/+ mice but not +/+ mice. The administration of 100mg/kg Gabapentin also attenuated reactive astrocyte activity and neuronal degeneration; the pattern of results was similar to that for lesion size. An analysis of phosphorylated p38 (pp38) expression revealed that Gabapentin suppressed the p38 mitogen-activated protein kinase (MAPK) signaling cascade by interrupting glutamate-signaling induced by the inhibition of VGCCs. The present findings demonstrated that the administration of the α2/δ subunit inhibitor, Gabapentin, had neuroprotective effects following brain injury.

  7. Brain Injury Risk from Primary Blast

    DTIC Science & Technology

    2012-02-29

    combined abdominal and thoracic protection that reduced blast levels to an order of magnitude below pulmonary injury threshold. The results were scaled to... contusions typically on or around the brainstem though there were no skull fractures for any blast intensity. Risk functions were developed that...primary blast exposure to the brain was found to be more than twice the pulmonary fatality injury risk. However, the blast level for 50% risk of mild

  8. Endocrine response to brain injury.

    PubMed

    Chioléro, R; Berger, M

    1994-11-01

    The neuroendocrine response (NER) is an essential component of the adaptive process to trauma, brain injury, and major surgery. While receiving additive humoral and neural afferent inputs, the brain nuclei responsible for the NER act mainly by efferent pathways to the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, the activations of which induce subsequent circulatory and metabolic responses. The NER to brain injury is similar to the response observed in patients with extracerebral injury, even if the response after brain injury is extremely variable. Generally, there is a biphasic pattern, with a sympathoadrenal storm associated with variable and altered stimulation of the HPA during the ebb phase. The first phase is followed by a decrease in both responses while other endocrine changes develop, involving mainly the counter-regulatory, gonadal, and thyroid hormones. The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome. Alterations of the thyroid hormones are largely related to a reduction in peripheral deiodination of thyroxin. Recent research shows that increased free-radical production and decreased selenium (an antioxidant) serum levels play an important role in thyroid metabolism. Two major issues remain unsolved: a) the precise definition of cerebral death, since endocrine brain function is not abolished in the state currently defined as brain death; and b) the question of whether substitutive hormone therapy should be applied in severe brain injury.

  9. Protections of SMND-309, a novel derivate of salvianolic acid B, on brain mitochondria contribute to injury amelioration in cerebral ischemia rats.

    PubMed

    Tian, Jingwei; Fu, Fenghua; Li, Guisheng; Gao, Yubai; Zhang, Yunjuan; Meng, Qingsheng; Li, Changlu; Liu, Fu

    2009-08-01

    SMND-309, a novel compound named (2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, is a new derivate of salvianolic acid B. The present study was conducted to investigate whether SMND-309 has a protective effect on brain injury after focal cerebral ischemia, and if it did so, to investigate its effects on brain mitochondria. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests and brain patho-physiological tests were used to evaluate the damage to central nervous system. Origin targets including mitochondria production of reactive oxygen species, antioxidant potentia, membrane potential, energy metabolism, mitochondrial respiratory enzymes activities and mitochondria swelling degree were evaluated. The results showed that SMND-309 decreased neurological deficit scores, reduced the number of dead hippocampal neuronal cells in accordance with its depression on mitochondria swelling degree, reactive oxygen species production, improvements on mitochondria swelling, energy metabolism, membrane potential level and mitochondrial respiratory chain complex activities. All of these findings indicate that SMND-309 exerted potent neuroprotective effects in the model of permanent cerebral ischemia, contributed to its protections on brain mitochondrial structure and function.

  10. Adenovirus-mediated brain-derived neurotrophic factor expression regulated by hypoxia response element protects brain from injury of transient middle cerebral artery occlusion in mice.

    PubMed

    Shi, Qindong; Zhang, Pengbo; Zhang, Junfeng; Chen, Xinlin; Lu, Haixia; Tian, Yumei; Parker, T L; Liu, Yong

    2009-11-20

    Some gene expression may be regulated by hypoxia-responsive element (HRE) that is bound by hypoxia-inducible factor-1 (HIF-1) which is up-regulated during cerebral ischemia. To explore ischemia/hypoxia-controlled expression and the neuroprotective effects of brain-derived neurotrophic factor (BDNF) after ischemic brain injury, an adenoviral vector using five copies of hypoxia response element (HRE) in the vascular endothelial growth factor gene to regulate the expression of BDNF gene (Ad5HRE:BDNF) was constructed, and its efficacy was verified for driving BDNF expression in cultured Hela cells under hypoxic condition by ELISA. We found that the concentration of BDNF in the Ad5HRE:BDNF-transfected culture media was 28-fold greater in a hypoxic condition than under normoxia. To examine the effect of Ad5HRE:BDNF on ischemic brain injury in vivo, Ad5HRE:BDNF was injected into right caudate putamen of adult mice 7 days prior to 60 min transient middle cerebral artery occlusion (MCAO). It was found that exogenous BDNF expression was increased in the Ad5HRE-BDNF-treated group and infarct volume of the Ad5HRE:BDNF-treated group at 3 days after MCAO was significantly smaller than that of vehicle- or AdNull-treated groups. Moreover, Ad5HRE:BDNF injection resulted in significantly improved sensorimotor scores 7 days after MCAO and induced a reduction in the number of Fluoro-Jade B-positive neurons and TUNEL-positive cells, compared with vehicle- or AdNull-injection. Our findings suggest that BDNF expression could be regulated in hypoxia/ischemia condition with five copies of HRE and ameliorates ischemic brain injury in a mouse focal cerebral ischemia model.

  11. Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain

    NASA Astrophysics Data System (ADS)

    Wu, Z. H.; Zhang, H.; Wang, X. Y.; Yang, R.; Liu, B.; Liu, Y.; Zhao, W. P.; Feng, H. Y.; Xue, L. G.; Hao, J. F.; Niu, B. T.; Wang, Z. H.

    2012-01-01

    The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.

  12. Traumatic Brain Injury and Dystonia

    MedlinePlus

    ... Symptoms of dystonia associated with TBI may be chronic or occur in episodes. Dystonia symptoms associated with ... a multi- disciplinary team with experience treating traumatic brain injury and/or movement disorders. • Learn as much as ...

  13. The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

    PubMed

    Ozerol, Elif; Bilgic, Sedat; Iraz, Mustafa; Cigli, Ahmet; Ilhan, Atilla; Akyol, Omer

    2009-02-01

    Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.

  14. Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

    PubMed

    Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

    2015-01-01

    It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

  15. 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…

  16. Concussion and Traumatic Brain Injury

    MedlinePlus

    ... long stays in intensive care units. Read More "Concussion" Articles Sports and Concussion / NIH Research on Concussion and the Brain / Doug Flutie: "Be on the Safe Side." / Concussion and Traumatic Brain Injury Summer 2015 Issue: Volume 10 ... Viewers & Players Friends of the National Library of Medicine (FNLM)

  17. 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…

  18. Angiotensin Converting Enzyme 2/Ang-(1–7)/Mas Axis Protects Brain from Ischemic Injury with a Tendency of Age-dependence

    PubMed Central

    Zheng, Jiao-Lin; Li, Guang-Ze; Chen, Shu-Zhen; Wang, Jin-Ju; Olson, James E.; Xia, Hui-Jing; Lazartigues, Eric; Zhu, Yu-Lan; Chen, Yan-Fang

    2016-01-01

    SUMMARY Background The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor pathway is an important component of the renin–angiotensin system and has been suggested to exert beneficial effects in ischemic stroke. Aims This study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age. Methods We used three-month and eight-month transgenic mice with neural over-expression of ACE2 (SA) and their age-matched non-transgenic (NT) controls. Neurological deficits and ischemic stroke volume were determined following middle cerebral artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on brain slices, the effects of the Mas receptor agonist (Ang1-7) or antagonist (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS) production and cell death were measured. Results (1) Middle cerebral artery occlusion -induced ischemic injury and neurological deficit were reduced in SA mice, especially in eight-month animals; (2) OGD-induced tissue swelling and cell death were decreased in SA mice with a greater reduction seen in eight-month mice; (3) Ang-(1–7) and A779 had opposite effects on OGD-induced responses, which correlated with changes in Nox2/Nox4 expression and ROS production. Conclusions Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic injury via the Nox/ROS signaling pathway, with a greater effect in older animals. PMID:24581232

  19. Fyn in Neurodevelopment and Ischemic Brain Injury

    PubMed Central

    Knox, Renatta; Jiang, Xiangning

    2016-01-01

    The Src Family kinases (SFKs) are nonreceptor protein tyrosine kinases that are implicated in many normal and pathological processes in the nervous system. The SFKs Fyn, Src, Yes, Lyn and Lck are expressed in the brain. This review will focus on Fyn, as Fyn mutant mice have striking phenotypes in the brain and Fyn has been shown to be involved in ischemic brain injury in adult rodents, and with our work, in neonatal animals. An understanding of Fyn’s role in neurodevelopment and disease will allow researchers to target pathological pathways while preserving protective ones. PMID:25720756

  20. Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid-sensing ion channel 1a and L-type calcium channels

    PubMed Central

    Wu, Wen-Ning; Wu, Peng-Fei; Chen, Xiang-Long; Zhang, Zui; Gu, Jun; Yang, Yuan-Jian; Xiong, Qiu-Ju; Ni, Lan; Wang, Fang; Chen, Jian-Guo

    2011-01-01

    BACKGROUND AND PURPOSE Sinomenine (SN), a bioactive alkaloid, has been utilized clinically to treat rheumatoid arthritis in China. Our preliminary experiments indicated that it could protect PC12 cells from oxygen-glucose deprivation-reperfusion (OGD-R), we thus investigated the possible effects of SN on cerebral ischaemia and the related mechanism. EXPERIMENTAL APPROACH Middle cerebral artery occlusion in rats was used as an animal model of ischaemic stroke in vivo. The mechanisms of the effects of SN were investigated in vitro using whole-cell patch-clamp recording, calcium imaging in PC12 cells and rat cortical neurons subjected to OGD-R. KEY RESULTS Pretreatment with SN (10 and 30 mg·kg−1, i.p.) significantly decreased brain infarction and the overactivation of calcium-mediated events in rats subjected to 2 h ischaemia followed by 24 h reperfusion. Extracellular application of SN inhibited the currents mediated by acid-sensing ion channel 1a and L-type voltage-gated calcium channels, in the rat cultured neurons, in a concentration-dependent manner. These inhibitory effects contribute to the neuroprotection of SN against OGD-R and extracellular acidosis-induced cytotoxicity. More importantly, administration of SN (30 mg·kg−1, i.p.) at 1 and 2 h after cerebral ischaemia also decreased brain infarction and improved functional recovery. CONCLUSION AND IMPLICATIONS SN exerts potent protective effects against ischaemic brain injury when administered before ischaemia or even after the injury. The inhibitory effects of SN on acid-sensing ion channel 1a and L-type calcium channels are involved in this neuroprotection. PMID:21585344

  1. Remote Limb Ischemic Postconditioning Protects Against Neonatal Hypoxic–Ischemic Brain Injury in Rat Pups by the Opioid Receptor/Akt Pathway

    PubMed Central

    Zhou, Yilin; Fathali, Nancy; Lekic, Tim; Ostrowski, Robert P.; Chen, Chunhua; Martin, Robert D.; Tang, Jiping; Zhang, John H.

    2013-01-01

    Background and Purpose Remote ischemic postconditoning, a phenomenon in which brief ischemic stimuli of 1 organ protect another organ against an ischemic insult, has been demonstrated to protect the myocardium and adult brain in animal models. However, mediators of the protection and underlying mechanisms remain to be elucidated. In the present study, we tested the hypothesis that remote limb ischemic postconditioning applied immediately after hypoxia provides neuroprotection in a rat model of neonatal hypoxia–ischemia (HI) by mechanisms involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. Methods HI was induced in postnatal Day 10 rat pups by unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia and reperfusion on both hind limbs immediately after HI. The opioid antagonist naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist morphine was administered to determine underlying mechanisms. Infarct volume, brain atrophy, and neurological outcomes after HI were evaluated. Expression of phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western blotting. Results Limb ischemic postconditioning significantly reduced infarct volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone and wortmannin abrogated the postconditioning-mediated infarct-limiting effect. Morphine given immediately after hypoxia also decreased infarct volume. Furthermore, limb ischemic postconditioning recovered Akt activity and decreased Bax expression, whereas no differences in phosphorylated ERK1/2expression were observed. Conclusions Limb ischemic postconditioning protects against neonatal HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. PMID:21183744

  2. Minor traumatic brain injury in sports.

    PubMed

    Schleimer, Jonathan A

    2002-12-01

    Mild traumatic brain injury (MTBI) is an all-too-frequent occurrence among amateur and professional athletes alike. The increased attention it has received in recent literature may suggest that incidence of this injury has risen. The frequency of MTBI in general may be rising with the increased interest in so-called noncontact sports such as soccer, snowboarding, skateboarding, and motocross. Despite significant improvements made in the quality of protective equipment, head injury remains common in football, soccer, and amateur boxing. The management of athletes who suffer traumatic head injury remains problematic for coaches, trainers, team physicians, primary care physicians, and neurologic specialists. This article addresses guidelines, and diagnostic and treatment protocols to help with the management of athletes with concussion and traumatic head injuries.

  3. 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.

  4. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

    PubMed

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

    2017-05-01

    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  5. Dysautonomia after pediatric brain injury

    PubMed Central

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

    2012-01-01

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

  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. The neurophysiology of brain injury.

    PubMed

    Gaetz, Michael

    2004-01-01

    This article reviews the mechanisms and pathophysiology of traumatic brain injury (TBI). Research on the pathophysiology of diffuse and focal TBI is reviewed with an emphasis on damage that occurs at the cellular level. The mechanisms of injury are discussed in detail including the factors and time course associated with mild to severe diffuse injury as well as the pathophysiology of focal injuries. Examples of electrophysiologic procedures consistent with recent theory and research evidence are presented. Acceleration/deceleration (A/D) forces rarely cause shearing of nervous tissue, but instead, initiate a pathophysiologic process with a well defined temporal progression. The injury foci are considered to be diffuse trauma to white matter with damage occurring at the superficial layers of the brain, and extending inward as A/D forces increase. Focal injuries result in primary injuries to neurons and the surrounding cerebrovasculature, with secondary damage occurring due to ischemia and a cytotoxic cascade. A subset of electrophysiologic procedures consistent with current TBI research is briefly reviewed. The pathophysiology of TBI occurs over time, in a pattern consistent with the physics of injury. The development of electrophysiologic procedures designed to detect specific patterns of change related to TBI may be of most use to the neurophysiologist. This article provides an up-to-date review of the mechanisms and pathophysiology of TBI and attempts to address misconceptions in the existing literature.

  8. Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2

    PubMed Central

    Zhao, Hailin; Mitchell, Sian; Ciechanowicz, Sarah; Savage, Sinead; Wang, Tianlong; Ji, Xunming; Ma, Daqing

    2016-01-01

    Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury. In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours. In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection. These data provide a new molecular mechanism for the potential application of argon as a neuroprotectant in HIE. PMID:27016422

  9. 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

  10. Ecdysterone protects gerbil brain from temporal global cerebral ischemia/reperfusion injury via preventing neuron apoptosis and deactivating astrocytes and microglia cells.

    PubMed

    Wang, Wei; Wang, Tao; Feng, Wan-Yu; Wang, Zhan-You; Cheng, Mao-Sheng; Wang, Yun-Jie

    2014-01-01

    Ecdysterone (EDS), a common derivative of ecdysteroid, has shown its effects on alleviating cognitive impairment and improving the cognition and memory. However, the mechanisms remain unknown. Using temporal global forebrain ischemia and reperfusion-induced brain injury as a model system, we investigated the roles of EDS in improving cognitive impairment in gerbil. Our results demonstrated that intraperitoneal injection of EDS obviously increased the number of surviving neuron cells by Nissl and neuronal nuclei (NeuN) staining. Indeed, the protecting effects of EDS are because of its ability to prevent the apoptosis of neuron cells as evidenced by TUNEL staining and caspase-3 deactivation in the brain of temporal global forebrain ischemia/reperfusion-treated gerbil. Moreover, EDS administration suppressed the ischemia stimulated activity of astrocytes and microglia cells by inhibiting the production of tumor necrosis alpha (TNF-α) in the brain of gerbil. More importantly, these actions of neurons and astrocytes/microglia cells in response to EDS treatment played pivotal roles in ameliorating the cognitive impairment in the ischemia/reperfusion-injured gerbil. In view of these observations, we not only decipher the mechanisms of EDS in reducing the syndrome of ischemia, but also provide novel perspectives to combat ischemic stroke.

  11. Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a cAMP/CREB-CD39-Dependent Manner.

    PubMed

    Cui, Mei; Ding, Hongyan; Chen, Fangzhe; Zhao, Yanxin; Yang, Qi; Dong, Qiang

    2016-01-01

    This study aimed to examine whether the neuroprotective effects of Mdivi-1 are attributable to extracellular ATP and adenosine. Mdivi-1 was administered prior to or post middle cerebral artery occlusion (MCAO). The extracellular adenosine was measured by in vivo microdialysis and high-pressure liquid chromatography (HPLC) in MCAO mouse model. Western blot was done to determine the influence of Mdivi-1 on the expression of CD39 and CREB phosphorylation both in vivo and in the cultured astrocytes. Intracellular cAMP and protein kinase A (PKA) activity were detected in primary astrocytes. Results showed that Mdivi-1 significantly reduced infarct volume and neurological scores when administered either prior to or post MCAO. Interestingly, pretreatment with Mdivi-1 resulted in marked increase of extracellular adenosine and concomitant decrease in ATP. The expression of CD39, but not CD73, was upregulated by Mdivi-1, which was associated with the elevated phosphorylated cAMP response element-binding protein (CREB), a transcription factor potentially regulating CD39 expression. In primary astrocytes, Mdivi-1 treatment induced increases in intracellular cAMP, PKA activity and CREB phosphorylation, and PKA-specific inhibitor completely reversed Mdivi-1-induced CD39 expression. Our results demonstrate that Mdivi-1 protects against ischemic brain injury through increasing extracellular adenosine, a process involving elevated CD39 expression that is likely modulated by cAMP/PKA/CREB cascade. Figure Potential mechanisms by which Mdivi-1 mediates the neuroprotection on cerebral ischemic stroke. Results from the present study indicate that Mdivi-1 protects against ischemic brain injury through increasing extracellular adenosine, a process involving elevated CD39 expression that is likely modulated by the cAMP/PKA/CREB cascades.

  12. Brain Injury Alters Volatile Metabolome.

    PubMed

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

    2016-06-01

    Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function-which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. Published by Oxford University Press on behalf of US Government 2016.

  13. Brain Injury Alters Volatile Metabolome

    PubMed Central

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

    2016-01-01

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

  14. Defense and Veterans Brain Injury Center

    MedlinePlus

    Skip to main content Search form Search Basket Contact Us DVBIC Defense and Veterans Brain Injury Center About DVBIC Leadership History Newsroom Contact Us FAQs About Traumatic Brain Injury TBI & the Military DoD Worldwide Numbers for TBI ...

  15. Traumatic Brain Injury (TBI) Data and Statistics

    MedlinePlus

    ... Cancel Submit Search The CDC Traumatic Brain Injury & Concussion Note: Javascript is disabled or is not supported ... this page: About CDC.gov . Traumatic Brain Injury & Concussion Basic Information Get the Facts Signs and Symptoms ...

  16. Hypersomnia Following Traumatic Brain Injury

    PubMed Central

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

    2007-01-01

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

  17. Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain injury via gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 signaling pathway

    PubMed Central

    Wang, Yang; Fan, Xuegong; Tang, Tao; Fan, Rong; Zhang, Chunhu; Huang, Zebing; Peng, Weijun; Gan, Pingping; Xiong, Xingui; Huang, Wei; Huang, Xi

    2016-01-01

    Oxidative stress chiefly contributes to the disruption of the BBB following traumatic brain injury (TBI). The Chinese herbal medicine rhubarb is a promising antioxidant in treating TBI. Here we performed in vivo and in vitro experiments to determine whether rhubarb and its absorbed bioactive compound protected the BBB after TBI by increasing ZO-1 expression through inhibition of gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 pathway. Rats were subjected to the controlled cortical impact (CCI) model, and primary rat cortical astrocytes were exposed to scratch-wound model. The liquid chromatography with tandem mass spectrometry method showed that rhein was the compound absorbed in the brains of CCI rats after rhubarb administration. The wet-dry weights and Evans blue measurements revealed that rhubarb and rhein ameliorated BBB damage and brain edema in CCI rats. Western blots showed that rhubarb and rhein downregulated GFAP in vitro. RT-PCR, immunohistochemistry, Western blot and dichlorodihydrofluorescein diacetate analysis indicated that rhubarb prevented activation of gp91phox subunit of NADPH oxidase induced ROS production, subsequently inhibited ERK/MMP-9 pathway in vivo and in vitro. Interestingly, rhein and rhubarb similarly protected the BBB by inhibiting this signaling cascade. The results provide a novel herbal medicine to protect BBB following TBI via an antioxidative molecular mechanism. PMID:27901023

  18. Traumatic Brain Injury (TBI) in Kids

    MedlinePlus

    ... head injury) or by an object penetrating the skull (called a penetrating injury). Some TBIs result in ... to) several types of injury to the brain: Skull fracture occurs when the skull cracks. Pieces of ...

  19. 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.

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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.

  5. Management of penetrating brain injury.

    PubMed

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

    2011-07-01

    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.

  6. 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

  7. Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury

    PubMed Central

    Niatsetskaya, Zoya V; Charlagorla, Pradeep; Matsukevich, Dzmitry A; Sosunov, Sergey A; Mayurasakorn, Korapat; Ratner, Veniamin I; Polin, Richard A; Starkov, Anatoly A; Ten, Vadim S

    2012-01-01

    Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO2), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO2 85% to 95%) may be beneficial for infants with birth asphyxia. PMID:22108720

  8. Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury.

    PubMed

    Niatsetskaya, Zoya V; Charlagorla, Pradeep; Matsukevich, Dzmitry A; Sosunov, Sergey A; Mayurasakorn, Korapat; Ratner, Veniamin I; Polin, Richard A; Starkov, Anatoly A; Ten, Vadim S

    2012-02-01

    Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO(2)), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO(2) 85% to 95%) may be beneficial for infants with birth asphyxia.

  9. Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury.

    PubMed

    Newaz, M A; Yousefipour, Z; Nawal, N N A

    2005-08-01

    %; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.

  10. Sleep and Traumatic Brain Injury.

    PubMed

    Baumann, Christian R

    2016-03-01

    Post-traumatic sleep-wake disturbances are frequent and often chronic complications after traumatic brain injury. The most prevalent sleep-wake disturbances are insomnia, excessive daytime sleepiness, and pleiosomnia, (i.e., increased sleep need). These disturbances are probably of multifactorial origin, but direct traumatic damage to key brain structures in sleep-wake regulation is likely to contribute. Diagnosis and treatment consist of standard approaches, but because of misperception of sleep-wake behavior in trauma patients, subjective testing alone may not always suffice.

  11. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H₁ and H₂ receptors in vitro.

