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Sample records for experimental brain edema

  1. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice

    PubMed Central

    Zeynalov, Emil; Jones, Susan M.; Seo, Jeong-Woo; Snell, Lawrence D.; Elliott, J. Paul

    2015-01-01

    Background Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2) and tolvaptan (V2) are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke. Methods Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO) with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan) or orally (tolvaptan) for 48 hours. Physiological variables, neurological deficit scores (NDS), plasma and urine sodium and osmolality were recorded. Brain water content (BWC) and Evans Blue (EB) extravasation index were evaluated at the end point. Results Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle) to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle). Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle) to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05). Conclusion Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke. PMID:26275173

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

    PubMed

    Mase, M

    1990-07-01

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

  3. Aquaporin-4 Deletion in Mice Reduces Encephalopathy and Brain Edema in Experimental Acute Liver Failure

    PubMed Central

    Rama Rao, Kakulavarapu V.; Verkman, A. S.; Curtis, Kevin M.; Norenberg, Michael D.

    2014-01-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6 ± 0.3 and 2.3 ± 0.4 %, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. PMID:24321433

  4. Aquaporin-4 and brain edema.

    PubMed

    Papadopoulos, Marios C; Verkman, Alan S

    2007-06-01

    Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury.

  5. Protective Effect of Quercetin against Oxidative Stress and Brain Edema in an Experimental Rat Model of Subarachnoid Hemorrhage

    PubMed Central

    Dong, Yu-shu; Wang, Ju-lei; Feng, Da-yun; Qin, Huai-zhou; Wen, Hua; Yin, Zhong-min; Gao, Guo-dong; Li, Chuan

    2014-01-01

    Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation. PMID:24516353

  6. Aquaporin-4 and traumatic brain edema.

    PubMed

    Xu, Miao; Su, Wei; Xu, Qiu-ping

    2010-04-01

    Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.

  7. Evaluation of brain edema using magnetic resonance proton relaxation times

    SciTech Connect

    Fu, Y.; Tanaka, K.; Nishimura, S. )

    1990-01-01

    Experimental and clinical studies on the evaluation of water content in cases of brain edema were performed in vivo, using MR proton relaxation times (longitudinal relaxation time, T1; transverse relaxation time, T2). Brain edema was produced in the white matter of cats by the direct infusion method. The correlations between proton relaxation times obtained from MR images and the water content of white matter were studied both in autoserum-infused cats and in saline-infused cats. The correlations between T1 as well as T2 and the water content in human vasogenic brain edema were also examined and compared with the data obtained from the serum group. T1 and T2 showed good correlations with the water content of white matter not only in the experimental animals but also in the clinical cases. The quality of the edema fluid did not influence relaxation time and T1 seemed to represent almost solely the water content of the tissue. T2, however, was affected by the nature of existence of water and was more sensitive than T1 in detecting extravasated edema fluid. It seems feasible therefore to evaluate the water content of brain edema on the basis of T1 values.

  8. International brain edema symposia 1967-2011.

    PubMed

    Kuroiwa, Toshihiko

    2013-01-01

    This is a brief review of previous international brain edema symposia. The symposia that took place from 1965 to 1999 were summarized by Igor Klatzo and A. Marmarou in the proceedings Brain Edema XI [1]. In this article the author summarized the symposia, including latest five. Images from previous symposia such as the cover pages of the proceedings and snapshots of organizers were included. The outline and key words of the symposia were summarized in tables. The name of the prize winner and the title of the memorial lectures in recent symposia were also summarized in a table. PMID:23564096

  9. Ulinastatin attenuates brain edema after traumatic brain injury in rats.

    PubMed

    Cui, Tao; Zhu, Gangyi

    2015-03-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. The objective of this study was to evaluate whether Ulinastatin (UTI), a serine protease inhibitor, attenuates brain edema following TBI. Our results showed that treatment with UTI at a dose of 50,000 U/kg attenuated the brain edema, as assayed by water content 24 h after TBI induction. This attenuation was associated with a significant decrease of the expression level of aquaporin-4. In addition, we showed that UTI treatment also markedly inhibited the expression of pro-inflammatory cytokines including IL-1β and TNF-α as well as activity of NF-κB. Collectively, our findings suggested that UTI may be a promising strategy to treat brain edema following TBI.

  10. The Role of Matricellular Proteins in Brain Edema after Subarachnoid Hemorrhage.

    PubMed

    Suzuki, Hidenori; Fujimoto, Masashi; Shiba, Masato; Kawakita, Fumihiro; Liu, Lei; Ichikawa, Naoki; Kanamaru, Kenji; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi

    2016-01-01

    Accumulated evidence suggests that blood-brain barrier disruption or brain edema is an important pathologic manifestation for poor outcome after aneurysmal subarachnoid hemorrhage. Many molecules may be involved, acting simultaneously or at different stages during blood-brain barrier disruption via multiple independent or interconnected signaling pathways. Matricellular protein is a class of nonstructural, secreted, and multifunctional extracellular matrix proteins, which potentially mediates brain edema formation. This study reviews the role of osteopontin and tenascin-C, representatives of matricellular proteins, in the context of brain edema formation after subarachnoid hemorrhage in both clinical and experimental settings.

  11. Proton nuclear magnetic resonance studies on brain edema

    SciTech Connect

    Naruse, S.; Horikawa, Y.; Tanaka, C.; Hirakawa, K.; Nishikawa, H.; Yoshizaki, K.

    1982-06-01

    The water in normal and edematous brain tissues of rats was studied by the pulse nuclear magnetic resonance (NMR) technique, measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). In the normal brain, T1 and T2 were single components, both shorter than in pure water. Prolongation and separation of T2 into two components, one fast and one slow, were the characteristic findings in brain edema induced by both cold injury and triethyl tin (TET), although some differences between the two types of edema existed in the content of the lesion and in the degree of changes in T1 and T2 values. Quantitative analysis of T1 and T2 values in their time course relating to water content demonstrated that prolongation of T1 referred to the volume of increased water in tissues examined, and that two phases of T2 reflected the distribution and the content of the edema fluid. From the analysis of the slow component of T2 versus water content during edema formation, it was demonstrated that the increase in edema fluid was steady, and its content was constant during formation of TET-induced edema. On the contrary, during the formation of cold-injury edema, water-rich edema fluid increased during the initial few hours, and protein-rich edema fluid increased thereafter. It was concluded that proton NMR relaxation time measurements may provide new understanding in the field of brain edema research.

  12. Mathematical modelling of blood-brain barrier failure and edema

    NASA Astrophysics Data System (ADS)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  13. Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia.

    PubMed

    Amiry-Moghaddam, Mahmood; Xue, Rong; Haug, Finn-Mogens; Neely, John D; Bhardwaj, Anish; Agre, Peter; Adams, Marvin E; Froehner, Stanley C; Mori, Susumu; Ottersen, Ole P

    2004-03-01

    The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin-4 (AQP4). Here we show by high-resolution immunogold analysis of the blood-brain-barrier that AQP4 is expressed in brain endothelial cells as well as in the perivascular membranes of astrocyte endfeet. A selective removal of perivascular AQP4 by alpha-syntrophin deletion delays the buildup of brain edema (assessed by Diffusion-weighted MRI) following water intoxication, despite the presence of a normal complement of endothelial AQP4. This indicates that the perivascular membrane domain, which is peripheral to the endothelial blood-brain barrier, may control the rate of osmotically driven water entry. This study is also the first to demonstrate that the time course of edema development differs among brain regions, probably reflecting differences in aquaporin-4 distribution. The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema.

  14. Drowning stars: Reassessing the role of astrocytes in brain edema

    PubMed Central

    Thrane, Alexander S.; Thrane, Vinita Rangroo; Nedergaard, Maiken

    2014-01-01

    Edema formation frequently complicates brain infarction, tumors and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this ‘glymphatic’ system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or ‘paravasculitis’ plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients and thus enable more targeted therapy. PMID:25236348

  15. Effects of metformin treatment on glioma-induced brain edema.

    PubMed

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

  16. Effects of metformin treatment on glioma-induced brain edema

    PubMed Central

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

  17. Effects of metformin treatment on glioma-induced brain edema

    PubMed Central

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

  18. Effects of metformin treatment on glioma-induced brain edema.

    PubMed

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

  19. Ultrastructural Pathology of Oligodendroglial Cells in Traumatic and Hydrocephalic Human Brain Edema: A Review.

    PubMed

    Castejón, Orlando J

    2015-01-01

    Oligodendroglial cell changes in human traumatic brain injuries and hydrocephalus have been reviewed and compared with experimental brain edema. Resting unreactive oligodendrocytes, reactive oligodendrocytes, anoxic-ischemic oligodendrocytes, hyperthrophic phagocytic oligodendrocytes, and apoptotic oligodendrocytes are found. Anoxic-ischemic oligodendrocytes exhibit enlargement of endoplasmic reticulum, Golgi complex, and enlargement and disassembly of nuclear envelope. They appear in contact with degenerated myelinated axons. Hypertrophic phagocytic oligodendrocytes engulf degenerated myelinated axons exerting myelinolytic effects. A continuum oncotic and apoptotic cell death type leading to necrosis is observed. The vasogenic and cytotoxic components of brain edema are discussed in relation to oligodendroglial cell changes and reactivity. PMID:26548433

  20. Diabetes aggravates nanoparticles induced breakdown of the blood-brain barrier permeability, brain edema formation, alterations in cerebral blood flow and neuronal injury. An experimental study using physiological and morphological investigations in the rat.

    PubMed

    Sharma, Hari Shanker; Patnaik, Ranjana; Sharma, Aruna

    2010-12-01

    The possibility that diabetes aggravates nanoparticles induced blood-brain barrier (BBB) breakdown, edema formation and brain pathology was examined in a rat model. Engineered nanoparticles from metals Ag and Cu (50-60 mn) were administered (50 mg/kg, i.p.) once daily for 7 days in normal and streptozotocine induced diabetic rats. On the 8th day, BBB permeability to Evans blue and radioactive iodine (131I-sodium) was examined in 16 brain regions. In these brain regions alterations in regional CBF was also evaluated using radiolabelled (125I) carbonized microspheres (o.d. 15 +/- 6 microm). Regional brain edema and Na+, K+ and Cl- ion analysis were done in 8 selected brain regions. Histopathology was used to detect neuronal damage employing Nissl staining. Nanoparticles treatment in diabetic rats showed much more profound disruption of the BBB to Evans blue albumin (EBA) and radioiodine in almost all the 16 regions examined as compared to the normal animals. In these diabetic animals reduction in regional cerebral blood flow (CBF) was more pronounced than in normal rats. Edema development as seen using water content and increase in Na+ and a decrease in K+ ion were most marked in diabetic rats as compared to normal rats after nanoparticles treatment. Cell changes in the regions of BBB disruptions were also exacerbated in diabetic rats compared to normal group after nanoparticles treatment. Taken together, these observations are the first to show that diabetic rats are more susceptible to nanoparticles induced cerebrovascular reactions in the brain and neuronal damage. The possible mechanisms and significance of the present findings are discussed. PMID:21121280

  1. Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation.

    PubMed

    Clough, R W; Neese, S L; Sherill, L K; Tan, A A; Duke, A; Roosevelt, R W; Browning, R A; Smith, D C

    2007-06-29

    Development of cerebral edema (intracellular and/or extracellular water accumulation) following traumatic brain injury contributes to mortality and morbidity that accompanies brain injury. Chronic intermittent vagus nerve stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20 Hz, biphasic pulses every 30 min) following traumatic brain injury enhances recovery of motor and cognitive function in rats in the weeks following brain injury; however, the mechanisms of facilitated recovery are unknown. The present study examines the effects of VNS on development of acute cerebral edema following unilateral fluid percussion brain injury (FPI) in rats, concomitant with assessment of their behavioral recovery. Two hours following FPI, VNS was initiated. Behavioral testing, using both beam walk and locomotor placing tasks, was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by the customary method of region-specific brain weights before and after complete dehydration. Results of this study replicated that VNS initiated at 2 h after FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days after FPI assessed by beam walk performance (P<0.01); and 2) tended to improve locomotor placing performance at the same time point (P=0.18). Most interestingly, results of this study showed that development of edema within the cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI rats receiving VNS compared with non-VNS FPI rats (P<0.04). Finally, a correlation analysis between beam walk performance and cerebral edema following FPI revealed a significant inverse correlation between behavior performance and cerebral edema. Together, these results suggest that VNS facilitation of motor recovery following experimental brain injury in rats is associated with VNS-mediated attenuation of cerebral edema. PMID:17543463

  2. Water entry into astrocytes during brain edema formation.

    PubMed

    Nase, Gabriele; Helm, P Johannes; Enger, Rune; Ottersen, Ole P

    2008-06-01

    The process of brain edema formation has been studied extensively at the macroscopic level. In contrast, little is known about water fluxes and volume changes at the cellular level in the initial phase of brain edema. Insight in these "microscopic" events could pave the way for more efficient prevention and therapy. Here, we report measurements of brain cell volume responses recorded in vivo in a model of systemic hyponatremia. Transgenic mice expressing fluorescent proteins in astrocytes were subjected to hypo-osmotic stress and two photon laser scanning microscopy. Volume measurements of glial cells in the cerebellum and the visual cortex indicate that individual astrocytes undergo a position-dependent increase in cell volume by a factor of two or more during edema formation. Our data are the first to show that volume changes can be monitored at the cellular level in vivo and demonstrate that astrocytes are sites of water entry in the initial phase of brain edema formation. The uptake of water in astrocytes is likely to reflect the strong expression of aquaporin-4 in these cells.

  3. Thrombin exacerbates brain edema in focal cerebral ischemia.

    PubMed

    Hua, Y; Wu, J; Keep, R F; Hoff, J T; Xi, G

    2003-01-01

    Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.

  4. Edema

    MedlinePlus

    ... involve your entire body. Causes of edema include Eating too much salt Sunburn Heart failure Kidney disease Liver problems from cirrhosis Pregnancy Problems with lymph nodes, especially after mastectomy Some ...

  5. Lethal brain edema, shock, and coagulopathy after scorpion envenomation.

    PubMed

    Cavari, Yuval; Lazar, Isaac; Shelef, Ilan; Sofer, Shaul

    2013-03-01

    We report the case of a 2-year-old Bedouin boy in whom developed severe and unusual complications after being stung, most probably, by the yellow scorpion Leiurus quinquestriatus hebraeus. Five hours after arrival to the emergency department, the boy had multisystem organ failure involving the central nervous system (seizure activity followed by coma with dilated, nonreactive pupils, and severe brain edema), shock (noncardiogenic), disseminated intravascular coagulation, renal failure, hepatic failure, and watery diarrhea, causing his death. In view of the relevant literature, we discuss the pathophysiologic events ultimately leading to his death. PMID:23280335

  6. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-09-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

  7. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    PubMed Central

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  8. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury.

    PubMed

    Sturdivant, Nasya M; Smith, Sean G; Ali, Syed F; Wolchok, Jeffrey C; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  9. Cerebral Edema in Traumatic Brain Injury: Pathophysiology and Prospective Therapeutic Targets.

    PubMed

    Winkler, Ethan A; Minter, Daniel; Yue, John K; Manley, Geoffrey T

    2016-10-01

    Traumatic brain injury is a heterogeneous disorder resulting from an external force applied to the head. The development of cerebral edema plays a central role in the evolution of injury following brain trauma and is closely associated with neurologic outcomes. Recent advances in the understanding of the molecular and cellular pathways contributing to the posttraumatic development of cerebral edema have led to the identification of multiple prospective therapeutic targets. The authors summarize the pathogenic mechanisms underlying cerebral edema and highlight the molecular pathways that may be therapeutically targeted to mitigate cerebral edema and associated sequelae following traumatic brain injury. PMID:27637397

  10. Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

    PubMed

    McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

    2016-01-01

    No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test. PMID:26463968

  11. Effect of body temperature on brain edema and encephalopathy in the rat after hepatic devascularization.

    PubMed

    Traber, P; DalCanto, M; Ganger, D; Blei, A T

    1989-03-01

    Brain edema is a fatal complication of fulminant hepatic failure and its pathogenesis remains unclear. To determine its presence in a model of ischemic hepatic failure, rats were subjected to a portacaval anastomosis followed by hepatic artery ligation. Brain water was measured using the sensitive gravimetric method. Preliminary studies revealed marked hypothermia in devascularized animals kept at room temperature (26.9 degrees +/- 2.8 degrees C). An additional group of devascularized rats was kept in an incubator. As expected for hypothermia, such animals had a lower arterial pressure and heart rate; the duration of encephalopathy was markedly prolonged. Water content of the cortical gray matter was only increased in normothermic devascularized rats: 80.14% +/- 0.31%, normal; 80.06% +/- 0.22%, portacaval shunt only; 80.42% +/- 0.26%, devascularized at room temperature; 81.29% +/- 0.38%, devascularized at controlled temperature (p less than 0.001). Such differences could not be detected using the dry-weight technique in whole cerebral hemispheres. Astrocyte changes in the cortical gray matter were noted in both edematous and nonedematous devascularized groups, coupled with the presence of vesicles containing horseradish peroxidase in the endothelial capillary cell. This suggests that in this model, brain edema may be due to both a cytotoxic mechanism and changes in the permeability of the blood-brain barrier. Future studies with this widely used model will require strict control of temperature to allow interpretation of experimental results. A therapeutic role for hypothermia in the management of brain edema deserves further attention. PMID:2914649

  12. Proton relaxation in acute and subacute ischemic brain edema

    SciTech Connect

    Boisvert, D.P.; Handa, Y.; Allen, P.S. )

    1990-01-01

    The relation between regional ischemic brain edema and tissue proton relaxation rates (R1 = 1/T1; R2 = 1/T2) were studied in 16 macaque monkeys subjected to MCA occlusion. In vivo R2 measurements were obtained from multiple spin-echo (eight echoes) images taken at 2-, 3-, 4-, and 72-hr postischemia. In vitro R1 and R2 values were determined for corresponding regions after sacrifice at 4 hr (n = 8) or at 72-hr postischemia in seven surviving animals. The water content of the white and gray matter tissue samples was measured by the wet/dry method. Four animals (25%) showed ipsilateral regions of increased signal intensity as early as 2 hr after MCA occlusion. All seven animals imaged at 72 hr displayed such regions. Despite the absence of measured changes in tissue water content, significant decreases in R2, but not in R1, occurred at 4 hr. At this stage, R2 values correlated more closely than R1 with individual variations in water content. At 72 hr, marked decreases in both R1 and R2 were measured in ischemic deep gray matter and white matter. Cortical gray matter was unchanged. In edematous gray and white matter, both R1 and R2 correlated closely with tissue water content, but R2 was consistently 10 to 20 times more sensitive than R1. Biexponential R2 decay was observed at 4 and 72 hr, but only in the white matter region that became severely edematous at 72 hr.

  13. Midline-shift corresponds to the amount of brain edema early after hemispheric stroke--an MRI study in rats.

    PubMed

    Walberer, Maureen; Blaes, Franz; Stolz, Erwin; Müller, Clemens; Schoenburg, Markus; Tschernatsch, Marlene; Bachmann, Georg; Gerriets, Tibo

    2007-04-01

    Vasogenic brain edema formation is a serious complication in hemispheric stroke. Its space-occupying effect can lead to midline-shift (MLS), cerebral herniation, and death. Clinical studies indicate that quantification of MLS can predict cerebral herniation and subsequent death at early time-points, even before clinical deterioration becomes apparent. The present experimental study was designed to determine the relation between MLS, absolute edema volume, lesion size, and clinical findings in a rat stroke model. Middle cerebral artery-occlusion was performed in 24 rats using the suture technique. Clinical evaluation and magnetic resonance imaging (MRI) (Bruker PharmaScan 7.0T) was performed 24 hours later. Lesion volume, the volume-increase within the affected hemisphere (%HEV), and MLS were quantified on T2-weighted images. The absolute increase of hemispheric water content (DeltaH2O) was determined in a subgroup using the wet-dry method (n=12). MLS correlated significantly with the total amount of brain edema (magnetic resonance imaging study: r=0.82; P<0.01; wet-dry analysis r=0.80; P<0.01). MLS correlated only moderately with T2-lesion volume (r=0.55; P<0.01). No significant correlation could be detected between MLS and clinical scores (r=0.26; P>0.05). MLS thus quantitatively reflects the amount of vasogenic brain edema within the affected hemisphere at early time-points. MLS quantification can be regarded as an easily assessable and valid global quantitative parameter for brain edema and thus might facilitate the surgical and nonsurgical management of edema in acute stroke patients. PMID:17413996

  14. Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema.