    PubMed

    Zhang, Luyi; Yao, Ke; Fan, Yanying; He, Ping; Wang, Xiaofen; Hu, Weiwei; Chen, Zhong

    2012-12-01

    Although it is believed that carnosine has protective effects on various cell types, its effect on microvascular endothelial cells has not been well defined. In the present study, we investigated the protective effects of carnosine in microvascular endothelial cells using an in vitro rotenone-induced oxidative stress model. Mouse brain microvascular endothelial cells were exposed to 1 μmol/L rotenone for 18 h. In some experiments, carnosine (100 nmol/L-1 mmol/L) was added 30 min prior to rotenone exposure. When used, histamine receptor antagonists (100 nmol/L-10 μmol/L) were added 15 min before carnosine treatment. After rotenone exposure, apoptosis of microvascular cells was analysed by Hoechst 33342 staining, whereas mitochondrial membrane potential was assessed by JC-1 staining. Intracellular carnosine and histamine levels were determined using HPLC or ultra-HPLC. Over the range 1 μmol/L-1 mmol/L, carnosine concentration-dependently decreased the number of apoptotic cells after 18 h exposure to rotenone. This effect was reversed by the histamine H1 receptor antagonists pyrilamine and diphenhydramine (1 and 10 μmol/L) and the H2 receptor antagonists cimetidine (100 nmol/L-10 μmol/L) and zolatidine (10 μmol/L). α-Fluoromethylhistidine (100 μmol/L), a selective and irreversible inhibitor of histidine decarboxylase, also significantly inhibited the protective effects of carnosine. At 0.1 mmol/L, carnosine restored the decrease in mitochondrial membrane potential after 6 h exposure to 1 μmol/L rotenone and this effect was also reversed by the H1 and H2 receptor antagonists. Moreover, intracellular carnosine levels increased as early as 1 h after carnosine treatment, whereas intracellular histamine levels increased 18 h after carnosine treatment. The results of the present study indicate that carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury via histamine H1 and H2 receptors. The

  12. Sedation in Traumatic Brain Injury

    PubMed Central

    Flower, Oliver; Hellings, Simon

    2012-01-01

    Several different classes of sedative agents are used in the management of patients with traumatic brain injury (TBI). These agents are used at induction of anaesthesia, to maintain sedation, to reduce elevated intracranial pressure, to terminate seizure activity and facilitate ventilation. The intent of their use is to prevent secondary brain injury by facilitating and optimising ventilation, reducing cerebral metabolic rate and reducing intracranial pressure. There is limited evidence available as to the best choice of sedative agents in TBI, with each agent having specific advantages and disadvantages. This review discusses these agents and offers evidence-based guidance as to the appropriate context in which each agent may be used. Propofol, benzodiazepines, narcotics, barbiturates, etomidate, ketamine, and dexmedetomidine are reviewed and compared. PMID:23050154

  13. The sigma-1 receptor agonist 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects against newborn excitotoxic brain injury by stabilizing the mitochondrial membrane potential in vitro and inhibiting microglial activation in vivo.

    PubMed

    Wegleiter, Karina; Hermann, Martin; Posod, Anna; Wechselberger, Karina; Stanika, Ruslan I; Obermair, Gerald J; Kiechl-Kohlendorfer, Ursula; Urbanek, Martina; Griesmaier, Elke

    2014-11-01

    Premature birth represents a clinical situation of risk for brain injury. The diversity of pathophysiological processes complicates efforts to find effective therapeutic strategies. Excitotoxicity is one important factor in the pathogenesis of preterm brain injury. The observation that sigma-1 receptor agonists possess neuroprotective potential, at least partly mediated by a variety of anti-excitotoxic mechanisms, has generated great interest in targeting those receptors to counteract brain injury. The objective of this study was to evaluate the effect of the highly specific sigma-1 receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) to protect against excitotoxic developmental brain injury in vivo and in vitro. Primary hippocampal neurons were pre-treated with PPBP before glutamate was applied and subsequently analyzed for cell death (PI/calcein AM), mitochondrial activity (TMRM) and morphology of the neuronal network (WGA) using confocal microscopy. Using an established neonatal mouse model we also determined whether systemic injection of PPBP significantly attenuates excitotoxic brain injury. PPBP significantly reduced neuronal cell death in primary hippocampal neurons exposed to glutamate. Neurons treated with PPBP showed a less pronounced loss of mitochondrial membrane potential and fewer morphological changes after glutamate exposure. A single intraperitoneal injection of PPBP given one hour after the excitotoxic insult significantly reduced microglial cell activation and lesion size in cortical gray and white matter. The present study provides strong support for the consideration of sigma-1 receptor agonists as a candidate therapy for the reduction of neonatal excitotoxic brain lesions and might offer a novel target to counteract developmental brain injury.

  14. A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

    PubMed

    Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

    2014-12-01

    Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

  15. Treatment window for hypothermia in brain injury.

    PubMed

    Markgraf, C G; Clifton, G L; Moody, M R

    2001-12-01

    The goal of this study was to evaluate the therapeutic window for hypothermia treatment following experimental brain injury by measuring edema formation and functional outcome. Traumatic brain injury (TBI) was produced in anesthetized rats by using cortical impact injury. Edema was measured in the ipsilateral and contralateral hemispheres by subtracting dry weight from wet weight, and neurological function was assessed using a battery of behavioral tests 24 hours after TBI. In injured rats, it was found that brain water levels were elevated at I hour postinjury, compared with those in sham-injured control animals, and that edema peaked at 24 hours and remained elevated for 4 days. Hypothermia (3 hours at 30 degrees C) induced either immediately after TBI or 60 minutes after TBI significantly reduced early neurological deficits. Delay of treatment by 90 or 120 minutes postinjury did not result in this neurological protection. Immediate administration of hypothermia also significantly decreased the peak magnitude of edema at 24 hours and 48 hours postinjury, compared with that in normothermic injured control animals. When delayed by 90 minutes, hypothermia did not affect the pattern of edema formation. When hypothermia was administered immediately or 60 minutes after TBI, injured rats showed an improvement in functional outcome and a decrease in edema. Delayed hypothermia treatment had no effect on functional outcome or on edema.

  16. A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats

    PubMed Central

    Li, Guoling; Tian, Yufei; Zhang, Yuzhong; Hong, Ying; Hao, Yingzhi; Chen, Chunxiao; Wang, Penglong; Lei, Haimin

    2015-01-01

    Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC50 = 4.249 µM). In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-κB/p65 (NF-κB/p65) and cyclooxygenase-2 (COX-2) expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF) expression, decreased oxidative stress, and up-regulation of Ca2+–Mg2+ ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke. PMID:26370988

  17. Protection by Neuroglobin Expression in Brain Pathologies

    PubMed Central

    Baez, Eliana; Echeverria, Valentina; Cabezas, Ricardo; Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Barreto, George E.

    2016-01-01

    Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes. PMID:27672379

  18. 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.

  19. [Role of sodium cromoglycate in brain protection and its effects on tumor necrosis factor-alpha and interleukin-1beta after global cerebral ischemia-reperfusion injury in gerbils].

    PubMed

    Shen, Ning; Gan, Xiao-Liang; Pang, Hu-Yu; He, Zi-Qing

    2009-03-01

    To investigate the role of sodium cromoglycate in brain protection and its effects on brain tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expressions after global cerebral ischemia-reperfusion (IR) injury in gerbils. Twenty-four healthy male gerbils were randomized into 3 equal groups, namely the sham-operated group with isolation of the bilateral carotid arteries but without occlusion, IR injury model group with bilateral carotid artery occlusion, and sodium cromoglycate treatment group with bilateral carotid artery occlusion and sodium cromoglycate administration at 25 mg/kg via the lingual vein as soon as the reperfusion start with another dose 1 h later. The animals were then sacrificed and the thalamus were removed, fixed in 10% formaldehyde and sliced for observation under light microscope with HE staining. The rest brain tissues were prepared into homogenate to determine the content of TNF-alpha and IL-1beta. The right hemispheres of the gerbils were measured for wet weight and dry weight to calculate the water content in the brain. The water content in the brain of the gerbils in the model group was the highest among the groups, and that in sodium cromoglycate treatment group was significantly less than that of the model group (P<0.05). Microscopic examination showed the most severe brain tissue damage in the model group with also the highest TNF-alpha and IL-1beta levels in the brain. The brain TNF-alpha and IL-1beta levels in sodium cromoglycate group were significantly decreased as compared with those in the model group (P<0.05). Sodium cromoglycate can alleviate brain IR injury possibly by lowering the TNF-alpha and IL-1beta levels in the brain tissues.

  20. Hypopituitarism after traumatic brain injury.

    PubMed

    Fernandez-Rodriguez, Eva; Bernabeu, Ignacio; Castro, Ana I; Casanueva, Felipe F

    2015-03-01

    The prevalence of hypopituitarism after traumatic brain (TBI) injury is widely variable in the literature; a meta-analysis determined a pooled prevalence of anterior hypopituitarism of 27.5%. Growth hormone deficiency is the most prevalent hormone insufficiency after TBI; however, the prevalence of each type of pituitary deficiency is influenced by the assays used for diagnosis, severity of head trauma, and time of evaluation. Recent studies have demonstrated improvement in cognitive function and cognitive quality of life with substitution therapy in GH-deficient patients after TBI.

  1. hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury.

    PubMed

    Jiang, Peng; Chen, Chen; Wang, Ruimin; Chechneva, Olga V; Chung, Seung-Hyuk; Rao, Mahendra S; Pleasure, David E; Liu, Ying; Zhang, Quanguang; Deng, Wenbin

    2013-01-01

    Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but the utilization of hPSC-derived astroglia as cell therapy for neurological diseases has not been well studied. Astroglia are heterogeneous, and not all astroglia are equivalent in promoting neural repair. A prerequisite for cell therapy is to derive defined cell populations with superior therapeutic effects. Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate that hESC-derived Olig2(+) progenitors generate a subtype of previously uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ substantially from astroglia differentiated from Olig2-negative hESC-derived neural progenitor cells (NPC-Astros), particularly in their neuroprotective properties. When grafted into brains subjected to global ischaemia, Olig2PC-Astros exhibit superior neuroprotective effects and improved behavioural outcome compared to NPC-Astros. Thus, this new paradigm of human astroglial differentiation is useful for studying the heterogeneity of human astroglia, and the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral ischaemia and other neurological diseases.

  2. NAP prevents acute cerebral oxidative stress and protects against long-term brain injury and cognitive impairment in a model of neonatal hypoxia-ischemia.

    PubMed

    Greggio, Samuel; de Paula, Simone; de Oliveira, Iuri M; Trindade, Cristiano; Rosa, Renato M; Henriques, João A P; DaCosta, Jaderson C

    2011-10-01

    Hypoxia-ischemia (HI) is a common cause of neonatal brain damage with lifelong morbidities in which current therapies are limited. In this study, we investigated the effect of neuropeptide NAP (NAPVSIPQ) on early cerebral oxidative stress, long-term neurological function and brain injury after neonatal HI. Seven-day-old rat pups were subjected to an HI model by applying a unilateral carotid artery occlusion and systemic hypoxia. The animals were randomly assigned to groups receiving an intraperitoneal injection of NAP (3 μg/g) or vehicle immediately (0 h) and 24 h after HI. Brain DNA damage, lipid peroxidation and reduced glutathione (GSH) content were determined 24 h after the last NAP injection. Cognitive impairment was assessed on postnatal day 60 using the spatial version of the Morris water maze learning task. Next, the animals were euthanized to assess the cerebral hemispheric volume using the Cavalieri principle associated with the counting point method. We observed that NAP prevented the acute HI-induced DNA and lipid membrane damage and also recovered the GSH levels in the injured hemisphere of the HI rat pups. Further, NAP was able to prevent impairments in learning and long-term spatial memory and to significantly reduce brain damage up to 7 weeks following the neonatal HI injury. Our findings demonstrate that NAP confers potent neuroprotection from acute brain oxidative stress, long-term cognitive impairment and brain lesions induced by neonatal HI through, at least in part, the modulation of the glutathione-mediated antioxidant system.

  3. Antenatal supplementation of taurine for protection of fetal rat brain with intrauterine growth restriction from injury by reducing neuronal apoptosis.

    PubMed

    Liu, Jing; Liu, Li; Wang, Xiao-Feng; Teng, Hui-Yun; Yang, Na

    2012-10-01

    This study aimed to investigate whether antenatal taurine can reduce neuronal apoptosis in fetal rat brains with intrauterine growth restriction (IUGR) and its possible mechanisms. A total of 15 pregnant rats were randomly divided into the following three groups: control, IUGR, and IUGR+ antenatal taurine supplements. Neuronal apoptosis was detected using transferase-mediated dUTP biotin nick end-labeling (TUNEL); the expression of Bcl-2, Bax, and caspase-3 mRNA and proteins was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. In IUGR groups, the results were as follows: (1) the expression of Bcl-2 decreased whereas the expression of Bax increased, accordingly, the ratio of Bcl-2/Bax decreased, (2) the expression of caspase-3 increased significantly, and (3) apoptotic neuron counts in IUGR groups was significantly increased compared with controls. In taurine supplement groups, the results were as follows: (1) the expression of Bcl-2 increased whereas the expression of Bax decreased, accordingly, the ratio of Bcl-2/Bax increased, (2) the expression of caspase-3 in fetal rat cerebral cortex tissues decreased significantly, and (3) the number of apoptotic neurons was significantly decreased compared with IUGR groups. In addition, the changes in the expression of Bcl-2, Bax, and caspase-3 mRNA and protein were correlated. So we concluded that antenatal supplementation of taurine may reduce neuronal apoptosis in IUGR fetal rats via up-regulating the ratio of Bcl-2/Bax and down-regulating the expression of caspase-3. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. 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:…

  5. 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:…

  6. Brain Temperature: Physiology and Pathophysiology after Brain Injury

    PubMed Central

    Mrozek, Ségolène; Vardon, Fanny; Geeraerts, Thomas

    2012-01-01

    The regulation of brain temperature is largely dependent on the metabolic activity of brain tissue and remains complex. In intensive care clinical practice, the continuous monitoring of core temperature in patients with brain injury is currently highly recommended. After major brain injury, brain temperature is often higher than and can vary independently of systemic temperature. It has been shown that in cases of brain injury, the brain is extremely sensitive and vulnerable to small variations in temperature. The prevention of fever has been proposed as a therapeutic tool to limit neuronal injury. However, temperature control after traumatic brain injury, subarachnoid hemorrhage, or stroke can be challenging. Furthermore, fever may also have beneficial effects, especially in cases involving infections. While therapeutic hypothermia has shown beneficial effects in animal models, its use is still debated in clinical practice. This paper aims to describe the physiology and pathophysiology of changes in brain temperature after brain injury and to study the effects of controlling brain temperature after such injury. PMID:23326261

  7. A neuropsychiatric perspective on traumatic brain injury.

    PubMed

    Lux, Warren E

    2007-01-01

    Traumatic brain injury (TBI) due to closed mechanisms causes strain injuries to axons that increase in number and severity as injury severity increases. Axons that project up from the brain stem are vulnerable, even in milder concussive injuries, and include axons that participate in key monoaminergic pathways. Although called diffuse axonal injury, the supra-tentorial injury component typically shows an anterior preponderance in humans. As the injury forces increase, cerebral contusions may be superimposed on the axonal strain injuries, and these contusions show an anterior preponderance as well. The chronic neuropsychiatric manifestations of TBI reflect this injury distribution. In the cognitive sphere, these manifestations almost always include power function disturbances marked by difficulties with cognitive processing speed, multitasking, and cognitive endurance. These disturbances may then be followed by disturbances in executive function and self-awareness as injury severity increases. In the behavioral sphere, mood disturbances and disorders of behavioral control and regulation are particularly common.

  8. 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…

  9. 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…

  10. Surveillance of traumatic brain injuries in Utah.

    PubMed Central

    Thurman, D J; Jeppson, L; Burnett, C L; Beaudoin, D E; Rheinberger, M M; Sniezek, J E

    1996-01-01

    From 1990 through 1992 we conducted surveillance of cases requiring hospital admission and of fatal cases of traumatic brain injury among residents of Utah and found an annual incidence rate of 108.8 per 100,000 population. The greatest number of injuries occurred among men and persons aged 15 to 24 years. Motor vehicles were the leading cause of injury, followed by falls and assaults. The incidence rate we found is substantially lower than previously published rates of traumatic brain injury. This may be the result of a decrease in the incidence of these injuries in the decade since earlier studies were done, as well as changing hospital admission criteria that serve to exclude less severe cases of injury. Despite the apparent decline in rates, our findings indicate the continued importance of traumatic brain injury as a public health problem and the need to develop more effective prevention strategies that will address the major causes of these injuries. PMID:8987423

  11. Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress.

    PubMed

    Bazan, Nicolas G

    2005-04-01

    The biosynthesis of oxygenated arachidonic acid messengers triggered by cerebral ischemia-reperfusion is preceded by an early and rapid phospholipase A2 activation reflected in free arachidonic and docosahexaenoic acid (DHA) accumulation. These fatty acids are released from membrane phospholipids. Both fatty acids are derived from dietary essential fatty acids; however, only DHA, the omega-3 polyunsaturated fatty acyl chain, is concentrated in phospholipids of various cells of brain and retina. Synaptic membranes and photoreceptors share the highest content of DHA of all cell membranes. DHA is involved in memory formation, excitable membrane function, photoreceptor cell biogenesis and function, and neuronal signaling, and has been implicated in neuroprotection. In addition, this fatty acid is required for retinal pigment epithelium cell (RPE) functional integrity. Here we provide an overview of the recent elucidation of a specific mediator generated from DHA that contributes at least in part to its biological significance. In oxidative stress-challenged human RPE cells and rat brain undergoing ischemia-reperfusion, 10,17S-docosatriene (neuroprotectin D1, NPD1) synthesis evolves. In addition, calcium ionophore A23187, IL-1beta, or the supply of DHA enhances NPD1 synthesis. A time-dependent release of endogenous free DHA followed by NPD1 formation occurs, suggesting that a phospholipase A2 releases the mediator's precursor. When NPD1 is infused during ischemia-reperfusion or added to RPE cells during oxidative stress, apoptotic DNA damage is down-regulated. NPD1 also up-regulates the anti-apoptotic Bcl-2 proteins Bcl-2 and BclxL and decreases pro-apoptotic Bax and Bad expression. Moreover, NPD1 inhibits oxidative stress-induced caspase-3 activation. NPD1 also inhibits IL-1beta-stimulated expression of COX-2. Overall, NPD1 protects cells from oxidative stress-induced apoptosis. Because photoreceptors are progressively impaired after RPE cell damage in retinal

  12. 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…

  13. 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…

  14. 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,…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. Head Injuries

    MedlinePlus

    ... before. Often, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  20. Anesthesia for Patients with Traumatic Brain Injuries.

    PubMed

    Bhattacharya, Bishwajit; Maung, Adrian A

    2016-12-01

    Traumatic brain injury (TBI) represents a wide spectrum of disease and disease severity. Because the primary brain injury occurs before the patient enters the health care system, medical interventions seek principally to prevent secondary injury. Anesthesia teams that provide care for patients with TBI both in and out of the operating room should be aware of the specific therapies and needs of this unique and complex patient population.

  1. Neuroprotective effect of picroside II in brain injury in mice.

    PubMed

    Wang, Yida; Fang, Wei; Wu, Liang; Yao, Xueya; Wu, Suzhen; Wang, Jie; Xu, Zhen; Tian, Fubo; He, Zhenzhou; Dong, Bin

    2016-01-01

    Various types of brain injury which led to the damage of brain tissue structure and neurological dysfunction continues to be the major causes of disability and mortality. Picroside II (PII) possesses a wide range of pharmacological effects and has been proved to ameliorate ischemia and reperfusion injury of kidney and brain. However, critical questions remain about other brain injuries. We investigated the protective effect of PII in four well-characterized murine models of brain injury. Models showed a subsequent regional inflammatory response and oxidative stress in common, which might be improved by the administration of PII (20 mg/kg). Meanwhile, a series of morphological and histological analyses for reinforcement was performed. In traumatic, ischemic and infectious induced injuries, it was observed that the survival rate, apoptosis related proteins, Caspase-3, and the expression of acute inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly alleviated after PII injection, but PII treatment alone showed no effect on them as well. The western blot results indicated that TLR4 and NF-κB were clearly downregulated with PII administration. In conclusion, our results suggested that PII with a recommended concentration of 20 mg/kg could provide neuroprotective effects against multi-cerebral injuries in mice by suppressing the over-reactive inflammatory responses and oxidative stress and attenuating the damage of brain tissue for further neurological recovery.

  2. Neuroprotective effect of picroside II in brain injury in mice

    PubMed Central

    Wang, Yida; Fang, Wei; Wu, Liang; Yao, Xueya; Wu, Suzhen; Wang, Jie; Xu, Zhen; Tian, Fubo; He, Zhenzhou; Dong, Bin

    2016-01-01

    Various types of brain injury which led to the damage of brain tissue structure and neurological dysfunction continues to be the major causes of disability and mortality. Picroside II (PII) possesses a wide range of pharmacological effects and has been proved to ameliorate ischemia and reperfusion injury of kidney and brain. However, critical questions remain about other brain injuries. We investigated the protective effect of PII in four well-characterized murine models of brain injury. Models showed a subsequent regional inflammatory response and oxidative stress in common, which might be improved by the administration of PII (20 mg/kg). Meanwhile, a series of morphological and histological analyses for reinforcement was performed. In traumatic, ischemic and infectious induced injuries, it was observed that the survival rate, apoptosis related proteins, Caspase-3, and the expression of acute inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly alleviated after PII injection, but PII treatment alone showed no effect on them as well. The western blot results indicated that TLR4 and NF-κB were clearly downregulated with PII administration. In conclusion, our results suggested that PII with a recommended concentration of 20 mg/kg could provide neuroprotective effects against multi-cerebral injuries in mice by suppressing the over-reactive inflammatory responses and oxidative stress and attenuating the damage of brain tissue for further neurological recovery. PMID:28078024

  3. Psychosis following traumatic brain injury.

    PubMed

    Arciniegas, David B; Harris, Susie N; Brousseau, Kristin M

    2003-11-01

    Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.

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

    PubMed Central

    CHEN, AI; XIONG, LI-JING; TONG, YU; MAO, MENG

    2013-01-01

    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

  5. Hypopituitarism following traumatic brain injury.

    PubMed

    Popovic, V; Aimaretti, G; Casanueva, F F; Ghigo, E

    2005-06-01

    Recent studies have demonstrated that hypopituitarism, and in particular growth hormone (GH) deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or years following head trauma. In addition, it has been shown that post-traumatic neuroendocrine abnormalities occur early and with high frequency. These findings may have significant implications for the recovery and rehabilitation of patients with TBI. Although data emerging after 2000 demonstrate the relevance of the problem, in general there is a lack of awareness in the medical community about the incidence and clinical repercussions of the pathology. Most, but not all, head trauma associated with hypopituitarism is the result of motor accidents. The subjects at risk are those who have suffered moderate-to severe head trauma although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. Onset of pituitary deficits can evolve over years following injury. For the assessment of the GH-IGF axis in TBI patients, plasma IGF-I concentrations, plus dynamic GH testing is indicated. Some degree of hypopituitarism is found in 35-40% of TBI patients. Among multiple pituitary deficits, the most common ones were GHD and gonadotrophin deficiency. In most series 10-15% presented with severe GHD and 15% with partial GHD after stimulating GH secretion confirming that the most common isolated deficit is GHD. Psychometric evaluation together with neurocognitive testing shows variability of disability and the possibility that untreated TBI induced hypopituitarism contributes to the chronic neurobehavioral problems seen in many head-injured patients warrants consideration. Preliminary data, from small pilot, open-label studies show that subjects treated with GH experience significant improvements in concentration, memory, depression, anxiety and fatigue. In conclusion, pituitary failure can occur even in minor head

  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. Neurorestoration after traumatic brain injury through angiotensin II receptor blockage

    PubMed Central

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

    2015-01-01

    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

  8. Fluid markers of traumatic brain injury.

    PubMed

    Zetterberg, Henrik; Blennow, Kaj

    2015-05-01

    Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

  9. Downregulation of miRNA-134 protects neural cells against ischemic injury in N2A cells and mouse brain with ischemic stroke by targeting HSPA12B.