    PubMed

    Zeynalov, Emil; Jones, Susan M; Elliott, J Paul

    2016-01-01

    Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among the most important players in the development and evolution of stroke-evoked brain edema is the hormone arginine-vasopressin and its receptors, V1a and V2. Recently, the V1a and V2 receptor blocker conivaptan has been attracting attention as a potential drug to reduce brain edema after stroke. However, animal models which involve conivaptan applications in stroke research need to be modified based on feasible routes of administration. Here the outcomes of 48 hr continuous intravenous (IV) are compared with intraperitoneal (IP) conivaptan treatments after experimental stroke in mice. We developed a protocol in which middle cerebral artery occlusion was combined with catheter installation into the jugular vein for IV treatment of conivaptan (0.2 mg) or vehicle. Different cohorts of animals were treated with 0.2 mg bolus of conivaptan or vehicle IP daily. Experimental stroke-evoked brain edema was evaluated in mice after continuous IV and IP treatments. Comparison of the results revealed that the continuous IV administration of conivaptan alleviates post-ischemic brain edema in mice, unlike the IP administration of conivaptan. We conclude that our model can be used for future studies of conivaptan applications in the context of stroke and brain edema. PMID:27684044

  15. Brain Edema after Repeat Gamma Knife Radiosurgery for a Large Arteriovenous Malformation: A Case Report

    PubMed Central

    Kim, Joo Whan; Chung, Hyun-Tai; Han, Moon Hee; Kim, Dong Gyu

    2016-01-01

    Brain edema due to venous thrombosis following stereotactic radiosurgery for a cerebral arteriovenous malformation (AVM) has rarely been reported. We report a patient with a large AVM in the eloquent area, and brain edema developed in this area after repeat Gamma knife stereotactic radiosurgery (GKRS). An 18-year-old female presented with a 4-year-history of persistent headache. Magnetic resonance imaging and transfemoral carotid angiogram revealed a high-flow large AVM in the left parieto-occipital area. Brain edema developed and aggravated patient's symptoms after time-staged GKRS. The cause of edema was thought to be the failure of the surrounding venous channels to drain the venous flow from the normal brain and the drainage was hampered by the persistent shunt flow from the AVM, which was due to the thrombosis of one huge draining vein of the AVM. The microsurgical resection of the AVM nidus eliminated shunt flow and completely normalized the brain edema. Microsurgical resection of the AVM nidus completely normalized the brain edema due to thrombosis of a draining vein of an AVM develops after SRS. PMID:27574486

  16. Brain Edema after Repeat Gamma Knife Radiosurgery for a Large Arteriovenous Malformation: A Case Report.

    PubMed

    Kim, Joo Whan; Chung, Hyun-Tai; Han, Moon Hee; Kim, Dong Gyu; Paek, Sun Ha

    2016-08-01

    Brain edema due to venous thrombosis following stereotactic radiosurgery for a cerebral arteriovenous malformation (AVM) has rarely been reported. We report a patient with a large AVM in the eloquent area, and brain edema developed in this area after repeat Gamma knife stereotactic radiosurgery (GKRS). An 18-year-old female presented with a 4-year-history of persistent headache. Magnetic resonance imaging and transfemoral carotid angiogram revealed a high-flow large AVM in the left parieto-occipital area. Brain edema developed and aggravated patient's symptoms after time-staged GKRS. The cause of edema was thought to be the failure of the surrounding venous channels to drain the venous flow from the normal brain and the drainage was hampered by the persistent shunt flow from the AVM, which was due to the thrombosis of one huge draining vein of the AVM. The microsurgical resection of the AVM nidus eliminated shunt flow and completely normalized the brain edema. Microsurgical resection of the AVM nidus completely normalized the brain edema due to thrombosis of a draining vein of an AVM develops after SRS. PMID:27574486

  17. Histological examination on edema formation in the rabbit brain exposed to head-down tilt.

    PubMed

    Shimoyama, R; Kawai, Y

    2000-07-01

    Previous studies demonstrated that exposure to simulated microgravity, head-down tilt (HDT), caused cephalad fluid shift, increased capillary pressure in the head, and produced facial edema and nasal congestion. It is also known that exposure to HDT affects hemodynamics in the brain. Cerebral blood flow (CBF) velocity increases for at least 6 hours after the onset of 6 degrees HDT in humans. Intracranial pressure (ICP) elevates during 6 degrees HDT in humans and monkeys. However, there is little information regarding edema formation in the brain due to HDT except a morphological study reported by Kaplansky and colleagues who showed that perivascular edema occurred in the monkey brain after 7 days of 6 degrees HDT. Thus, it is interesting to examine whether edema formation occurs in the other animal model for simulation of microgravity, since several factors such as the duration of HDT, angle of HDT, and species difference may affect the result. In the present study, formation of brain edema was investigated by histological examinations in rabbits exposed to 45 degrees HDT for 2 days or 8 days. We hypothesized that HDT causes brain edema which can be demonstrated as extravasation of plasma constituents and histological changes.

  18. Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression.

    PubMed

    Ampawong, Sumate; Chaisri, Urai; Viriyavejakul, Parnpen; Nontprasert, Apichart; Grau, Georges E; Pongponratn, Emsri

    2014-01-01

    The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.

  19. Sulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure

    PubMed Central

    Jayakumar, A.R.; Valdes, V.; Tong, X.Y.; Shamaladevi, N.; Gonzalez, W.; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, non-selective cation channel (NCCa-ATP channel). We therefore examined its potential role in the astrocyte swelling/brain edema associated with ALF. Cultured astrocytes treated with 5 mM ammonia showed a 3-fold increase in the sulfonylurea receptor type 1 (SUR1) protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with glibenclamide significantly reduced the ammonia-induced cell swelling in cultured astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured astrocytes was significantly reduced by co-treatment of cells with BAY 11-7082, an inhibitor of NF-κB, indicating the involvement of an NF-κB-mediated SUR1 upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1 mRNA level was also found to be increased in the thioacetamide (TAA) rat model of ALF. Additionally, we found a significant increase in SUR1 protein expression in rat brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide significantly reduced the brain edema in this model of ALF. These findings strongly suggest the involvement of NCCa-ATP channel in the astrocyte swelling/brain edema in ALF, and that targeting this channel may represent a useful approach for the treatment of the brain edema associated with ALF. PMID:24443056

  20. Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia.

    PubMed

    Kiyatkin, Eugene A; Brown, P Leon; Sharma, Hari S

    2007-09-01

    To clarify the role of brain temperature in permeability of the blood-brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 degrees C) and warm (29 degrees C) environmental conditions and internal temperatures were monitored both centrally (nucleus accumbens, NAcc) and peripherally (skin and nonlocomotor muscle). Once NAcc temperatures peaked or reached 41.5 degrees C (a level suggesting possible lethality), animals were administered Evans blue dye (protein tracer that does not normally cross the BBB), rapidly anaesthetized, perfused and had their brains removed. All METH-treated animals showed brain and body hyperthermia associated with relative skin hypothermia, suggesting metabolic activation coupled with peripheral vasoconstriction. While METH-induced NAcc temperature elevation varied from 37.60 to 42.46 degrees C (or 1.2-5.1 degrees C above baseline), it was stronger at 29 degrees C (+4.13 degrees C) than 23 degrees C (+2.31 degrees C). Relative to control, METH-treated animals had significantly higher brain levels of water, Na(+), K(+) and Cl(-), suggesting brain edema, and intense immunostaining for albumin, indicating breakdown of the BBB. METH-treated animals also showed strong immunoreactivity for glial fibrillary acidic protein (GFAP), possibly suggesting acute abnormality or damage of astrocytes. METH-induced changes in brain water, albumin and GFAP correlated linearly with NAcc temperature (r = 0.93, 0.98 and 0.98, respectively), suggesting a key role of brain hyperthermia in BBB permeability, development of brain edema and subsequent functional and structural neural abnormalities. Therefore, along with a direct destructive action on neural cells and functions, brain hyperthermia, via breakdown of the BBB, may be crucial for both decompensation of brain functions and cell injury following acute METH intoxication, possibly contributing to neurodegeneration resulting from chronic drug use.

  1. Effects of cervical-lymphatic blockade on brain edema and infarction volume in cerebral ischemic rats.

    PubMed

    Si, Jinchao; Chen, Lianbi; Xia, Zuoli

    2006-10-31

    To observe the effects of cervical-lymphatic blockade (CLB) on brain edema and infarction volume of ischemic (MCAO) rat, we examined changes in cerebral water content, Ca2+ and glutamate concentrations, cerebral infarction volume and mRNA expression levels of N-methyl-D-aspartame receptor 1 (NMDA receptor 1) in the ischemic (left) hemisphere. The present results demonstrated that all the above indices in rats with middle cerebral artery occlusion plus cervical lymphatic blockade (MCAO+CLB) were markedly higher than those with only middle cerebral artery occlusion (MCAO) at different time points. These results indicated [corrected] that CLB can aggravate cerebral ischemia by increasing brain edema and infarction volume.

  2. Dimethyl fumarate attenuates cerebral edema formation by protecting the blood-brain barrier integrity.

    PubMed

    Kunze, Reiner; Urrutia, Andrés; Hoffmann, Angelika; Liu, Hui; Helluy, Xavier; Pham, Mirko; Reischl, Stefan; Korff, Thomas; Marti, Hugo H

    2015-04-01

    Brain edema is a hallmark of various neuropathologies, but the underlying mechanisms are poorly understood. We aim to characterize how tissue hypoxia, together with oxidative stress and inflammation, leads to capillary dysfunction and breakdown of the blood-brain barrier (BBB). In a mouse stroke model we show that systemic treatment with dimethyl fumarate (DMF), an antioxidant drug clinically used for psoriasis and multiple sclerosis, significantly prevented edema formation in vivo. Indeed, DMF stabilized the BBB by preventing disruption of interendothelial tight junctions and gap formation, and decreased matrix metalloproteinase activity in brain tissue. In vitro, DMF directly sustained endothelial tight junctions, inhibited inflammatory cytokine expression, and attenuated leukocyte transmigration. We also demonstrate that these effects are mediated via activation of the redox sensitive transcription factor NF-E2 related factor 2 (Nrf2). DMF activated the Nrf2 pathway as shown by up-regulation of several Nrf2 target genes in the brain in vivo, as well as in cerebral endothelial cells and astrocytes in vitro, where DMF also increased protein abundance of nuclear Nrf2. Finally, Nrf2 knockdown in endothelial cells aggravated subcellular delocalization of tight junction proteins during ischemic conditions, and attenuated the protective effect exerted by DMF. Overall, our data suggest that DMF protects from cerebral edema formation during ischemic stroke by targeting interendothelial junctions in an Nrf2-dependent manner, and provide the basis for a completely new approach to treat brain edema. PMID:25725349

  3. 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

  4. Telmisartan reduced cerebral edema by inhibiting NLRP3 inflammasome in mice with cold brain injury.

    PubMed

    Wei, Xin; Hu, Chen-Chen; Zhang, Ya-Li; Yao, Shang-Long; Mao, Wei-Ke

    2016-08-01

    The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation. PMID:27465336

  5. Quick detection of brain tumors and edemas: a bounding box method using symmetry.

    PubMed

    Saha, Baidya Nath; Ray, Nilanjan; Greiner, Russell; Murtha, Albert; Zhang, Hong

    2012-03-01

    A significant medical informatics task is indexing patient databases according to size, location, and other characteristics of brain tumors and edemas, possibly based on magnetic resonance (MR) imagery. This requires segmenting tumors and edemas within images from different MR modalities. To date, automated brain tumor or edema segmentation from MR modalities remains a challenging, computationally intensive task. In this paper, we propose a novel automated, fast, and approximate segmentation technique. The input is a patient study consisting of a set of MR slices, and its output is a subset of the slices that include axis-parallel boxes that circumscribe the tumors. Our approach is based on an unsupervised change detection method that searches for the most dissimilar region (axis-parallel bounding boxes) between the left and the right halves of a brain in an axial view MR slice. This change detection process uses a novel score function based on Bhattacharya coefficient computed with gray level intensity histograms. We prove that this score function admits a very fast (linear in image height and width) search to locate the bounding box. The average dice coefficients for localizing brain tumors and edemas, over ten patient studies, are 0.57 and 0.52, respectively, which significantly exceeds the scores for two other competitive region-based bounding box techniques. PMID:21719256

  6. Reduction of cerebral edema after traumatic brain injury using an osmotic transport device.

    PubMed

    McBride, Devin W; Szu, Jenny I; Hale, Chris; Hsu, Mike S; Rodgers, Victor G J; Binder, Devin K

    2014-12-01

    Traumatic brain injury (TBI) is significant, from a public health standpoint, because it is a major cause of the morbidity and mortality of young people. Cerebral edema after a TBI, if untreated, can lead to devastating damage of the remaining tissue. The current therapies of severe TBI (sTBI), as outlined by the Brain Trauma Foundation, are often ineffective, thus a new method for the treatment of sTBI is necessary. Herein, the reduction of cerebral edema, after TBI, using an osmotic transport device (OTD) was evaluated. Controlled cortical impact (CCI) was performed on adult female CD-1 mice, and cerebral edema was allowed to form for 3 h, followed by 2 h of treatment. The treatment groups were craniectomy only, craniectomy with a hydrogel, OTD without bovine serum albumin (BSA), and OTD. After CCI, brain water content was significantly higher for animals treated with a craniectomy only, craniectomy with a hydrogel, and OTD without BSA, compared to that of control animals. However, when TBI animals were treated with an OTD, brain water content was not significantly higher than that of controls. Further, brain water content of TBI animals treated with an OTD was significantly reduced, compared to that of untreated TBI animals, TBI animals treated with a craniectomy and a hydrogel, and TBI animals treated with an OTD without BSA. Here, we demonstrate the successful reduction of cerebral edema, as determined by brain water content, after TBI using an OTD. These results demonstrate proof of principle for direct water extraction from edematous brain tissue by direct osmotherapy using an OTD.

  7. Cerebral edema following iodine-131 therapy for thyroid carcinoma metastatic to the brain

    SciTech Connect

    Datz, F.L.

    1986-05-01

    Brain metastases are rare in well-differentiated thyroid carcinoma but when present they can lead to the patient's death. Iodine-131 therapy for intracerebral thyroid carcinoma metastases causes radiation-induced acute cerebral edema that can lead to CNS complications and even death. We present a case in which a patient with intracerebral /sup 131/I uptake developed seizures, slurred speech, and muscle weakness 12 hr following /sup 131/I therapy. The patient's CT scan, post-therapy, confirmed an intracranial metastasis with a significant amount of surrounding edema. Radiotherapists, when using external beam radiation to treat intracerebral metastases, commonly place these patients on steroids, glycerol, or mannitol prior to instituting therapy, to prevent complications from radiation-induced cerebral edema. This technique could be applied to /sup 131/I therapy of intracranial thyroid carcinoma metastases as well.

  8. Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats.

    PubMed

    Irisawa, Yumi; Adachi, Naoto; Liu, Keyue; Arai, Tatsuru; Nagaro, Takumi

    2008-09-01

    We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.

  9. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

    PubMed

    Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

    2014-03-01

    Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

  10. Effect of dl-3-n-butylphthalide on brain edema in rats subjected to focal cerebral ischemia.

    PubMed

    Deng, W; Feng, Y

    1997-06-01

    The present study evaluated the effect of dl-3-n-butylphthalide(NBP), a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO), producing permanent focal ischemia in the right cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements, and the sodium, potassium concentrations with ion-selective electrodes. In this model, NBP at the dose of 80, 160 and 240 mg/kg p.o. 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry, sodium accumulation and potassium loss. Nimodipine treatment (5 mg/kg s.c.) also reduced brain edema (P < 0.05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.

  11. Segmentation of tumor and edema along with healthy tissues of brain using wavelets and neural networks.

    PubMed

    Demirhan, Ayşe; Toru, Mustafa; Guler, Inan

    2015-07-01

    Robust brain magnetic resonance (MR) segmentation algorithms are critical to analyze tissues and diagnose tumor and edema in a quantitative way. In this study, we present a new tissue segmentation algorithm that segments brain MR images into tumor, edema, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The detection of the healthy tissues is performed simultaneously with the diseased tissues because examining the change caused by the spread of tumor and edema on healthy tissues is very important for treatment planning. We used T1, T2, and FLAIR MR images of 20 subjects suffering from glial tumor. We developed an algorithm for stripping the skull before the segmentation process. The segmentation is performed using self-organizing map (SOM) that is trained with unsupervised learning algorithm and fine-tuned with learning vector quantization (LVQ). Unlike other studies, we developed an algorithm for clustering the SOM instead of using an additional network. Input feature vector is constructed with the features obtained from stationary wavelet transform (SWT) coefficients. The results showed that average dice similarity indexes are 91% for WM, 87% for GM, 96% for CSF, 61% for tumor, and 77% for edema.

  12. Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation.

    PubMed

    Wang, Yu-Feng; Parpura, Vladimir

    2016-01-01

    Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas, associated with maladapted astrocytic plasticity. The astrocytic plasticity includes both morphological and functional plasticity. The former involves a reactive gliosis and the subsequent glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K(+) and glutamate, as well as the integrity of the blood-brain barrier (BBB). The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein (GFAP) and water channel protein aquaporin 4 (AQP4) to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the BBB. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the BBB, but also leads to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation. PMID:27242440

  13. Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation

    PubMed Central

    Wang, Yu-Feng; Parpura, Vladimir

    2016-01-01

    Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas, associated with maladapted astrocytic plasticity. The astrocytic plasticity includes both morphological and functional plasticity. The former involves a reactive gliosis and the subsequent glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K+ and glutamate, as well as the integrity of the blood-brain barrier (BBB). The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein (GFAP) and water channel protein aquaporin 4 (AQP4) to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the BBB. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the BBB, but also leads to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation. PMID:27242440

  14. Perilesional brain edema and seizure activity in patients with calcified neurocysticercosis

    PubMed Central

    Nash, Theodore E.; Pretell, E. Javier; Lescano, Andres. G.; Bustos, Javier A.; Gilman, Robert H.; Gonzalez, Armando E.; Garcia, Héctor H.

    2013-01-01

    Background Cysticercosis due to Taenia solium is a leading cause of adult acquired seizures and epilepsy that frequently occurs in patients with only calcified larval cysts. Transient episodes of perilesional brain edema occur around calcified foci but its importance, association with seizures, incidence, and pathophysiology are unknown. Methods One hundred and ten persons with only calcified lesions and a history of seizures or severe headaches were followed prospectively in a cohort design to assess the incidence of seizure relapses. In a nested case-control sub study, perilesional edema was assessed by MRI at the time a seizure occurred in the symptomatic patient and in a matched asymptomatic control, amongst the 110 followed. Results Median follow up was 32.33 months (SD 19.99). Twenty-nine people had an incident seizure with an estimated 5 year seizure incidence of 36%. Twenty-four patients of the 29 with seizure relapse had an MRI evaluation within five days of the event. Perilesional edema was found in 12 (50.0%) compared to 2 of 23 asymptomatic matched controls (8.7%). Conclusions Perilesional edema occurs frequently and is associated with episodic seizure activity in calcified neurocysticercosis. Our findings are likely representative of symptomatic patients in endemic regions and suggest a unique and possibly preventable cause of seizures in this population. PMID:18986841

  15. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema.

    PubMed

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten; Thomsen, Carsten; Juhler, Marianne; Laursen, Henning; Broholm, Helle

    2011-12-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined. Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p < 0.05). The capillary length in the meningiomas was positively correlated to the PTBE (p = 0.038). If VEGF is responsible for the formation of PTBE, the edema may be treated with the anti-VEGF drug Bevacizumab (Avastin), which has been shown to reduce PTBE in patients with glioblastoma multiforme. PMID:22085359

  16. Multi-fractal texture features for brain tumor and edema segmentation

    NASA Astrophysics Data System (ADS)

    Reza, S.; Iftekharuddin, K. M.

    2014-03-01

    In this work, we propose a fully automatic brain tumor and edema segmentation technique in brain magnetic resonance (MR) images. Different brain tissues are characterized using the novel texture features such as piece-wise triangular prism surface area (PTPSA), multi-fractional Brownian motion (mBm) and Gabor-like textons, along with regular intensity and intensity difference features. Classical Random Forest (RF) classifier is used to formulate the segmentation task as classification of these features in multi-modal MRIs. The segmentation performance is compared with other state-of-art works using a publicly available dataset known as Brain Tumor Segmentation (BRATS) 2012 [1]. Quantitative evaluation is done using the online evaluation tool from Kitware/MIDAS website [2]. The results show that our segmentation performance is more consistent and, on the average, outperforms other state-of-the art works in both training and challenge cases in the BRATS competition.

  17. A fatal adverse effect of cefazolin administration: severe brain edema in a patient with multiple meningiomas.

    PubMed

    Tribuddharat, Sirirat; Sathitkarnmanee, Thepakorn; Kitkhuandee, Amnat; Theerapongpakdee, Sunchai; Ngamsaengsirisup, Kriangsak; Chanthawong, Sarinya

    2016-01-01

    Cefazolin is commonly administered before surgery as a prophylactic antibiotic. Hypersensitivity to cefazolin is not uncommon, and the symptoms mostly include urticaria, skin reaction, diarrhea, vomiting, and transient neutropenia, which are rarely life threatening. We present a rare case of fatal cefazolin hypersensitivity in a female who was diagnosed with multiple meningiomas and scheduled for craniotomy and tumor removal. Immediately after cefazolin IV administration, the patient developed acute hypertensive crisis, which resolved within 10 minutes after the treatment. This was followed by unexplained metabolic acidosis. The patient then developed severe brain edema 100 minutes later. The patient had facial edema when her face was exposed for the next 30 minutes. A computed tomography scan revealed global brain edema with herniation. She was admitted to the intensive care unit for symptomatic treatment and died 10 days after surgery from multiorgan failure. The serum IgE level was very high (734 IU/mL). Single-dose administration of cefazolin for surgical prophylaxis may lead to rare, fatal adverse reaction. The warning signs are sudden, unexplained metabolic acidosis, hypertensive crisis, tachycardia, and facial angioedema predominating with or without cutaneous symptoms like urticaria. PMID:26929668

  18. An Unusual Transudative Pleural Effusion Succeeded by Pulmonary and Brain Edema and Death

    PubMed Central

    Mortazavimoghaddam, Sayyed Gholam Reza; Riasi, H. R.