    PubMed

    Chi, W; Meng, F; Li, Y; Wang, Q; Wang, G; Han, S; Wang, P; Li, J

    2014-09-26

    MicroRNAs (miRNAs) have emerged as a major regulator in neurological diseases, and understanding their molecular mechanism in modulating cerebral ischemic injury may provide potential therapeutic targets for ischemic stroke. However, as one of 19 differentially expressed miRNAs in mouse brain with middle cerebral artery occlusion (MCAO), the role of miR-134 in ischemic injury is not well understood. In this study, the miR-134 expression level was manipulated both in oxygen-glucose deprivation (OGD)-treated N2A neuroblastoma cells in vitro and mouse brain with MCAO-induced ischemic stroke in vivo, and its possible targets of heat shock protein A5 (HSPA5) and HSPA12B were determined by bioinformatics analysis and dual luciferase assay. The results showed that overexpression of miR-134 exacerbated cell death and apoptosis both in vitro and in vivo. Conversely, downregulating miR-134 levels reduced cell death and apoptosis. Furthermore, non-expression of miR-134 enhanced HSPA12B protein levels in OGD-treated N2A cells as well as in the ischemic region. It could attenuate brain infarction size and neural cell damage, and improve neurological outcomes in mice with ischemic stroke, whereas upregulation of miR-134 had the opposite effect. In addition, HSPA12B was validated to be a target of miR-134 and its short interfering RNAs (siRNAs) could block miR-134 inhibitor-induced neuroprotection in OGD-treated N2A cells. In conclusion, downregulation of miR-134 could induce neuroprotection against ischemic injury in vitro and in vivo by negatively upregulating HSPA12B protein expression.

  10. Voltage-dependent anion channels (VDACs) promote mitophagy to protect neuron from death in an early brain injury following a subarachnoid hemorrhage in rats.

    PubMed

    Li, Jian; Lu, Jianfei; Mi, Yongjie; Shi, Zhao; Chen, Chunhua; Riley, John; Zhou, Changman

    2014-07-21

    The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48h after SAH injury in rats. Specifically evaluating whether mitophagy, through voltage dependant anion channels (VDACs) interacting with microtubule-associated protein 1 light chain 3, could orchestrate the induction of apoptotic and necrotic cell death in neurons, a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH, SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain edema, BBB disruption, and neurobehavioral testing. We also used western blotting techniques to analyze the expressions of key mitophagic/autophagic proteins and pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin treatment significantly improved the mortality rate, cerebral edema, and neurobehavioral deficits; apoptotic and necrotic cell death in neurons were reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain injury following SAH. Immunohistochemical staining and western blot analysis demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced by VDAC1 following SAH injury may in fact play a significant role in neuroprotection, the mechanism which may be through the attenuation of the apoptosic and necrosic molecular pathways. This translates a preservation of functional integrity and an improvement in mortality.

  11. Cell-based therapy for traumatic brain injury.

    PubMed

    Gennai, S; Monsel, A; Hao, Q; Liu, J; Gudapati, V; Barbier, E L; Lee, J W

    2015-08-01

    Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.

  12. Protective conditioning of the brain: expressway or roadblock?

    PubMed Central

    Mergenthaler, Philipp; Dirnagl, Ulrich

    2011-01-01

    Abstract The brain responds to noxious stimulation with protective signalling. Over the last decades, a number of experimental strategies have been established to study endogenous brain protection. Pre-, per-, post- and remote ‘conditioning’ are now widely used to unravel the underlying mechanisms of endogenous neuroprotection. Some of these strategies are currently being tested in clinical trials to protect the human brain against anticipated damage or to boost protective responses during or after injury. Here we summarize the principles of ‘conditioning’ research and current efforts to translate this knowledge into effective treatment of patients. Conditioning to induce protected brain states provides an experimental window into endogenous brain protection and can lead to the discovery of drugs mimicking the effects of conditioning. Mechanisms of endogenous brain tolerance can be activated through a wide variety of stimuli that signal ‘danger’ to the brain. These danger signals lead to the induction of regulator and effector mechanisms, which suppress death and induce survival pathways, decrease metabolism, as well as increase substrate delivery. We conclude that preclinical research on endogenous brain protection has greatly benefited from conditioning strategies, but that clinical applications are challenging, and that we should not prematurely rush into ill-designed and underpowered clinical trials. PMID:21708907

  13. Traumatic brain injury associated coagulopathy.

    PubMed

    de Oliveira Manoel, Airton Leonardo; Neto, Antonio Capone; Veigas, Precilla V; Rizoli, Sandro

    2015-02-01

    The presence of coagulopathy is common after severe trauma. The aim of this study was to identify whether isolated severe traumatic brain injury (TBI) is an independent risk factor for coagulopathy. Prospective observational cohort of adult patients admitted to a Level I Trauma Center within 6 h of injury. Patients were categorized according to the abbreviated injury scale (AIS): Group 1-isolated severe TBI (AIS head ≥ 3 + AIS non-head < 3); Group 2-severe multisystem trauma associated with severe TBI (AIS head ≥ 3 + AIS non-head ≥ 3); Group 3-severe multisystem trauma without TBI (AIS head < 3 + AIS non-head ≥ 3). Primary outcome was the development of coagulopathy. Secondary outcome was in-hospital mortality. Three hundred and forty five patients were included (Group 1 = 48 patients, Group 2 = 137, and Group 3 = 160). Group 1 patients had the lowest incidence of coagulopathy and disseminated intravascular coagulopathy, and in general presented with better coagulation profile measured by either classic coagulation tests, thromboelastography or clotting factors. Isolated severe TBI was not an independent risk factor for the development of coagulopathy (OR 1.06; 0.35-3.22 CI, p = 0.92), however, isolated severe TBI patients who developed coagulopathy had higher mortality rates than isolated severe TBI patients without coagulopathy (66 vs. 16.6 %, p < 0.05). The presence of coagulopathy (OR 5.61; 2.65-11.86 CI, p < 0.0001) and isolated severe TBI (OR 11.51; 3.9-34.2 CI, p < 0.0001) were independent risk factors for in-hospital mortality. Isolated severe TBI is not an independent risk factor for the development of coagulopathy. However, severe TBI patients who develop coagulopathy have extremely high mortality rates.

  14. 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.

  15. Sleep in traumatic brain injury.

    PubMed

    Mazwi, Nicole L; Fusco, Heidi; Zafonte, Ross

    2015-01-01

    Sleep disturbances affect more than half of survivors of traumatic brain injury (TBI) and have the potential to undermine rehabilitation, recovery, and outcomes. Normal sleep architecture has been well-described and the neurophysiology of sleep is becoming better understood in recent years, though this complex process continues to be dissected for better appreciation. There are numerous types of sleep disorder, most of which fall under two categories: dyssomnias and parasomnias. In more challenging scenarios patients may be plagued with more than one dyssomnia and/or parasomnia simultaneously, complicating the diagnostic and therapeutic approach. Objective and subjective methods are used to evaluate sleep disorders and help distinguish them from psychiatric and environmental contributors to poor sleep. There are several pharmacologic and nonpharmacologic treatments options for sleep disturbances after TBI, many of which have been particularly helpful in restoring adequate quantity and quality of sleep for survivors. However, to date no consensus has been established regarding how to treat this entity, and it may be that a multimodal approach is ultimately best.

  16. Hypothermia for traumatic brain injury.

    PubMed

    Lewis, Sharon R; Evans, David Jw; Butler, Andrew R; Schofield-Robinson, Oliver J; Alderson, Phil

    2017-09-21

    Hypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. To determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long-term functional outcomes and complications. We ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registers, and screened reference lists. We also re-ran these searches pre-publication in June 2017; the result from this search is presented in 'Studies awaiting classification'. We included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC). Two review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia. We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability

  17. The protective effect of different airway humidification liquids to lung after tracheotomy in traumatic brain injury: The role of pulmonary surfactant protein-A (SP-A).

    PubMed

    Su, Xinyang; Li, Zefu; Wang, Meilin; Li, Zhenzhu; Wang, Qingbo; Lu, Wenxian; Li, Xiaoli; Zhou, Youfei; Xu, Hongmei

    2016-02-10

    The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used. Brain tissue samples were taken to determine water content, while lung tissue samples were taken to determine wet/dry weight ratio (W/D), histological changes and expression levels of SP-A mRNA and SP-A protein. 30 patients with brain injury and tracheotomy were selected and divided into two groups based on the airway humidification liquid instilled in the trachea tube, 0.45% NaCl and 0.9% NaCl+ambroxol. Blood was then extracted from the patients to measure the levels of SP-A, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The difference between group C and other groups in lung W/D and expression levels of SP-A mRNA and SP-A protein was significant (P<0.05). In comparison, the histological changes showed that the lung tissue damage was smallest in group C compared to the three other groups. Aspect of patients, 0.45% NaCl group and 0.9% NaCl+ambroxol group were significantly different in the levels of SP-A, IL-6, IL-8 and TNF-α (P<0.01). In the present study, 0.9% NaCl+ambroxol promote the synthesis and secretion of pulmonary surfactant, and has anti-inflammatory and antioxidant effects, which inhibit the release of inflammatory factors and cytokines, making it an ideal airway humidification liquid.

  18. Reducing Secondary Insults in Traumatic Brain Injury

    DTIC Science & Technology

    2013-04-01

    persons, and leaves 99,000 persons permanently disabled [1]. The total cost for treatment and rehabilitation of patients with brain injuries is...registry based or retrospective or include only secondary insults that occur in the intensive care unit ( ICU ) setting. Most prior investigations have...in the surgical and neurosurgical ICU diagnosed with a traumatic brain injury requiring a diagnostic procedure were eligible for the study. The study

  19. Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats.

    PubMed

    Ge, Xu-Hua; Zhu, Guo-Ji; Geng, De-Qin; Zhang, Han-Zhi; He, Juan-Mei; Guo, Ai-Zhen; Ma, Lin-Lin; Yu, De-Hua

    2017-03-01

    Although Metformin, a first-line antidiabetic drug, can ameliorate ischemia/reperfusion (I/R) induced brain damage, but how metformin benefits injured hippocampus and the mechanisms are still largely unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of metformin against ischemic brain damage induced by cerebral I/R and to explore whether the Akt-mediated down-regulation of the phosphorylation of JNK3 signaling pathway contributed to the protection provided by metformin. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The open field tasks and Morris water maze were used to assess the effect of metformin on anxiety-like behavioral and cognitive impairment after I/R. Cresyl Violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting was performed to measure the phosphorylation of Akt1, JNK3, c-Jun and the expression of cleaved caspase-3. Through ischemia/reperfusion (I/R) rat model, we found that metformin could attenuate the deficits of hippocampal related behaviors and inhibit cell apoptosis. The western blot data showed that metformin could promote the activation of Akt1 and reduce the phosphorylation of JNK3 and c-Jun as well as elevation of cleaved caspase-3 in I/R brains. PI3K inhibitor reversed all the protective effects, further indicating that metformin protect hippocampus from ischemic damage through PI3K/Akt1/JNK3/c-Jun signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Modeling premature brain injury and recovery

    PubMed Central

    Scafidi, Joey; Fagel, Devon M.; Ment, Laura R.; Vaccarino, Flora M.

    2009-01-01

    Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain. PMID:19482072

  1. The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

    PubMed

    Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

    2014-08-22

    Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. 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…

  3. 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,…

  4. 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…

  5. 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,…

  6. Mechanisms of gender-linked ischemic brain injury

    PubMed Central

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

    2010-01-01

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

  7. LIVER INJURY, LIVER PROTECTION, AND SULFUR METABOLISM

    PubMed Central

    Miller, L. L.; Whipple, G. H.

    1942-01-01

    Protein-depleted dogs are very susceptible to injurious agents—in particular, chloroform. Methionine given shortly before chloroform anesthesia will give complete protection against chloroform. Methionine (or cysteine plus choline) given 3 or 4 hours after chloroform anesthesia will give significant protection against the liver injury of chloroform anesthesia. Methionine given more than 4 hours after chloroform anesthesia gives no protection against liver injury. Choline alone given before chloroform gives no protection against liver injury. The protein-depleted dogs have livers which are deficient in both nitrogen and sulfur, but sulfur is depleted more than is the nitrogen. The N/S ratio therefore rises. Methionine or cystine feeding promptly makes up this liver sulfur deficit. Viable liver cells are necessary for this uptake of sulfur. Livers of fetuses in utero or of newborn pups tolerate a chloroform anesthesia which will cause fatal liver injury in adults. The nitrogen and sulfur values of these fetus or pup livers are within the high normal values for adults. Blood-forming cells are present in the fetus or pup livers during this period. When these blood islands are eliminated during the 3rd or 4th week of life, the liver then becomes normally susceptible to chloroform liver injury. Methionine or methionine-rich protein digests (e.g. casein) or various proteins by mouth or by vein should prove useful to protect the liver against certain types of injury and to aid in organ repair. PMID:19871248

  8. [A man with severe traumatic brain injury].

    PubMed

    Oudeman, Eline A; Martins Jarnalo, Carine O; van Ouwerkerk, Willem J R

    2013-01-01

    We present a 41-year-old man with severe traumatic brain injury. Cranial imaging studies revealed cerebral contusion and a longitudinal fracture of the temporal bone. Several days later brain herniated into the left external auditory canal. Imaging studies showed the known skull fracture with a direct connection between the external acoustic meatus and the intracranial structures.

  9. Modeling Blast-Related Brain Injury

    DTIC Science & Technology

    2008-12-01

    02139 D. Moore Defense and Veterans Brain Injury Center (WRAMC) 6900 Georgia Ave. NW, Washington, DC 20307 L. Noels University of Liege Chemin des...chevreuils 1, B4000 Liege , Belgium ABSTRACT Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain in

  10. [Effects of alcohol consumption on traumatic brain injury].

    PubMed

    Katada, Ryuichi

    2011-10-01

    It has been well known that alcohol consumption affects traumatic brain injury. The mechanism of detrimental effect of ethanol on traumatic brain injury has not been clarified. This review focused on the relationship among traumatic brain injury, ethanol and aquaporin-4. We have reported that ethanol increased brain edema after brain contusion and decreased survival rates in rats. It was suggested that increasing brain edema by ethanol after brain contusion may be caused by oxidative stress. Brain edema consists of cytotoxic brain edema, vasogenic brain edema, interstitial brain edema and osmotic edema. Ethanol mainly increases cytotoxic brain edema. Both alcohol consumption and brain contusion cause oxidative stress. Antioxidant treatment decreases cytotoxic brain edema. Aquaporin-4, an water channel, was increased by ethanol 24 hr after traumatic brain injury in rat. The aquaporin-4 inhibitor decreased brain edema after brain contusion and increased survival rates under ethanol consumption. Aquaporin-4 may have strict relation between ethanol and brain edema increasing after brain contusion.

  11. 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. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  12. Purines: forgotten mediators in traumatic brain injury.

    PubMed

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

    2016-04-01

    Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. © 2016 International Society for Neurochemistry.

  13. 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

  14. Stereotypic movement disorder after acquired brain injury.

    PubMed

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

    2002-05-01

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

  15. 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.

  16. Cognitive outcome following traumatic brain injury.

    PubMed

    Dikmen, Sureyya S; Corrigan, John D; Levin, Harvey S; Machamer, Joan; Stiers, William; Weisskopf, Marc G

    2009-01-01

    To determine whether an association exists between traumatic brain injury (TBI) sustained in adulthood and cognitive impairment 6 months or longer after injury. Systematic review of the published, peer-reviewed literature. From 430 articles, we identified 11 primary and 22 secondary studies that examined cognitive impairment by using performance measures for adults who were at least 6 months post-TBI. There was clear evidence of an association between penetrating brain injury and impaired cognitive function. Factors that modified this association included preinjury intelligence, volume of brain tissue lost, and brain region injured. There was also suggestive evidence that penetrating brain injury may exacerbate the cognitive effects of normal aging. We found clear evidence for long-term cognitive deficits associated with severe TBI. There was suggestive evidence that moderately severe brain injuries are associated with cognitive impairments. There was inadequate/insufficient evidence to determine whether an association exists between a single, mild TBI and cognitive deficits 6 months or longer postinjury. In adults, penetrating, moderate, and severe TBIs are associated with cognitive deficits 6 months or longer postinjury. There is insufficient evidence to determine whether mild TBI is associated with cognitive deficits 6 months or longer postinjury.

  17. Recovery after brain injury: mechanisms and principles

    PubMed Central

    Nudo, Randolph J.

    2013-01-01

    The past 20 years have represented an important period in the development of principles underlying neuroplasticity, especially as they apply to recovery from neurological injury. It is now generally accepted that acquired brain injuries, such as occur in stroke or trauma, initiate a cascade of regenerative events that last for at least several weeks, if not months. Many investigators have pointed out striking parallels between post-injury plasticity and the molecular and cellular events that take place during normal brain development. As evidence for the principles and mechanisms underlying post-injury neuroplasticity has been gleaned from both animal models and human populations, novel approaches to therapeutic intervention have been proposed. One important theme has persisted as the sophistication of clinicians and scientists in their knowledge of neuroplasticity mechanisms has grown: behavioral experience is the most potent modulator of brain plasticity. While there is substantial evidence for this principle in normal, healthy brains, the injured brain is particularly malleable. Based on the quantity and quality of motor experience, the brain can be reshaped after injury in either adaptive or maladaptive ways. This paper reviews selected studies that have demonstrated the neurophysiological and neuroanatomical changes that are triggered by motor experience, by injury, and the interaction of these processes. In addition, recent studies using new and elegant techniques are providing novel perspectives on the events that take place in the injured brain, providing a real-time window into post-injury plasticity. These new approaches are likely to accelerate the pace of basic research, and provide a wealth of opportunities to translate basic principles into therapeutic methodologies. PMID:24399951

  18. 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

  19. The therapeutic protection of a living and dead Lactobacillus strain against aluminum-induced brain and liver injuries in C57BL/6 mice.

    PubMed

    Tian, Fengwei; Yu, Leilei; Zhai, Qixiao; Xiao, Yue; Shi, Ying; Jiang, Jinchi; Liu, Xiaoming; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2017-01-01

    Our previous study found that Lactobacillus plantarum CCFM639 had the ability to alleviate acute aluminum (Al) toxicity when the strain was introduced simultaneously with Al exposure. This research was designed to elucidate the therapeutic effects of living and dead L. plantarum CCFM639 against chronic Al toxicity and to gain insight into the protection modes of this strain. Animals were assigned into control, Al only, Al + living CCFM639, and Al + dead CCFM639 groups. The Al exposure model was established by drinking water for the first 4 weeks. The strain was given after Al exposure by oral gavage at 109 colony-forming units once per day for 12 weeks. The results show that the Al binding ability of dead CCFM639 was similar to that of living CCFM639 in vitro. The ingestion of living or dead CCFM639 has similar effects on levels of Al and trace element in tissues, but living strains led to more significant amelioration of oxidative stress and improvement of memory deficits in Al-exposed mice. In conclusion, in addition to intestinal Al sequestration, CCFM639 treatment offers direct protection against chronic Al toxicity by alleviation of oxidative stress. Therefore, L. plantarum CCFM639 has a potential as dietary supplement ingredient that provides protection against Al-induced injury.

  20. Role of Interleukin-10 in Acute Brain Injuries

    PubMed Central

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

    2017-01-01

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

  1. BDNF protects neurons following injury by modulation of caspase activity.

    PubMed

    Kim, Dong H; Zhao, Xiurong

    2005-01-01

    Neurotrophins can protect against apoptotic death following neuronal injury. In a previous article, we showed that activation of the trk receptor is required, but the subsequent mechanisms of action remain unclear. Because the caspase family of cysteine proteases plays a central role in the apoptotic process, we examined the effect of the neurotrophins on caspase activation. Primary neuronal cultures from the embryonic rat cortex were injured with radiation, oxygen deprivation, or oxygen-glucose deprivation. Neurons were treated with brain-derived growth factor (BDNF) or caspase inhibitors. The level of injury was assayed by measuring lactate dehydrogenase release. Western blots were used to note the presence and activation of the caspases 1, 2, 3, 8, and 9--with and without treatment with BDNF. Proenzymes for caspases 1, 2, and 3--but not for caspases 8 or 9 were expressed. With radiation or oxygen deprivation, but not oxygen-glucose deprivation, caspase 3 was activated. Treatment with BDNF was protective against radiation and oxygen deprivation only. Treatment with BDNF also blocked the activation of caspase 3. A similar effect was achieved by directly blocking caspase 1 or 3 activation using an inhibitor. In this study, we showed that BDNF treatment inhibits caspase 3 activation following neuronal injury. This is a central event: when injury did not lead to caspase 3 activation, BDNF treatment was not protective. These results suggest one mechanism by which the neurotrophins protect neurons following injury.

  2. 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

  3. 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.

  4. 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.

  5. The neuropsychiatry of depression after brain injury.

    PubMed

    Fleminger, Simon; Oliver, Donna L; Williams, W Huw; Evans, Jonathan

    2003-01-01

    Biological aspects of depression after brain injury, in particular traumatic brain injury (TBI) and stroke, are reviewed. Symptoms of depression after brain injury are found to be rather non-specific with no good evidence of a clear pattern distinguishing it from depression in those without brain injury. Nevertheless symptoms of disturbances of interest and concentration are particularly prevalent, and guilt is less evident. Variabilitiy of mood is characteristic. The prevalence of depression is similar after both stroke and TBI with the order of 20-40% affected at any point in time in the first year, and about 50% of people experience depression at some stage. There is no good evidence for areas of specific vulnerability in terms of lesion location, and early suggestions of a specific association with injury to the left hemisphere have not been confirmed. Insight appears to be related to depressed mood with studies of TBI indicating that greater insight over time post-injury may be associated with greater depression. We consider that this relationship may be due to depression appearing as people gain more awareness of their disability, but also suggest that changes in mood may result in altered awareness. The risk of suicide after TBI is reviewed. There appears to be about a three to fourfold increased risk of suicide after TBI, although much of this increased risk may be due to pre-injury factors in terms of the characteristics of people who suffer TBI. About 1% of people who have suffered TBI will commit suicide over a 15-year follow-up. Drug management of depression is reviewed. There is little specific evidence to guide the choice of antidepressant medication and most psychiatrists would start with a selective serotonin reuptake inhibitor (SSRI). It is important that the drug management of depression after brain injury is part of a full package of care that can address biological as well as psychosocial factors in management.