    2012-01-01

    Here we report a 22-year old woman with massive and bilateral transudative effusion succeeded by pulmonary edema and brain edema and death. Investigations for systemic disorders were negative. Exacerbation of dyspnea after intravenous fluid infusion was a main problem. As effusion was refractory to medical treatment, the patient was referred for surgical pleurodesis and bilateral surgical pleurodesis were done separately. Postsurgically, dyspnea exacerbation occurred after each common cold infection. Vertigo and high intracranial pressure were also a problem postsurgically. CSF pressure was 225 mm/H2O. Therapeutic lumbar puncture was done in two sequential weeks, and the patient was on acetazolamide 250 mg/trivise a day. Despite the medical treatment, progressive dyspnea, headache, and high intracranial pressure followed by death nine months after pleurodesis. As there is a gradient of pressure between pleura and CSF, after pleurodesis brain edema must be a consequence of inversing this gradient. In conclusion, when there are any abnormalities about fluid volume or pressure in any of these cavities, we have to study other cavities. PMID:22934227

  19. Volumetric electromagnetic phase-shift spectroscopy of brain edema and hematoma.

    PubMed

    Gonzalez, Cesar A; Valencia, Jose A; Mora, Alfredo; Gonzalez, Fernando; Velasco, Beatriz; Porras, Martin A; Salgado, Javier; Polo, Salvador M; Hevia-Montiel, Nidiyare; Cordero, Sergio; Rubinsky, Boris

    2013-01-01

    Motivated by the need of poor and rural Mexico, where the population has limited access to advanced medical technology and services, we have developed a new paradigm for medical diagnostic based on the technology of "Volumetric Electromagnetic Phase Shift Spectroscopy" (VEPS), as an inexpensive partial substitute to medical imaging. VEPS, can detect changes in tissue properties inside the body through non-contact, multi-frequency electromagnetic measurements from the exterior of the body, and thereby provide rapid and inexpensive diagnostics in a way that is amenable for use in economically disadvantaged parts of the world. We describe the technology and report results from a limited pilot study with 46 healthy volunteers and eight patients with CT radiology confirmed brain edema and brain hematoma. Data analysis with a non-parametric statistical Mann-Whitney U test, shows that in the frequency range of from 26 MHz to 39 MHz, VEPS can distinguish non-invasively and without contact, with a statistical significance of p<0.05, between healthy subjects and those with a medical conditions in the brain. In the frequency range of between 153 MHz to 166 MHz it can distinguish with a statistical significance of p<0.05 between subjects with brain edema and those with a hematoma in the brain. A classifier build from measurements in these two frequency ranges can provide instantaneous diagnostic of the medical condition of the brain of a patient, from a single set of measurements. While this is a small-scale pilot study, it illustrates the potential of VEPS to change the paradigm of medical diagnostic of brain injury through a VEPS classifier-based technology. Obviously substantially larger-scale studies are needed to verify and expand on the findings in this small pilot study.

  20. Volumetric Electromagnetic Phase-Shift Spectroscopy of Brain Edema and Hematoma

    PubMed Central

    Gonzalez, Cesar A.; Valencia, Jose A.; Mora, Alfredo; Gonzalez, Fernando; Velasco, Beatriz; Porras, Martin A.; Salgado, Javier; Polo, Salvador M.; Hevia-Montiel, Nidiyare; Cordero, Sergio; Rubinsky, Boris

    2013-01-01

    Motivated by the need of poor and rural Mexico, where the population has limited access to advanced medical technology and services, we have developed a new paradigm for medical diagnostic based on the technology of “Volumetric Electromagnetic Phase Shift Spectroscopy” (VEPS), as an inexpensive partial substitute to medical imaging. VEPS, can detect changes in tissue properties inside the body through non-contact, multi-frequency electromagnetic measurements from the exterior of the body, and thereby provide rapid and inexpensive diagnostics in a way that is amenable for use in economically disadvantaged parts of the world. We describe the technology and report results from a limited pilot study with 46 healthy volunteers and eight patients with CT radiology confirmed brain edema and brain hematoma. Data analysis with a non-parametric statistical Mann-Whitney U test, shows that in the frequency range of from 26 MHz to 39 MHz, VEPS can distinguish non-invasively and without contact, with a statistical significance of p<0.05, between healthy subjects and those with a medical conditions in the brain. In the frequency range of between 153 MHz to 166 MHz it can distinguish with a statistical significance of p<0.05 between subjects with brain edema and those with a hematoma in the brain. A classifier build from measurements in these two frequency ranges can provide instantaneous diagnostic of the medical condition of the brain of a patient, from a single set of measurements. While this is a small-scale pilot study, it illustrates the potential of VEPS to change the paradigm of medical diagnostic of brain injury through a VEPS classifier-based technology. Obviously substantially larger-scale studies are needed to verify and expand on the findings in this small pilot study. PMID:23691001

  1. The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.

    PubMed Central

    Criscuolo, G. R.

    1993-01-01

    Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention. Images Figure 1 Figure 2 Figure 3 PMID:7516104

  2. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    PubMed

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  3. Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema

    NASA Astrophysics Data System (ADS)

    Xie, J.; Qian, Z.; Yang, T.; Li, W.; Hu, G.

    2011-01-01

    The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (μs') and BWC. By recording μs' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

  4. Association Between a Quantitative CT Scan Measure of Brain Edema and Outcome After Cardiac Arrest

    PubMed Central

    Metter, Robert B.; Rittenberger, Jon C.; Guyette, Francis X.; Callaway, Clifton W.

    2011-01-01

    Background Cerebral edema is one physical change associated with brain injury and decreased survival after cardiac arrest. Edema appears on computed tomography (CT) scan of the brain as decreased x-ray attenuation by gray matter. This study tested whether the gray matter attenuation to white matter attenuation ratio (GWR) was associated with survival and functional recovery. Methods Subjects were patients hospitalized after cardiac arrest at a single institution between 1/1/2005 and 7/30/2010. Subjects were included if they had non-traumatic cardiac arrest and a non-contrast CT scan within 24 hours after cardiac arrest. Attenuation (Hounsfield Units) was measured in gray matter (caudate nucleus, putamen, thalamus, and cortex) and in white matter (internal capsule, corpus callosum and centrum semiovale). The GWR was calculated for basal ganglia and cerebrum. Outcomes included survival and functional status at hospital discharge. Results For 680 patients, 258 CT scans were available, but 18 were excluded because of hemorrhage (10), intravenous contrast (3) or technical artifact (5), leaving 240 CT scans for analysis. Lower GWR values were associated with lower initial Glasgow Coma Scale motor score. Overall survival was 36%, but decreased with decreasing GWR. The average of basal ganglia and cerebrum GWR provided the best discrimination. Only 2/58 subjects with average GWR<1.20 survived and both were treated with hypothermia. The association of GWR with functional outcome was completely explained by mortality when GWR<1.20. Conclusions Subjects with severe cerebral edema, defined by GWR<1.20, have very low survival with conventional care, including hypothermia. GWR estimates pre-treatment likelihood of survival after cardiac arrest. PMID:21592642

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

    PubMed

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

    1997-01-01

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

  6. Severity profile of penetrating ballistic-like brain injury on neurofunctional outcome, blood-brain barrier permeability, and brain edema formation.

    PubMed

    Shear, Deborah A; Lu, Xi-Chun May; Pedersen, Rebecca; Wei, Guo; Chen, Zhiyong; Davis, Angela; Yao, Changping; Dave, Jitendra; Tortella, Frank C

    2011-10-01

    This study evaluated the injury severity profile of unilateral, frontal penetrating ballistic-like brain injury (PBBI) on neurofunctional outcome, blood-brain barrier (BBB) permeability, and brain edema formation. The degree of injury severity was determined by the delivery of a water-pressure pulse designed to produce a temporary cavity by rapid (<40 ms) expansion of the probe's elastic balloon calibrated to equal 5%, 10%, 12.5%, or 15% of total rat brain volume (control groups consisted of sham surgery or insertion of the probe only). Neurofunctional assessments revealed motor and cognitive deficits related to the degree of injury severity, with the most clear-cut profile of PBBI injury severity depicted by the Morris water maze (MWM) results. A biphasic pattern of BBB leakage was detected in the injured hemisphere at all injury severity levels at 4 h post-injury, and again at 48-72 h post-injury, which remained evident out to 7 days post-PBBI in the 10% and 12.5% PBBI groups. Likewise, significant brain edema was detected in the injured hemisphere by 4 h post-injury and remained elevated out to 7 days post-injury in the 10% and 12.5% PBBI groups. However, following 5% PBBI, significant levels of edema were only detected from 24 h to 48h post-injury. These results identify an injury severity profile of BBB permeability, brain edema, and neurofunctional impairment that provides sensitive and clinically relevant outcome metrics for studying potential therapeutics.

  7. Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model.

    PubMed

    Ong, Qunya; Hochberg, Fred H; Cima, Michael J

    2015-11-10

    Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes.

  8. Brain natriuretic peptide levels in six basic underwater demolitions/SEAL recruits presenting with swimming induced pulmonary edema (SIPE).

    PubMed

    Shearer, Damon; Mahon, Richard

    2009-01-01

    Swimming induced pulmonary edema (SIPE) is associated with both SCUBA diving and strenuous surface swimming; however, the majority of reported cases and clinically observed cases tend to occur during or after aggressive surface swimming. Capillary stress failure appears to be central to the pathophysiology of this disorder. Regional pulmonary capillaries are exposed to relatively high pressures secondary to increased vascular volume, elevation of pulmonary vascular resistance, and regional differences in perfusion secondary to forces of gravity and high cardiac output. Acute pulmonary edema can be classified as either cardiogenic or noncardiogenic or both. Cardiogenic pulmonary edema occurs when the pulmonary capillary hydrostatic pressure exceeds plasma oncotic pressure. Noncardiogenic pulmonary edema occurs when pulmonary capillary permeability is increased. Given the pathophysiology noted above, SIPE can be described as a cardiogenic pulmonary edema, at least in part, since an increased transalveolar pressure gradient has been implicated in the pathogenesis of SIPE. Brain natriuretic peptide (BNP) is used in the clinical setting to differentiate cardiac from pulmonary sources of dyspnea, specifically to diagnose cardiogenic pulmonary edema. During clinical management, BNP levels were drawn on six BUD/S recruits simultaneously presenting with pulmonary complaints consistent with SIPE, after an extended surface bay swim. This paper analyzes that data after de-identification and reviews the pathophysiology and clinical management of SIPE.

  9. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

    PubMed Central

    YU, LIN-SHENG; FAN, YAN-YAN; YE, GUANGHUA; LI, JUNLI; FENG, XIANG-PING; LIN, KEZHI; DONG, MIUWU; WANG, ZHENYUAN

    2016-01-01

    The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditions, and were injected with water, CU, dimethyl sulfoxide (solvent control) or monosialoganglioside GM1. After 2 weeks, the morphological characteristics of the brain tissues were analyzed using optical and electron microscopy. In addition, aquaporin (AQP)-4 protein expression levels in brain tissue samples were analyzed using streptavidin-biotin complex immunohistochemistry and western blotting, and mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction. Severe brain edema, tissue structure disruption and increased AQP4 expression levels were detected in the brain tissues of the HH rats. Conversely, the rats treated with CU or GM1 exhibited attenuated HHBD-induced brain edema and tissue structure disruption, and decreased mRNA and protein expression levels of AQP4. The results of the present study suggested that CU treatment was able to attenuate HHBD-induced brain edema by downregulating the expression levels of AQP4 in a rat model. Therefore, CU may be considered a potential therapeutic drug for the treatment of patients with brain edema. PMID:26997983

  10. Relationship between specific gravity, water content, and serum protein extravasation in various types of vasogenic brain edema.

    PubMed

    Bothe, H W; Bodsch, W; Hossmann, K A

    1984-01-01

    Vasogenic brain edema was induced in cats by cold injury (six animals), brain tumors (five animals), and brain abscesses (six animals). Water and electrolyte content, specific gravity, blood volume, and the amount of extravasated serum proteins were determined in small tissue samples taken from gray and white matter at various distances from the lesion. Edema was strictly confined to the white matter of the affected hemisphere and declined from the lesion to the more peripheral regions. It was characterized by the extravasation of serum proteins and an increase of water and sodium content with little or unpredictable changes of potassium and blood volume. The calculated sodium content of edema fluid varied between 129 and 135 mueq/ml, and serum protein content between 8.1 and 11.9 mg/ml. In all three types of edema, specific gravity and water content correlated closely with the same slope and intercept of the calculated regression (y = 1.119-0.0011 x, r = -0.91). The results obtained indicate that the main denominator of specific gravity of edematous white matter is water content and that this relationship is not significantly altered by variations of blood volume or serum protein content. PMID:6475495

  11. Peripheral neuropathy in the Twitcher mutant. A new experimental model of endoneurial edema.

    PubMed

    Powell, H C; Knobler, R L; Myers, R R

    1983-07-01

    The Twitcher mouse (Twi/Twi) is a recently identified mutant experimental model for human globoid leukodystrophy. Affected mice develop neurologic abnormalities with demyelination of white matter and peripheral nerve due to an inherited enzyme deficiency. The neuropathy has unusual pathologic features:severe interstitial edema and infiltration by eosinophils. To investigate its pathogenesis and to identify the mechanism of demyelination, we studied vascular permeability and measured endoneurial fluid pressure. Significantly increased endoneurial fluid pressure was detected in clinically affected animals (average, 6.4 cm H2O) versus controls (1.7 cm H2O), and these data are the first measurements of EFP to be reported in mice. Increased vascular permeability to horseradish peroxidase was visualized by electron microscopy with leakage of horseradish peroxidase between endothelial cells and flooding of the endoneurial interstitium. Numerous eosinophils were present in the interstitium, as well as some polymorphonuclear cells, occasional erythrocytes, and degranulating mast cells. Abnormalities of nerve fibers included swelling of Schwann cells with intracytoplasmic inclusions, demyelination, and remyelination. As well as being a model for globoid leukodystrophy, the Twitcher is the first spontaneously occurring experimental model for endoneurial edema and increased endoneurial fluid pressure.

  12. The role of extracellular-5'-nucleotidase/CD73 in glioma peritumoural brain edema.

    PubMed

    Wang, Bo; Wang, Dong; Zhu, ZhiZhong; Wang, Wei; Zhang, XueBin; Tang, Fan; Zhou, Yu; Wang, HongGuang; Liu, MengYuan; Yao, Xin; Yan, XiaoLing

    2016-04-01

    During pathological conditions, extracellular-5'-nucleotidase/CD73 can protect neurons by reducing the permeability of the blood brain barrier. In recent years, it has been demonstrated that CD73 can negatively contribute to the growth of gliomas; however, the function of CD73 in glioma blood vessels is not clear. We analysed the expression of CD73 in 72 glioma patients using immunohistochemistry and correspondingly compared the results with the Edema index (EI). We established an in vitro model of the blood-tumour barrier and analysed the expression of CD73 in vascular endothelial cells. Lastly, CD73 expression was inhibited in endothelial cells, and the effects of this inhibition on tight junction structure and transendothelial resistance were observed. Compared to normal brains, the expression of CD73 in blood vessels of glioma patients was significantly decreased, and the amount was lower in the centre of the tumour than the periphery. The proportion of CD73-positive blood vessels had a positive correlation with the EI. The expression of CD73 in the in vitro endothelial cell blood-tumour barrier model was decreased. Lastly, inhibiting CD73 was found to decrease the expression of tight junction related proteins in endothelial cells and to decrease the value of transendothelial electric resistance. The expression of CD73 in glioma blood vessels was significantly decreased, which may play a multi-functional role in decreasing the expression of tight junction related proteins of brain microvascular endothelial cells and may also increase blood-tumour barrier permeability and accelerate the formation of PTBE. PMID:26884147

  13. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    PubMed

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (P<0.05-0.001, varied by the methods) and ameliorated motor function (P<0.05). The anti-glucocorticoid mifepristone or the anti-mineralocorticoid spironolactone abolished these effects, but orally administered corticosterone mimicked the ameliorating effects of exercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, P<0.01). Microglia and NG2 glia expressed NHE1 in the peri-ischemic region of rat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels.

  14. Brain edema and neurologic status with rapid infusion of 0.9% saline or 5% dextrose after head trauma.

    PubMed

    Shapira, Y; Artru, A A; Qassam, N; Navot, N; Vald, U

    1995-01-01

    We previously reported that intravenous (i.v.) administration of large volumes (0.2 ml/g) of either an isotonic dextrose-free solution or 5% dextrose solution given over 18 h after closed head trauma (CHT) in rats did not significantly affect neurological severity score or brain tissue specific gravity. However, it is possible that with more rapid administration, isotonic or 5% dextrose i.v. solutions may alter neurological outcome after CHT. Our study examined whether neurological severity score, brain tissue specific gravity and water content, and blood composition were significantly altered when 0.25 ml/g of either 0.9% saline or 5% dextrose was given i.v. over 0.5 h (rather than over 18 h) after CHT. Eight-four rats that survived ether anesthesia and CHT were randomly assigned to one of 11 experimental groups. Saline- and dextrose-treated rats were evaluated at 4 and 48 h after CHT and were compared to rats without CHT and to untreated rats at 4 and 48 h after CHT. There were no statistically significant differences in neurologic outcome and brain edema between the untreated and the saline-treated groups. However, 5% dextrose i.v. increased mortality (group 6 and 11, 50 and 0% survivors, respectively), decreased specific gravity in the noncontused hemisphere, and worsened neurologic outcome with and without CHT. Blood osmolality remained stable in comparison to the baseline value of 291.9 +/- 7.4 mOsm/kg (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7881236

  15. What predicts early volumetric edema increase following stereotactic radiosurgery for brain metastases?

    PubMed

    Hanna, Andrew; Boggs, D Hunter; Kwok, Young; Simard, Marc; Regine, William F; Mehta, Minesh

    2016-04-01

    A volumetric analysis of pre- and post-radiosurgery (PreSRS and PostSRS) edema in patients with cerebral metastases was performed to determine factors of a predictive model assessing the risk of developing increased edema relatively early after SRS. One-hundred-fourteen metastases in 55 patients were analyzed. Selection for this analysis required an MRI ≤ 30 days before SRS and an MRI ≤ 100 days after SRS. Tumor volumes were calculated on PreSRS, SRS, and PostSRS T1-weighted postgadolinium images while edema volumes were calculating using PreSRS and PostSRS fluid-attenuated inversion recovery MR images. An increase in edema was defined as an increase in measurable edema of at least 5%. We developed and evaluated a model predicting the relative risk (RR) of increased edema after SRS. Peritumoral edema increased in 18% (21/114) of the analyzed lesions. Melanoma/renal histology, recursive partitioning analysis class III, and prior WBRT carried RRs of developing postSRS edema increase of 2.45, 2.48, and 3.16, respectively (all P values <0.05). The PreSRS edema/tumor ratio predicted for a RR of 1.007/ratio unit, and steroid dose at time of SRS predicted for a RR of 0.89/mg (all P values <0.05). A predictive model for assessing the RR of increased edema after SRS was developed based from these data and may be useful in identifying patients who might benefit from prophylactic anti-edema therapies before, during, or after SRS. This model could be used as the basis of inclusion criteria for prospective trials investigating novel anti-edema therapies. PMID:26721241

  16. Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia

    PubMed Central

    Yao, Xiaoming; Derugin, Nikita; Manley, Geoffrey T.; Verkman, A. S.

    2015-01-01

    Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-hour transient MCAO produced by intraluminal suture blockade followed by 23 hours of reperfusion. In nine AQP4+/+ and nine AQP4−/− mice, infarct volume was significantly reduced by an average of 39 ± 4 % at 24 hours in AQP4−/− mice, cerebral hemispheric edema was reduced by 23 ± 3 %, and Evans blue extravasation was reduced by 31 ± 2 % (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4−/− mice. The reduced infarct volume in AQP4−/− mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke. PMID:25449874

  17. Improvement of cold injury-induced mouse brain edema by endothelin ETB antagonists is accompanied by decreases in matrixmetalloproteinase 9 and vascular endothelial growth factor-A.

    PubMed

    Michinaga, Shotaro; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Minami, Shizuho; Kimura, Akimasa; Hatanaka, Shunichi; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Koyama, Yutaka

    2015-09-01

    Brain edema is a potentially fatal pathological state that often occurs after brain injuries such as ischemia and trauma. However, therapeutic agents that fundamentally treat brain edema have not yet been established. We previously found that endothelin ETB receptor antagonists attenuate the formation and maintenance of vasogenic brain edema after cold injury in mice. In this study, the effects of ETB antagonists on matrixmetalloproteinase (MMP)9 and vascular endothelial growth factor (VEGF)-A expression were examined in the cold injury model. Cold injury was performed in the left brain of male ddY mice (5-6 weeks old) for the induction of vasogenic edema. Expression of MMP9 and VEGF-A mRNA in the mouse cerebrum was increased by cold injury. Immunohistochemical observations showed that the MMP9 and VEGF-A were mainly produced in reactive astrocytes in the damaged cerebrum. Intracerebroventricular administration of BQ788 (10 μg) or IRL-2500 (10 μg) (selective ETB antagonists) attenuated brain edema and disruption of the blood-brain barrier after cold injury. BQ788 and IRL-2500 reversed the cold injury-induced increases in MMP9 and VEGF-A expression. The induction of reactive astrocytes producing MMP9 and VEGF-A in the damaged cerebrum was attenuated by BQ788 and IRL-2500. These results suggest that attenuations of astrocytic MMP9 and VEGF-A expression by ETB antagonists may be involved in the amelioration of vasogenic brain edema.

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

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

  20. Differences in brain edema and intracranial pressure following traumatic brain injury across the estrous cycle: involvement of female sex steroid hormones.

    PubMed

    Maghool, Fatemeh; Khaksari, Mohammad; Siahposht Khachki, Ali

    2013-02-25

    It has been shown that sex steroid hormones have profound neuroprotective effects in experimental traumatic brain injury (TBI). Because the endogenous hormone levels are proven to differ with estrous cycle stage, we evaluated whether estrous cycle stage affects various outcomes following diffuse TBI. TBI was induced by Marmarou's method in normal cycling and in ovariectomized rats with physiologically relevant restoration of hormonal levels by hormone capsule implantation. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were measured before and different times after TBI and brain edema was assessed at 24h after trauma. Results indicated that after TBI, water content (WC) in traumatic proestrous (TP) rats was less than the one in traumatic non-proestrous (TNP) and ovariectomized (TOVX) and also in high estradiol (HE) and progesterone (HP) was statistically less than in TBI untreated groups.There was no significant difference in WC between high doses hormone treated and TP and also between TNP, TOVX, low estradiol (LE) and progesterone (LP) groups. At 4h and 24h after trauma, there was a significant difference in ICP between TP, HE and HP compared to TNP and other TBI nontreated groups. Also in these times, the CPP increased in TP and hormone treated groups compared with TOVX, but the difference between TNP and TOVX was not significant. The results indicate that the estrous cycle has a prominent role in TBI outcome's and the difference in female sex steroid levels might be the reason of the different neuroprotective effects in proestrous and non-proestrous groups.

  1. Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury.

    PubMed

    Jin, Hongbo; Li, Wenling; Dong, Changzheng; Ma, Li; Wu, Jiang; Zhao, Wenqing

    2016-01-01

    BACKGROUND This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury. MATERIAL AND METHODS Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method. RESULTS Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (P<0.05). The intervention effects of high-dose levetiracetam were more apparent. CONCLUSIONS Levetiracetam can lessen brain edema from fluid percussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent. PMID:26927633

  2. Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury

    PubMed Central

    Jin, Hongbo; Li, Wenling; Dong, Changzheng; Ma, Li; Wu, Jiang; Zhao, Wenqing

    2016-01-01

    Background This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury. Material/Methods Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method. Results Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (P<0.05). The intervention effects of high-dose levetiracetam were more apparent. Conclusions Levetiracetam can lessen brain edema from fluid percussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent. PMID:26927633

  3. Inhibition of HIF prolyl-4-hydroxylases by FG-4497 reduces brain tissue injury and edema formation during ischemic stroke.

    PubMed

    Reischl, Stefan; Li, Lexiao; Walkinshaw, Gail; Flippin, Lee A; Marti, Hugo H; Kunze, Reiner

    2014-01-01

    Ischemic stroke results in disruption of the blood-brain barrier (BBB), edema formation and neuronal cell loss. Some neuroprotective factors such as vascular endothelial growth factor (VEGF) favor edema formation, while others such as erythropoietin (Epo) can mitigate it. Both factors are controlled by hypoxia inducible transcription factors (HIF) and the activity of prolyl hydroxylase domain proteins (PHD). We hypothesize that activation of the adaptive hypoxic response by inhibition of PHD results in neuroprotection and prevention of vascular leakage. Mice, subjected to cerebral ischemia, were pre- or post-treated with the novel PHD inhibitor FG-4497. Inhibition of PHD activity resulted in HIF-1α stabilization, increased expression of VEGF and Epo, improved outcome from ischemic stroke and reduced edema formation by maintaining BBB integrity. Additional in vitro studies using brain endothelial cells and primary astrocytes confirmed that FG-4497 induces the HIF signaling pathway, leading to increased VEGF and Epo expression. In an in vitro ischemia model, using combined oxygen and glucose deprivation, FG-4497 promoted the survival of neurons. Furthermore, FG-4497 prevented the ischemia-induced rearrangement and gap formation of the tight junction proteins zonula occludens 1 and occludin, both in cultured endothelial cells and in infarcted brain tissue in vivo. These results indicate that FG-4497 has the potential to prevent cerebral ischemic damage by neuroprotection and prevention of vascular leakage.

  4. Inhibition of HIF prolyl-4-hydroxylases by FG-4497 reduces brain tissue injury and edema formation during ischemic stroke.

    PubMed

    Reischl, Stefan; Li, Lexiao; Walkinshaw, Gail; Flippin, Lee A; Marti, Hugo H; Kunze, Reiner

    2014-01-01

    Ischemic stroke results in disruption of the blood-brain barrier (BBB), edema formation and neuronal cell loss. Some neuroprotective factors such as vascular endothelial growth factor (VEGF) favor edema formation, while others such as erythropoietin (Epo) can mitigate it. Both factors are controlled by hypoxia inducible transcription factors (HIF) and the activity of prolyl hydroxylase domain proteins (PHD). We hypothesize that activation of the adaptive hypoxic response by inhibition of PHD results in neuroprotection and prevention of vascular leakage. Mice, subjected to cerebral ischemia, were pre- or post-treated with the novel PHD inhibitor FG-4497. Inhibition of PHD activity resulted in HIF-1α stabilization, increased expression of VEGF and Epo, improved outcome from ischemic stroke and reduced edema formation by maintaining BBB integrity. Additional in vitro studies using brain endothelial cells and primary astrocytes confirmed that FG-4497 induces the HIF signaling pathway, leading to increased VEGF and Epo expression. In an in vitro ischemia model, using combined oxygen and glucose deprivation, FG-4497 promoted the survival of neurons. Furthermore, FG-4497 prevented the ischemia-induced rearrangement and gap formation of the tight junction proteins zonula occludens 1 and occludin, both in cultured endothelial cells and in infarcted brain tissue in vivo. These results indicate that FG-4497 has the potential to prevent cerebral ischemic damage by neuroprotection and prevention of vascular leakage. PMID:24409307

  5. Blood Brain Barrier KCa3.1 Channels: Evidence for a Role in Brain Na Uptake and Edema in Ischemic Stroke

    PubMed Central

    Chen, Yi-Je; Wallace, Breanna K.; Yuen, Natalie; Jenkins, David P.; Wulff, Heike; O’Donnell, Martha E.

    2014-01-01

    Background and Purpose KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na+ and Cl− from the blood into the brain transcellularly through the cooperation of multiple co-transporters, exchangers, pumps and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na+ transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport. Methods The expression of KCa3.1 on cultured cerebral microvascular endothelial cells (CMEC), isolated microvessels and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on CMEC was examined by K+ flux assays and patch-clamp. Magnetic resonance spectroscopy and imaging were used to measure brain Na+ uptake and edema formation in rats with focal ischemic stroke following TRAM-34 treatment. Results KCa3.1 current and channel protein were identified on bovine CMEC and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na+ uptake, and cytotoxic edema in the ischemic brain. Conclusions BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 appears to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke. PMID:25477223

  6. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.

    PubMed

    Zielińska, Magdalena; Popek, Mariusz; Albrecht, Jan

    2014-01-01

    Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan. PMID:24072671

  7. Neurological deficits and brain edema after intracerebral hemorrhage in Mongolian gerbils.

    PubMed

    Kuroiwa, T; Okauchi, M; Hua, Y; Schallert, T; Keep, R F; Xi, G

    2008-01-01

    We examined the time course of neurological deficits in gerbils after an intracerebral hemorrhage (ICH) induced by autologous blood infusion and examined its correlation with the severity of perihematomal edema. Mongolian gerbils (n = 15) were subjected to stereotaxic autologous blood infusion (30 or 60 microL) into the left caudate nucleus. Corner-turn and forelimb-placing tests were performed before, and 1 and 3 days after ICH. Perihematomal water content was measured by tissue gravimetry. Gerbils developed neurological deficits and perihematomal edema at day 1 after ICH. Both neurological deficits and perihematomal edema were significantly greater in animals with 60 microL blood infusion compared to the 30 microL infusion group, and both neurological deficits and edema were also greater at 3 days compared to 1 day after ICH. The severity of neurological deficits paralleled the degree of perihematomal edema. We conclude that the Mongolian gerbil is a suitable model for studies on the behavioral effects of ICH. PMID:19066097

  8. An improved gravimetric measure of cerebral edema.

    PubMed

    Marmarou, A; Tanaka, K; Shulman, K

    1982-02-01

    Significant errors are introduced into the measurement of brain tissue water by the specific gravity technique when the edema fluid contains protein. Protein adds to the tissue solids, increasing the density of the tissue, and masks the proportional increase of brain water. Existing equations relating measured specific gravity and tissue water are not applicable, and a new formula was developed that compensates for the protein component of edema and reduces the experimental error. The new method was applied to the measurement of tissue water in cat brain made edematous by direct infusion of fluids of known composition and volume to test the theory. This technique for improving the gravimetric assessment of brain edema is presented.

  9. Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.

    PubMed

    Tado, Masahiro; Mori, Tatsuro; Fukushima, Masamichi; Oshima, Hideki; Maeda, Takeshi; Yoshino, Atsuo; Aizawa, Shin; Katayama, Yoichi

    2014-04-01

    To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (p<0.003). Increases in cerebrovascular permeability and water content, however, became maximal within 24 h (p<0.001) after injury (p<0.01), respectively. Administration of bevacizumab did not influence these changes in cerebrovascular permeability and water content, but led to a significant rise in the neurological deficits at 72 h-14 days (p<0.05 or 0.01) and the volume of contusion necrosis at 21 days (p<0.001) after injury. These findings suggest that increased expression of VEGF after injury does not contribute to the formation of contusion edema, but attenuates the formation of contusion necrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion. PMID:24294928

  10. Pulmonary edema

    MedlinePlus

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  11. Loss of AQP4 polarized localization with loss of β-dystroglycan immunoreactivity may induce brain edema following intracerebral hemorrhage.

    PubMed

    Qiu, Guo-Ping; Xu, Jin; Zhuo, Fei; Sun, Shan-Quan; Liu, Hui; Yang, Mei; Huang, Juan; Lu, Wei-Tian; Huang, Si-Qin

    2015-02-19

    The aquaporin-4 (AQP4) water channel contributes to brain water homeostasis in perivascular and subpial membrane domains of astrocytes where it is concentrated. These membranes form the interface between the neuropil and the extracellular liquid spaces. The brain-selective deletion of the dystroglycan (DG) gene causes a disorganization of AQP4 on the astroglial endfeet. First, we analyzed the expression of AQP4, β-DG in the brain following intracerebral hemorrhage (ICH) and correlated AQP4 expression with the expression pattern of the β-DG, which is a component of dystrophin-dystroglycan complex (DDC). Besides, the vessels ultrastructure and brain water content were investigated at different time points post-ICH (day 1, day 3, day 7). We found that AQP4 polarity was disturbed in parallel with the loss of β-DG in the perihematomal area post-ICH. At day 1 post-ICH, brain edema was obvious and the damage of vascular ultrastructure was the most severe. These results suggest a role for β-DG in targeting and stabilizing AQP4 channel in astrocytic cells, which may be critical for water homeostasis in brain. PMID:25545558

  12. Interferon-Stimulated Gene 15 Upregulation Precedes the Development of Blood–Brain Barrier Disruption and Cerebral Edema after Traumatic Brain Injury in Young Mice

    PubMed Central

    Todd, Tracey; Daniels, Zachary; Bazan, Nicolas G.; Belayev, Ludmila

    2015-01-01

    Abstract Recent studies show that myosin light chain kinase (MLCK) plays a pivotal role in development of cerebral edema, a known complication following traumatic brain injury (TBI) in children and a contributing factor to worsened neurologic recovery. Interferon-stimulated gene 15 (ISG15) is upregulated after cerebral ischemia and is neuroprotective. The significant role of ISG15 after TBI has not been studied. Postnatal Day (PND) 21 and PND24 mice were subjected to lateral closed-skull injury with impact depth of 2.0 or 2.25 mm. Behavior was examined at 7 d using two-object novel recognition and Wire Hang tests. Mice were sacrificed at 6 h, 12 h, 24 h, 48 h, 72 h, and 7 d. ISG15 and MLCK were analyzed by Western blot and immunohistochemistry, blood–brain barrier (BBB) disruption with Evans Blue (EB), and cerebral edema with wet/dry weights. EB extravasation and edema peaked at 72 h in both ages. PND21 mice had more severe neurological deficits, compared with PND24 mice. PND24 mice showed peak ISG15 expression at 6 h, and PND21 mice at 72 h. MLCK peaked in both age groups at 12 h and co-localized with ISG15 on immunohistochemistry and co-immunoprecipitation. These studies provide evidence, ISG15 is elevated following TBI in mice, preceding MLCK elevation, development of BBB disruption, and cerebral edema. PMID:25669448

  13. Changes in cannabinoid receptors, aquaporin 4 and vimentin expression after traumatic brain injury in adolescent male mice. Association with edema and neurological deficit.

    PubMed

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Viveros, Maria-Paz; Garcia-Segura, Luis M

    2015-01-01

    Traumatic brain injury (TBI) incidence rises during adolescence because during this critical neurodevelopmental period some risky behaviors increase. The purpose of this study was to assess the contribution of cannabinoid receptors (CB1 and CB2), blood brain barrier proteins (AQP4) and astrogliosis markers (vimentin) to neurological deficit and brain edema formation in a TBI weight drop model in adolescent male mice. These molecules were selected since they are known to change shortly after lesion. Here we extended their study in three different timepoints after TBI, including short (24h), early mid-term (72h) and late mid-term (two weeks). Our results showed that TBI induced an increase in brain edema up to 72 h after lesion that was directly associated with neurological deficit. Neurological deficit appeared 24 h after TBI and was completely recovered two weeks after trauma. CB1 receptor expression decreased after TBI and was negatively correlated with edema formation and behavioral impairments. CB2 receptor increased after injury and was associated with high neurological deficit whereas no correlation with edema was found. AQP4 increased after TBI and was positively correlated with edema and neurological impairments as occurred with vimentin expression in the same manner. The results suggest that CB1 and CB2 differ in the mechanisms to resolve TBI and also that some of their neuroprotective effects related to the control of reactive astrogliosis may be due to the regulation of AQP4 expression on the end-feet of astrocytes.

  14. Changes in Cannabinoid Receptors, Aquaporin 4 and Vimentin Expression after Traumatic Brain Injury in Adolescent Male Mice. Association with Edema and Neurological Deficit

    PubMed Central

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Viveros, Maria-Paz; Garcia-Segura, Luis M.

    2015-01-01

    Traumatic brain injury (TBI) incidence rises during adolescence because during this critical neurodevelopmental period some risky behaviors increase. The purpose of this study was to assess the contribution of cannabinoid receptors (CB1 and CB2), blood brain barrier proteins (AQP4) and astrogliosis markers (vimentin) to neurological deficit and brain edema formation in a TBI weight drop model in adolescent male mice. These molecules were selected since they are known to change shortly after lesion. Here we extended their study in three different timepoints after TBI, including short (24h), early mid-term (72h) and late mid-term (two weeks). Our results showed that TBI induced an increase in brain edema up to 72 h after lesion that was directly associated with neurological deficit. Neurological deficit appeared 24 h after TBI and was completely recovered two weeks after trauma. CB1 receptor expression decreased after TBI and was negatively correlated with edema formation and behavioral impairments. CB2 receptor increased after injury and was associated with high neurological deficit whereas no correlation with edema was found. AQP4 increased after TBI and was positively correlated with edema and neurological impairments as occurred with vimentin expression in the same manner. The results suggest that CB1 and CB2 differ in the mechanisms to resolve TBI and also that some of their neuroprotective effects related to the control of reactive astrogliosis may be due to the regulation of AQP4 expression on the end-feet of astrocytes. PMID:26039099

  15. Antagonists of the Vasopressin V1 Receptor and of the β(1)-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes - but the Mechanisms Differ.

    PubMed

    Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting; Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting

    2014-07-01

    Brain edema is a serious complication in ischemic stroke because even relatively small changes in brain volume can compromise cerebral blood flow or result in compression of vital brain structures on account of the fixed volume of the rigid skull. Literature data indicate that administration of either antagonists of the V1 vasopressin (AVP) receptor or the β1-adrenergic receptor are able to reduce edema or infarct size when administered after the onset of ischemia, a key advantage for possible clinical use. The present review discusses possible mechanisms, focusing on the role of NKCC1, an astrocytic cotransporter of Na(+), K(+), 2Cl(-) and water and its activation by highly increased extracellular K(+) concentrations in the development of cytotoxic cell swelling. However, it also mentions that due to a 3/2 ratio between Na(+) release and K(+) uptake by the Na(+),K(+)-ATPase driving NKCC1 brain extracellular fluid can become hypertonic, which may facilitate water entry across the blood-brain barrier, essential for development of edema. It shows that brain edema does not develop until during reperfusion, which can be explained by lack of metabolic energy during ischemia. V1 antagonists are likely to protect against cytotoxic edema formation by inhibiting AVP enhancement of NKCC1-mediated uptake of ions and water, whereas β1-adrenergic antagonists prevent edema formation because β1-adrenergic stimulation alone is responsible for stimulation of the Na(+),K(+)-ATPase driving NKCC1, first and foremost due to decrease in extracellular Ca(2+) concentration. Inhibition of NKCC1 also has adverse effects, e.g. on memory and the treatment should probably be of shortest possible duration.

  16. Antagonists of the Vasopressin V1 Receptor and of the β1-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes – but the Mechanisms Differ

    PubMed Central

    Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting; Hertz, Leif; Xu, Junnan; Chen, Ye; Gibbs, Marie E; Du, Ting

    2014-01-01

    Brain edema is a serious complication in ischemic stroke because even relatively small changes in brain volume can compromise cerebral blood flow or result in compression of vital brain structures on account of the fixed volume of the rigid skull. Literature data indicate that administration of either antagonists of the V1 vasopressin (AVP) receptor or the β1-adrenergic receptor are able to reduce edema or infarct size when administered after the onset of ischemia, a key advantage for possible clinical use. The present review discusses possible mechanisms, focusing on the role of NKCC1, an astrocytic cotransporter of Na+, K+, 2Cl- and water and its activation by highly increased extracellular K+ concentrations in the development of cytotoxic cell swelling. However, it also mentions that due to a 3/2 ratio between Na+ release and K+ uptake by the Na+,K+-ATPase driving NKCC1 brain extracellular fluid can become hypertonic, which may facilitate water entry across the blood-brain barrier, essential for development of edema. It shows that brain edema does not develop until during reperfusion, which can be explained by lack of metabolic energy during ischemia. V1 antagonists are likely to protect against cytotoxic edema formation by inhibiting AVP enhancement of NKCC1-mediated uptake of ions and water, whereas β1-adrenergic antagonists prevent edema formation because β1-adrenergic stimulation alone is responsible for stimulation of the Na+,K+-ATPase driving NKCC1, first and foremost due to decrease in extracellular Ca2+ concentration. Inhibition of NKCC1 also has adverse effects, e.g. on memory and the treatment should probably be of shortest possible duration. PMID:25342939

  17. Local transcutaneous electrical stimulation (TENS) effects in experimental inflammatory edema and pain.

    PubMed

    Resende, Marcos A; Sabino, George G; Cândido, Claudia R M; Pereira, Leani S M; Francischi, Janetti N

    2004-11-19

    Few studies in the literature associated transcutaneous electrical stimulation (TENS) use with an antiinflammatory activity. The purpose of this study was to investigate the effects of low (10 Hz)- and high (130 Hz)-frequency TENS on hyperalgesia and edema that occur after injection of carrageenan in rat paw. After induction of inflammation, either low- or high-frequency TENS was applied in the rat paw for 20 min, and the effect of TENS treatment on escape or paw withdrawal and edema was measured. Both low- and high-frequency TENS inhibited by 100% the hyperalgesia but not the edema response. However, low-frequency TENS presented longer lasting effect as compared with high-frequency TENS. Naltrexone-treated animals showed a complete reversion of the analgesic effect induced by low- but not high-frequency TENS. Thus, our data demonstrated absence of an antiinflammatory effect associated to TENS use and confirmed the participation of endogenous opioids on low TENS-induced analgesia.