  6. Hyperbaric oxygen therapy improves cognitive functioning after brain injury.

    PubMed

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

    2013-12-15

    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.

  7. Assessing connectivity related injury burden in diffuse traumatic brain injury.

    PubMed

    Solmaz, Berkan; Tunç, Birkan; Parker, Drew; Whyte, John; Hart, Tessa; Rabinowitz, Amanda; Rohrbach, Morgan; Kim, Junghoon; Verma, Ragini

    2017-03-15

    Many of the clinical and behavioral manifestations of traumatic brain injury (TBI) are thought to arise from disruption to the structural network of the brain due to diffuse axonal injury (DAI). However, a principled way of summarizing diffuse connectivity alterations to quantify injury burden is lacking. In this study, we developed a connectome injury score, Disruption Index of the Structural Connectome (DISC), which summarizes the cumulative effects of TBI-induced connectivity abnormalities across the entire brain. Forty patients with moderate-to-severe TBI examined at 3 months postinjury and 35 uninjured healthy controls underwent magnetic resonance imaging with diffusion tensor imaging, and completed behavioral assessment including global clinical outcome measures and neuropsychological tests. TBI patients were selected to maximize the likelihood of DAI in the absence of large focal brain lesions. We found that hub-like regions, with high betweenness centrality, were most likely to be impaired as a result of diffuse TBI. Clustering of participants revealed a subgroup of TBI patients with similar connectivity abnormality profiles who exhibited relatively poor cognitive performance. Among TBI patients, DISC was significantly correlated with post-traumatic amnesia, verbal learning, executive function, and processing speed. Our experiments jointly demonstrated that assessing structural connectivity alterations may be useful in development of patient-oriented diagnostic and prognostic tools. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  8. The neuropathology of traumatic brain injury.

    PubMed

    Mckee, Ann C; Daneshvar, Daniel H

    2015-01-01

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

  9. Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury.

    PubMed

    Ji, Feng-Tao; Liang, Jian-Jun; Miao, Li-Ping; Wu, Qiang; Cao, Ming-Hui

    2015-08-01

    Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by ischemic stroke, protects the brain from ischemia/reperfusion injury and improves neuronal function. However, whether propofol is able to protect the blood brain barrier (BBB) and the underlying mechanisms have remained to be elucidated. In the present study, a rat model of cerebral ischemia/reperfusion was established, using a thread embolism to achieve middle cerebral artery occlusion. Rats were treated with propofol (propofol post-conditioning) or physiological saline (control) administered by intravenous injection 30 min following reperfusion. Twenty-four hours following reperfusion, neurobehavioral manifestations were assessed. The levels of cephaloedema, damage to the BBB and expression levels of matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun N-terminal kinase (pJNK) were determined in order to evaluate the effects of propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group, the levels of brain water content and Evans blue content, as well as the expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the propofol post-conditioning group. These results indicated that propofol post-conditioning improved the neurobehavioral manifestations and attenuated the BBB damage and cephaloedema induced following cerebral ischemia/reperfusion. This effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the concurrent decrease in JNK phosphorylation.

  10. Could cord blood cell therapy reduce preterm brain injury?

    PubMed

    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.

  11. 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

  12. Stem cell therapies for perinatal brain injuries.

    PubMed

    Vawda, Reaz; Woodbury, Jennifer; Covey, Matthew; Levison, Steven W; Mehmet, Huseyin

    2007-08-01

    This chapter reviews four groups of paediatric brain injury. The pathophysiology of these injuries is discussed to establish which cells are damaged and therefore which cells represent targets for cell replacement. Next, we review potential sources of cellular replacements, including embryonic stem cells, fetal and neonatal neural stem cells and a variety of mesenchymal stem cells. The advantages and disadvantages of each source are discussed. We review published studies to illustrate where stem cell therapies have been evaluated for therapeutic gain and discuss the hurdles that will need to be overcome to achieve therapeutic benefit. Overall, we conclude that children with paediatric brain injuries or inherited genetic disorders that affect the brain are worthy candidates for stem cell therapeutics.

  13. Public attitudes towards survivors of brain injury.

    PubMed

    Linden, M A; Rauch, R J; Crothers, I R

    2005-11-01

    To explore the effects of religious identity, gender and socioeconomic status (SES) on public attitudes towards survivors of brain injury. An independent groups design was used to compare the attitudes of Northern Irish participants. The participants were asked to complete a modified form of the Community Attitudes to Mental Illness scale. The new questionnaire replaced the original scales' emphasis on mental illness with that of brain injury. Complete data was available for 179 participants for the religious identity and gender analysis and 124 for gender and SES. Analyses of variance were conducted on these variables. Significant differences between male and female attitudes were found along with significant interactions between religious identity and gender and SES and gender. Religious, economic and gender-based divisions in society affect attitudes towards survivors of brain injury.

  14. Emergency Neurological Life Support: Traumatic Brain Injury.

    PubMed

    Garvin, Rachel; Venkatasubramanian, Chitra; Lumba-Brown, Angela; Miller, Chad M

    2015-12-01

    Traumatic Brain Injury (TBI) was chosen as an Emergency Neurological Life Support topic due to its frequency, the impact of early intervention on outcomes for patients with TBI, and the need for an organized approach to the care of such patients within the emergency setting. This protocol was designed to enumerate the practice steps that should be considered within the first critical hour of neurological injury.

  15. 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

  16. Osmolar therapy in pediatric traumatic brain injury.

    PubMed

    Bennett, Tellen D; Statler, Kimberly D; Korgenski, E Kent; Bratton, Susan L

    2012-01-01

    To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine whether the 2003 guidelines for severe pediatric traumatic brain injury impacted clinical practice regarding osmolar therapy. Retrospective cohort study. Pediatric Health Information System database, January, 2001 to December, 2008. Children (age <18 yrs) with traumatic brain injury and head/neck Abbreviated Injury Scale score ≥ 3 who received mechanical ventilation and intensive care. : None. The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline, and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have intracranial pressure monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008. Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without intracranial pressure monitoring suggest opportunities to improve the quality of pediatric traumatic brain injury care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.

  17. MDCT imaging of traumatic brain injury

    PubMed Central

    Pezzullo, Martina; Delpierre, Isabelle; Sadeghi, Niloufar

    2016-01-01

    The aim of emergency imaging is to detect treatable lesions before secondary neurological damage occurs. CT plays a primary role in the acute setting of head trauma, allowing accurate detection of lesions requiring immediate neurosurgical treatment. CT is also accurate in detecting secondary injuries and is therefore essential in follow-up. This review discusses the main characteristics of primary and secondary brain injuries. PMID:26607650

  18. The influence of damage distribution on serious brain injury in occupants in frontal motor vehicle crashes.

    PubMed

    Coimbra, Raul; Conroy, Carol; Hoyt, David B; Pacyna, Sharon; May, MarSue; Erwin, Steve; Tominaga, Gail; Kennedy, Frank; Sise, Michael; Velky, Tom

    2008-07-01

    In spite of improvements in motor vehicle safety systems and crashworthiness, motor vehicle crashes remain one of the leading causes of brain injury. The purpose of this study was to determine if the damage distribution across the frontal plane affected brain injury severity of occupants in frontal impacts. Occupants in "head on" frontal impacts with a Principal Direction of Force (PDOF) equal to 11, 12, or 1o'clock who sustained serious brain injury were identified using the Crash Injury Research Engineering Network (CIREN) database. Impacts were further classified based on the damage distribution across the frontal plane as distributed, offset, and extreme offset (corner). Overall, there was no significant difference for brain injury severity (based on Glasgow Coma Scale<9, or brain injury AIS>2) comparing occupants in the different impact categories. For occupants in distributed frontal impacts, safety belt use was protective (odds ratio (OR)=0.61) and intrusion at the occupant's seat position was four times more likely to result in severe (Glasgow Coma Scale (GCS)<9) brain injury (OR=4.35). For occupants in offset frontal impacts, again safety belt use was protective against severe brain injury (OR=0.25). Possibly due to the small number of brain-injured occupants in corner impacts, safety belts did not significantly protect against increased brain injury severity during corner impacts. This study supports the importance of safety belt use to decrease brain injury severity for occupants in distributed and offset frontal crashes. It also illustrates how studying "real world" crashes may provide useful information on occupant injuries under impact circumstances not currently covered by crash testing.

  19. 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

  20. Protective effects of taurine against closed head injury in rats.

    PubMed

    Sun, Ming; Zhao, Yumei; Gu, Yi; Zhang, Yazhuo

    2015-01-01

    Taurine, an abundant amino acid in the nervous system, is reported to reduce ischemic brain injury in a dose-dependent manner. This study was designed to investigate whether taurine protected the brain against closed head injury (CHI) in rats. Taurine was administered intravenously 30 min after CHI. It was found that taurine lessened body-weight loss and improved neurological functions at 7 days after CHI. Moreover, it lowered brain edema and blood-brain barrier permeability, enhanced activity of superoxide dismutase and the level of glutathione, and reduced levels of malondialdehyde and lactic acid in traumatic tissue 24 h after CHI. In addition, it attenuated neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. All of these effects were dose dependent. These data demonstrated the dose-dependent protection of taurine against experimental CHI and suggest that taurine treatment might be beneficial in reducing trauma-induced oxidative damage to the brain, thus showing the potential for clinical implications.

  1. Olive leaf extract inhibits lead poisoning-induced brain injury

    PubMed Central

    Wang, Yu; Wang, Shengqing; Cui, Wenhui; He, Jiujun; Wang, Zhenfu; Yang, Xiaolu

    2013-01-01

    Olive leaves have an antioxidant capacity, and olive leaf extract can protect the blood, spleen and hippocampus in lead-poisoned mice. However, little is known about the effects of olive leaf extract on lead-induced brain injury. This study was designed to determine whether olive leaf extract can inhibit lead-induced brain injury, and whether this effect is associated with antioxidant capacity. First, we established a mouse model of lead poisoning by continuous intragastric administration of lead acetate for 30 days. Two hours after successful model establishment, lead-poisoned mice were given olive leaf extract at doses of 250, 500 or 1 000 mg/kg daily by intragastric administration for 50 days. Under the transmission electron microscope, olive leaf extract attenuated neuronal and capillary injury and reduced damage to organelles and the matrix around the capillaries in the frontal lobe of the cerebral cortex in the lead-poisoned mice. Olive leaf extract at a dose of 1 000 mg/kg had the greatest protective effect. Spectrophotometry showed that olive leaf extract significantly increased the activities of superoxide dismutase, catalase, alkaline phosphatase and acid phosphatase, while it reduced malondialdehyde content, in a dose-dependent manner. Furthermore, immunohistochemical staining revealed that olive leaf extract dose-dependently decreased Bax protein expression in the cerebral cortex of lead-poisoned mice. Our findings indicate that olive leaf extract can inhibit lead-induced brain injury by increasing antioxidant capacity and reducing apoptosis. PMID:25206510

  2. [Preface and comments: Protection of the brain and the spinal cord].

    PubMed

    Nishikawa, Toshiaki

    2007-03-01

    Basic and clinical investigations have been performed, focusing on the mechanism of ischemic brain and spinal cord injuries, and preventive measures against ischemic insults such as drug therapy, hypothermia, maintenace of blood flow to brain and spinal cord, preconditioning, and no use of high dose fentanyl. In this special issue, five experts have provided new relevant information concerning brain and spinal cord protection. Further research in brain and spinal cord protection will contribute to better understanding of ischemic central nervous system injuries and to the establishment of novel therapies for protection of central nervous system.

  3. The prehospital management of traumatic brain injury.

    PubMed

    Goldberg, Scott A; Rojanasarntikul, Dhanadol; Jagoda, Andrew

    2015-01-01

    Traumatic brain injury (TBI) is an important cause of death and disability, particularly in younger populations. The prehospital evaluation and management of TBI is a vital link between insult and definitive care and can have dramatic implications for subsequent morbidity. Following a TBI the brain is at high risk for further ischemic injury, with prehospital interventions targeted at reducing this secondary injury while optimizing cerebral physiology. In the following chapter we discuss the prehospital assessment and management of the brain-injured patient. The initial evaluation and physical examination are discussed with a focus on interpretation of specific physical examination findings and interpretation of vital signs. We evaluate patient management strategies including indications for advanced airway management, oxygenation, ventilation, and fluid resuscitation, as well as prehospital strategies for the management of suspected or impending cerebral herniation including hyperventilation and brain-directed hyperosmolar therapy. Transport decisions including the role of triage models and trauma centers are discussed. Finally, future directions in the prehospital management of traumatic brain injury are explored. © 2015 Elsevier B.V. All rights reserved.

  4. Neurorestorative Treatments for Traumatic Brain Injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2011-01-01

    Traumatic brain injury (TBI) remains a major cause of death and permanent disability worldwide, especially in children and young adults. A total of 1.5 million people experience head trauma each year in the United States, with an annual economic cost exceeding $56 billion. Unfortunately, almost all Phase III TBI clinical trials have yet to yield a safe and effective neuroprotective treatment, raising questions regarding the use of neuroprotective strategies as the primary therapy for acute brain injuries. Recent preclinical data suggest that neurorestorative strategies that promote angiogenesis (formation of new blood vessels from pre-existing endothelial cells), axonal remodeling (axonal sprouting and pruning), neurogenesis (generation of new neurons) and synaptogenesis (formation of new synapses) provide promising opportunities for the treatment of TBI. This review discusses select cell-based and pharmacological therapies that activate and amplify these endogenous restorative brain plasticity processes to promote both repair and regeneration of injured brain tissue and functional recovery after TBI. PMID:21122475

  5. 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

  6. 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.

  7. Treating neonatal brain injury - promise and inherent research challenges.

    PubMed

    Sävman, Karin; Brown, Kelly L

    2010-01-01

    In this review we discuss current challenges faced by researchers and clinician-scientists in the pursuit of therapeutics to treat hypoxic-ischemic (HI) brain injury in term infants. At present, there is an absence of neuroprotective drugs that are safe and effective for the protection of neonates from neurological sequels after HI. We discuss secondary neurotoxic processes elicited by HI that may be targets for therapeutic interventions with a specific focus on inflammatory mechanisms. Advances in research to unravel these cellular processes and molecular mechanisms that drive injurious processes after HI have traditionally been plagued by conflicting results when assessing different times for intervention, different models for brain injury, and the adult versus neonate brain. We attribute impeded drug development in part to such disparate results and general difficulties to conduct a stringent, comprehensive analysis of candidate drugs prior to clinical trials. It will be imperative to implement changes in the clinic and laboratory in order for future drug initiatives to achieve success. We also provide a brief discussion on the pursuit of anti-inflammatory molecules and monitoring methods that are the focus of current patents and that, in our opinion, may lead to important new developments in the treatment of HI brain injury in newborn infants.

  8. 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

  9. 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.

  10. Advanced monitoring in traumatic brain injury: microdialysis.

    PubMed

    Carpenter, Keri L H; Young, Adam M H; Hutchinson, Peter J

    2017-04-01

    Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry. A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdialysis into the complex, interlinked traumatic brain injury disorders of electrophysiological changes, white matter injury, inflammation and metabolism. Microdialysis has matured into being a standard clinical monitoring modality that takes its place alongside intracranial pressure and brain tissue oxygen tension measurement in specialist neurocritical care centres, as well as being a research tool able to shed light on brain metabolism, inflammation, therapeutic approaches, blood-brain barrier transit and drug effects on downstream targets. Recent consensus on microdialysis monitoring is paving the way for improved neurocritical care protocols. Furthermore, there is scope for future improvements both in terms of the catheters and microdialysate analyser technology, which may further enhance its applicability.

  11. 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

  12. Better Sleep May Signal Recovery from Brain Injury

    MedlinePlus

    ... 162672.html Better Sleep May Signal Recovery From Brain Injury New research suggests sleep-wake cycles are ... Dec. 21, 2016 (HealthDay News) -- Recovery from traumatic brain injury appears to go hand-in-hand with ...

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

    MedlinePlus

    ... Cancel Submit Search The CDC Traumatic Brain Injury & Concussion Note: Javascript is disabled or is not supported ... this page: About CDC.gov . Traumatic Brain Injury & Concussion Basic Information Get the Facts Signs and Symptoms ...

  14. Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury.

    PubMed

    Liu, Ying-Liang; Xu, Zhi-Ming; Yang, Guo-Yuan; Yang, Dian-Xu; Ding, Jun; Chen, Hao; Yuan, Fang; Tian, Heng-Li

    2017-08-03

    Sesamin, a major lignan of sesame oil, was reported to have neuroprotective effects in several brain injury models. However, its protective action in maintaining blood-brain barrier (BBB) integrity has not been studied. In this study we investigated the effects of sesamin on the BBB in a mouse model of traumatic brain injury (TBI) and explored the underlying mechanisms. Adult male C57BL/6 mice were subjected to a controlled cortical impact (CCI) injury and then received sesamin (30 mg·kg(-1)·d(-1), ip). The mice were euthanized on the 1(st) and 3(rd) days after CCI injury and samples were collected for analysis. Sesamin treatment significantly attenuated CCI-induced brain edema on the 1(st) and 3(rd) days after the injury, evidenced by the decreases in water content, tissue hemoglobin levels, Evans blue extravasation and AQP4 expression levels in the ipsilateral cortical tissue compared with the vehicle-treated group. Furthermore, sesamin treatment significantly alleviated CCI-induced loss of the tight junction proteins ZO-1 and occludin in the brain tissues. The neuroprotective mechanisms of sesamin were further explored in cultured mouse brain microvascular bEnd.3 cells subjected to biaxial stretch injury (SI). Pretreatment with sesamin (50 μmol/L) significantly alleviated SI-induced loss of ZO-1 in bEnd.3 cells. Furthermore, we revealed that pretreatment with sesamin significantly attenuated SI-induced oxidative stress and early-stage apoptosis in bEnd.3 cells by decreasing the activation of ERK, p-38 and caspase-3. In conclusion, sesamin alleviates BBB disruption at least partly through its anti-oxidative and anti-apoptotic effects on endothelial cells in CCI injury. These findings suggest that sesamin may be a promising potential therapeutic intervention for preventing disruption of the BBB after TBI.

  15. Protection of retinal function by sulforaphane following retinal ischemic injury.

    PubMed

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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…

  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. Future directions in brain injury research.

    PubMed

    Gennarelli, Thomas A

    2014-01-01

    This paper reviews the potential future directions that are important for brain injury research, especially with regard to concussion. The avenues of proposed research are categorized according to current concepts of concussion, types of concussion, and a global schema for globally reducing the burden of concussion.

  19. 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

  20. 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…

  1. 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…

  2. 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.…

  3. 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…

  4. Clinical review: ketones and brain injury.

    PubMed

    White, Hayden; Venkatesh, Balasubramanian

    2011-04-06

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

  5. Clinical review: Ketones and brain injury

    PubMed Central

    2011-01-01

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

  6. Traumatic Brain Injury: A Guidebook for Educators.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Office for Special Education Services.

    This guidebook is designed to help New York school staff better understand the specialized needs of students with traumatic brain injury (TBI) and appropriately apply educational interventions to improve special and general education services for these students. It provides information on the following areas: (1) the causes, incidence, and…

  7. Traumatic Brain Injury. Quick Turn Around (QTA).

    ERIC Educational Resources Information Center

    Markowitz, Joy; Linehan, Patrice

    This brief paper summarizes information concerning use of the traumatic brain injury (TBI) disability classification by states and the nature of state-level activities related to the education of children and youth with TBI. It notes addition of the TBI disability category to the Individuals with Disabilities Education Act in 1990 and provides the…

  8. 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…

  9. 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…

  10. 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…

  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. 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…

  14. 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…

  15. 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.…

  16. Seizures Following Traumatic Brain Injury in Childhood.

    ERIC Educational Resources Information Center

    Williams, Dennis

    This guide provides information on seizures in students with traumatic brain injury (TBI) and offers guidelines for classroom management. First, a classification system for seizures is presented with specific types of seizures explained. Post-traumatic seizures are specifically addressed as is the importance of seizure prevention when possible.…

  17. 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…

  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. 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…

  20. Traumatic brain injury and posttraumatic stress disorder.

    PubMed

    Bahraini, Nazanin H; Breshears, Ryan E; Hernández, Theresa D; Schneider, Alexandra L; Forster, Jeri E; Brenner, Lisa A

    2014-03-01

    Given the upsurge of research in posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), much of which has focused on military samples who served in Iraq and Afghanistan, the purpose of this article is to review the literature published after September 11th, 2001 that addresses the epidemiology, pathophysiology, evaluation, and treatment of PTSD in the context of TBI.

  1. Experimental models of repetitive brain injuries.

    PubMed

    Weber, John T

    2007-01-01

    Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer). A continually emerging hypothesis is that repeated mild injuries may cause cumulative damage to the brain, resulting in long-term cognitive dysfunction. The growing attention to this hypothesis is reflected in several recent experimental studies of repeated mild TBI in vivo. These reports generally demonstrate cellular and cognitive dysfunction after repetitive injury using rodent TBI models. In some cases, data suggests that the effects of a second mild TBI may be synergistic, rather than additive. In addition, some studies have found increases in cellular markers associated with Alzheimer's disease after repeated mild injuries, which demonstrates a direct experimental link between repetitive TBI and neurodegenerative disease. To complement the findings from humans and in vivo experimentation, my laboratory group has investigated the effects of repeated trauma in cultured brain cells using a model of stretch-induced mechanical injury in vitro. In these studies, hippocampal cells exhibited cumulative damage when mild stretch injuries were repeated at either 1-h or 24-h intervals. Interestingly, the extent of damage to the cells was dependent on the time between repeated injuries. Also, a very low level of stretch, which produced no cell damage on its own, induced cell damage when it was repeated several times at a short interval (every 2 min). Although direct comparisons to the clinical situation are difficult, these types of repetitive, low-level, mechanical stresses may be similar to the insults received by certain athletes, such as boxers, or hockey and soccer players. This type of in vitro model could provide a reliable system in which to study the mechanisms underlying cellular dysfunction following repeated injuries. As

  2. Child and adolescent traumatic brain injury: correlates of injury severity.

    PubMed

    Max, J E; Lindgren, S D; Knutson, C; Pearson, C S; Ihrig, D; Welborn, A

    1998-01-01

    A record review focused on children and adolescents, with a history of traumatic brain injury, who were consecutively admitted to a brain injury clinic in which all new patients are psychiatrically evaluated. Significant correlates of severity of injury in the cognitive, education and communication domains of functioning included Performance IQ but not Verbal IQ nor standardized ratings of language or learning disability. Current organic personality syndrome (OPS) but not attention deficit hyperactivity disorder or oppositional defiant disorder/conduct disorder diagnostic status was significantly related to severity. In conclusion, the findings in this referred sample are similar to prospective studies indicating that Performance IQ appears sensitive in reflecting brain damage. The finding linking OPS to severity of injury is not surprising. This is because OPS is a diagnosis which is dependent on the clinician's judgment of the likelihood that the organic factor is etiologically related to a defined behavioural syndrome. The diagnosis therefore requires a clinical judgment that the threshold of severity of a presumed organic etiological factor has been reached.

  3. 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.

  4. 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

  5. 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'.

  6. 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.,…

  7. 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.,…

  8. Neuroprotection against Surgically-Induced Brain Injury

    PubMed Central

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

    2007-01-01

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

  9. Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

    PubMed

    Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

    2012-05-10

    Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Adenosine and protection from acute kidney injury

    PubMed Central

    Yap, Steven C.; Lee, H. Thomas

    2012-01-01

    Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury. PMID:22080856

  11. Erythropoietin: Powerful Protection of Ischemic and Post-Ischemic Brain

    PubMed Central

    Nguyen, Anh Q.; Cherry, Brandon H.; Scott, Gary F.; Ryou, Myoung-Gwi; Mallet, Robert T.

    2015-01-01

    Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 minutes of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the

  12. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

    PubMed Central

    Feng, Yangzheng; Paul, Ian A.; LeBlanc, Michael H.

    2011-01-01

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity. PMID:16533659

  13. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat.

    PubMed

    Feng, Yangzheng; Paul, Ian A; LeBlanc, Michael H

    2006-03-31

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

  14. Erythropoietin as a novel brain and kidney protective agent.

    PubMed

    Moore, E M; Bellomo, R; Nichol, A D

    2011-05-01

    Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.

  15. Traumatic brain injury imaging research roadmap.

    PubMed

    Wintermark, M; Coombs, L; Druzgal, T J; Field, A S; Filippi, C G; Hicks, R; Horton, R; Lui, Y W; Law, M; Mukherjee, P; Norbash, A; Riedy, G; Sanelli, P C; Stone, J R; Sze, G; Tilkin, M; Whitlow, C T; Wilde, E A; York, G; Provenzale, J M

    2015-03-01

    The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic

  16. Traumatic Brain Injury - Multiple Languages

    MedlinePlus

    ... this page, please enable JavaScript. Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (Af-Soomaali ) ... हिन्दी (Hindi) Bilingual PDF Health Information Translations Japanese (日本語) Expand Section Brain Scan - 日本語 (Japanese) Bilingual ...

  17. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  18. Astrocyte roles in traumatic brain injury

    PubMed Central

    Burda, Joshua E.; Bernstein, Alexander M.; Sofroniew, Michael V.

    2015-01-01

    Astrocytes sense changes in neural activity and extracellular space composition. In response, they exert homeostatic mechanisms critical for maintaining neural circuit function, such as buffering neurotransmitters, modulating extracellular osmolarity and calibrating neurovascular coupling. In addition to upholding normal brain activities, astrocytes respond to diverse forms of brain injury with heterogeneous and progressive changes of gene expression, morphology, proliferative capacity and function that are collectively referred to as reactive astrogliosis. Traumatic brain injury (TBI) sets in motion complex events in which noxious mechanical forces cause tissue damage and disrupt central nervous system (CNS) homeostasis, which in turn trigger diverse multi-cellular responses that evolve over time and can lead either to neural repair or secondary cellular injury. In response to TBI, astrocytes in different cellular microenvironments tune their reactivity to varying degrees of axonal injury, vascular disruption, ischemia and inflammation. Here we review different forms of TBI-induced astrocyte reactivity and the functional consequences of these responses for TBI pathobiology. Evidence regarding astrocyte contribution to post-traumatic tissue repair and synaptic remodeling is examined, and the potential for targeting specific aspects of astrogliosis to ameliorate TBI sequelae is considered. PMID:25828533

  19. Traumatic Brain Injury-Associated Coagulopathy

    PubMed Central

    Zhang, Jianning; Jiang, Rongcai; Liu, Li; Watkins, Timothy; Zhang, Fangyi

    2012-01-01

    Abstract Traumatic injury is a common cause of coagulopathy, primarily due to blood loss and hemodilution secondary to fluid resuscitation. Traumatic injury-associated coagulopathy often follows a course of transition from hyper- to hypocoagulable state exemplified in disseminated intravascular coagulation. The incidence of coagulopathy is significantly higher in patients with traumatic brain injury (TBI), especially those with penetrating trauma compared to injury to the trunk and limbs. This occurs despite the fact that patients with isolated TBI bleed less and receive restricted volume load of fluids. TBI-associated coagulopathy is extensively documented to associate with poor clinical outcomes, but its pathophysiology remains poorly understood. Studies in the past have shown that brain tissue is highly enriched in key procoagulant molecules. This review focuses on the biochemical and cellular characteristics of these molecules and pathways that could make brain uniquely procoagulant and prone to coagulopathy. Understanding this unique procoagulant environment will help to identify new therapeutic targets that could reverse a state of coagulopathy with minimal impacts on hemostasis, a critical requirement for neurosurgical treatments of TBI. PMID:23020190

  20. A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo.

    PubMed

    Nuñez-Figueredo, Yanier; Ramírez-Sánchez, Jeney; Hansel, Gisele; Simões Pires, Elisa Nicoloso; Merino, Nelson; Valdes, Odalys; Delgado-Hernández, René; Parra, Alicia Lagarto; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Salbego, Christianne; Costa, Silvia L; Souza, Diogo O; Pardo-Andreu, Gilberto L

    2014-10-01

    We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca2+ accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 μM) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca2+ accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat

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

    PubMed Central

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

    2014-01-01

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

  2. Motorcycle protective clothing: protection from injury or just the weather?

    PubMed

    de Rome, Liz; Ivers, Rebecca; Fitzharris, Michael; Du, Wei; Haworth, Narelle; Heritier, Stephane; Richardson, Drew

    2011-11-01

    Apart from helmets, little is known about the effectiveness of motorcycle protective clothing in reducing injuries in crashes. The study aimed to quantify the association between usage of motorcycle clothing and injury in crashes. Cross-sectional analytic study. Crashed motorcyclists (n=212, 71% of identified eligible cases) were recruited through hospitals and motorcycle repair services. Data was obtained through structured face-to-face interviews. The main outcome was hospitalization and motorcycle crash-related injury. Poisson regression was used to estimate relative risk (RR) and 95% confidence intervals for injury adjusting for potential confounders. Motorcyclists were significantly less likely to be admitted to hospital if they crashed wearing motorcycle jackets (RR=0.79, 95% CI: 0.69-0.91), pants (RR=0.49, 95% CI: 0.25-0.94), or gloves (RR=0.41, 95% CI: 0.26-0.66). When garments included fitted body armour there was a significantly reduced risk of injury to the upper body (RR=0.77, 95% CI: 0.66-0.89), hands and wrists (RR=0.55, 95% CI: 0.38-0.81), legs (RR=0.60, 95% CI: 0.40-0.90), feet and ankles (RR=0.54, 95% CI: 0.35-0.83). Non-motorcycle boots were also associated with a reduced risk of injury compared to shoes or joggers (RR=0.46, 95% CI: 0.28-0.75). No association between use of body armour and risk of fracture injuries was detected. A substantial proportion of motorcycle designed gloves (25.7%), jackets (29.7%) and pants (28.1%) were assessed to have failed due to material damage in the crash. Motorcycle protective clothing is associated with reduced risk and severity of crash related injury and hospitalization, particularly when fitted with body armour. The proportion of clothing items that failed under crash conditions indicates a need for improved quality control. While mandating usage of protective clothing is not recommended, consideration could be given to providing incentives for usage of protective clothing, such as tax exemptions for safety

  3. Traumatic Brain Injury and Neuropsychiatric Complications.

    PubMed

    Ahmed, Saeed; Venigalla, Hema; Mekala, Hema Madhuri; Dar, Sara; Hassan, Mudasar; Ayub, Shahana

    2017-01-01

    Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a penetrating injury results in damage to the brain. It is the most frequent cause of hospitalization in young people with a higher prevalence in men. TBI is the leading cause of disability and mortality between the ages 1 and 45. TBI can be caused either by the direct result of trauma or due to a complication of the primary injury. The most common etiological factors for TBI are falls, road traffic accidents, violent physical assaults, and injuries associated with athletic activities. Following TBI, significant neurologic complications may occur which include seizures, dementia, Alzheimer's disease, and cranial nerve injuries. In addition, people may suffer from various psychiatric complications such as depression, posttraumatic stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, and other cognitive and behavioral sequel that might significantly increase the comorbidity of the victims. Considering all of the above complications, TBI is one of the significant public health burdens. Literature has shown that only about 25% of people achieve long-term functional independence following TBI. In this paper, we focused not only on the epidemiology but also the etiology, complications following TBI and understanding their underlying pathogenesis. Further, we focused on analyzing the options to improve the treatment and rehabilitation following TBI in future.

  4. The gut reaction to traumatic brain injury

    PubMed Central

    Katzenberger, Rebeccah J; Ganetzky, Barry; Wassarman, David A

    2015-01-01

    Traumatic brain injury (TBI) is a complex disorder that affects millions of people worldwide. The complexity of TBI partly stems from the fact that injuries to the brain instigate non-neurological injuries to other organs such as the intestine. Additionally, genetic variation is thought to play a large role in determining the nature and severity of non-neurological injuries. We recently reported that TBI in flies, as in humans, increases permeability of the intestinal epithelial barrier resulting in hyperglycemia and a higher risk of death. Furthermore, we demonstrated that genetic variation in flies is also pertinent to the complexity of non-neurological injuries following TBI. The goals of this review are to place our findings in the context of what is known about TBI-induced intestinal permeability from studies of TBI patients and rodent TBI models and to draw attention to how studies of the fly TBI model can provide unique insights that may facilitate diagnosis and treatment of TBI. PMID:26291482

  5. Substance P mediates reduced pneumonia rates after traumatic brain injury.

    PubMed

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

    2014-09-01

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

  6. Iodide Protects Heart Tissue from Reperfusion Injury

    PubMed Central

    Iwata, Akiko; Morrison, Michael L.; Roth, Mark B.

    2014-01-01

    Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury. PMID:25379708

  7. Military traumatic brain injury: a review.

    PubMed

    Chapman, Julie C; Diaz-Arrastia, Ramon

    2014-06-01

    Military mild traumatic brain injury (mTBI) differs from civilian injury in important ways. Although mTBI sustained in both military and civilian settings are likely to be underreported, the combat theater presents additional obstacles to reporting and accessing care. The impact of blast forces on the nervous system may differ from nonblast mechanisms, mTBI although studies comparing the neurologic and cognitive sequelae in mTBI survivors have not provided such evidence. However, emotional distress appears to figure prominently in symptoms following military mTBI. This review evaluates the extant literature with an eye towards future research directions.

  8. Optic radiation injury in a patient with traumatic brain injury.

    PubMed

    Yeo, Sang Seok; Kim, Seong Ho; Kim, Oh Lyong; Kim, Min-Su; Jang, Sung Ho

    2012-01-01

    This study reports on a patient who showed an optic radiation (OR) injury on diffusion tensor imaging (DTI) following head trauma. The patient, who had suffered a traffic accident, underwent conservative management for diffuse axonal injury and contusions in the left midbrain, temporal lobe and anterior to mid-portion of left OR. He complained of right homonymous hemianopsia from the onset of TBI and right bilateral homonymous hemianopsia was detected at the 6-month Humphrey visual field test. A 20 year-old man with traumatic brain injury (TBI) and eight age-matched normal subjects were recruited for this study. The left OR of the patient showed a discontinuation around the mid-portion. The FA (fractional anisotropy) values of the posterior portions of left OR decreased over two standard deviations of normal controls, but the ADC (apparent diffusion coefficient) values of these sites increased over two standard deviations of normal controls. Consequently, it was assumed that the main injury site of the left OR was located around the posterior portion of the left OR. This results suggest that DTI may be a useful technique for detection of an OR injury in patients with TBI.

  9. Progesterone for neuroprotection in pediatric traumatic brain injury.

    PubMed

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

    2015-03-01

    To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury. National Library of Medicine PubMed literature review. The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is 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 traumatic brain injury is reviewed. Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury 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 traumatic brain injury have been published, and two multicenter phase III trials are underway. 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 traumatic brain injury. 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

  10. 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

  11. Chronic Endocrinopathies in Traumatic Brain Injury Disease.

    PubMed

    Masel, Brent E; Urban, Randy

    2015-12-01

    The aim of this review was to explain the role played by pituitary hormonal deficiencies in the traumatic brain injury (TBI) disease process. Chronic dysfunction of the pituitary axis is observed in approximately 35% of individuals who sustain a moderate-to-severe TBI. The most common deficiency is that of growth hormone, followed by gonadotropin, cortisol, and thyroid. The medical, psychological, and psychiatric consequences of untreated hypopituitarism are extensive and can be devastating. Many of the consequences of a chronic symptomatic TBI have, in the past, been solely attributed to the brain injury per se. Analysis of the signs and symptoms of pituitary axis dysfunction suggests that many of these consequences can be attributed to post-traumatic hypopituitarism (PTH). PTH may well play a significant role in the progressive signs and symptoms that follow a chronic TBI.

  12. Traumatic Brain Injury in Sports: A Review

    PubMed Central

    Sahler, Christopher S.; Greenwald, Brian D.

    2012-01-01

    Traumatic brain injury (TBI) is a clinical diagnosis of neurological dysfunction following head trauma, typically presenting with acute symptoms of some degree of cognitive impairment. There are an estimated 1.7 to 3.8 million TBIs each year in the United States, approximately 10 percent of which are due to sports and recreational activities. Most brain injuries are self-limited with symptom resolution within one week, however, a growing amount of data is now establishing significant sequelae from even minor impacts such as headaches, prolonged cognitive impairments, or even death. Appropriate diagnosis and treatment according to standardized guidelines are crucial when treating athletes who may be subjected to future head trauma, possibly increasing their likelihood of long-term impairments. PMID:22848836

  13. [Diagnosis and treatment of traumatic brain injury].

    PubMed

    Rickels, E

    2009-02-01

    Traumatic brain injury (TBI) is still the major cause of death under 45 years of age and an important one for children under 15. Its incidence is 332/100,000 inhabitants. It results from an impact with the skull with/without lesion of the brain but at least a short-term neurological disorder. All other injuries to the skull should be called concussion. The duration of unconsciousness defines the severity of TBI. Patients with TBI should be admitted to a surgical ward. Those retaining consciousness and with GCS scores of 15 might be allowed to go home if under surveillance. With GCS of <15 or with risk factors, TBI requires a CT scan and in-hospital surveillance. Acutely life-threatening, i.e. space-occupying, bleeding must be operated on immediately. Epidural or subdural bleeding, especially in comatose patients, is still a vital risk and thus requires immediate surgery.

  14. The neuroethics and neurolaw of brain injury.

    PubMed

    Aggarwal, Neil Krishan; Ford, Elizabeth

    2013-01-01

    Neuroethics and neurolaw are fields of study that involve the interface of neuroscience with clinical and legal decision-making. The past two decades have seen increasing attention being paid to both fields, in large part because of the advances in neuroimaging techniques and improved ability to visualize and measure brain structure and function. Traumatic brain injury (TBI), along with its acute and chronic sequelae, has emerged as a focus of neuroethical issues, such as informed consent for treatment and research, diagnostic and prognostic uncertainties, and the subjectivity of interpretation of data. The law has also more frequently considered TBI in criminal settings for exculpation, mitigation and sentencing purposes and in tort and administrative law for personal injury, disability and worker's compensation cases. This article provides an overview of these topics with an emphasis on the current challenges that the neuroscience of TBI faces in the medicolegal arena.

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

    PubMed

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

    2012-04-01

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

  16. Compound mechanism hypothesis on +Gz induced brain injury and dysfunction of learning and memory

    NASA Astrophysics Data System (ADS)

    Sun, Xi-Qing; Li, Jin-Sheng; Cao, Xin-Sheng; Wu, Xing-Yu

    2005-08-01

    We systematically studied the effect of high- sustained +Gz on the brain and its mechanism in past ten years by animal centrifuge experiments. On the basis of the facts we observed and the more recent advances in acceleration physiology, we put forward a compound mechanism hypothesis to offer a possible explanation for +Gz-induced brain injury and dysfunction of learning and memory. It states that, ischemia during high G exposure might be the main factor accounting for +Gz-induced brain injury and dysfunction of learning and memory, including transient depression of brain energy metabolism, disturbance of ion homeostasis, increased blood-brain barrier permeability, increased brain nitric oxide synthase expression, and the protective effect of heat shock protein 70. In addition, the large rapid change of intracranial pressure and increased stress during +Gz exposure, and the hemorrheologic change after +Gz exposure might be one of the important factors accounting for +Gz-induced brain injury and dysfunction of learning and memory.

  17. Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats.

    PubMed

    Tajiri, Naoki; Acosta, Sandra A; Shahaduzzaman, Md; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana; Kim, Dae Won; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, Julie; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa; Cooper, Denise; Kaneko, Yuji; Borlongan, Cesar V; Bickford, Paula C

    2014-01-01

    Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1' dioactadecyl-3-3-3',3'-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen.

  18. Intravenous Transplants of Human Adipose-Derived Stem Cell Protect the Brain from Traumatic Brain Injury-Induced Neurodegeneration and Motor and Cognitive Impairments: Cell Graft Biodistribution and Soluble Factors in Young and Aged Rats

    PubMed Central

    Tajiri, Naoki; Acosta, Sandra A.; Shahaduzzaman, Md; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana; Kim, Dae Won; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, Julie; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa

    2014-01-01

    Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 106 hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1′ dioactadecyl-3-3-3′,3′-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen. PMID:24381292

  19. Sleep deprivation has a neuroprotective role in a traumatic brain injury of the rat.

    PubMed

    Martinez-Vargas, Marina; Estrada Rojo, Francisco; Tabla-Ramon, Erika; Navarro-Argüelles, Hilda; Ortiz-Lailzon, Nathan; Hernández-Chávez, Alejandro; Solis, Barbara; Martínez Tapia, Ricardo; Perez Arredondo, Adan; Morales-Gomez, Julio; Gonzalez-Rivera, Ruben; Nava-Talavera, Karen; Navarro, Luz

    2012-11-07

    During the process of a brain injury, responses to produce damage and cell death are activated, but self-protective responses that attempt to maintain the integrity and functionality of the brain are also activated. We have previously reported that the recovery from a traumatic brain injury (TBI) is better in rats if it occurs during the dark phase of the diurnal cycle when rats are in the waking period. This suggests that wakefulness causes a neuroprotective role in this type of injury. Here we report that 24h of total sleep deprivation after a TBI reduces the morphological damage and enhances the recovery of the rats, as seen on a neurobiological scale.

  20. I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

    PubMed

    Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

    2005-01-01

    I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

  1. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury.

    PubMed

    Packard, Amy E B; Hedges, Jason C; Bahjat, Frances R; Stevens, Susan L; Conlin, Michael J; Salazar, Andres M; Stenzel-Poore, Mary P

    2012-02-01

    Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia-reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury.

  2. 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

  3. Cystatin C Has a Dual Role in Post-Traumatic Brain Injury Recovery

    PubMed Central

    Martinez-Vargas, Marina; Soto-Nuñez, Maribel; Tabla-Ramon, Erika; Solis, Barbara; Gonzalez-Rivera, Ruben; Perez-Arredondo, Adan; Estrada-Rojo, Francisco; Castell, Andres; Molina-Guarneros, Juan; Navarro, Luz

    2014-01-01

    Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles) increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles) decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage. PMID:24714089

  4. Blast-induced Mild Traumatic Brain Injury

    DTIC Science & Technology

    2010-01-01

    hemorrhagic lesions including intraparenchymal, subdural, and subarachnoid bleeding. Blast injury also induces a variety of histological effects...and microscopic intracerebral, subarachnoid and subdural hemorrhage , severity related to proximity of explosion to head Decreased rotarod and grip...tensor imaging study. J Neurosurg 2005;103:298-303. 66. Wilde EA, McCauley SR, Hunter JV, et al. Diffusion tensor imaging of acute mild traumatic brain

  5. Monitoring Brain Injury With TSALLIS Entropy

    DTIC Science & Technology

    2001-10-25

    significant but still remains to be studied. Literature has pointed to the role of q in the entropy computation for EEG studies [10]. In our study it is... EEG in the form of reduction during the bad physiological function outcome. The reduction level and recovery rate of TE are also consistent with...USA Abstract- Nonextensive entropy measure, Tsallis Entropy (TE), was undertaken to monitor the brain injury after cardiac arrest. EEG of human and

  6. Inflammatory neuroprotection following traumatic brain injury

    PubMed Central

    Russo, Matthew V.; McGavern, Dorian B.

    2017-01-01

    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

  7. The effects of nicotinamide on apoptosis and blood-brain barrier breakdown following traumatic brain injury.

    PubMed

    Hoane, Michael R; Kaplan, Shelby A; Ellis, Amy L

    2006-12-13

    Nicotinamide has been shown to protect against many of the pathophysiological factors associated with both ischemic and traumatic brain injuries. The present study evaluated the neuroprotective effect of nicotinamide on the breakdown of the blood-brain barrier (BBB) and apoptosis expression following traumatic brain injury (TBI). Animals were prepared with a unilateral cortical contusion injury (CCI). Fifteen minutes following injury the animals received either nicotinamide (500 mg/kg, ip) or 0.9% saline. The animals were perfused at 5, 24, and 72 h post-injury. BBB integrity was assessed by endogenous rat IgG immunoreactivity. Recent studies have shown that IgG immunoreactivity is a reliable measure of BBB integrity. The results indicated that IgG immunoreactivity was greatest at 5 h and declined at 24 h after injury. Nicotinamide significantly reduced IgG expression at every time point following injury. Apoptosis was examined using the TUNEL method. The results indicated that TUNEL immunoreactivity peaked at 24 h. TUNEL(+) cells were classified morphologically as nonapoptotic (Type I) or apoptotic (Type II) to verify that the neuroprotective effects of nicotinamide occur by inhibiting apoptosis or necrosis. Administration of nicotinamide significantly reduced the expression of all TUNEL(+) cells in the tissue surrounding the lesion cavity. Specifically there was a significant reduction in the number of Type I, Type II, and Total TUNEL(+) cells in the nicotinamide-treated animals. In addition, nicotinamide reduced lesion cavity expansion 72 h following CCI. These findings suggest that nicotinamide reduces BBB breach and neuronal cell loss acutely following injury and that these reductions may account for the beneficial behavioral effects seen in previous studies.

  8. [Decompressive craniectomy in traumatic brain injury and malignant brain infarction].

    PubMed

    Greiner, Christoph

    2008-10-01

    High intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury and malignant cerebral infarction. After failure of general therapeutic maneuvers and first line therapies, "second tier" therapies have to be considered. Decompressive craniectomy is an advanced treatment option for controlling intracranial pressure (ICP). In this review indications and techniques of decompressive craniectomy are described and current literature is discussed. The author concludes that decompressive craniectomy is no routine, but should be considered in individual cases.