  18. Antitoxic Immunity in Experimental Cholera: Observations with Purified Antigens and the Rat Foot Edema Model

    PubMed Central

    Finkelstein, Richard A.; Hollingsworth, Russell C.

    1970-01-01

    The recently introduced choleragen-induced rat foot edema model has been employed as a bioassay for evaluating the immunogenicity of three purified preparations containing cholera exo-enterotoxin antigen, choleragen, choleragenoid, and Formalin-treated choleragen (formagen). The results indicated that choleragen evoked antitoxic immunity. Both the degree of resistance to challenge and the serum antibody levels of immunized animals were found to be related to the immunizing dose. Responses to the natural toxoid, choleragenoid, were erratic: some animals responded well and some failed to respond with either serum antibody or resistance to challenge. On the other hand, the artificially prepared toxoid, formagen, was found to be superior to the parent toxin in immunogenicity. Resistance to the choleragen-induced rat foot edema could be transferred passively by means of antibody-containing serum from previously immunized animals. Each of the antigens induced a state of hypersensitivity manifested by an immediate edematous response to challenge with either choleragen or choleragenoid. This condition, which was also passively transferable, suggests that untoward reactions should be anticipated in people receiving multiple doses of immunogens containing the cholera exo-enterotoxin antigen. Some of these observations were repeated, in a preliminary fashion, in an apparently equally suitable mouse foot edema model. PMID:16557760

  19. Reversible restricted-diffusion lesion representing transient intramyelinic cytotoxic edema in a patient with traumatic brain injury.

    PubMed

    Al Brashdi, Yahya H; Albayram, Mehmet S

    2015-08-01

    We report this case to increase the awareness of magnetic resonance imaging (MRI) features of reversible white matter abnormalities in diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in a patient with traumatic brain injury (TBI). An eight-year-old girl, who was hit by a truck, was brought to the emergency department by the emergency medical service (EMS). Eleven days later, she experienced cognitive impairment requiring MRI evaluation. DWI and ADC maps showed restricted diffusion in the white matter of the corpus callosum, peri-atrial white matter, and in the right centrum semiovale. There were no significant hemorrhagic foci in these regions, which showed complete resolution on follow up DWI MRI 13 days later. This reported case revealed TBI-related transient reversible intramyelinic cytotoxic edema. PMID:26306930

  20. Reduction of the prenatal hypoxic-ischemic brain edema with noscapine.

    PubMed

    Mahmoudian, M; Siadatpour, Zahra; Ziai, S A; Mehrpour, M; Benaissa, Faouzya; Nobakht, M

    2003-01-01

    Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.

  1. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

    PubMed

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

    2014-07-11

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

  2. Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress.

    PubMed

    Zhang, Bo; Wang, Bing; Cao, Shuhua; Wang, Yongqiang

    2015-11-01

    Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1β and TNF-α mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress. PMID:26557015

  3. Experimental Staphylococcus aureus brain abscess.

    PubMed

    Enzmann, D R; Britt, R R; Obana, W G; Stuart, J; Murphy-Irwin, K

    1986-01-01

    The virulent organism Staphylococcus aureus produced brain abscesses that were quantitatively and qualitatively different from those caused by less virulent organisms. S. aureus abscesses created larger lesions, as earlier ependymitis, delayed progress toward healing, and caused areas of inflammatory escape outside the collagen capsule. Imaging tests revealed similar findings: the abscesses were larger, had more extensive central necrosis, and showed earlier evidence of ependymitis. This virulent organism also demonstrated that white matter is more susceptible than overlying gray matter to destruction by infection. The pattern of spread and other histologic findings suggest that collagen capsule formation has less of an infection "containment" function than was previously thought. PMID:3085444

  4. Human brain mapping: Experimental and computational approaches

    SciTech Connect

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J.; Sanders, J.; Belliveau, J.

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

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

    PubMed Central

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

    2016-01-01

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

  6. The effect of saponification on the mucopolysaccharides of the ground substance of the human brain: the relation to focal edema and multiple sclerosis.

    PubMed

    Feigin, I

    1981-03-01

    The acid mucopolysaccharides of brain tissues are disclosed by their metachromatic staining with toluidine blue following saponification with potassium hydroxide, presumably as a result of the liberation of acid groups previously esterified. Earlier histochemical studies had disclosed the presence of neutral mucopolysaccharides by staining with the periodic acid-Schiff technique, and such staining is intensified by prior saponification. Many biochemical studies have reported the presence of both acid and neutral mucopolysaccharides in brain tissues. Within the white matter following brain edema, the quantity of stained mucopolysaccharides is decreased in the plaques of multiple sclerosis and pontine myelinolysis, and in the lesions of diffuse sclerosis. All of these are characterized by myelin loss with relative preservation of axons. The known physiological effects of the mucopolysaccharides on the water content of normal tissues, and on the properties and diffusability of the increments of fluid that constitute edema, lead to the suggestion that edema may play a major role in the pathogenesis of the demyelinating diseases, including multiple sclerosis.

  7. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases

    PubMed Central

    Berghoff, Anna S; Fuchs, Elisabeth; Ricken, Gerda; Mlecnik, Bernhard; Bindea, Gabriela; Spanberger, Thomas; Hackl, Monika; Widhalm, Georg; Dieckmann, Karin; Prayer, Daniela; Bilocq, Amelie; Heinzl, Harald; Zielinski, Christoph; Bartsch, Rupert; Birner, Peter; Galon, Jerome; Preusser, Matthias

    2016-01-01

    The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). TIL density was not associated with corticosteroid administration (p > 0.05). A significant difference in infiltration density according to TIL subtype was present (p < 0.001; Chi Square); high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8+ TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging (p = 0.031). The density of CD3+ (15 vs. 6 mo; p = 0.015), CD8+ (15 vs. 11 mo; p = 0.030) and CD45RO+ TILs (18 vs. 8 mo; p = 0.006) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo; p < 0.001). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612, p < 0.001). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings. PMID:26942067

  8. Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review

    PubMed Central

    Lin, Xiaoping; Xu, Zhijun; Wang, Pengfei; Xu, Yan; Zhang, Gensheng

    2016-01-01

    Neurogenic pulmonary edema (NPE) is occasionally observed in patients with traumatic brain injury (TBI); however, this condition is often underappreciated. NPE is frequently misdiagnosed due to its atypical clinical performance, thus delaying appropriate treatment. A comprehensive management protocol of NPE in patients with TBI has yet to be established. The current study reported the case of a 67-year-old man with severe TBI who was transferred to our intensive care unit (ICU). On day 7 after hospitalization, the patient suddenly suffered tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern drainage. Intravenous diuretics, tranquilizer and glucocorticoid were administered due to suspected left heart failure attack. Chest radiography examination supported the diagnosis of pulmonary edema; however, hypotension and hypovolemia were subsequently observed. Pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then implemented. In addition, levosimendan, an inotropic agent, was introduced to improve cardiac output. The patient had complete recovered from pulmonary edema and regained consciousness on day 11 of hospitalization. The current case demonstrated that PiCCO monitoring may serve a central role in the integrated management of NPE in patients with TBI. Levosimendan may be a potential medicine in treating cardiac dysfunction, along with its benefit from improving neurological function in NPE patients. PMID:27698733

  9. Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review

    PubMed Central

    Lin, Xiaoping; Xu, Zhijun; Wang, Pengfei; Xu, Yan; Zhang, Gensheng

    2016-01-01

    Neurogenic pulmonary edema (NPE) is occasionally observed in patients with traumatic brain injury (TBI); however, this condition is often underappreciated. NPE is frequently misdiagnosed due to its atypical clinical performance, thus delaying appropriate treatment. A comprehensive management protocol of NPE in patients with TBI has yet to be established. The current study reported the case of a 67-year-old man with severe TBI who was transferred to our intensive care unit (ICU). On day 7 after hospitalization, the patient suddenly suffered tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern drainage. Intravenous diuretics, tranquilizer and glucocorticoid were administered due to suspected left heart failure attack. Chest radiography examination supported the diagnosis of pulmonary edema; however, hypotension and hypovolemia were subsequently observed. Pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then implemented. In addition, levosimendan, an inotropic agent, was introduced to improve cardiac output. The patient had complete recovered from pulmonary edema and regained consciousness on day 11 of hospitalization. The current case demonstrated that PiCCO monitoring may serve a central role in the integrated management of NPE in patients with TBI. Levosimendan may be a potential medicine in treating cardiac dysfunction, along with its benefit from improving neurological function in NPE patients.

  10. Molecular pathophysiology of cerebral edema.

    PubMed

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  11. Molecular pathophysiology of cerebral edema

    PubMed Central

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  12. Clinical Outcomes of Wulingsan Subtraction Decoction Treatment of Postoperative Brain Edema and Fever as a Complication of Glioma Neurosurgery

    PubMed Central

    Jin, Wei-rong; Zhang, Feng-e; Diao, Bao-zhong; Zhang, Yue-ying

    2016-01-01

    Objective. To evaluate the efficacy of Wulingsan subtraction (五苓散加减 WLSS) decoction in the treatment of postoperative brain edema and fever as a complication of glioma neurosurgery. Methods. This retrospective study was conducted at the Department of Neurosurgery of Liaocheng People's Hospital. Patients hospitalized between March 2011 and December 2014 were divided into three groups: Group A received WLSS oral liquid (50 mL), twice a day; Group B received an intravenous infusion of mannitol; and Group C received WLSS combined with mannitol (n = 30 patients per group). All patients were treated for 10 days continuously. Therapeutic efficacy was evaluated by measuring body temperature and indicators of renal function before and 3, 5, and 10 days after treatment. Results. Compared to the other two groups, significantly greater clinical efficacy was observed in the patients treated with mannitol (Group B; P < 0.05), although marked clinical efficacy was also observed over time in patients treated with WLSS (Group A). After 5 days, the quantifiable effects of the WLSS and mannitol combination group (Group C) were substantial (P < 0.05). The renal damage in Group B was more obvious after 5 days and 10 days. Conclusion. Compared with mannitol treatment alone, WLSS combined with mannitol induced a more rapid reduction in body temperature. Our findings suggest that patients should be started on mannitol for 3 days and then switched to WLSS to achieve obvious antipyretic effects and protect renal function. This method of treatment should be considered for clinical applications. PMID:27019661

  13. 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

  14. MR of brain radiation injury: experimental studies in cats

    SciTech Connect

    Hecht-Leavitt, C.; Grossman, R.I.; Curran, W.J. Jr.; McGrath, J.T.; Biery, D.N.; Joseph, P.M.; Nelson, D.F.

    1987-05-01

    Two of six cats receiving small-field, single-dose, brain irradiation of 35 Gy with 6 MeV photons developed brain abnormalities in the irradiated area on MR images at 6 and 8 months, respectively, after treatment. The lesions were of high intensity on T2-weighted images and did not enhance after IV administration of gadolinium-DTPA. An additional lesion in one of these cats displayed high signal on T2-weighted images and enhanced on T1-weighted images after IV gadolinium-DTPA. Pathologic correlation revealed that the nonenhancing T2-weighted lesions consisted of edema or demyelinated regions without inflammation while the gadolinium-enhanced lesion demonstrated necrosis with inflammatory infiltrate. Focal brain irradiation may produce noninflammatory demyelination and necrosis. These histologic entities may be potentially distinguished on MR with IV gadolinium-DTPA.

  15. Numerical impact simulation of gradually increased kinetic energy transfer has the potential to break up folded protein structures resulting in cytotoxic brain tissue edema.

    PubMed

    von Holst, Hans; Li, Xiaogai

    2013-07-01

    Although the consequences of traumatic brain injury (TBI) and its treatment have been improved, there is still a substantial lack of understanding the mechanisms. Numerical simulation of the impact can throw further lights on site and mechanism of action. A finite element model of the human head and brain tissue was used to simulate TBI. The consequences of gradually increased kinetic energy transfer was analyzed by evaluating the impact intracranial pressure (ICP), strain level, and their potential influences on binding forces in folded protein structures. The gradually increased kinetic energy was found to have the potential to break apart bonds of Van der Waals in all impacts and hydrogen bonds at simulated impacts from 6 m/s and higher, thereby superseding the energy in folded protein structures. Further, impacts below 6 m/s showed none or very slight increase in impact ICP and strain levels, whereas impacts of 6 m/s or higher showed a gradual increase of the impact ICP and strain levels reaching over 1000 KPa and over 30%, respectively. The present simulation study shows that the free kinetic energy transfer, impact ICP, and strain levels all have the potential to initiate cytotoxic brain tissue edema by unfolding protein structures. The definition of mild, moderate, and severe TBI should thus be looked upon as the same condition and separated only by a gradual severity of impact.

  16. Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies.

    PubMed

    Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M; Hoane, Michael R

    2016-06-01

    With the numerous failures of pharmaceuticals to treat traumatic brain injury in humans, more researchers have become interested in combination therapies. This is largely due to the multimodal nature of damage from injury, which causes excitotoxicity, oxidative stress, edema, neuroinflammation and cell death. Polydrug treatments have the potential to target multiple aspects of the secondary injury cascade, while many previous therapies focused on one particular aspect. Of specific note are vitamins, minerals and nutrients that can be utilized to supplement other therapies. Many of these have low toxicity, are already FDA approved and have minimal interactions with other drugs, making them attractive targets for therapeutics. Over the past 20 years, interest in supplementation and supraphysiologic dosing of nutrients for brain injury has increased and indeed many vitamins and nutrients now have a considerable body of the literature backing their use. Here, we review several of the prominent therapies in the category of nutraceutical treatment for brain injury in experimental models, including vitamins (B2, B3, B6, B9, C, D, E), herbs and traditional medicines (ginseng, Gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids). While there is still much work to be done, several of these have strong potential for clinical therapies, particularly with regard to polydrug regimens. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26723564

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

    PubMed

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

    1996-04-01

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

  18. Blood-brain barrier in acute liver failure

    PubMed Central

    Nguyen, Justin H.

    2011-01-01

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

  19. Unilateral pulmonary edema following acute subglottic edema.

    PubMed

    Morisaki, H; Ochiai, R; Takeda, J; Nagano, M

    1990-01-01

    Presented here is a case of unilateral pulmonary edema following acute subglottic edema after removal of an endotracheal tube. A 3-year-old boy, diagnosed as having nondiphtheric croup and pectus excavatum deformity, was scheduled for repair of a cleft lip. No complication occurred during the operation. After removal of the endotracheal tube, he showed dyspnea and cyanosis and was later found to have acute subglottic edema. After reintubation of the trachea, frothy pink fluid was discharged from the tube, and chest roentgenogram showed a right-sided alveolar infiltrate. Many factors may cause unilateral pulmonary edema, but it is suggested that acute subglottic edema and unilateral bronchial fragility strongly affected this episode.

  20. Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

    PubMed Central

    Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

  1. A Quantitative MRI Method for Imaging Blood-Brain Barrier Leakage in Experimental Traumatic Brain Injury

    PubMed Central

    Watts, Lora Talley; Jiang, Zhao; Shen, Qiang; Li, Yunxia; Duong, Timothy Q.

    2014-01-01

    Blood-brain barrier (BBB) disruption is common following traumatic brain injury (TBI). Dynamic contrast enhanced (DCE) MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field) and magnetization (M0) distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI), and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI. PMID:25478693

  2. Pharmacological Preventions of Brain Injury Following Experimental Germinal Matrix Hemorrhage: an Up-to-Date Review.

    PubMed

    Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Qianwei; Hua, Feng; Zhang, John; Zhu, Gang; Chen, Zhi

    2016-02-01

    Germinal matrix hemorrhage (GMH) is defined as the rupture of immature blood vessels in the subependymal zone of premature infants with significant mortality and morbidity. Considering the notable social and ecological stress brought by GMH-induced brain injury and sequelae, safe and efficient pharmacological preventions are badly needed. Currently, several appropriate animal models are available to mimic the clinical outcomes of GMH in human patients. In the long run, hemorrhagic strokes are the research target. Previously, we found that minocycline was efficient to alleviate GMH-induced brain edema and posthemorrhagic hydrocephalus (PHH) in rats, which may be closely related to the activation of cannabinoid receptor 2 (CB2R). However, how the two molecules correlate and the underlined molecular pathway remain unknown. To extensively understand current experimental GMH treatment, this literature review critically evaluates existing therapeutic strategies, potential treatments, and potentially involved molecular mechanisms. Each strategy has its own advantages and disadvantages. Some of the mechanisms are still controversial, requiring an increasing number of animal experiments before the therapeutic strategy would be widely accepted.

  3. Pathogenesis of optic disc edema in raised intracranial pressure.

    PubMed

    Hayreh, Sohan Singh

    2016-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with

  4. Cross-brain neurofeedback: scientific concept and experimental platform.

    PubMed

    Duan, Lian; Liu, Wei-Jie; Dai, Rui-Na; Li, Rui; Lu, Chun-Ming; Huang, Yu-Xia; Zhu, Chao-Zhe

    2013-01-01

    The present study described a new type of multi-person neurofeedback with the neural synchronization between two participants as the direct regulating target, termed as "cross-brain neurofeedback." As a first step to implement this concept, an experimental platform was built on the basis of functional near-infrared spectroscopy, and was validated with a two-person neurofeedback experiment. This novel concept as well as the experimental platform established a framework for investigation of the relationship between multiple participants' cross-brain neural synchronization and their social behaviors, which could provide new insight into the neural substrate of human social interactions.

  5. ANAEROBIC GLYCOLYSIS OF THE BRAIN IN EXPERIMENTAL POLIOMYELITIS

    PubMed Central

    Wood, Harland G.; Rusoff, Irving I.; Reiner, John M.

    1945-01-01

    The rate of anaerobic glycolysis of brain tissue was compared for normal animals and animals with experimentally induced poliomyelitis, using two different strains of mice and two different procedures. The report of interference of poliomyelitis with anaerobic glycolysis of brain was not confirmed. In one series there was a small increase and in the other series a small decrease in the brain QCOCO2N2 calculated for infected animals as compared to normal animals. When the calculations were made on the basis of wet weight of brain there was no difference in glycolysis. It is considered that the methods so far used for study of the enzymes may be inadequate, and that no decision is as yet possible on the effect of poliomyelitis on anaerobic glycolysis. PMID:19871449

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

    PubMed

    Povlishock, John

    2016-01-01

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

  7. Mechanisms of Astrocyte-Mediated Cerebral Edema

    PubMed Central

    Stokum, Jesse A.; Kurland, David B.; Gerzanich, Volodymyr; Simard, J. Marc

    2014-01-01

    Cerebral edema formation stems from disruption of blood brain barrier (BBB) integrity and occurs after injury to the CNS. Due to the restrictive skull, relatively small increases in brain volume can translate into impaired tissue perfusion and brain herniation. In excess, cerebral edema can be gravely harmful. Astrocytes are key participants in cerebral edema by virtue of their relationship with the cerebral vasculature, their unique compliment of solute and water transport proteins, and their general role in brain volume homeostasis. Following the discovery of aquaporins, passive conduits of water flow, aquaporin 4 (AQP4) was identified as the predominant astrocyte water channel. Normally, AQP4 is highly enriched at perivascular endfeet, the outermost layer of the BBB, whereas after injury, AQP4 expression disseminates to the entire astrocytic plasmalemma, a phenomenon termed dysregulation. Arguably, the most important role of AQP4 is to rapidly neutralize osmotic gradients generated by ionic transporters. In pathological conditions, AQP4 is believed to be intimately involved in the formation and clearance of cerebral edema. In this review, we discuss aquaporin function and localization in the BBB during health and injury, and we examine post-injury ionic events that modulate AQP4- dependent edema formation. PMID:24996934

  8. [Vulvar edema in pregnancy].

    PubMed

    Radomański, T; Sikorski, R; Baszak, E

    1998-12-01

    Reported is a case of massive vulvar edema complicating pregnancy probably as a result of mycotic vulvovaginitis or chemical vulvitis associated with drugs being used in the medication. Medical therapy failed to relieve the edema while the mechanical drainage showed to be an effective method of treatment. PMID:10224778

  9. Magnetic Resonance Imaging in Experimental Traumatic Brain Injury.

    PubMed

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

    2016-01-01

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

  10. Using anesthetics and analgesics in experimental traumatic brain injury.

    PubMed

    Rowe, Rachel K; Harrison, Jordan L; Thomas, Theresa C; Pauly, James R; Adelson, P David; Lifshitz, Jonathan

    2013-08-01

    Valid modeling of traumatic brain injury (TBI) requires accurate replication of both the mechanical forces that cause the primary injury and the conditions that lead to secondary injuries observed in human patients. The use of animals in TBI research is justified by the lack of in vitro or computer models that can sufficiently replicate the complex pathological processes involved. Measures to reduce nociception and distress must be implemented, but the administration of anesthetics and analgesics can influence TBI outcomes, threatening the validity of the research. In this review, the authors present evidence for the interference of anesthetics and analgesics in the natural course of brain injury in animal models of TBI. They suggest that drugs should be selected for or excluded from experimental TBI protocols on the basis of IACUC-approved experimental objectives in order to protect animal welfare and preserve the validity of TBI models. PMID:23877609

  11. Amiodarone has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced paw edema.

    PubMed

    Halici, Zekai; Dengiz, Gunnur Ozbakis; Odabasoglu, Fehmi; Suleyman, Halis; Cadirci, Elif; Halici, Mesut

    2007-07-01

    Amiodarone is a widely used anti-arrhythmic agent. We have investigated alterations in the glutathione (GSH) level and the activities of anti-oxidative enzymes (superoxide dismutase, catalase, glutathione s-transferase and glutathione reductase) and myeloperoxidase, as marker of acute inflammation, following oral administration of amiodarone and diclofenac in rats with carrageenan-induced paw edema. In the present study, we found that 1) Amiodarone reduced the development of carrageenan-induced paw edema, to a greater degree than diclofenac; 2) Amiodarone and diclofenac alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from edema; 3) Amiodarone and diclofenac ameliorated depressions in the GSH level and the activities of superoxide dismutase and glutathione reductase enzymes caused by carrageenan injection; and 4) All doses of amiodarone and diclofenac caused an amplification in myeloperoxidase activity resulting from induced paw edema. These results suggest that the anti-inflammatory effect of amiodarone on carrageenan-induced acute inflammation can be attributed to its ameliorating effect on the oxidative damage.