  9. Neuroprotection of Selective Brain Cooling After Penetrating Ballistic-like Brain Injury in Rats.

    PubMed

    Wei, Guo; Lu, Xi-Chun M; Shear, Deborah A; Yang, Xiaofang; Tortella, Frank C

    2011-01-01

    Induced hypothermia has been reported to provide neuroprotection against traumatic brain injury. We recently developed a novel method of selective brain cooling (SBC) and demonstrated its safety and neuroprotection efficacy in a rat model of ischemic brain injury. The primary focus of the current study was to evaluate the potential neuroprotective efficacy of SBC in a rat model of penetrating ballistic-like brain injury (PBBI) with a particular focus on the acute cerebral pathophysiology, neurofunction, and cognition. SBC (34°C) was induced immediately after PBBI, and maintained for 2 hours, followed by a spontaneous re-warming. Intracranial pressure (ICP) and regional cerebral blood flow were monitored continuously for 3 hours, and the ICP was measured again at 24 hours postinjury. Brain swelling, blood-brain barrier permeability, intracerebral hemorrhage, lesion size, and neurological status were assessed at 24 hours postinjury. Cognitive abilities were evaluated in a Morris water maze task at 12-16 days postinjury. Results showed that SBC significantly attenuated PBBI-induced elevation of ICP (PBBI = 33.2 ± 10.4; PBBI + SBC = 18.8 ± 6.7 mmHg) and reduced brain swelling, blood-brain barrier leakage, intracerebral hemorrhage, and lesion volume by 40%-45% for each matrix, and significantly improved neurologic function. However, these acute neuroprotective benefits of SBC did not translate into improved cognitive performance in the Morris water maze task. These results indicate that 34°C SBC is effective in protecting against acute brain damage and related neurological dysfunction. Further studies are required to establish the optimal treatment conditions (i.e., duration of cooling and/or combined therapeutic approaches) needed to achieve significant neurocognitive benefits.

  10. C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment.

    PubMed

    Marín-Prida, Javier; Pentón-Rol, Giselle; Rodrigues, Fernando Postalli; Alberici, Luciane Carla; Stringhetta, Karina; Leopoldino, Andréia Machado; Naal, Zeki; Polizello, Ana Cristina Morseli; Llópiz-Arzuaga, Alexey; Rosa, Marcela Nunes; Liberato, José Luiz; Santos, Wagner Ferreira Dos; Uyemura, Sergio Akira; Pentón-Arias, Eduardo; Curti, Carlos; Pardo-Andreu, Gilberto L

    2012-12-01

    Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120mmHg for 45min, which was followed by 15min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM phosphate and/or 100μM Ca(2+), C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment.

  11. Chronic neurodegenerative consequences of traumatic brain injury.

    PubMed

    Chauhan, Neelima B

    2014-01-01

    Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.

  12. 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.

  13. Position statement: definition of traumatic brain injury.

    PubMed

    Menon, David K; Schwab, Karen; Wright, David W; Maas, Andrew I

    2010-11-01

    A clear, concise definition of traumatic brain injury (TBI) is fundamental for reporting, comparison, and interpretation of studies on TBI. Changing epidemiologic patterns, an increasing recognition of significance of mild TBI, and a better understanding of the subtler neurocognitive neuroaffective deficits that may result from these injuries make this need even more critical. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health has therefore formed an expert group that proposes the following definition: In this article, we discuss criteria for considering or establishing a diagnosis of TBI, with a particular focus on the problems how a diagnosis of TBI can be made when patients present late after injury and how mild TBI may be differentiated from non-TBI causes with similar symptoms. Technologic advances in magnetic resonance imaging and the development of biomarkers offer potential for improving diagnostic accuracy in these situations. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. The molecular pathophysiology of concussive brain injury.

    PubMed

    Barkhoudarian, Garni; Hovda, David A; Giza, Christopher C

    2011-01-01

    Concussion or mild traumatic brain injury (mTBI) is a condition that affects hundreds of thousands of patients worldwide. Understanding the pathophysiology of this disorder can help manage its acute and chronic repercussions. Immediately following mTBI, there are several metabolic, hemodynamic, structural, and electric changes that alter normal cerebral function. These alterations can increase the brain's vulnerability to repeat injury and long-term disability. This review evaluates current studies from the bench to the bedside of mTBI. Acute and chronic effects of concussion are measured in both animal and clinical studies. Also, the effect of repeat concussions is analyzed. Concussion-induced pathophysiology with regards to glucose metabolism changes, mitochondrial dysfunction, axonal injury, and structural damage are evaluated. Translational studies such as functional magnetic resonance imaging, magnetic resonance spectroscopy and diffusion tensor imaging prove to be effective clinical tools for both prognostic and treatment parameters. Understanding the neurobiology of concussion will lead to development and validation of physiological biomarkers of this common injury. These biomarkers (eg, laboratory tests, imaging, electrophysiology) will then allow for improved detection, better functional assessment and evidence-based return to play recommendations. Published by Elsevier Inc.

  15. 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

  16. What Protects Certain Nerves from Stretch Injury?

    PubMed

    Schraut, Nicholas B; Walton, Sharon; Bou Monsef, Jad; Shott, Susan; Serici, Anthony; Soulii, Lioubov; Amirouche, Farid; Gonzalez, Mark H; Kerns, James M

    2016-01-01

    The human tibial nerves is less prone to injury following joint arthroplasty compared with the peroneal nerves. Besides the anatomical distribution, other features may confer protection from stretch injury. We therefore examined the size, shape and connective tissue distribution for the two nerves. The tibial and peroneal nerves from each side of nine fresh human cadavers we reharvested mid-thigh. Proximal segments manually stretched 20%-25% were fixed in aldehyde, while the adjacent distal segments were fixed in their natural length. Paraffin sections stained by Masson's trichrome method for connective tissue were examined by light microscopy. Tibial nerves had 2X more fascicles compared with the peroneal, but the axonal content appeared similar. Analysis showed that neither nerve had a significant reduction in cross sectional area of the fascicles following stretch. However, fascicles from stretched tibial nerves become significantly more oval compared with those from unstretched controls and peroneal nerves. Tibial nerves had a greater proportion that was extrafascicular tissue (50-55%) compared with peroneal nerves (38%-42%). This epineurium was typically adipose tissue. Perineurial thickness in both nerves was directly related to fascicular size. Tibial nerves have several unique histological features associated with size, shape and tissue composition compared with the peroneal nerve. We suggest that more fascicles with their tightly bound perineurium and more robust epineurium afford protection against stretch injury. Mechanical studies should clarify how size and shape contribute to nerve protection and/or neurapraxia.

  17. Protective approaches against myocardial ischemia reperfusion injury

    PubMed Central

    Li, Xianchi; Liu, Min; Sun, Rongrong; Zeng, Yi; Chen, Shuang; Zhang, Peiying

    2016-01-01

    Myocardial ischemia-reperfusion is the leading cause for the events of cardiovascular disease, and is considered as a major contributor to the morbidity and mortality associated with coronary occlusion. The myocardial damage caused by ischemia-reperfusion injury constitutes the primary pathological manifestation of coronary artery disease. It results from the interaction between the substances that accumulate during ischemia and those that are delivered on reperfusion. The level of this damage can range from a small insult resulting in limited myocardial damage to a large injury culminating in myocyte death. Importantly, major ischemia-reperfusion injury to the heart can result in permanent disability or death. Given the worldwide prevalence of coronary artery disease, developing a strategy to provide cardioprotection against ischemia-reperfusion-induced damage is of great importance. Currently, the treatment of reperfusion injury following ischemia is primarily supportive, since no specific target-oriented therapy has been validated thus far. Nevertheless, therapeutic approaches to protect against myocardial ischemia-reperfusion injury remain an active area of investigation given the detrimental effects of this phenomenon. PMID:28101167

  18. Fetal inflammatory response and brain injury in the preterm newborn.

    PubMed

    Malaeb, Shadi; Dammann, Olaf

    2009-09-01

    Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

  19. 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…

  20. Large animal models of traumatic brain injury.

    PubMed

    Dai, Jun-Xi; Ma, Yan-Bin; Le, Nan-Yang; Cao, Jun; Wang, Yang

    2017-10-03

    Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. Mixed published articles and books associated with large animal models of TBI were researched and summarized. We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

  1. Recent advances in imaging preterm brain injury.

    PubMed

    Boardman, J P; Dyet, L E

    2007-08-01

    Survivors of preterm birth are at high risk of neurocognitive impairment in childhood, but the disturbances to brain growth and function that underlie impairment are not completely understood. Improvements in perinatal care have led to a reduction in the major destructive parenchymal brain lesions that are associated with motor impairment, such as cystic periventricular leucomalacia and haemorrhagic parenchymal infarction. However, with the application of advanced magnetic resonance (MR) imaging and processing techniques in the neonatal period, subtle alterations in brain development have become apparent. These changes occur with similar frequency to long-term neurocognitive impairment, and may therefore represent candidate neural substrates for this group of disorders. Here we review the range of lesions and associated outcomes that are seen in the current era of perinatal care, and discuss how state of the art MR imaging techniques have helped to define the neural systems affected by preterm birth, and have provided insights into understanding mechanisms of injury.

  2. Inflammation and Neuroprotection in Traumatic Brain Injury

    PubMed Central

    Corps, Kara N.; Roth, Theodore L.; McGavern, Dorian B.

    2016-01-01

    IMPORTANCE Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI. OBJECTIVES To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI. EVIDENCE REVIEW We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. FINDINGS Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning

  3. Inflammation and neuroprotection in traumatic brain injury.

    PubMed

    Corps, Kara N; Roth, Theodore L; McGavern, Dorian B

    2015-03-01

    Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI. To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI. We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning as well as the local cues to which they are

  4. Perceived needs following traumatic brain injury.

    PubMed

    Corrigan, John D; Whiteneck, Gale; Mellick, Dave

    2004-01-01

    (1) Provide population-based estimates of perceived needs following traumatic brain injury (TBI) and the prevalence of unmet needs 1 year postinjury; (2) identify relations among needs that define unique clusters of individuals; and (3) identify risk factors for experiencing selected needs. Telephone survey 1 year after injury of a prospective cohort of all people hospitalized with TBI in the state of Colorado during 2000. Self-reported need for assistance in 13 areas of functioning. A total of 58.8% of persons hospitalized with TBI experienced at least 1 need during the year following injury; 40.2% will experience at least 1 unmet need 1 year after injury. Most frequently experienced needs were "improving your memory, solving problems better" (34.1%), "managing stress, emotional upsets" (27.9%), and "managing your money, paying bills" (23.3%). Cluster analysis revealed 8 distinctive groupings of subjects. If a need existed, those least likely to be met involved cognitive abilities, employment, and alcohol and/or drug use. Results were consistent with findings from previous assessments of need for services based on surveys of convenience samples; however, the prevalence of unmet needs 1 year after injury may be higher than previously suspected. More post-hospital services addressing cognitive and emotional problems appear needed. Risk factors for experiencing needs suggest potential avenues for clinical intervention.

  5. 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

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

    PubMed

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

    2015-06-01

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

  7. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury.

    PubMed

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

    2014-09-01

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

  8. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

    PubMed Central

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

    2014-01-01

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

  9. 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…

  10. 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…

  11. Mild Traumatic Brain Injury and Diffuse Axonal Injury in Swine

    PubMed Central

    Browne, Kevin D.; Chen, Xiao-Han; Meaney, David F.

    2011-01-01

    Abstract Until recently, mild traumatic brain injury (mTBI) or “concussion” was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness. PMID:21740133

  12. The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome.

    PubMed

    McDonald, Stuart J; Sun, Mujun; Agoston, Denes V; Shultz, Sandy R

    2016-04-26

    Traumatic injuries are physical insults to the body that are prevalent worldwide. Many individuals involved in accidents suffer injuries affecting a number of extremities and organs, otherwise known as multitrauma or polytrauma. Traumatic brain injury is one of the most serious forms of the trauma-induced injuries and is a leading cause of death and long-term disability. Despite over dozens of phase III clinical trials, there are currently no specific treatments known to improve traumatic brain injury outcomes. These failures are in part due to our still poor understanding of the heterogeneous and evolving pathophysiology of traumatic brain injury and how factors such as concomitant extracranial injuries can impact these processes. Here, we review the available clinical and pre-clinical studies that have investigated the possible impact of concomitant injuries on traumatic brain injury pathobiology and outcomes. We then list the pathophysiological processes that may interact and affect outcomes and discuss promising areas for future research. Taken together, many of the clinical multitrauma/polytrauma studies discussed in this review suggest that concomitant peripheral injuries may increase the risk of mortality and functional deficits following traumatic brain injury, particularly when severe extracranial injuries are combined with mild to moderate brain injury. In addition, recent animal studies have provided strong evidence that concomitant injuries may increase both peripheral and central inflammatory responses and that structural and functional deficits associated with traumatic brain injury may be exacerbated in multiply injured animals. The findings of this review suggest that concomitant extracranial injuries are capable of modifying the outcomes and pathobiology of traumatic brain injury, in particular neuroinflammation. Though additional studies are needed to further identify the factors and mechanisms involved in central and peripheral injury

  13. 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

  14. Concussive brain injury from explosive blast.

    PubMed

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

    2014-09-01

    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. 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. 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. 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.

  15. 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

  16. Role of Thalamus in Recovery of Traumatic Brain Injury

    PubMed Central

    Munivenkatappa, Ashok; Agrawal, Amit

    2016-01-01

    Degree of recovery after traumatic brain injury is highly variable that lasts for many weeks to months. The evidence of brain structures involved in recovery mechanisms is limited. This review highlights evidence of the brain structure particularly thalamus in neuroplasticity mechanism. Thalamus with its complex global networking has potential role in refining the cortical and other brain structures. Thalamic nuclei activation both naturally or by neurorehabilitation in injured brain can enhance and facilitate the improvement of posttraumatic symptoms. This review provides evidence from literature that thalamus plays a key role in recovery mechanism after injury. The study also emphasize that thalamus should be specifically targeted in neurorehabilitation following brain injury. PMID:28163509

  17. Occupant injury protection in automobile collisions.

    PubMed

    Peters, G A; Peters, B J

    1999-12-01

    Modern technology has produced automotive vehicles that have become both a luxury and a necessity in modern civilization. They have become highly useful, even more varied in form and function, and capable of high speeds on crowded roadways. One unfortunate consequence is the high frequency of accidents and the greater severity of injuries when collisions do occur. In response, modern technology has produced a variety of safety and health features, devices and designs intended for better occupant protection on in high speed vehicles. Injury reduction has become a prime design objective, but there are residual risks, which, as technology evolves, require effective communication to those risk. There can be little risk avoidance behavior without awareness of the hazards and effective communication to the vehicle occupant, as to what could and should be done for self-protection. For example, one out of three drivers apparently fails to understand the function of head restraints, few understand the 'safe zone' posture required for air bags and many believe safety features should be adjusted only for comfort. Some of the current residual injury producing problems in occupant systems are specifically described here in order to illustrate what is needed in terms of both design remedies and health promotion activities.

  18. Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases.

    PubMed

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

    2017-01-01

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

  19. The Role of Ghrelin in Neuroprotection after Ischemic Brain Injury

    PubMed Central

    Spencer, Sarah J.; Miller, Alyson A.; Andrews, Zane B.

    2013-01-01

    Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects. In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke. Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits. We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic. PMID:24961317

  20. Visual impairments in the first year after traumatic brain injury.

    PubMed

    Greenwald, Brian D; Kapoor, Neera; Singh, Adeepa D

    2012-01-01

    This article reviews literature regarding individuals with traumatic brain injury who have vision related impairments up to one year, post-injury. Such impairments may impact rehabilitation of activities of daily living and mobility since vision is integral in much of what one does on a daily basis. Search of Medline, Ovid, and PubMed was performed using terms including: traumatic brain injury, visual deficits after brain injury, vision and traumatic brain injury, and ADLs after brain injury. Eighteen studies were analyzed and reviewed. A range of visual and visual-motor impairments are seen across the severity of traumatic brain injury. Visual impairment negatively impacts independence in mobility and activities of daily living. Common sensorimotor visual symptoms reported by those with traumatic brain injury include blurred vision, reading problems, double vision or eyestrain, dizziness or disequilibrium in visually-crowded environments, visual field defects, light sensitivity, and color blindness. This review should alert the reader to common visual complaints and defects seen after traumatic brain injury. It is important to screen persons who have suffered traumatic brain injury for sensorimotor vision deficits early on in recovery so that these issues may be addressed and recovery of function and independence in the community are not delayed.

  1. Traumatic brain injury research priorities: the Conemaugh International Brain Injury Symposium.

    PubMed

    Zitnay, George A; Zitnay, Kevin M; Povlishock, John T; Hall, Edward D; Marion, Donald W; Trudel, Tina; Zafonte, Ross D; Zasler, Nathan; Nidiffer, F Don; DaVanzo, John; Barth, Jeffrey T

    2008-10-01

    In 2005, an international symposium was convened with over 100 neuroscientists from 13 countries and major research centers to review current research in traumatic brain injury (TBI) and develop a consensus document on research issues and priorities. Four levels of TBI research were the focus of the discussion: basic science, acute care, post-acute neurorehabilitation, and improving quality of life (QOL). Each working group or committee was charged with reviewing current research, discussion and prioritizing future research directions, identifying critical issues that impede research in brain injury, and establishing a research agenda that will drive research over the next five years, leading to significantly improved outcomes and QOL for individuals suffering brain injuries. This symposium was organized at the request of the Congressional Brain Injury Task Force, to follow up on the National Institutes of Health Consensus Conference on TBI as mandated by the TBI ACT of 1996. The goal was to review what progress had been made since the National Institutes of Health (NIH) Consensus Conference, and also to follow up on the 1990's Decade of the Brain Project. The major purpose of the symposium was to provide recommendations to the U.S. Congress on a priority basis for research, treatment, and training in TBI over the next five years.

  2. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  3. De novo artistic behaviour following brain injury.

    PubMed

    Pollak, Thomas A; Mulvenna, Catherine M; Lythgoe, Mark F

    2007-01-01

    The effect of brain injury and disease on the output of established artists is an object of much study and debate. The emergence of de novo artistic behaviour following such injury or disease, while very rare, has been recorded in cases of frontotemporal dementia, epilepsy, subarachnoid haemorrhage and Parkinson's disease. This may be an underdiagnosed phenomenon and may represent an opportunity to further understand the neural bases of creative thought and behaviour in man and those of cognitive change after brain injury. There is clearly an important role for hemispheric localization of pathology, which is usually within the temporal cortex, upon the medium of artistic expression, and a likely role for mild frontal cortical dysfunction in producing certain behavioural and cognitive characteristics that may be conducive to the production of art. Possible mechanisms of 'artistic drive' and 'creative idea generation' in these patients are also considered. The increased recognition and responsible nurturing of this behaviour in patients may serve as a source of great comfort to individuals and their families at an otherwise difficult time.

  4. Linked Records of Children with Traumatic Brain Injury*

    PubMed Central

    Bennett, T. D.; Dean, J. M.; Keenan, H. T.; McGlincy, M. H.; Thomas, A. M.; Cook, L. J.

    2015-01-01

    Summary Objective Record linkage may create powerful datasets with which investigators can conduct comparative effectiveness studies evaluating the impact of tests or interventions on health. All linkages of health care data files to date have used protected health information (PHI) in their linkage variables. A technique to link datasets without using PHI would be advantageous both to preserve privacy and to increase the number of potential linkages. Methods We applied probabilistic linkage to records of injured children in the National Trauma Data Bank (NTDB, N = 156,357) and the Pediatric Health Information Systems (PHIS, N = 104,049) databases from 2007 to 2010. 49 match variables without PHI were used, many of them administrative variables and indicators for procedures recorded as International Classification of Diseases, 9th revision, Clinical Modification codes. We validated the accuracy of the linkage using identified data from a single center that submits to both databases. Results We accurately linked the PHIS and NTDB records for 69% of children with any injury, and 88% of those with severe traumatic brain injury eligible for a study of intervention effectiveness (positive predictive value of 98%, specificity of 99.99%). Accurate linkage was associated with longer lengths of stay, more severe injuries, and multiple injuries. Conclusion In populations with substantial illness or injury severity, accurate record linkage may be possible in the absence of PHI. This methodology may enable linkages and, in turn, comparative effectiveness studies that would be unlikely or impossible otherwise. PMID:26021580

  5. Inflicted traumatic brain injury: advances in evaluation and collaborative diagnosis.

    PubMed

    Glick, Jill C; Staley, Kelley

    2007-01-01

    The determination that a traumatic brain injury is not accidental requires data collection from multiple domains: historical, clinical, laboratory, radiographic, environmental and psychosocial. These essential, yet disparate, types of information must be synthesized in a collaborative and interdisciplinary process to formulate a medical opinion with regard to the cause of an injury, and the final opinion has tremendous consequences for children and families. Medically directed child protection teams have emerged as the standard of care in many children's hospitals and child abuse pediatrics is now a recognized medical subspecialty with board certification available in the next several years. Not only do the child and family benefit from this coordinated effort, but there are also great benefits for the members of the child protection team: more clearly defined responsibilities, redirected focus on treatment for the surgeon, and increased confidence that the opinion is based upon consensus and current scientific knowledge. By this process and its division of labor, the child abuse pediatrician assumes responsibility for ensuring that a final medical opinion is arrived at, and then advocates for appropriate disposition for the child. The child abuse pediatrician is responsible for establishing institutional standards for family evaluation, collecting all necessary medical data and directing a consensus-based decision making process that is based upon current medical knowledge, medical literature and experience. The child abuse pediatrician also assumes the role of primary communication conduit for investigational agencies and the courts. The neurosurgeon is a key member of the child protection team and relies on the team to obtain necessary historical information to address consistency of the mechanism with the sustained injuries and has an integral role in determining the team's final opinion. An interdisciplinary response to inflicted traumatic brain injury is the

  6. Wearable nanosensor system for monitoring mild traumatic brain injuries in football players

    NASA Astrophysics Data System (ADS)

    Ramasamy, Mouli; Varadan, Vijay K.

    2016-04-01

    Football players are more to violent impacts and injuries more than any athlete in any other sport. Concussion or mild traumatic brain injuries were one of the lesser known sports injuries until the last decade. With the advent of modern technologies in medical and engineering disciplines, people are now more aware of concussion detection and prevention. These concussions are often overlooked by football players themselves. The cumulative effect of these mild traumatic brain injuries can cause long-term residual brain dysfunctions. The principle of concussion is based the movement of the brain in the neurocranium and viscerocranium. The brain is encapsulated by the cerebrospinal fluid which acts as a protective layer for the brain. This fluid can protect the brain against minor movements, however, any rapid movements of the brain may mitigate the protective capability of the cerebrospinal fluid. In this paper, we propose a wireless health monitoring helmet that addresses the concerns of the current monitoring methods - it is non-invasive for a football player as helmet is not an additional gear, it is efficient in performance as it is equipped with EEG nanosensors and 3D accelerometer, it does not restrict the movement of the user as it wirelessly communicates to the remote monitoring station, requirement of individual monitoring stations are not required for each player as the ZigBee protocol can couple multiple transmitters with one receiver. A helmet was developed and validated according to the above mentioned parameters.

  7. Microglial Activation in Traumatic Brain Injury

    PubMed Central

    Donat, Cornelius K.; Scott, Gregory; Gentleman, Steve M.; Sastre, Magdalena

    2017-01-01

    Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and mediating the immune response against peripheral infection. Microglia rapidly become activated in response to CNS damage. Depending on the nature of the stimulus, microglia can take a number of activation states, which correspond to altered microglia morphology, gene expression and function. It has been reported that early microglia activation following traumatic brain injury (TBI) may contribute to the restoration of homeostasis in the brain. On the other hand, if they remain chronically activated, such cells display a classically activated phenotype, releasing pro-inflammatory molecules, resulting in further tissue damage and contributing potentially to neurodegeneration. However, new evidence suggests that this classification is over-simplistic and the balance of activation states can vary at different points. In this article, we review the role of microglia in TBI, analyzing their distribution, morphology and functional phenotype over time in animal models and in humans. Animal studies have allowed genetic and pharmacological manipulations of microglia activation, in order to define their role. In addition, we describe investigations on the in vivo imaging of microglia using translocator protein (TSPO) PET and autoradiography, showing that microglial activation can occur in regions far remote from sites of focal injuries, in humans and animal models of TBI. Finally, we outline some novel potential therapeutic approaches that prime microglia/macrophages toward the beneficial restorative microglial phenotype after TBI. PMID:28701948

  8. Venlafaxine protects methylglyoxal-induced apoptosis in the cultured human brain microvascular endothelial cells.

    PubMed

    Lv, Qinghua; Gu, Chengyao; Chen, Caijing

    2014-05-21

    It was reported that venlafaxine protects microvascular endothelial cells injury in several models. But the mechanisms of venlafaxine protects cell injury still poor understanding. Here, we shows that in the cultured human brain microvascular endothelial cells (HBMEC), we found that venlafaxine protects methylglyoxal (MGO)-induced cell injury, and the venlafaxine significant reduction in the level of reactive oxygen species, down-regulated expression of pro-apoptotic activated caspase-3 and Bax, increased BDNF release and expression of anti-apoptotic Bcl-2 in the cultured HBMEC. Furthermore, we found that venlafaxine inhibits MGO-induced phosphorylation of JNK. Moreover, venlafaxine increased AKT phosphorylation and the protective effects of venlafaxine was inhibited by PI3K/AKT inhibitor. These findings suggest that venlafaxine protects MGO-induced HBMEC injury through PI3K/AKT and JNK pathway as the potential underlying mechanisms of HBMEC injury in diabetes.

  9. Inflammatory signalling associated with brain dead organ donation: from brain injury to brain stem death and posttransplant ischaemia reperfusion injury.

    PubMed

    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.

  10. Traumatic Brain Injury: Are We Conducting Enough Resarch

    DTIC Science & Technology

    2017-04-17

    FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 7 APR 2017 1. Your paper, entitled Traumatic Brain Injury: Are We Conducting Enough...review and approval.) NA - Pubmed searches w ere the only source of data 6. TITLE OF MATERIAL TO BE PUBLISHED OR PRESENTED: Traumatic Brain Injury...Traumatic Brain Injury: Are We Conducting Enough Research? Capt Mariya Gusman MD, Lt Col Jonathan A Sosnov MD, Jeffrey T Howard PhD Background

  11. Baseline Establishment Using Virtual Environment Traumatic Brain Injury Screen (VETS)

    DTIC Science & Technology

    2015-06-01

    treating brain injuries is utilizing 16 an effective screening technique to target treatment for those individuals who need it most. Requirements for an...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS BASELINE ESTABLISHMENT USING VIRTUAL ENVIRONMENT TRAUMATIC BRAIN INJURY SCREEN (VETS) by Casey...ENVIRONMENT TRAUMATIC BRAIN INJURY SCREEN (VETS) 5. FUNDING NUMBERS 6. AUTHOR(S) Casey G. DeMunck 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES

  12. 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

  13. Hypersexuality or altered sexual preference following brain injury.

    PubMed

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

    1986-08-01

    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.

  14. Psychiatric disorders after traumatic brain injury.

    PubMed

    van Reekum, R; Bolago, I; Finlayson, M A; Garner, S; Links, P S

    1996-05-01

    Substantial psychological and neurobehavioural evidence is available to support the hypothesis that traumatic brain injury (TBI) is a risk factor for subsequent psychiatric disorders. However, studies utilizing established psychiatric diagnostic schemes to study these outcomes after TBI are scarce, and no studies have included an assessment of personality disorders in addition to the major psychiatric disorders. This study utilizes structured psychiatric interviews to measure the prevalence of DSM-III(R) disorders in a sample of 18 subjects derived from a TBI rehabilitation programme. Results revealed high rates for major depression, bipolar affective disorder, generalized anxiety disorder, borderline and avoidant personality disorders. Co-morbidity was also high. A preliminary study of postulated predictive factors revealed possible roles for sex and for initial severity of injury. The study supports the association between TBI and psychiatric disorder, and suggests the need for monitoring, for prevention, and for treatment of psychiatric disorders after TBI.

  15. Venous System in Acute Brain Injury: Mechanisms of Pathophysiological Change and Function

    PubMed Central

    Xu, Liang; Matei, Nathanael; Tang, Jiping; Feng, Hua; Zhang, JohnH

    2015-01-01

    Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. Hitherto, the role of vein drainage in the pathophysiology of acute brain injury has been overlooked, due to an under appreciation of the magnitude of the impact of veins in circulation. In this review, we summarize the changes in the vein morphology and functions that are known, or likely to occur related to acute brain injury, and aim to advance the therapeutic management of acute brain injury by shifting the focus from reperfusion to another term: recirculation. Recent progress in the neurobiological understanding of the vascular neural network has demonstrated that cerebral venous systems are able to respond to acute brain injury by regulating the blood flow disharmony following brain edema, blood brain barrier disruption, ischemia, and hemorrhage. With the evidence presented in this review, future clinical management of acutely brain injured patients will expand to include the recirculation concept, establishing a harmony between arterial and venous systems, in addition to the established recanalization and reperfusion strategies. PMID:25783658

  16. Fear of falling after brain injury.

    PubMed

    Collicutt McGrath, Joanna

    2008-07-01

    To investigate the prevalence and nature of fear of falling in a sample of people with severe acquired brain injury. A descriptive study. A regional inpatient neurological rehabilitation unit. One hundred and five adults with acquired brain injury of mixed aetiology. All 105 participants were rated by observers who were asked to judge the degree to which fear behaviour interfered with rehabilitation therapy (activity limitation). Eighty-two participants also rated themselves. They were asked to report the degree of distress caused by fear. Both participants and observers were asked to describe the focus of any reported fear. Two stepwise logistic regression analyses were carried out to identify variables that predicted fear giving rise to significant activity limitation and fear giving rise to significant subjective distress. Self and observer rating scales designed and constructed specifically for the study. Raters reported significant fear-related activity limitation in 12-15% of participants. Significant fear-related subjective distress was reported by 40% of participants. Fear of falling, fear of physical harm and fear of not making sufficient rehabilitation progress dominated the reports of both observers and participants. The variables predicting significant activity limitation were premorbid alcohol misuse, low functional ability and the occurrence of a fall since onset. The variables predicting significant subjective distress were poor motor coordination and organization, and good verbal comprehension. Fear of falling is a clinically significant phenomenon in younger adults recovering from severe acquired brain injury. Fear sufficient to cause high degrees of subjective distress was often not evident to observers. Proactive questioning about fear of falling is therefore advisable when working clinically with this group.

  17. Brain Injury Vision Symptom Survey (BIVSS) Questionnaire.

    PubMed

    Laukkanen, Hannu; Scheiman, Mitchell; Hayes, John R

    2017-01-01

    Validation of the Brain Injury Vision Symptom Survey (BIVSS), a self-administered survey for vision symptoms related to traumatic brain injury (TBI). A 28-item vision symptom questionnaire was completed by 107 adult subjects (mean age 42.1, 16.2 SD, range 18-75) who self-reported as having sustained mild-to-moderate TBI and two groups of reference adult subjects (first-year optometry students: mean age 23.2, 2.8 SD, range 20-39; and 71 third-year optometry students: mean age 26.0, 2.9 SD, range 22-42) without TBI. Both a Likert-style method of analysis with factor analysis and a Rasch analysis were used. Logistic regression was used to determine sensitivity and specificity. At least 27 of 28 questions were completed by 93.5% of TBI subjects, and all 28 items were completed by all of the 157 reference subjects. BIVSS sensitivity was 82.2% for correctly predicting TBI and 90.4% for correctly predicting the optometry students. Factor analysis identified eight latent variables; six factors were positive in their risk for TBI. Other than dry eye and double vision, the TBI patients were significantly more symptomatic than either cohort of optometry students by at least one standard deviation (p < 0.001). Twenty-five of 28 questions were within limits for creating a single-dimension Rasch scale. Nearly all of the adult TBI subjects were able to self-complete the BIVSS, and there was significant mean score separation between TBI and non-TBI groups. The Rasch analysis revealed a single dimension associated with TBI. Using the Likert method with the BIVSS, it may be possible to identify different vision symptom profiles with TBI patients. The BIVSS seems to be a promising tool for better understanding the complex and diverse nature of vision symptoms that are associated with brain injury.

  18. Seizures and the Role of Anticonvulsants After Traumatic Brain Injury.

    PubMed

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

    2016-10-01

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

  19. Synthetic neurosteroids on brain protection

    PubMed Central

    Rey, Mariana; Coirini, Héctor

    2015-01-01

    Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids administration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute promising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions. PMID:25788907

  20. Effects of crystalloid-colloid solutions on traumatic brain injury.

    PubMed

    Elliott, Melanie B; Jallo, Jack J; Gaughan, John P; Tuma, Ronald F

    2007-01-01

    The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.

  1. Sports-related traumatic brain injury.

    PubMed

    Phillips, Shawn; Woessner, Derek

    2015-06-01

    Concussions have garnered more attention in the medical literature, media, and social media. As such, in the nomenclature according to the Centers for Disease Control and Prevention, the term concussion has been supplanted by the term mild traumatic brain injury. Current numbers indicate that 1.7 million TBIs are documented annually, with estimates around 3 million annually (173,285 sports- and recreation-related TBIs among children and adolescents). The Sideline Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are commonly used sideline tools.

  2. Severe Brain Injury in Massachusetts: Assessing the Continuum of Care.

    PubMed

    Lorenz, Laura; Katz, Gabrielle

    2015-12-10

    Acquired brain injury (ABI) is a major public health problem in Massachusetts (Hackman et al, 2014) and includes traumatic brain injury (TBI), stroke, ABI-related infectious diseases, metabolic disorders affecting the central nervous system (brain and spinal cord), and brain tumor. Advances in emergency medical care and neurosurgery mean that more people are surviving severe traumatic brain injury (Trexler et al, 2014). Yet many patients with severe TBI in particular, are not receiving inpatient services after initial treatment (Hackman et al, 2014; CDC, 2014) or later that are known to be effective (Malec & Kean, 2015; Lewis & Horn, 2015; BI Commission, 2011; Kolakowsky-Hayner et al, 2000; Interviews). These services include post-acute rehabilitation, case management, and brain injury-specific community programming (CDC, 2014; BI Commission, 2011; Interviews). Governance and data for decision-making are also major gaps in the continuum of care for severe brain injury in MA (Interviews; NASHIA, 2005). The last two decades saw a surge in interest in the brain, with advances in neuroscience, diagnosis and measurement of brain injury, rehabilitation services, and brain theory (Boyle, 2001). Severe brain injury however is the new "hidden epidemic" in our society. For many, an injury to the brain is not a short-term event that can be "cured" but the beginning of a life-long disability (CDC, 2014; Langlois et al, 2006). Fortunately, even after a severe brain injury, when the right rehabilitation is provided at the right time, the "rest of life" journey can be a positive one for many (Marquez de la Plata, 2015; Langlois et al, 2006). Severe brain injury can lead to a "new normal" as patients regain skills, find new meaning and in life, and take on new family, volunteer, and work roles. Throughout this brief, the term "severe brain injury" refers to "severe acquired brain injury," or any injury to the brain that occurs after birth. This definition does not include

  3. Why Some Kids Take Longer to Recover from Brain Injury

    MedlinePlus

    ... Why Some Kids Take Longer to Recover From Brain Injury Scans reveal white-matter decline after some ... 15, 2017 WEDNESDAY, March 15, 2017 (HealthDay News) -- Brain scans may reveal which children will take longer ...

  4. 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

  5. Early Systolic Dysfunction Following Traumatic Brain Injury: A Cohort Study.

    PubMed

    Krishnamoorthy, Vijay; Rowhani-Rahbar, Ali; Gibbons, Edward F; Rivara, Frederick P; Temkin, Nancy R; Pontius, Crystal; Luk, Kevin; Graves, Morgan; Lozier, Danielle; Chaikittisilpa, Nophanan; Kiatchai, Taniga; Vavilala, Monica S

    2017-06-01

    Prior studies have suggested that traumatic brain injury may affect cardiac function. Our study aims were to determine the frequency, longitudinal course, and admission risk factors for systolic dysfunction in patients with moderate-severe traumatic brain injury. Prospective cohort study. Level 1 trauma center. Transthoracic echocardiogram within 1 day and over the first week after moderate-severe traumatic brain injury; transthoracic echocardiogram within 1 day after mild traumatic brain injury (comparison group). Systolic function was assessed by transthoracic echocardiogram, and systolic dysfunction was defined as fractional shortening less than 25%. Multivariable Poisson regression models examined admission risk factors for systolic dysfunction. Systolic function in 32 patients with isolated moderate-severe traumatic brain injury and 32 patients with isolated mild traumatic brain injury (comparison group) was assessed with transthoracic echocardiogram. Seven (22%) moderate-severe traumatic brain injury and 0 (0%) mild traumatic brain injury patients had systolic dysfunction within the first day after injury (p < 0.01). All patients with early systolic dysfunction recovered in 1 week. Younger age (relative risk, 0.87; 95% CI, 0.79-0.94; for 1 yr increase in age) and lower admission Glasgow Coma Scale score (relative risk, 0.34; 95% CI, 0.20-0.58; for one unit increase in Glasgow Coma Scale) were independently associated with the development of systolic dysfunction among moderate-severe traumatic brain injury patients. Early systolic dysfunction can occur in previously healthy patients with moderate-severe traumatic brain injury, and it is reversible over the first week of hospitalization. Younger age and lower admission Glasgow Coma Scale score are independently associated with the development of systolic dysfunction after moderate-severe traumatic brain injury.

  6. Protecting the brain during neurosurgical procedures: strategies that can work.

    PubMed

    El Beheiry, Hossam

    2012-10-01

    The quest for neuroprotection strategies during periods of neuronal vulnerability persists despite decades of basic and clinical research. This review will focus on the latest developments in the area of clinical brain protection with the major emphasis on strategies that can be beneficial during neurosurgical procedures. Brain protection in neurosurgical patients may be achieved by nonpharmacological and pharmacological strategies. Pharmacological neuroprotection including anaesthetic administration have not been recently shown to be successful. Alternatively, nonpharmacological strategies including maintenance of cerebral perfusion by adequate control of mean arterial pressure (≥80 mmHg), liberal normoglycaemia (7.8-10 mmol/l), adequate haemoglobin levels (preoperative ≥120 g/l and intraoperative ≥90 g/l) and induction of hypertension (20-40% of preoperative values) in certain neurosurgical situations can be beneficial as neuroprotectants during neurosurgery. Mild hypothermia (32-35°C) failed to achieve neuroprotective effects in several situations of brain injury. The findings of this review suggest that the anaesthesiologist is compelled to use nonpharmacological strategies sometimes based on empiric evidence to protect the brain during neurosurgical procedures. These strategies are simple, have high benefit/risk ratios and are inexpensive. Rigorous controlled clinical studies are needed to investigate the neuroprotective efficacy of these commonly used nonpharmacological methods.

  7. 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

  8. A prototypical Sigma-1 receptor antagonist protects against brain ischemia.

    PubMed

    Schetz, John A; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W

    2007-11-21

    Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this study it potently protects against oxidative stress-related cell death in vitro at low concentrations. The protective potency of haloperidol and a number of other butyrophenone compounds positively correlate with their affinity for a cloned Sigma-1 receptor, and the protection is mimicked by a Sigma-1 receptor-selective antagonist (BD1063), but not an agonist (PRE-084). In vivo, an acute low dose (0.05 mg/kg s.c.) of haloperidol reduces by half the ischemic lesion volume induced by a transient middle cerebral artery occlusion. These in vitro and in vivo pre-clinical results suggest that a low dose of acutely administered haloperidol might have a novel application as a protective agent against ischemic cerebral stroke and other types of brain injury with an ischemic component.

  9. Blast-related mild traumatic brain injury: mechanisms of injury and impact on clinical care.

    PubMed

    Elder, Gregory A; Cristian, Adrian

    2009-04-01

    Mild traumatic brain injury has been called the signature injury of the wars in Iraq and Afghanistan. In both theaters of operation, traumatic brain injury has been a significant cause of mortality and morbidity, with blast-related injury the most common cause. Improvised explosive devices have been the major cause of blast injuries. It is estimated that 10% to 20% of veterans returning from these operations have suffered a traumatic brain injury, and there is concern that blast-related injury may produce adverse long-term health affects and affect the resilience and in-theater performance of troops. Blast-related injury occurs through several mechanisms related to the nature of the blast overpressure wave itself as well as secondary and tertiary injuries. Animal studies clearly show that blast overpressure waves are transmitted to the brain and can cause changes that neuropathologically are most similar to diffuse axonal injury. One striking feature of the mild traumatic brain injury cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of mild traumatic brain injury with posttraumatic stress disorder. The overlap in symptoms between the disorders has made distinguishing them clinically challenging. The high rates of mild traumatic brain injury and posttraumatic stress disorder in the current operations are of significant concern for the long-term health of US veterans with associated economic implications.

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

    PubMed

    Hamed, Sherifa A

    2017-04-01

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

  11. Airbag protection versus compartment intrusion effect determines the pattern of injuries in multiple trauma motor vehicle crashes.

    PubMed

    Loo, G T; Siegel, J H; Dischinger, P C; Rixen, D; Burgess, A R; Addis, M D; O'Quinn, T; McCammon, L; Schmidhauser, C B; Marsh, P; Hodge, P A; Bents, F

    1996-12-01

    A prospective study of the interaction between airbag (AB) and seat-belt (Bt) protection versus vehicular compartment (VC) intrusion effects on injury patterns in motor vehicle crash (MVC) trauma patients. Two hundred MVC patients, nonejected drivers or front seat passengers with multiple trauma or severe lower extremity (LE) trauma admitted to two Level I trauma centers. In frontal crashes, airbags (AB) more than Bt reduced Glasgow Coma Scale severity in brain injury, face fracture, shock, and the need for MVC extrication (all p < 0.05). Frontal AB also had a protective effect on LE fractures (41% vs. 66%, p < 0.01), but had no significant protective effect on pelvic fractures. When AB protection was present, it prevented brain and face fracture injuries caused by impact contacts and reduced the incidence of these injuries resulting from VC intrusions (p < 0.05). Thoracoabdominal injuries resulting from steering wheel intrusion showed AB protection against intrusions of twice the magnitude of those seen in non-AB vehicles (p < 0.05). In frontal MVCs, AB reduced LE fracture contact injuries but did not prevent LE fractures resulting from intrusions of instrument panel, toepan, or floor pedal structures. In lateral MVCs, Bt did not protect against brain, face, thorax, or pelvic injuries. Safety measures beyond frontal airbags must address frontal crash LE injuries induced by steering wheel, instrument panel, and toepan passenger compartment structure intrusions. Lateral crash injuries may profit from side AB supplemental restraint protection.

  12. Helmet efficacy against concussion and traumatic brain injury: a review.

    PubMed

    Sone, Je Yeong; Kondziolka, Douglas; Huang, Jason H; Samadani, Uzma

    2017-03-01

    Helmets are one of the earliest and most enduring methods of personal protection in human civilization. Although primarily developed for combat purposes in ancient times, modern helmets have become highly diversified to sports, recreation, and transportation. History and the scientific literature exhibit that helmets continue to be the primary and most effective prevention method against traumatic brain injury (TBI), which presents high mortality and morbidity rates in the US. The neurosurgical and neurotrauma literature on helmets and TBI indicate that helmets provide effectual protection against moderate to severe head trauma resulting in severe disability or death. However, there is a dearth of scientific data on helmet efficacy against concussion in both civilian and military aspects. The objective of this literature review was to explore the historical evolution of helmets, consider the effectiveness of helmets in protecting against severe intracranial injuries, and examine recent evidence on helmet efficacy against concussion. It was also the goal of this report to emphasize the need for more research on helmet efficacy with improved experimental design and quantitative standardization of assessments for concussion and TBI, and to promote expanded involvement of neurosurgery in studying the quantitative diagnostics of concussion and TBI. Recent evidence summarized by this literature review suggests that helmeted patients do not have better relative clinical outcome and protection against concussion than unhelmeted patients.

  13. Traumatic Brain Injury in the Workplace.

    PubMed

    Paci, Michael; Infante-Rivard, Claire; Marcoux, Judith

    2017-09-01

    Work-related traumatic brain injuries (TBIs) are not well documented in the literature. Published studies mostly rely on worker databases that fail to provide clinically relevant information. Our objective is to describe the characteristics of hospitalized patients and their work-related TBI. We used the Québec provincial trauma and TBI program databases to identify all patients with a diagnosis of work-related TBI admitted to the Montreal General Hospital, a level 1 trauma center, between 2000 and 2014. Data from their medical records were extracted using a predetermined information sheet. Simple descriptive statistics (means and percentages) were used to summarize the data. A total of 285 cases were analyzed. Workplace TBI patients were middle-aged (mean, 43.62 years), overwhelmingly male (male:female 18:1), mostly healthy, and had completed a high school level education. Most workers were from the construction industry; falling was the most common mechanism of injury. The majority of patients (76.8%) presented with a mild TBI; only a minority (14%) required neurosurgery. The most common finding on computed tomography was skull fracture. The median length of hospitalization was 7 days, after which most patients were discharged directly home. A total of 8.1% died of their injuries. Our study found that most hospitalized victims of work-related TBI had mild injury; however, some required neurosurgical intervention and a non-negligible proportion died of their injury. Improving fall prevention, accurately document helmet use and increasing the safety practice in the construction industry may help decrease work-related TBI burden.

  14. A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

    DTIC Science & Technology

    2012-09-01

    not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT...of function after brain damage using a neural prosthesis (Complete main body of manuscript is included in the appendix.) Authors: David J. Guggenmos...feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as

  15. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    PubMed

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  16. 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

  17. A mouse model of human repetitive mild traumatic brain injury.

    PubMed

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

    2012-01-15

    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 min. 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.

  18. Serum Iron Protects from Renal Postischemic Injury.

    PubMed

    Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

    2017-08-07

    Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-κB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

  19. Detrimental consequences of brain injury on peripheral cells.

    PubMed

    Catania, Anna; Lonati, Caterina; Sordi, Andrea; Gatti, Stefano

    2009-10-01

    Acute brain injury and brain death exert detrimental effects on peripheral host cells. Brain-induced impairment of immune function makes patients more vulnerable to infections that are a major cause of morbidity and mortality after stroke, trauma, or subarachnoid hemorrhage (SAH). Systemic inflammation and organ dysfunction are other harmful consequences of CNS injury. Brain death, the most severe consequence of brain injury, causes inflammatory changes in peripheral organs that can contribute to the inferior outcome of organs transplanted from brain-dead donors. Understanding of the mechanisms underlying the detrimental effects of brain injury on peripheral organs remains incomplete. However, it appears that sympathetic nervous system (SNS)-activation contributes to elicit both inflammation and immunodepression. Indeed, norepinephrine (NE)-induced production of chemokines in liver and other organs likely participates in local and systemic inflammatory changes. Conversely, catecholamine-stimulated interleukin-10 (IL-10) production by blood monocytes exerts immunosuppressive effects. Activation of the hypothalamic-pituitary-adrenal axis (HPA) by increased inflammatory cytokines within the brain is a significant component in the CNS-induced immune function inhibition. Non-neurologic consequences of brain injury show impressive similarities regardless of the brain insult and appear to depend on altered neuroimmune circuits. Modulation of these circuits could reduce extra-brain damage and improve patient outcome in both vascular and traumatic brain injury.