  12. Distribution of opiate alkaloids in brain tissue of experimental animals

    PubMed Central

    Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-01-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

  13. [Edema and the tropics].

    PubMed

    Holzer, B R

    2004-11-01

    People visiting or living in tropical or subtropical regions are exposed to various factors, which can lead to edema. Tourists staying for only a short time in the tropics are exposed to different risks, with other disease patterns, than people living in the tropics or immigrants from tropical regions. The differential diagnosis of edema and swelling is extensive and it can sometimes be difficult to distinguish classical edema with fluid retention in the extravascular interstitial space, from lymphedema or swelling due to other aetiologies. The patients often connect the edema to their stay in the tropics although it may have been pre-existing with no obvious relation to their travels. Already the long trip in the plane can lead to an "economy class syndrome" due to deep venous thrombosis. Contacts with animal or plant toxins, parasites or parasitic larvae can produce peripheral edema. The diagnosis can often only be made by taking a meticulous history, checking for eosinophilia and with the help of serological investigations. Chronic lymphedema or elephantiasis of the limbs is often due to blocked lymph vessels by filarial worms. It has to be distinguished from other forms as e.g. podoconiosis due to blockage by mineral particles in barefoot walking people. The trend to book adventure and trekking holidays at high altitude leads to high altitude peripheral edema or non-freezing cold injuries such as frostbites and trench foot. Edema can be an unwanted side effect of a range of drugs e.g. nifedipine, which is used to prevent and treat high altitude pulmonary edema. Protein malnutrition, (Kwashiorkor), and vitamin B6 deficiency, (Beri-Beri) are very rarely observed in immigrants and almost never in tourists. A very painful swelling of fingers and hands in children and young adults of African origin can be observed during a sickle cell crisis. Many protein loosing nephropathies connected with plant and animal toxins but also bacterial, viral or parasitic agents, can

  14. [Cardiogenic and non cardiogenic pulmonary edema: pathomechanisms and causes].

    PubMed

    Glaus, T; Schellenberg, S; Lang, J

    2010-07-01

    The development of pulmonary edema is divided in cardiogenic and non-cardiogenic. Cardiogenic edema pathogenically is caused by elevated hydrostatic pressure in the pulmonary capillaries due to left sided congestive heart failure. Non-cardiogenic pulmonary edema is categorized depending on the underlying pathogenesis in low-alveolar pressure, elevated permeability or neurogenic edema. Some important examples of causes are upper airway obstruction like in laryngeal paralysis or strangulation for low alveolar pressure, leptospirosis and ARDS for elevated permeability, and epilepsy, brain trauma and electrocution for neurogenic edema. The differentiation between cardiogenic versus non-cardiogenic genesis is not always straightforward, but most relevant, because treatment markedly differs between the two. Of further importance is the identification of the specific underlying cause in non-cardiogenic edema, not only for therapeutic but particularly for prognostic reasons. Depending on the cause the prognosis ranges from very poor to good chance of complete recovery. PMID:20582896

  15. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.

    PubMed

    Yousuf, Mohammad A; Tan, Chunfeng; Torres-Altoro, Melissa I; Lu, Fang-Min; Plautz, Erik; Zhang, Shanrong; Takahashi, Masaya; Hernandez, Adan; Kernie, Steven G; Plattner, Florian; Bibb, James A

    2016-07-01

    Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation

  16. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.

    PubMed

    Yousuf, Mohammad A; Tan, Chunfeng; Torres-Altoro, Melissa I; Lu, Fang-Min; Plautz, Erik; Zhang, Shanrong; Takahashi, Masaya; Hernandez, Adan; Kernie, Steven G; Plattner, Florian; Bibb, James A

    2016-07-01

    Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation

  17. Experimental model for civilian ballistic brain injury biomechanics quantification.

    PubMed

    Zhang, Jiangyue; Yoganandan, Narayan; Pintar, Frank A; Guan, Yabo; Gennarelli, Thomas A

    2007-01-01

    Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275 m/s and 9 mm, 395 m/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were captured at 20,000 frames/second (fps) using high-speed digital video images. Pressures ranged from 644.6 to -92.8 kPa. Entry pressures in gelatin models were higher than exit pressures, whereas in Sylgard models entry pressures were lower or equivalent to exit pressures. Gelatin responded with brittle-type failure, while Sylgard demonstrated a ductile pattern through formation of micro-bubbles along projectile path. Temporary cavities in Sylgard models were 1.5-2x larger than gelatin models. Pressures in Sylgard models were more sensitive to projectile velocity and diameter increase, indicating Sylgard was more rate sensitive than gelatin. Based on failure patterns and brain tissue rate-sensitive characteristics, Sylgard was found to be an appropriate simulant. Compared with spherical projectile data, full-metal jacket (FMJ) projectiles produced different temporary cavity and pressures, demonstrating shape effects. Models using Sylgard gel and FMJ projectiles are appropriate to enhance understanding and mechanisms of ballistic brain injury. PMID:17166502

  18. Experimental Models Combining Traumatic Brain Injury and Hypoxia.

    PubMed

    Thelin, Eric P

    2016-01-01

    Traumatic brain injury (TBI) is one of the most common causes of death and disability, and cerebral hypoxia is a frequently occurring harmful secondary event in TBI patients. The hypoxic conditions that occur on the scene of accident, where the airways are often obstructed or breathing is in other ways impaired, could be reproduced using animal TBI models where oxygen delivery is strictly controlled throughout the entire experimental procedure. Monitoring physiological parameters of the animal is of utmost importance in order to maintain an adequate quality of the experiment. Peripheral oxygen saturation, O2 pressure (pO2) in the blood, or fraction of inhaled O2 (FiO2) could be used as goals to validate the hypoxic conditions. Different models of traumatic brain injury could be used to inflict desired injury type, whereas effects then could be studied using radiological, physiological and functional tests. In order to confirm that the brain has been affected by a hypoxic injury, appropriate substances in the affected cerebral tissue, cerebrospinal fluid, or serum should be analyzed. PMID:27604734

  19. Experimental model for civilian ballistic brain injury biomechanics quantification.

    PubMed

    Zhang, Jiangyue; Yoganandan, Narayan; Pintar, Frank A; Guan, Yabo; Gennarelli, Thomas A

    2007-01-01

    Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275 m/s and 9 mm, 395 m/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were captured at 20,000 frames/second (fps) using high-speed digital video images. Pressures ranged from 644.6 to -92.8 kPa. Entry pressures in gelatin models were higher than exit pressures, whereas in Sylgard models entry pressures were lower or equivalent to exit pressures. Gelatin responded with brittle-type failure, while Sylgard demonstrated a ductile pattern through formation of micro-bubbles along projectile path. Temporary cavities in Sylgard models were 1.5-2x larger than gelatin models. Pressures in Sylgard models were more sensitive to projectile velocity and diameter increase, indicating Sylgard was more rate sensitive than gelatin. Based on failure patterns and brain tissue rate-sensitive characteristics, Sylgard was found to be an appropriate simulant. Compared with spherical projectile data, full-metal jacket (FMJ) projectiles produced different temporary cavity and pressures, demonstrating shape effects. Models using Sylgard gel and FMJ projectiles are appropriate to enhance understanding and mechanisms of ballistic brain injury.

  20. Correlations between Blood–Brain Barrier Disruption and Neuroinflammation in an Experimental Model of Penetrating Ballistic-Like Brain Injury

    PubMed Central

    Cartagena, Casandra M.; Lu, Xi-Chun M.; Konopko, Melissa; Dave, Jitendra R.; Tortella, Frank C.; Shear, Deborah A.

    2014-01-01

    Abstract Blood–brain barrier (BBB) disruption is a pathological hallmark of severe traumatic brain injury (TBI) and is associated with neuroinflammatory events contributing to brain edema and cell death. The goal of this study was to elucidate the profile of BBB disruption after penetrating ballistic-like brain injury (PBBI) in conjunction with changes in neuroinflammatory markers. Brain uptake of biotin-dextran amine (BDA; 3 kDa) and horseradish peroxidase (HRP; 44 kDa) was evaluated in rats at 4 h, 24 h, 48 h, 72 h, and 7 days post-PBBI and compared with the histopathologic and molecular profiles for inflammatory markers. BDA and HRP both displayed a uniphasic profile of extravasation, greatest at 24 h post-injury and which remained evident out to 48 h for HRP and 7 days for BDA. This profile was most closely associated with markers for adhesion (mRNA for intercellular adhesion molecule-1) and infiltration of peripheral granulocytes (mRNA for matrix metalloproteinase-9 [MMP-9] and myeloperoxidase staining). Improvement of BBB dysfunction coincided with increased expression of markers implicated in tissue remodeling and repair. The results of this study reveal a uniphasic and gradient opening of the BBB after PBBI and suggest MMP-9 and resident inflammatory cell activation as candidates for future neurotherapeutic intervention after PBBI. PMID:24138024

  1. Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury.

    PubMed

    Zhao, Zaorui; Faden, Alan I; Loane, David J; Lipinski, Marta M; Sabirzhanov, Boris; Stoica, Bogdan A

    2013-12-01

    Geranylgeranylacetone (GGA) is an inducer of heat-shock protein 70 (HSP70) that has been used clinically for many years as an antiulcer treatment. It is centrally active after oral administration and is neuroprotective in experimental brain ischemia/stroke models. We examined the effects of single oral GGA before treatment (800 mg/kg, 48 hours before trauma) or after treatment (800 mg/kg, 3 hours after trauma) on long-term functional recovery and histologic outcomes after moderate-level controlled cortical impact, an experimental traumatic brain injury (TBI) model in mice. The GGA pretreatment increased the number of HSP70(+) cells and attenuated posttraumatic α-fodrin cleavage, a marker of apoptotic cell death. It also improved sensorimotor performance on a beam walk task; enhanced recovery of cognitive/affective function in the Morris water maze, novel object recognition, and tail-suspension tests; and improved outcomes using a composite neuroscore. Furthermore, GGA pretreatment reduced the lesion size and neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex when compared with vehicle-treated TBI controls. Notably, GGA was also effective in a posttreatment paradigm, showing significant improvements in sensorimotor function, and reducing cortical neuronal loss. Given these neuroprotective actions and considering its longstanding clinical use, GGA should be considered for the clinical treatment of TBI. PMID:23942364

  2. Discrimination between different types of white matter edema with diffusion-weighted MR imaging.

    PubMed

    Ebisu, T; Naruse, S; Horikawa, Y; Ueda, S; Tanaka, C; Uto, M; Umeda, M; Higuchi, T

    1993-01-01

    Brain edema can be classified into three categories: vasogenic, cytotoxic, and interstitial. The mechanism of edema is thought to be different in each type. The authors studied the movement of water molecules in each type of white matter edema in a rat model by using diffusion-weighted magnetic resonance imaging. Conventional T2-weighted imaging did not allow distinction between the three types of white matter edema; the three types of edema were, however, distinguished by using diffusion-weighted imaging. The apparent diffusion coefficient (ADC) of water was different in each type of edema. Water molecules in cytotoxic edema induced by triethyl-tin intoxication showed a smaller and less anisotropic ADC than in normal white matter. In contrast, water in vasogenic edema induced by cold injury had a larger and more anisotropic ADC than in normal white matter. Water in interstitial edema due to kaolin-induced hydrocephalus had an anisotropic and very large ADC. PMID:8280975

  3. Latest advances in edema

    NASA Technical Reports Server (NTRS)

    Villavicencio, J. L.; Hargens, A. R.; Pikoulicz, E.

    1996-01-01

    Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

  4. Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema

    PubMed Central

    Tang, Guanghui; Yang, Guo-Yuan

    2016-01-01

    Aquaporin-4 (AQP4) is a family member of water-channel proteins and is dominantly expressed in the foot process of glial cells surrounding capillaries. The predominant expression at the boundaries between cerebral parenchyma and major fluid compartments suggests the function of aquaporin-4 in water transfer into and out of the brain parenchyma. Accumulating evidences have suggested that the dysregulation of aquaporin-4 relates to the brain edema resulting from a variety of neuro-disorders, such as ischemic or hemorrhagic stroke, trauma, etc. During edema formation in the brain, aquaporin-4 has been shown to contribute to the astrocytic swelling, while in the resolution phase, it has been seen to facilitate the reabsorption of extracellular fluid. In addition, aquaporin-4-deficient mice are protected from cytotoxic edema produced by water intoxication and brain ischemia. However, aquaporin-4 deletion exacerbates vasogenic edema in the brain of different pathological disorders. Recently, our published data showed that the upregulation of aquaporin-4 in astrocytes probably contributes to the transition from cytotoxic edema to vasogenic edema. In this review, apart from the traditional knowledge, we also introduce our latest findings about the effects of mesenchymal stem cells (MSCs) and microRNA-29b on aquaporin-4, which could provide powerful intervention tools targeting aquaporin-4. PMID:27690011

  5. Physical and technical aspects of ultrasonic brain imaging through thick skull bones: 2. Experimental studies

    NASA Astrophysics Data System (ADS)

    Baykov, S. V.; Babin, L. V.; Molotilov, A. M.; Neiman, S. I.; Riman, V. V.; Svet, V. D.; Selyanin, A. I.

    2003-07-01

    Experimental results of the ultrasonic imaging of brain structures through thick skull bones are presented. The model imaging system and the ultrasonic images of blood vessel models and images obtained in vivo for some brain structures are described.

  6. The Effect of Complete Decongestive Therapy on Edema Volume Reduction and Pain in Women With Post Breast Surgery Lymph Edema

    PubMed Central

    Angooti Oshnari, Leila; Hosseini, Seyed Ali; Haghighat, Shahpar; Hossein Zadeh, Samaneh

    2016-01-01

    Background Upper extremity lymph edema is the most common side effect of breast cancer treatment that may produce significant physical and psychological morbidity. Pain is the frequent symptom of lymph edema that causes impairment of activities in daily life. Objectives The aim of this study was assessment of the effect of complex decongestive therapy (CDT) on upper extremity lymph edema and pain in women with post breast surgery lymph edema. Patients and Methods In this quasi- experimental research with before- after design, 36 women with moderate lymph edema after breast surgery participated in the program. Edema volume was measured by water displacement method; pain values were evaluated by visual analog scale (VAS). Data were recorded before intervention and 2 and 4 weeks after it. CDT included the first phase (intensive phase) and the second phase (maintenance phase). Each phase lasted 2 weeks. After use of Shapiro Wilk test for normality, analysis of variances with GEE and repeated measurements were used to analyze the data. Results After one month doing CDT program, significant decrease of edema was noticed (P < 0.0001), also pain decreased during 2 and 4 weeks after intervention (P < 0.0001). Conclusions This study indicated that CDT program is effective in reducing lymph edema volume and pain in women with moderate post breast surgery lymph edema. It seems that raising patients’ awareness and training healthcare professionals regarding lymph edema preventive strategies have an important role in earlier and better combating this complication. PMID:27482330

  7. SIRT2 inhibition exacerbates neuroinflammation and blood-brain barrier disruption in experimental traumatic brain injury by enhancing NF-κB p65 acetylation and activation.

    PubMed

    Yuan, Fang; Xu, Zhi-Ming; Lu, Li-Yan; Nie, Hui; Ding, Jun; Ying, Wei-Hai; Tian, Heng-Li

    2016-02-01

    Sirtuin 2 (SIRT2) is a member of the sirtuin family of NAD(+) -dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI). We investigated the effects of SIRT2 inhibition on experimental TBI using the controlled cortical impact (CCI) injury model. Adult male mice underwent CCI or sham surgery. A selective brain-permeable SIRT2 inhibitor, AK-7, was administrated 30 min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with AK-7 (20 mg/kg), compared with the vehicle group, following TBI (p < 0.05 at 1 day and p < 0.05 at 3 days, respectively). Concomitantly, AK-7 administration greatly worsened neurobehavioral deficits on days 3 and 7 after CCI. Furthermore, blood-brain barrier disruption and matrix metalloproteinases (MMP)-9 activity increased following SIRT2 inhibition. AK-7 treatment increased TBI-induced microglial activation both in vivo and in vitro, accompanied by a large increase in the expression and release of inflammatory cytokines. Mechanistically, SIRT2 inhibition increased both K310 acetylation and nuclear translocation of NF-κB p65, leading to enhanced NF-κB activation and up-regulation of its target genes, including aquaporin 4 (AQP4), MMP-9, and pro-inflammatory cytokines. Together, these data demonstrate that SIRT2 inhibition exacerbates TBI by increasing NF-κB p65 acetylation and activation. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. SIRT2 is a member of the sirtuin family of NAD+-dependent protein deacetylases. Our study suggests that the SIRT2 inhibitor AK-7 exacerbates traumatic brain injury (TBI) via a potential mechanism involving increased acetylation and nuclear translocation of NF-κB p65, resulting in up-regulation of NF-κB target genes

  8. Von-Willebrand Factor Influences Blood Brain Barrier Permeability and Brain Inflammation in Experimental Allergic Encephalomyelitis

    PubMed Central

    Noubade, Rajkumar; del Rio, Roxana; McElvany, Benjamin; Zachary, James F.; Millward, Jason M.; Wagner, Denisa D.; Offner, Halina; Blankenhorn, Elizabeth P.; Teuscher, Cory

    2008-01-01

    Weibel-Palade bodies within endothelial cells are secretory granules known to release von Willebrand Factor (VWF), P-selectin, chemokines, and other stored molecules following histamine exposure. Mice with a disrupted VWF gene (VWFKO) have endothelial cells that are deficient in Weibel-Palade bodies. These mice were used to evaluate the role of VWF and/or Weibel-Palade bodies in Bordetella pertussis toxin-induced hypersensitivity to histamine, a subphenotype of experimental allergic encephalomyelitis, the principal autoimmune model of multiple sclerosis. No significant differences in susceptibility to histamine between wild-type and VWFKO mice were detected after 3 days; however, histamine sensitivity persisted significantly longer in VWFKO mice. Correspondingly, encephalomyelitis onset was earlier, disease was more severe, and blood brain barrier (BBB) permeability was significantly increased in VWFKO mice, as compared with wild-type mice. Moreover, inflammation was selectively increased in the brains, but not spinal cords, of VWFKO mice as compared with wild-type mice. Early increases in BBB permeability in VWFKO mice were not due to increased encephalitogenic T-cell activity since BBB permeability did not differ in adjuvant-treated VWFKO mice as compared with littermates immunized with encephalitogenic peptide plus adjuvant. Taken together, these data indicate that VWF and/or Weibel-Palade bodies negatively regulate BBB permeability changes and autoimmune inflammatory lesion formation within the brain elicited by peripheral inflammatory stimuli. PMID:18688020

  9. Salidroside Improves Behavioral and Histological Outcomes and Reduces Apoptosis via PI3K/Akt Signaling after Experimental Traumatic Brain Injury

    PubMed Central

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Background Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Methodology/Principal Findings Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside_significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside_also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Conclusions/Significance Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis

  10. Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier

    PubMed Central

    Nacer, Adéla; Movila, Alexandru; Sohet, Fabien; Girgis, Natasha M.; Gundra, Uma Mahesh; Loke, P'ng; Daneman, Richard; Frevert, Ute

    2014-01-01

    Cerebral malaria claims the lives of over 600,000 African children every year. To better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, Plasmodium berghei ANKA (PbA) infected CBA/CaJ mice, which develop experimental cerebral malaria (ECM), and P. yoelii 17XL (PyXL) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. Using a combination of intravital imaging and flow cytometry, we show that significantly more CD8+ T cells, neutrophils, and macrophages are recruited to postcapillary venules during ECM compared to hyperparasitemia. ECM correlated with ICAM-1 upregulation on macrophages, while vascular endothelia upregulated ICAM-1 during ECM and hyperparasitemia. The arrest of large numbers of leukocytes in postcapillary and larger venules caused microrheological alterations that significantly restricted the venous blood flow. Treatment with FTY720, which inhibits vascular leakage, neurological signs, and death from ECM, prevented the recruitment of a subpopulation of CD45hi CD8+ T cells, ICAM-1+ macrophages, and neutrophils to postcapillary venules. FTY720 had no effect on the ECM-associated expression of the pattern recognition receptor CD14 in postcapillary venules suggesting that endothelial activation is insufficient to cause vascular pathology. Expression of the endothelial tight junction proteins claudin-5, occludin, and ZO-1 in the cerebral cortex and cerebellum of PbA-infected mice with ECM was unaltered compared to FTY720-treated PbA-infected mice or PyXL-infected mice with hyperparasitemia. Thus, blood brain barrier opening does not involve endothelial injury and is likely reversible, consistent with the rapid recovery of many patients with CM. We conclude that the ECM-associated recruitment of large numbers of activated leukocytes, in particular CD8+ T cells and ICAM+ macrophages, causes a severe restriction in

  11. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  12. Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest.