  20. Impaired Pituitary Axes Following Traumatic Brain Injury

    PubMed Central

    Scranton, Robert A.; Baskin, David S.

    2015-01-01

    Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

  1. Update in mild traumatic brain injury.

    PubMed

    Freire-Aragón, María Dolores; Rodríguez-Rodríguez, Ana; Egea-Guerrero, Juan José

    2017-08-10

    There has been concern for many years regarding the identification of patients with mild traumatic brain injury (TBI) at high risk of developing an intracranial lesion (IL) that would require neurosurgical intervention. The small percentage of patients with these characteristics and the exceptional mortality associated with mild TBI with IL have led to the high use of resources such as computerised tomography (CT) being reconsidered. The various protocols developed for the management of mild TBI are based on the identification of risk factors for IL, which ultimately allows more selective indication or discarding both the CT application and the hospital stay for neurological monitoring. Finally, progress in the study of brain injury biomarkers with prognostic utility in different clinical categories of TBI has recently been incorporated by several clinical practice guidelines, which has allowed, together with clinical assessment, a more accurate prognostic approach for these patients to be established. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  2. Bridge Between Neuroimmunity and Traumatic Brain Injury

    PubMed Central

    Kelso, Matthew L.; Gendelman, Howard E.

    2014-01-01

    The pathophysiology of degenerative, infectious, inflammatory and traumatic diseases of the central nervous system includes a significant immune component. As to the latter, damage to the cerebral vasculature and neural cell bodies, caused by traumatic brain injury (TBI) activates innate immunity with concomitant infiltration of immunocytes into the damaged nervous system. This leads to pro-inflammatory cytokine and prostaglandin production and lost synaptic integrity and more generalized neurotoxicity. Engagement of adaptive immune responses follows including the production of antibodies and lymphocyte proliferation. These affect the tempo of disease along with tissue repair and as such provide a number of potential targets for pharmacological treatments for TBI. However, despite a large body of research, no such treatment intervention is currently available. In this review we will discuss the immune response initiated following brain injuries, drawing on knowledge gained from a broad array of experimental and clinical studies. Our discussion seeks to address potential therapeutic targets and propose ways in which the immune system can be controlled to promote neuroprotection. PMID:24025052

  3. Motorcycle-Related Traumatic Brain Injuries: Helmet Use and Treatment Outcome

    PubMed Central

    Nnadi, Mathias Ogbonna Nnanna; Bankole, Olufemi Babatola; Fente, Beleudanyo Gbalipre

    2015-01-01

    Summary. With increasing use of motorcycle as means of transport in developing countries, traumatic brain injuries from motorcycle crashes have been increasing. The only single gadget that protects riders from traumatic brain injury is crash helmet. Objective. The objectives were to determine the treatment outcome among traumatic brain injury patients from motorcycle crashes and the rate of helmet use among them. Methods. It was a prospective, cross-sectional study of motorcycle-related traumatic brain injury patients managed in our center from 2010 to 2014. Patients were managed using our unit protocol for traumatic brain injuries. Data for the study were collected in accident and emergency, intensive care unit, wards, and outpatient clinic. The data were analyzed using Environmental Performance Index (EPI) info 7 software. Results. Ninety-six patients were studied. There were 87 males. Drivers were 65. Only one patient wore helmet. Majority of them were between 20 and 40 years. Fifty-three patients had mild head injuries. Favorable outcome among them was 84.35% while mortality was 12.5%. Severity of the injury affected the outcome significantly. Conclusion. Our study showed that the helmet use by motorcycle riders was close to zero despite the existing laws making its use compulsory in Nigeria. The outcome was related to severity of injuries. PMID:26317112

  4. Post-traumatic stress disorder and traumatic brain injury.

    PubMed

    Motzkin, Julian C; Koenigs, Michael R

    2015-01-01

    Disentangling the effects of "organic" neurologic damage and psychological distress after a traumatic brain injury poses a significant challenge to researchers and clinicians. Establishing a link between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been particularly contentious, reflecting difficulties in establishing a unique diagnosis for conditions with overlapping and sometimes contradictory symptom profiles. However, each disorder is linked to a variety of adverse health outcomes, underscoring the need to better understand how neurologic and psychiatric risk factors interact following trauma. Here, we present data showing that individuals with a TBI are more likely to develop PTSD, and that individuals with PTSD are more likely to develop persistent cognitive sequelae related to TBI. Further, we describe neurobiological models of PTSD, highlighting how patterns of neurologic damage typical in TBI may promote or protect against the development of PTSD in brain-injured populations. These data highlight the unique course of PTSD following a TBI and have important diagnostic, prognostic, and treatment implications for individuals with a dual diagnosis.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  7. Haemostatic drugs for traumatic brain injury.

    PubMed

    Perel, Pablo; Roberts, Ian; Shakur, Haleema; Thinkhamrop, Bandit; Phuenpathom, Nakornchai; Yutthakasemsunt, Surakrant

    2010-01-20

    Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial evaluated the effect of rFVIIa in 97 TBI patients with evidence of intracerebral bleeding in a

  8. Haemostatic drugs for traumatic brain injury

    PubMed Central

    Perel, Pablo; Roberts, Ian; Shakur, Haleema; Thinkhamrop, Bandit; Phuenpathom, Nakornchai; Yutthakasemsunt, Surakrant

    2014-01-01

    Background Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. Objectives To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. Search methods We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). Selection criteria We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Data collection and analysis Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. Main results We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial

  9. 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

  10. Ethics of neuroimaging after serious brain injury.

    PubMed

    Weijer, Charles; Peterson, Andrew; Webster, Fiona; Graham, Mackenzie; Cruse, Damian; Fernández-Espejo, Davinia; Gofton, Teneille; Gonzalez-Lara, Laura E; Lazosky, Andrea; Naci, Lorina; Norton, Loretta; Speechley, Kathy; Young, Bryan; Owen, Adrian M

    2014-05-20

    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. 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 explore conceptual issues in the

  11. Male body image following acquired brain injury.

    PubMed

    Howes, Hannah; Edwards, Stephen; Benton, David

    2005-02-01

    The purpose of this study was to investigate body image concerns and psycho-emotional health in males with acquired brain injury (ABI). Using a between subjects study of 25 males with ABI and 25 matched controls, variables were analysed using correlations and 2 x 2 analyses of variance (ANOVAs) with head injury and injury type as independent variables. Body image and psycho-emotional health were evaluated using self-report questionnaires. Disability and cognitive impairment were measured using a mixture of self-report, cognitive testing and clinical notes. Results indicated that males with ABI had significantly lower self-esteem and body dissatisfaction on a number of items relating to physical and sexual functioning. There were significant differences in body image between stroke and TBI, but there was no corresponding relationship with psycho-emotional health. These body image differences might be explained by age. The finding that ABI has a negative effect on body image and that this relates to psycho-emotional health should be investigated further, perhaps being included in future rehabilitation strategies.

  12. Brain injury, neuroinflammation and Alzheimer's disease

    PubMed Central

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

    2013-01-01

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

  13. Brain injury, neuroinflammation and Alzheimer's disease.

    PubMed

    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.

  14. An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment.

    PubMed

    Jean, Aurélie; Nyein, Michelle K; Zheng, James Q; Moore, David F; Joannopoulos, John D; Radovitzky, Raúl

    2014-10-28

    Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.

  15. 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…

  16. 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…

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

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

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

  18. 77 FR 34363 - Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model Systems... Program--Disability Rehabilitation Research Project (DRRP)-- Traumatic Brain Injury Model Systems Centers... priority for Traumatic Brain Injury Model Systems (TBIMS) Centers. The Assistant Secretary may use...

  19. [Metallothionein-I/II in brain injury repair mechanism and its application in forensic medicine].

    PubMed

    Li, Dong; Li, Ru-bo; Lin, Ju-li

    2013-10-01

    Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.

  20. The neuroinflammatory response in humans after traumatic brain injury.

    PubMed

    Smith, C; Gentleman, S M; Leclercq, P D; Murray, L S; Griffin, W S T; Graham, D I; Nicoll, J A R

    2013-10-01

    Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury. This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed 'blind' by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury. A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter. These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years. © 2012 British Neuropathological Society.

  1. 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…

  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. 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…

  4. 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…

  5. 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,…

  6. 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…

  7. 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,…

  8. Pathological Fingerprints, Systems Biology and Biomarkers of Blast Brain Injury

    DTIC Science & Technology

    2009-06-01

    microglia as ’sensors’ of injury in the pineal gland of rats following a non-penetrative blast." Neurosci Res 27(4): 317-322. ...including blood brain barrier disruption, glia activation and neuronal alterations. 15. SUBJECT TERMS blast; brain injury; experimental models

  9. Telerehabilitation needs: a survey of persons with acquired brain injury.

    PubMed

    Ricker, Joseph H; Rosenthal, Mitchell; Garay, Edward; DeLuca, John; Germain, Anneliese; Abraham-Fuchs, Klaus; Schmidt, Kai-Uwe

    2002-06-01

    To survey individuals with acquired brain injury to assess multiple facets of interest, access, and familiarity necessary to implement new telerehabilitation technologies. Anonymous mail survey. Community. Seventy-one respondents to a survey. These individuals had experienced acquired brain injury (predominantly severe traumatic brain injury [TBI]) and were living in the community. Surveys were mailed by a state chapter of the Brain Injury Association to a random selection of members with acquired brain injury. Survey designed specifically for this investigation. The survey responses indicate that there is great interest in the possibility of accessing telerehabilitative services among individuals with acquired brain injury. In particular, there was strong interest expressed in services that could be used to assist with problems in memory, attention, problem-solving, and activities of daily living. Telemedicine, and more specifically telerehabilitation, holds great promise as an adjunct to traditional clinical service delivery. Little research in this area has been applied, however, to individuals with acquired brain injuries. Although on the surface, telerehabilitation seems to be an appropriate assessment and treatment modality for individuals with brain injury, it will only succeed if those individuals have the interest-and the access-necessary to use new and evolving technologies.

  10. 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…

  11. Novel Nitroxide Resuscitation Strategies in Experimental Traumatic Brain Injury

    DTIC Science & Technology

    2010-03-01

    peroxidase activity after traumatic brain injury. J Neurotrauma 2003;20:437–445. 68. Mavelli I, Rigo A, Federico R, et al. Superoxide dismutase, glu... Engel , C.C., and Castro, C.A. (2008). Mild traumatic brain injury in U.S. soldiers returning from Iraq. N. Engl. J. Med. 358, 453–463. Ling, G., Bandak

  12. Gut-Brain Axis in Gastric Mucosal Damage and Protection

    PubMed Central

    Sgambato, Dolores; Capuano, Annalisa; Sullo, Maria Giuseppa; Miranda, Agnese; Federico, Alessandro; Romano, Marco

    2016-01-01

    Abstract: Background The gut-brain axis plays a potential role in numerous physiological and pathological conditions. Several substances link stomach with central nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropin-releasing factor-containing nerve fibers and capsaicin-sensitive nerves are principal mediators of the harmful and protective central nervous system-mediated effects on gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and calcitonin gene-related peptide play a role as final effectors of gastric protection. Methods We undertook a structured search of bibliographic databases for peer-reviewed research literature with the aim of focusing on the role of gut-brain axis in gastric damage and protection. In particular, we examined manuscripts dealing with the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon–like peptide-1, and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have been examined. Results We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the role of gut brain axis in gastric mucosal damage and protection. Conclusions A dense neuronal network links stomach with central nervous system and a number of neurotransmitters and peptides functionally and anatomically related to central nervous system play a major role in contributing to gastric mucosal integrity. Exploiting the mechanisms underlying the connection between brain and gut may lead to a better understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention and, eventually, management of gastric damage. PMID:26903151

  13. Barbiturates for acute traumatic brain injury.

    PubMed

    Roberts, I

    2000-01-01

    Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with a high mortality rate. Barbiturates are believed to reduce intracranial pressure by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and therefore may adversely effect cerebral perfusion pressure. To assess the effects of barbiturates in reducing raised intracranial pressure, mortality and morbidity in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. The review draws largely on the search strategy developed for the Cochrane Injuries Group as a whole. However, in addition the Cochrane Library was searched in December 1996 using the text terms "barbiturate*," "pentobarb*," "phenobarb*," "head," and "brain." An updated search was done in April 1999. Randomised or quasi randomised trials of any one or more of the barbiturate class of drugs (amobarbital, barbital, hexobarbital, mephobarbital, methohexital, murexide, pentobarbital, phenobarbital, secobarbital, thiobarbiturate) where study participants had a clinically diagnosed acute traumatic brain injury of any severity. The reviewer extracted the data and assessed the quality of allocation concealment in the trials. The pooled relative risk for death (barbiturate vs no barbiturate) was 1.09 (95%CI 0.81 to 1.47). The pooled effect of barbiturates on adverse neurological outcome, measured using the Glasgow Outcome Scale (death, persistent vegetative state or severe disability) was 1.15 (95% 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on intracranial pressure. In the study by Eisenberger et al, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% vs 83%). The relative risk for uncontrolled ICP was 0.81 (95%CI 0.62 to 1.06). Similarly, in the study by Ward et al, mean ICP was lower in the

  14. Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.

    PubMed

    Yuan, Jing; Wang, Aihua; He, Yan; Si, Zhihua; Xu, Shan; Zhang, Shanchao; Wang, Kun; Wang, Dawei; Liu, Yiming

    2016-10-01

    Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Surgical brain injury: prevention is better than cure.

    PubMed

    Jadhav, Vikram; Zhang, John H

    2008-05-01

    Neurosurgical procedures can cause inevitable brain damage resulting from the procedure itself. Unavoidable cortical and parenchymal incisions, intraoperative hemorrhage, brain lobe retraction and thermal injuries from electrocautery can cause brain injuries attributable exclusively to the neurosurgical operations and collectively referred to as surgical brain injury (SBI). This particular brain damage cannot be demarcated from the underlying brain pathology and has not been studied previously. Recently, we developed rat and mouse models to study SBI and the underlying cellular mechanisms. The animal modeling mimics a neurosurgical operation and causes commonly encountered postoperative complications such as brain edema following blood brain barrier (BBB) disruption, and neuronal cell death. Furthermore, the SBI animal model allows screening of known experimental neuroprotective agents and therapeutic agents being tried in clinical trials as possible pretreatments before neurosurgical procedures. In the present review, we elaborate on SBI and its clinical impact, the SBI animal models and their clinical relevance, and the importance of blanket neuroprotection before neurosurgical procedures.

  16. 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

  17. Missed diagnosis of traumatic brain injury in patients with traumatic spinal cord injury.

    PubMed

    Sharma, Bhanu; Bradbury, Cheryl; Mikulis, David; Green, Robin

    2014-04-01

    To determine the frequency of missed acute care traumatic brain injury diagnoses in patients with traumatic spinal cord injury, and to examine risk factors for missed traumatic brain injury diagnosis. Prospective magnetic resonance imaging and neuro-psychological assessment plus retrospective medical record review, including computed tomography. Ninety-two adults with traumatic spinal cord injury recruited from a large, tertiary spinal cord injury program, initially referred from urban teaching hospitals with neurotrauma facilities. Diagnosis of traumatic brain injury made with clinical neurological indices (i.e., Glasgow Coma Scale, post-traumatic amnesia, and loss of consciousness), neuroimaging (computed tomography and structural magnetic resonance imaging), and neuropsychological tests of attention and speed of processing, memory, and executive function; all measures were validated on a case-by-case basis to rule out confounds. Missed traumatic brain injury diagnoses were made via acute care medical record review and were corroborated by patient/family report where possible. The frequency of missed traumatic brain injury diagnoses in our sample was 58.5%. Missed traumatic brain injury diagnoses were more frequent in injuries sustained outside of a motor vehicle collision (MVC), with 75.0% of acute care traumatic brain injury diagnoses missed in non-MVC patients vs. 42.9% missed in MVC patients. Among patients with non-MVC injuries, a comparable percentage of missed traumatic brain injury diagnoses were observed in patients with cervical (79%) and sub-cervical injuries (80%). In more than half of the traumatic spinal cord injury patients referred for in-patient rehabilitation, acute care diagnoses of traumatic brain injury were missed. A risk factor for missed diagnosis was an injury caused by a mechanism other than an MVC (e.g., falls, assaults), perhaps due to reduced expectations of traumatic brain injury in non-MVC patients. In our research study, we

  18. 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

  19. 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.,…

  20. The enigma of "hidden" traumatic brain injury.

    PubMed

    Gordon, W A; Brown, M; Sliwinski, M; Hibbard, M R; Patti, N; Weiss, M J; Kalinsky, R; Sheerer, M

    1998-12-01

    To examine individuals with "hidden" traumatic brain injury (TBI), defined in this study as those who sustained a blow to the head, with altered mental status, and experienced a substantial number of the cognitive, behavioral, and emotional sequelae typically associated with brain injury but did not make the causal connection between the injury and its consequences. Comparison of four groups of individuals matched for age, gender, years of education, and duration of loss of consciousness. This study of hidden TBI followed the identification of 143 individuals who, within a larger study of people with TBI who live in the community, identified themselves as "nondisabled" (they were to be part of the comparison sample) but who had experienced a blow to the head that left them at minimum dazed and confused. 21 of these 143 individuals also reported large numbers of symptoms (eg, headaches, memory problems) associated with TBI. This group (Hidden TBI-High Symptoms group) was compared to three other matched samples: one with known TBI (Known Mild TBI group) and one with no disability (No Disability group) (both of which were drawn from the larger study), and one group of individuals who identified themselves as having no disability but who had experienced a blow to the head that resulted in a few symptoms (Head Trauma-Low Symptoms group). All study participants were administered an interview that incorporated several existing instruments documenting levels of reported symptoms, emotional well-being/distress, and vocational/social handicaps. The Hidden TBI-High Symptoms group was found to be similar to the Known Mild TBI group in terms of the number and types of symptoms experienced, whereas the Head Trauma-Low Symptoms group was similar in this respect to the No Disability group. The two former groups also evidenced high levels of emotional distress, whereas the two latter groups did not. However, on measures of handicap, the Hidden TBI-High Symptoms and Head Trauma

  1. Endogenous neural stem/progenitor cells stabilize the cortical microenvironment after traumatic brain injury.

    PubMed

    Dixon, Kirsty J; Theus, Michelle H; Nelersa, Claudiu M; Mier, Jose; Travieso, Lissette G; Yu, Tzong-Shiue; Kernie, Steven G; Liebl, Daniel J

    2015-06-01

    Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestin(δ) promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.

  2. Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury

    PubMed Central

    Dixon, Kirsty J.; Theus, Michelle H.; Nelersa, Claudiu M.; Mier, Jose; Travieso, Lissette G.; Yu, Tzong-Shiue; Kernie, Steven G.

    2015-01-01

    Abstract Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestinδ promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI. PMID:25290253

  3. 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.

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

    PubMed

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

    2012-04-01

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

  5. 78 FR 12334 - Proposed Collection; Comment Request: Federal Interagency Traumatic Brain Injury Research (FITBIR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... 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...

  6. Rehabilitation of persons with traumatic brain injury.

    PubMed

    The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury. The statement provides state-of-the-art information regarding effective rehabilitation measures for persons who have suffered a traumatic brain injury (TBI) and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience for this statement includes, but is not limited to, pediatricians, family practitioners, internists, neurologists, physiatrists, psychologists, and behavioral medicine specialists. Participants were a non-Federal, nonadvocate, 16-member panel representing the fields of neuropsychology, neurology, psychiatry, behavioral medicine, family medicine, pediatrics, physical medicine and rehabilitation, speech and hearing, occupational therapy, nursing, epidemiology, biostatistics and the public. In addition, 23 experts from these same fields presented data to the panel and a conference audience of 883. The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. A compendium of evidence was prepared by the panel which included a contribution from a patient with TBI, a report from an Evidence Based Practice Center of the Agency for Health Care Policy and Research, and a report from the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined

  7. Critical care management of traumatic brain injury.

    PubMed

    Menon, D K; Ercole, A

    2017-01-01

    Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials. However, observational studies have informed the development of authoritative international guidelines, and the use of multimodality monitoring may facilitate rational approaches to optimizing acute physiology, allowing clinicians to optimize the balance between benefit and risk from these interventions in individual patients. Such approaches, along with the emerging impact of advanced neuroimaging, genomics, and protein biomarkers, could lead to the development of precision medicine approaches to the intensive care management of TBI.

  8. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

  9. Hippocampal head atrophy after traumatic brain injury.

    PubMed

    Ariza, Mar; Serra-Grabulosa, Josep M; Junqué, Carme; Ramírez, Blanca; Mataró, Maria; Poca, Antonia; Bargalló, Nuria; Sahuquillo, Juan

    2006-01-01

    Traumatic brain injury (TBI) causes hippocampal damage. The hippocampus can be macroscopically divided into the head, body and tail, which differ in terms of their sensitivity to excitability and also in terms of their cortical connections. We investigated whether damage also varies according to the hippocampal area involved, and studied the relationship of hippocampal reductions with memory performance. Twenty TBI patients and matched controls were examined. MRI measurements were performed separately for the hippocampal head, body and tail. Memory outcome was measured by Rey's auditory verbal learning test, Rey's complex figure test and a modified version of Warrington's facial recognition memory test. Group comparison showed that patients had bilateral hippocampal atrophy, mainly involving the hippocampal head. Moreover, TBI subjects showed verbal memory deficits which presented slight correlations with left hippocampal head atrophy.

  10. Cerebrovascular pathophysiology following mild traumatic brain injury.

    PubMed

    Len, T K; Neary, J P

    2011-03-01

    Mild traumatic brain injury (mTBI) or sport-induced concussion has recently become a prominent concern not only in the athletic setting (i.e. sports venue) but also in the general population. The majority of research to date has aimed at understanding the neurological and neuropsychological outcomes of injury as well as return-to-play guidelines. Remaining relatively unexamined has been the pathophysiological aspect of mTBI. Recent technological advances including transcranial Doppler ultrasound and near infrared spectroscopy have allowed researchers to examine the systemic effects of mTBI from rest to exercise, and during both asymptomatic and symptomatic conditions. In this review, we focus on the current research available from both human and experimental (animal) studies surrounding the pathophysiology of mTBI. First, the quest for a unified definition of mTBI, its historical development and implications for future research is discussed. Finally, the impact of mTBI on the control and regulation of cerebral blood flow, cerebrovascular reactivity, cerebral oxygenation and neuroautonomic cardiovascular regulation, all of which may be compromised with mTBI, is discussed. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  11. 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.

  12. 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

  13. Systemic manifestations of traumatic brain injury.

    PubMed

    Gaddam, Samson Sujit Kumar; Buell, Thomas; Robertson, Claudia S

    2015-01-01

    Traumatic brain injury (TBI) affects functioning of various organ systems in the absence of concomitant non-neurologic organ injury or syst