    PubMed

    Tress, Erika E; Clark, Robert S B; Foley, Lesley M; Alexander, Henry; Hickey, Robert W; Drabek, Tomas; Kochanek, Patrick M; Manole, Mioara D

    2014-08-22

    Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was induced in 16-18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24 h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB.

  13. [Pathopshysiological mechanisms in macular edema].

    PubMed

    Turlea, Cristian; Zolog, Ileana; Blăjan, Codruta; Roşca, C; Turlea, Magdalena; Munteanu, Mihnea; Boruga, Ovidiu

    2014-01-01

    The treatment of diabetic macular edema has known a fast development in the last 5 years where the transition from laser monotherapy to intravitreal pharmacotherapy is becoming standard practice. Intravitreal injections therapy is in a continuous development with promising positive results. The use of intratvitreal devices in the treatment of macular edema of vascular cause has become a viable alternative also in treating diabetic macular edema. Several clinical studies have revealed the superiority of intravitreal treatment versus laser monotherapy. This article is evaluating and reviewing present and future treatments used to combat diabetic macular edema. [corrected].

  14. BRAIN DAMAGE AND BEHAVIOR, A CLINICAL-EXPERIMENTAL STUDY.

    ERIC Educational Resources Information Center

    SCHULMAN, JEROME L.; AND OTHERS

    THIS MONOGRAPH RELATES RESULTS OF A STUDY WHICH WAS UNDERTAKEN TO ATTEMPT TO ANSWER THREE QUESTIONS--TO WHAT EXTENT DO EIGHT TECHNIQUES COMMONLY USED TO DIAGNOSE BRAIN DAMAGE CO-VARY, TO WHAT EXTENT DO THE VARIOUS BEHAVIORAL SYMPTOMS THAT OCCUR WITH BRAIN DAMAGE CO-VARY, AND TO WHAT EXTENT DO THE DIAGNOSTIC MEASURES, SINGLY OR IN GROUPS, PREDICT…

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

    PubMed

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

    2011-01-01

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

  16. Development and experimentation of an eye/brain/task testbed

    NASA Technical Reports Server (NTRS)

    Harrington, Nora; Villarreal, James

    1987-01-01

    The principal objective is to develop a laboratory testbed that will provide a unique capability to elicit, control, record, and analyze the relationship of operator task loading, operator eye movement, and operator brain wave data in a computer system environment. The ramifications of an integrated eye/brain monitor to the man machine interface are staggering. The success of such a system would benefit users of space and defense, paraplegics, and the monitoring of boring screens (nuclear power plants, air defense, etc.)

  17. Experimental evidence for the accumulation of egg pigment in the brain cavities of Xenopus tadpoles.

    PubMed

    Kordylewski, L

    1983-07-01

    The origin and fate of darkly pigmented clusters of cells that float freely in the brain cavities of the tadpoles of Xenopus laevis have been experimentally investigated. The results point to the conclusion that the clusters are the sites of egg pigment accumulation, which remain within the brain cavities or at its walls until metamorphosis.

  18. Perimicrovascular edema in the frontal cortex in a rat model of intraperitoneal sepsis.

    PubMed

    Ari, Ilknur; Kafa, Ilker M; Kurt, M Ayberk

    2006-03-01

    Septic encephalopathy is a complication of sepsis, and it is closely associated with the increased mortality of the sufferers. Pathophysiology of septic encephalopathy is not still completely understood. In an attempt to provide insight into the pathogenesis of septic encephalopathy, a light and electron microscopic investigation has been carried out in a rat model of intraperitoneal sepsis. Experimental fecal peritonitis was induced in Wistar rats which have been monitored for 6 h and sacrificed to harvest the samples of frontal cortex. Vital parameters and morphometric data obtained from investigation of the microvessels were then compared with the sham-operated and unoperated controls. In addition to the discernible drop in the blood pressure and in rectal temperature following initial increases, unstable but usually increased heart rate and marked respiratory failure were recorded. Estimation of the percentage of the microvessel area occupied by edema revealed the presence of significantly more perimicrovascular edema in the experimental fecal peritonitis group compared to both sham-operated and unoperated controls, while no significant difference was present between the latter two groups. Electron microscopic investigation confirmed the presence of distinctive perimicrovascular edema in the fecal peritonitis group although the endothelial cells were linked by tight junctions which appeared morphologically intact. Although it might be premature to draw any strict parallels between the septic encephalopathy in humans and the findings observed in the present model, the results may suggest that the edema observed around the microvessels would bare a role in the pathogenesis of the septic encephalopathy probably by affecting the exchange of oxygen and nutrients with carbon dioxide and waste products between the blood and brain parenchyma.

  19. Experimental Injury Biomechanics of the Pediatric Head and Brain

    NASA Astrophysics Data System (ADS)

    Margulies, Susan; Coats, Brittany

    Traumatic brain injury (TBI) is a leading cause of death and disability among children and young adults in the United States and results in over 2,500 childhood deaths, 37,000 hospitalizations, and 435,000 emergency department visits each year (Langlois et al. 2004). Computational models of the head have proven to be powerful tools to help us understand mechanisms of adult TBI and to determine load thresholds for injuries specific to adult TBI. Similar models need to be developed for children and young adults to identify age-specific mechanisms and injury tolerances appropriate for children and young adults. The reliability of these tools, however, depends heavily on the availability of pediatric tissue material property data. To date the majority of material and structural properties used in pediatric computer models have been scaled from adult human data. Studies have shown significant age-related differences in brain and skull properties (Prange and Margulies 2002; Coats and Margulies 2006a, b), indicating that the pediatric head cannot be modeled as a miniature adult head, and pediatric computer models incorporating age-specific data are necessary to accurately mimic the pediatric head response to impact or rotation. This chapter details the developmental changes of the pediatric head and summarizes human pediatric properties currently available in the literature. Because there is a paucity of human pediatric data, material properties derived from animal tissue are also presented to demonstrate possible age-related differences in the heterogeneity and rate dependence of tissue properties. The chapter is divided into three main sections: (1) brain, meninges, and cerebral spinal fluid (CSF); (2) skull; and (3) scalp.

  20. Magnesium and ketamine attenuate cognitive dysfunction following experimental brain injury.

    PubMed

    Smith, D H; Okiyama, K; Gennarelli, T A; McIntosh, T K

    1993-07-23

    We evaluated the therapeutic effects of two noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, MgCl2 and ketamine, both individually and together, on cognitive dysfunction observed following parasagittal fluid-percussion (FP) brain injury in the rat. Using a modified Morris water maze technique, we found significant attenuation of post-traumatic memory dysfunction in animals treated with either MgCl2 (125 mumol) or ketamine (4 mg/kg) (P < 0.005). Combined MgCl2 and ketamine treatment also preserved memory function (P < 0.005), with no apparent additive effect.

  1. Experimental modeling of explosive blast-related traumatic brain injuries.

    PubMed

    Alley, Matthew D; Schimizze, Benjamin R; Son, Steven F

    2011-01-01

    This study aims to characterize the interaction of explosive blast waves through simulated anatomical systems. We have developed physical models and a systematic approach for testing traumatic brain injury (TBI) mechanisms and occurrences. A simplified series of models consisting of spherical poly(methyl methacrylate) (PMMA) shells housing synthetic gelatins as brain simulants have been utilized. A series of experiments was conducted to compare the sensitivity of the system response to mechanical properties of the simulants under high strain-rate explosive blasts. Small explosive charges were directed at the models to produce a realistic blast wave in a scaled laboratory setting. Blast profiles were measured and analyzed to compare system response severity. High-speed shadowgraph imaging captured blast wave interaction with the head model while particle tracking captured internal response for displacement and strain correlation. The results suggest amplification of shock waves inside the head near material interfaces due to impedance mismatches. In addition, significant relative displacement was observed between the interacting materials suggesting large strain values of nearly 5%. Further quantitative results were obtained through shadowgraph imaging of the blasts confirming a separation of time scales between blast interaction and bulk movement. These results lead to a conclusion that primary blast effects may potentially contribute significantly to the occurrence of military associated TBI. PMID:20580931

  2. Dosimetric Predictors of Laryngeal Edema

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Adapala, Prashanth; Endres, Eugene J. C; Brack, Collin; Fiorino, Claudio; Sormani, Maria Pia; Parker, Brent

    2007-07-01

    Purpose: To investigate dosimetric predictors of laryngeal edema after radiotherapy (RT). Methods and Materials: A total of 66 patients were selected who had squamous cell carcinoma of the head and neck with grossly uninvolved larynx at the time of RT, no prior major surgical operation except for neck dissection and tonsillectomy, treatment planning data available for analysis, and at least one fiberoptic examination of the larynx within 2 years from RT performed by a single observer. Both the biologically equivalent mean dose at 2 Gy per fraction and the cumulative biologic dose-volume histogram of the larynx were extracted for each patient. Laryngeal edema was prospectively scored after treatment. Time to endpoint, moderate or worse laryngeal edema (Radiation Therapy Oncology Group Grade 2+), was calculated with log rank test from the date of treatment end. Results: At a median follow-up of 17.1 months (range, 0.4- 50.0 months), the risk of Grade 2+ edema was 58.9% {+-} 7%. Mean dose to the larynx, V30, V40, V50, V60, and V70 were significantly correlated with Grade 2+ edema at univariate analysis. At multivariate analysis, mean laryngeal dose (continuum, hazard ratio, 1.11; 95% confidence interval, 1.06-1.15; p < 0.001), and positive neck stage at RT (N0-x vs. N +, hazard ratio, 3.66; 95% confidence interval, 1.40-9.58; p = 0.008) were the only independent predictors. Further stratification showed that, to minimize the risk of Grade 2+ edema, the mean dose to the larynx has to be kept {<=}43.5 Gy at 2 Gy per fraction. Conclusion: Laryngeal edema is strictly correlated with various dosimetric parameters; mean dose to the larynx should be kept {<=}43.5 Gy.

  3. Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Jing; Kobori, Nobuhide; Redell, John B.; Hylin, Michael J.; Hood, Kimberly N.; Moore, Anthony N.

    2016-01-01

    ) allows for the accumulation of circulating fluids and proinflammatory cells in the injured brain. These processes can exacerbate TBI pathology and outcome. While the role of inflammation in the injured tissue has been examined in some detail, the contribution of peripheral inflammation in BBB breakdown and ensuing pathology has not been well defined. We present experimental evidence to indicate that the stimulation of nicotinic acetylcholine α7 receptors (nAChRa7s) can reduce peripheral inflammation and BBB breakdown after TBI. These results suggest that activators of nAChRa7 may have therapeutic utility for the treatment of TBI. PMID:26937017

  4. Experimental traumatic brain injury alters ethanol consumption and sensitivity.

    PubMed

    Lowing, Jennifer L; Susick, Laura L; Caruso, James P; Provenzano, Anthony M; Raghupathi, Ramesh; Conti, Alana C

    2014-10-15

    Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal

  5. Acute Hemorrhagic Edema of Infancy.

    PubMed

    Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C

    2016-01-01

    Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.

  6. Pulmonary edema of scuba divers.

    PubMed

    Hampson, N B; Dunford, R G

    1997-01-01

    A syndrome of acute pulmonary edema has been previously reported among scuba divers in cold, European waters. Because of the temperatures involved, the name "cold-induced pulmonary edema" was coined in the original 1989 description. We report six individuals who developed the identical syndrome, five while diving in Puget Sound and one in the Gulf of Mexico. The four women and two men ranged in age from 24 to 60 yr. They experienced one to six episodes apiece, each with the development severe dyspnea at depth without excessive exertion. Associated symptoms included cough, weakness, expectoration of froth, chest discomfort, orthopnea, wheezing, hemoptysis, and dizziness. Emergency medical evaluation of four divers revealed rales on examination and pulmonary edema on chest radiograph. In one diver with pulmonary edema on chest radiograph, pulmonary capillary wedge pressure was normal when measured acutely. Symptoms resolved either spontaneously over 1-2 days or with standard medial treatment for pulmonary edema. Prior history of cardiovascular disease was negative except for hypertension and mitral valve prolapse in one diver. Cardiac evaluations following recovery from the acute episodes were normal. Episodes in the cold waters of Puget Sound sometimes occurred despite the use of dry suits. Furthermore, one diver developed recurrent episodes in 27 degrees C water off Cozumel, Mexico. Development of pulmonary edema while scuba diving constitutes a distinct clinical entity which may occur in either "cold" or "warm" water. It is not associated with a decompression mechanism. Personnel caring for divers should be aware of the syndrome in order to provide optimal medical management.

  7. Pathologic electrographic changes after experimental traumatic brain injury

    PubMed Central

    Bragin, Anatol; Li, Lin; Almajano, Joyel; Alvarado-Rojas, Catalina; Reid, Aylin Y.; Staba, Richard J.; Engel, Jerome

    2016-01-01

    Summary Objective To investigate possible electroencephalography (EEG) correlates of epileptogenesis after traumatic brain injury (TBI) using the fluid percussion model. Methods Experiments were conducted on adult 2- to 4-month-old male Sprague-Dawley rats. Two groups of animals were studied: (1) the TBI group with depth and screw electrodes implanted immediately after the fluid percussion injury (FPI) procedure, and (2) a naive age-matched control group with the same electrode implantation montage. Pairs of tungsten microelectrodes (50 µm outer diameter) and screw electrodes were implanted in neocortex inside the TBI core, areas adjacent to TBI, and remote areas. EEG activity, recorded on the day of FPI, and continuously for 2 weeks, was analyzed for possible electrographic biomarkers of epileptogenesis. Video-EEG monitoring was also performed continuously in the TBI group to capture electrographic and behavioral seizures until the caps came off (28–189 days), and for 1 week, at 2, 3, and 6 months of age, in the control group. Results Pathologic high-frequency oscillations (pHFOs) with a central frequency between 100 and 600 Hz, were recorded from microelectrodes, beginning during the first two post-FPI weeks, in 7 of 12 animals in the TBI group (58%) and never in the controls. pHFOs only occurred in cortical areas within or adjacent to the TBI core. These were associated with synchronous multiunit discharges and popSpikes, duration 15–40 msec. Repetitive pHFOs and EEG spikes (rHFOSs) formed paroxysmal activity, with a unique arcuate pattern, in the frequency band 10–16 Hz in the same areas as isolated pHFOs, and these events were also recorded by screw electrodes. Although loss of caps prevented long-term recordings from all rats, pHFOs and rHFOSs occurred during the first 2 weeks in all four animals that later developed seizures, and none of the rats without these events developed late seizures. Significance pHFOs, similar to those associated with

  8. Decreased light attenuation in cerebral cortex during cerebral edema detected using optical coherence tomography

    PubMed Central

    Rodriguez, Carissa L. R.; Szu, Jenny I.; Eberle, Melissa M.; Wang, Yan; Hsu, Mike S.; Binder, Devin K.; Park, B. Hyle

    2014-01-01

    Abstract. Cerebral edema develops in response to a variety of conditions, including traumatic brain injury and stroke, and contributes to the poor prognosis associated with these injuries. This study examines the use of optical coherence tomography (OCT) for detecting cerebral edema in vivo. Three-dimensional imaging of an in vivo water intoxication model in mice was performed using a spectral-domain OCT system centered at 1300 nm. The change in attenuation coefficient was calculated and cerebral blood flow was analyzed using Doppler OCT techniques. We found that the average attenuation coefficient in the cerebral cortex decreased over time as edema progressed. The initial decrease began within minutes of inducing cerebral edema and a maximum decrease of 8% was observed by the end of the experiment. Additionally, cerebral blood flow slowed during late-stage edema. Analysis of local regions revealed the same trend at various locations in the brain, consistent with the global nature of the cerebral edema model used in this study. These results demonstrate that OCT is capable of detecting in vivo optical changes occurring due to cerebral edema and highlights the potential of OCT for precise spatiotemporal detection of cerebral edema. PMID:25674578

  9. Neural tissue regeneration in experimental brain injury model with channeled scaffolds of acrylate copolymers.

    PubMed

    Martínez-Ramos, Cristina; Gómez-Pinedo, Ulises; Esparza, Maria Angeles Garcia; Soria, José Miguel; Barcia, Juan A; Monleón Pradas, Manuel

    2015-06-26

    The objective of the present study was to evaluate the biocompatibility and cell hosting ability of a copolymer scaffold based on ethyl acrylate (EA) and hydroxyl ethyl acrylate (HEA) in vivo after an experimental brain injury. Wistar rats were subjected to cryogenic traumatic brain injury. We evaluated the tissue response to the implanted materials after 8 weeks. The materials were implanted devoid of cells; they provoked a minimal scar response by the host tissue and permitted the invasion of neurons and glia inside them. We also found new blood vessels surrounding and inside the implant. Thus, the copolymer scaffold proves to offer a suitable environment producing a cellular network potentially useful in brain repair after brain injury.

  10. Memantine alleviates brain injury and neurobehavioral deficits after experimental subarachnoid hemorrhage.

    PubMed

    Huang, Chih-Yuan; Wang, Liang-Chao; Wang, Hao-Kuang; Pan, Chia-Hsin; Cheng, Ya-Yun; Shan, Yan-Shen; Chio, Chung-Ching; Tsai, Kuen-Jer

    2015-01-01

    Subarachnoid hemorrhage (SAH) causes brain injury via glutamate excitotoxicity, which leads to an excessive Ca(2+) influx and this starts an apoptotic cascade. Memantine has been proven to reduce brain injury in several types of brain insults. This study investigated the neuro-protective potential of memantine after SAH and explored the underlying mechanisms. An endovascular perforation rat model of SAH was used and Sprague-Dawley rats were randomized into sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the neuro-behavioral functions, blood-brain barrier (BBB) permeability and neuronal cell preservation. The mechanisms of action of memantine, with its N-methyl-D-aspartate (NMDA) antagonistic characteristics on nitric oxide synthase (NOS) expression and peroxynitrite formation, were also investigated. The apoptotic cascade after SAH was suppressed by memantine. Neuronal NOS (nNOS) expression, peroxynitrite formation, and subsequent oxidative/nitrosative stress were also reduced. Memantine effectively preserved BBB integrity, rescued neuronal injury, and improved neurological outcome in experimental SAH. Memantine has neuro-protective potential in experimental SAH and may help combat SAH-induced brain damage in the future.

  11. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats.

    PubMed

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-09-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any injury or running exercise to compare with the effect of TBI and SWR. Immunohistochemistry, Western blotting, skilled ladder rung walking test, and 2,3,5-triphenyltetrazolium chloride staining analysis for the evaluation of NT-3 expression were used to assess brain damage and recovery. [Results] The TBI-induced decrease in NT-3 expression was recovered by wheel running exercise. Moreover, decreased ischemic volume and progressive neurobehavioral outcome were observed in the SWR group. [Conclusion] Spontaneous running exercise promotes brain recovery and motor function through an increase in expression of NT-3. PMID:24259924

  12. Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury.

    PubMed

    Yüksel, Hatice; Yavuz, Özlem; Iş, Merih; Çomunoğlu, Nil; Üzüm, Gülay; Akyüz, Feyzullah; Yıldırım, Hayriye Ak

    2013-11-01

    This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T + S). The T, T + V and T + S groups were subjected to TBI. The T + V group was administered vehicle [ethanol:saline (1/2)] and the T + S group was administered 1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the T + S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the T + S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the T + S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.

  13. Experimental and theoretical characterization of the voltage distribution generated by deep brain stimulation

    PubMed Central

    Miocinovic, Svjetlana; Lempka, Scott F.; Russo, Gary S.; Maks, Christopher B.; Butson, Christopher R.; Sakaie, Ken E.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2008-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson’s disease and shows great promise for numerous other disorders. While the fundamental purpose of DBS is to modulate neural activity with electric fields, little is known about the actual voltage distribution generated in the brain by DBS electrodes and as a result it is difficult to accurately predict which brain areas are directly affected by the stimulation. The goal of this study was to characterize the spatial and temporal characteristics of the voltage distribution generated by DBS electrodes. We experimentally recorded voltages around active DBS electrodes in either a saline bath or implanted in the brain of a non-human primate. Recordings were made during voltage-controlled and current-controlled stimulation. The experimental findings were compared to volume conductor electric field models of DBS parameterized to match the different experiments. Three factors directly affected the experimental and theoretical voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage drop at the electrode-electrolyte interface and the conductivity of the tissue medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity and anisotropy of the tissue medium. While the voltage distribution does not directly predict the neural response to DBS, the results of this study do provide foundational building blocks for understanding the electrical parameters of DBS and characterizing its effects on the nervous system. PMID:19118551

  14. Experimental investigation of the mechanical properties of brain simulants used for cranial gunshot simulation.

    PubMed

    Lazarjan, Milad Soltanipour; Geoghegan, Patrick Henry; Jermy, Mark Christopher; Taylor, Michael

    2014-06-01

    The mechanical properties of the human brain at high strain rate were investigated to analyse the mechanisms that cause backspatter when a cranial gunshot wound occurs. Different concentrations of gelatine and a new material (M1) developed in this work were tested and compared to bovine brain samples. Kinetic energy absorption and expansion rate of the samples caused by the impact of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22 long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high speed camera (24,000fps). The AR projectile had, in the region of interest, an average kinetic energy (Ek) of 42±1.3J. On average, the bovine brain absorbed 50±5% of Ek, and the simulants 46-58±5%. The Ek of the .22 LR was 141±3.7J. The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The expansion of the sample, after penetration, was measured. The bovine brain experienced significant plastic deformation whereas the gelatine solution exhibited a principally elastic response. The permanent damage patterns in the M1 material were much closer to those in brain tissue, than were the damage patterns in the gelatine. The results provide a first step to developing a realistic experimental simulant for the human brain which can produce the same blood backspatter patterns as a human brain during a cranial gunshot. These results can also be used to improve the 3D models of human heads used in car crash and blast trauma injury research.

  15. Naloxone-induced pulmonary edema.

    PubMed

    Schwartz, J A; Koenigsberg, M D

    1987-11-01

    We present the case of a 68-year-old woman with acute pulmonary edema secondary to the administration of naloxone to reverse an inadvertent narcotic overdose. The patient presented following a 12-hour history of increasingly bizarre behavior and confusion. A total IV dose of 1.6 mg naloxone was administered in an attempt to reverse the suspected overconsumption of a codeine-containing cough suppressant. She immediately became agitated, tachycardic, and diaphoretic; a clinical diagnosis of acute pulmonary edema was made. Following treatment with furosemide, nitroglycerin, and morphine sulfate, the patient recovered completely without further incident. Although naloxone is thought to be a safe drug with few complications, it should not be used indiscriminantly, and the smallest doses necessary to elicit the desired response should be used. PMID:3662194

  16. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  17. Evaluation of Peritumoral Edema in the Delineation of Radiotherapy Clinical Target Volumes for Glioblastoma

    SciTech Connect

    Chang, Eric L. . E-mail: echang@mdanderson.org; Akyurek, Serap; Avalos, Tedde C; Rebueno, Neal C; Spicer, Chris C; Garcia, John C; Famiglietti, Robin; Allen, Pamela K.; Chao, K.S. Clifford; Mahajan, Anita; Woo, Shiao Y.; Maor, Moshe H.

    2007-05-01

    Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r {sup 2} 0.0007; p = 0.3). For patients with edema >75 cm{sup 3}, the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm{sup 3}, using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema.

  18. Activities of lysosomal enzymes in rabbit brain with experimental neurofibrillary changes.

    PubMed

    Suzuki, H; Takeda, M; Nakamura, Y; Tada, K; Hariguchi, S; Nishimura, T

    1988-06-29

    Rabbits were injected intracerebrally with aluminum salt leading to experimental neurofibrillary change formation as a model of Alzheimer neurofibrillary change. Eleven days after the injection, the brain tissues were excised from the cortex, hippocampus, and cervical region of spinal cord. Five lysosomal enzymes (cathepsin D, beta-glucuronidase, acid phosphatase, acid DNase, alkaline DNase) were assayed and compared with the control. Cathepsin D, acid DNase and beta-glucuronidase activities increased significantly in all 3 areas of aluminum-injected brain. On the other hand, acid phosphatase and alkaline DNase activities remained at the same level. The results showed the lysosomal enzymes did not change in parallel after aluminum administration, suggesting a role of the increased enzymes in the brain with neurofibrillary changes.

  19. Development of an experimental model of brain tissue heterotopia in the lung

    PubMed Central

    Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

    2007-01-01

    Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

  20. Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis.

    PubMed

    Guerra-Romero, L; Täuber, M G; Fournier, M A; Tureen, J H

    1992-09-01

    Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.

  1. Evidence of apoptotic cell death after experimental traumatic brain injury in the rat.

    PubMed Central

    Rink, A.; Fung, K. M.; Trojanowski, J. Q.; Lee, V. M.; Neugebauer, E.; McIntosh, T. K.

    1995-01-01

    Apoptosis plays an important role in many developmental and pathological processes of the central nervous system. However, the role of apoptosis in traumatic brain injury has not been determined. Using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) method, we detected many cells with extensive DNA fragmentation in different regions of the brains of rats subjected to experimental traumatic brain injury. Two types of TUNEL-positive cells were demonstrated by light and electron microscopy, including type I cells that displayed morphological features of necrotic cell death and type II cells that displayed morphological features of classic apoptotic cell death. TUNEL-positive cells were detectable for up to 72 hours after the initial injury. Gel electrophoresis of DNA extracted from affected areas of the injured brain containing both type I and II cells revealed only internucleosomal fragmentation at 185-bp intervals, a feature originally described in apoptotic cell death. These data suggest that apoptosis, in addition to necrotic cell death, occurs after traumatic brain injury, and that internucleosomal fragmentation of DNA may be associated with certain types of necrotic cell death. Images Figure 1 Figure 2 Figure 4 PMID:7495282

  2. Azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria

    PubMed Central

    2013-01-01

    Background Cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite Plasmodium falciparum. Drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. The potential of the medicinal plant Azadirachta indica (Neem) for the treatment of experimental cerebral malaria was evaluated in mice. Methods Experimental cerebral malaria was induced in mice by infection with Plasmodium berghei ANKA. Infected mice were administered with Azadirachta indica ethanolic extract at doses of 300, 500, or 1000 mg/kg intraperitoneally (i.p.) in experimental groups, or with the anti-malarial drugs chloroquine (12 mg/kg, i.p.) or artemether (1.6 mg/kg, i.p.), in the positive control groups. Treatment was initiated at the onset of signs of brain involvement and pursued for five days on a daily basis. Mice brains were dissected out and processed for the study of the effects of the extract on pyramidal cells’ fate and on markers of neuroinflammation and apoptosis, in the medial temporal lobe. Results Azadirachta indica ethanolic extract mitigated neuroinflammation, decreased the severity of brain oedema, and protected pyramidal neurons from apoptosis, particularly at the highest dose used, comparable to chloroquine and artemether. Conclusions The present findings suggest that Azadirachta indica ethanolic extract has protective effects on neuronal populations in the inflamed central nervous system, and justify at least in part its use in African and Asian folk medicine and practices. PMID:23984986

  3. [Lung edema in scuba diving].

    PubMed

    Hempe, S; Lierz, P

    2003-10-01

    The management of a diving-related emergency is frequently a great challenge for an emergency physician without a special diving medicine training or experiences. Almost every physician knows something about the medical therapy of diving-related accidents which are combined with a barotrauma or a decompression sickness. But there are still some rare symptoms and organ affections of diving-related emergencies which are unknown in common. In consideration of the present case of an acute diving-related lung edema we discuss the different reasons and differential diagnosis of diving emergencies.

  4. Methods to produce brain hyperthermia.

    PubMed

    Sharma, Hari Shanker

    2005-01-01

    With the increase in global warming, the problems of hyperthermia have recently attracted world-wide medical attention. Deaths due to heat-related illnesses that have occurred in many human populations in recent years are now recognized as a great social and medical problem. Interestingly, the detailed mechanisms of hyperthermia and probable therapeutic measures have still not been worked out. Thus, good experimental models to simulate hyperthermia under clinical conditions are needed to expand our knowledge in the field and to develop suitable therapeutic strategies in the future. This unit describes an animal model to induce hyperthermia that is comparable to the clinical situation. The model will be useful for studying the effects of heat-related illnesses on various organs and systems. Because hyperthermia is associated with brain dysfunction, methods to assess some crucial parameters of brain injury, such as breakdown of the blood-brain barrier and brain edema formation, are also described.

  5. Found in translation: understanding the biology and behavior of experimental traumatic brain injury

    PubMed Central

    Bondi, Corina O.; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Osier, Nicole D.; Carlson, Shaun W.; Dixon, C. Edward; Giza, Christopher C.; Kline, Anthony E.

    2014-01-01

    BONDI, C.O., B.D. Semple, L.J. Noble-Haeusslein, N.D. Osier, S.W. Carlson, C.E. Dixon, C.C. Giza and A.E. Kline. Found in translation: understanding the biology and behavior of experimental traumatic brain injury. NEUROSCI BIOBEHAV REV. The aim of this review is to discuss in greater detail the topics covered in the recent symposium entitled “Traumatic brain injury: laboratory and clinical perspectives,” presented at the 2014 International Behavioral Neuroscience Society annual meeting. Herein we review contemporary laboratory models of traumatic brain injury (TBI) including common assays for sensorimotor and cognitive behavior. New modalities to evaluate social behavior after injury to the developing brain, as well as the attentional set-shifting test (AST) as a measure of executive function in TBI, will be highlighted. Environmental enrichment (EE) will be discussed as a preclinical model of neurorehabilitation, and finally, an evidence-based approach to sports-related concussion will be considered. The review consists predominantly of published data, but some discussion of ongoing or future directions is provided. PMID:25496906

  6. Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study

    PubMed Central

    Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F.

    2015-01-01

    Background Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. Objectives This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. Methods High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Results Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Conclusions Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature. PMID:26601082

  7. Connecting clinical and experimental investigations of awareness in traumatic brain injury.

    PubMed

    Dockree, Paul M; O'Connell, Redmond G; Robertson, Ian H

    2015-01-01

    Questionnaire-based demonstrations of impaired self-awareness (SA) after traumatic brain injury (TBI) are not always supported by experimental studies of in-the-moment or online awareness. This chapter begins by describing the clinical phenomenon of impaired SA, how it is measured, and why its interdependency with mechanisms of online awareness may provide the scaffolding from which appraisals of cognitive functioning can be accurately revised following a brain injury. We review research that has measured unawareness of errors in routine action in TBI patients and propose more rigorous methodological approaches to studying the emergent properties of awareness with greater clarity in the laboratory. We discuss how neuropsychological and electrophysiologic studies are beginning to inform our understanding of impaired error processing in TBI patients and we highlight recent theory proposing that online metacognitive processes accumulate evidence of erroneous responses in a graded fashion. Neural signals with amplitudes that scale with the strength of accruing evidence and peak latencies that mark the threshold at which awareness emerges represent important neural mechanisms to examine the breakdown of error awareness after brain injury. We also discuss how errors can be investigated in relation to different sources of evidence that contribute to aware experiences after brain injury. Finally, we explore conditions beyond error signaling, and how different "objects of insight" that require retrospective and prospective judgments of confidence need to be examined in relation to the clinical phenomenon of impaired SA. PMID:25701904

  8. Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage

    PubMed Central

    Klinger-Gratz, Pascal P.; Fiechter, Michael; Z’Graggen, Werner J.; Gautschi, Oliver P.; El-Koussy, Marwan; Gralla, Jan; Schaller, Karl; Zbinden, Martin; Arnold, Marcel; Fischer, Urs; Mattle, Heinrich P.; Raabe, Andreas; Beck, Jürgen

    2016-01-01

    Background Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. Methods More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. Results Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). Conclusions Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift. PMID:26872068

  9. Reexpansion pulmonary edema in children

    PubMed Central

    Rodrigues, Antonio Lucas L.; Lopes, Carlos Eduardo; Romaneli, Mariana Tresoldi das N.; Fraga, Andrea de Melo A.; Pereira, Ricardo Mendes; Tresoldi, Antonia Teresinha

    2013-01-01

    OBJECTIVE To present a case of a patient with clinical and radiological features of reexpansion pulmonary edema, a rare and potentially fatal disease. CASE DESCRIPTION An 11-year-old boy presenting fever, clinical signs and radiological features of large pleural effusion initially treated as a parapneumonic process. Due to clinical deterioration he underwent tube thoracostomy, with evacuation of 3,000 mL of fluid; he shortly presented acute respiratory insufficiency and needed mechanical ventilation. He had an atypical evolution (extubated twice with no satisfactory response). Computerized tomography findings matched those of reexpansion edema. He recovered satisfactorily after intensive care, and pleural tuberculosis was diagnosed afterwards. COMMENTS Despite its rareness in the pediatric population (only five case reports gathered), the knowledge of this pathology and its prevention is very important, due to high mortality rates. It is recommended, among other measures, slow evacuation of the pleural effusion, not removing more than 1,500 mL of fluid at once. PMID:24142327

  10. [Therapeutic approach in persistent diabetic macular edema].

    PubMed

    Brănişteanu, Daniel; Moraru, Andreea

    2014-01-01

    Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

  11. Relationships between edema degree and clinical and biochemical parameters in posterior reversible encephalopathy syndrome: a preliminary study.

    PubMed

    Bo, Gao; Hui, Liang; Feng-Li, Liu; Cui, Lv

    2012-09-01

    The objective of the study was to investigate the associations between the degree of edema with the clinical and biochemical parameters such as serum lactate dehydrogenase (LDH), albumin (ALB) in posterior reversible encephalopathy syndrome (PRES) patients. Forty-nine patients with typical clinical symptoms and characteristic MR imaging findings of PRES were included in this study. Lactate dehydrogenase and ALB were analyzed with the immunoluminometric assays. Fluid-attenuated inversion recovery images were used to evaluate the distribution of the extent or severity of vasogenic edema by two observers. Correlation analysis between the scores of brain edema and the blood pressures, clinical conditions and biochemical parameters was performed. No significant difference of brain edema score was found between patients with eclampsia, chronic renal failure and other clinical condition (P > 0.05). Both mean arterial pressures and LDH level were moderately correlated with the scores of brain edema distribution (Spearman's ρ test, r = 0.405 and 0.497, respectively, P < 0.01). Serum ALB level was not correlated with the scores of brain edema distribution (P > 0.05). Larger and more diffuse lesions may be predicted by higher LDH level and blood pressure. The overall severity of the systemic process might be predicted by the degree of edema expression in PRES.

  12. Experimental carbon dioxide laser brain lesions and intracranial dynamics. Part 2. Effect on brain water content and its response to acute therapy

    SciTech Connect

    Tiznado, E.G.; James, H.E.; Moore, S.

    1985-04-01

    Experimental brain lesions were created over the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy. The brain water content was studied 2, 6, and 24 hours after the insult. Another two groups of animals received acute therapy with either dexamethasone (1 mg/kg) or furosemide (1 mg/kg). In all groups, Evans blue extravasation uniformly extended from the impact crater into the surrounding white matter. The brain water content in the gray matter was elevated from the control value by 2 hours after impact and remained elevated at 6 and 24 hours. The white matter brain water content did not increase until 6 hours after impact and remained elevated in the 24-hour group. After dexamethasone treatment, there was a significant decrease of water in the gray matter, but not in the white matter. With furosemide therapy, there was no reduction of gray or white matter brain water.

  13. C5a alters blood-brain barrier integrity in experimental lupus

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G. N.; Quigg, Richard J.; Alexander, Jessy J.

    2010-01-01

    .—Jacob, A., Hack, B., Chiang, E., Garcia, J. G. N., Quigg, R. J., Alexander, J. J. C5a alters blood-brain barrier integrity in experimental lupus. PMID:20065106

  14. Neuronal damage in pericontusional edema zone.

    PubMed

    Kushi, H; Saito, T; Makino, K; Hayashi, N

    2003-01-01

    In this study, we investigated the molecular biological and histopathological aspects of the etiological mechanisms for pericontusional edema zone (PEZ). The subjects were 5 patients with traumatic brain injury who underwent surgery to evacuate the resulting hematoma. The average age of the subjects was 52 +/- 27.5 years. The GCS at the time of admission was 5-9. At operation apart from evacuating the hematoma, the PEZ was also excised and then examined histopathologically. Cerebrospinal fluid (CSF) levels of IL-6, IL-8, and IL-10 were measured at the time of admission and at 24 and 72 hours. Histological examination revealed large numbers of neutrophils accumulating within blood vessels in the PEZ, with some focal migration. IL-6: CSF levels at the time of admission and at 24, 72, and 72 hours were 550, 4350, and 878000 pg/ml, respectively (median values). IL-8: CSF levels were 715, 804, and 24900 pg/ml, respectively. IL-10: CSF levels were 15, 4, and 5 pg/ml, respectively. High levels of IL-6 and IL-8 were seen from an early stage, and became markedly higher with enlargement of the PEZ. The PEZ is thought to be due to microvascular disturbance by neutrophils stimulated by inflammatory cytokines, and neuronal damage from migrated neutrophils. PMID:14753464

  15. The Pathophysiology of Repetitive Concussive Traumatic Brain Injury in Experimental Models; New Developments and Open Questions

    PubMed Central

    Brody, David L; Benetatos, Joseph; Bennett, Rachel E; Klemenhagen, Kristen C; Donald, Christine L Mac

    2015-01-01

    In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. PMID:25684677

  16. Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria

    PubMed Central

    Dende, Chaitanya; Meena, Jairam; Nagarajan, Perumal; Panda, Amulya K.; Rangarajan, Pundi N.; Padmanaban, Govindarajan

    2015-01-01

    Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8+ T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. PMID:26227888

  17. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

    2015-01-01

    Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

  18. Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia.

    PubMed

    Carone, D; Librizzi, L; Cattalini, A; Sala, G; Conti, E; Cuccione, E; Versace, A; Cai, R; Monza, L; de Curtis, M; Ferrarese, C; Beretta, S

    2015-07-30

    Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.

  19. On high b diffusion imaging in the human brain: ruminations and experimental insights✩

    PubMed Central

    Mulkern, Robert V.; Haker, Steven J.; Maier, Stephan E.

    2010-01-01

    Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber “tractography” results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,“ruminations,” which have been proposed to account for the nonmonoexponentiality to date. PMID:19520535

  20. On high b diffusion imaging in the human brain: ruminations and experimental insights.

    PubMed

    Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

    2009-10-01

    Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber "tractography" results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,"ruminations," which have been proposed to account for the nonmonoexponentiality to date. PMID:19520535

  1. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.

    PubMed

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A

    2015-09-01

    Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

  2. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.

    PubMed

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A

    2015-09-01

    Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.

  3. Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria.

    PubMed

    Dende, Chaitanya; Meena, Jairam; Nagarajan, Perumal; Panda, Amulya K; Rangarajan, Pundi N; Padmanaban, Govindarajan

    2015-01-01

    Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15-20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8(+) T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. PMID:26227888

  4. Reinke Edema: Watch For Vocal Fold Cysts.

    PubMed

    Tüzüner, Arzu; Demirci, Sule; Yavanoglu, Ahmet; Kurkcuoglu, Melih; Arslan, Necmi

    2015-06-01

    Reinke edema is one of the common cause of dysphonia middle-aged population, and severe thickening of vocal folds require surgical treatment. Smoking plays a major role on etiology. Vocal fold cysts are also benign lesions and vocal trauma blamed for acquired cysts. We would like to present 3 cases with vocal fold cyst related with Reinke edema. First case had a subepidermal epidermoid cyst with Reinke edema, which could be easily observed before surgery during laryngostroboscopy. Second case had a mucous retention cyst into the edematous Reinke tissue, which was detected during surgical intervention, and third case had a epidermoid cyst that occurred 2 months after before microlaryngeal operation regarding Reinke edema reduction. These 3 cases revealed that surgical management of Reinke edema needs a careful dissection and close follow-up after surgery for presence of vocal fold cysts.

  5. Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: an experimental study using immunohistochemistry at light and electron microscopy in the rat.

    PubMed

    Sharma, Hari Shanker; Muresanu, Dafin; Sharma, Aruna; Zimmermann-Meinzingen, Sibilla

    2010-06-01

    The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P < 0.01) and the induction of HSP to all the brain regions examined. Leakage of Evans blue albumin and increase in brain water content in these brain areas are also markedly reduced with Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.

  6. Experimental study of blast-induced traumatic brain injury using a physical head model.

    PubMed

    Zhang, Jiangyue; Pintar, Frank A; Yoganandan, Narayan; Gennarelli, Thomas A; Son, Steven F

    2009-11-01

    This study was conducted to quantify intracranial biomechanical responses and external blast overpressures using physical head model to understand the biomechanics of blast traumatic brain injury and to provide experimental data for computer simulation of blast-induced brain trauma. Ellipsoidal-shaped physical head models, made from 3-mm polycarbonate shell filled with Sylgard 527 silicon gel, were used. Six blast tests were conducted in frontal, side, and 45 degrees oblique orientations. External blast overpressures and internal pressures were quantified with ballistic pressure sensors. Blast overpressures, ranging from 129.5 kPa to 769.3 kPa, were generated using a rigid cannon and 1.3 to 3.0 grams of pentaerythritol tetranitrate (PETN) plastic sheet explosive (explosive yield of 13.24 kJ and TNT equivalent mass of 2.87 grams for 3 grams of material). The PETN plastic sheet explosive consisted of 63% PETN powder, 29% plasticizer, and 8% nitrocellulose with a density of 1.48 g/cm3 and detonation velocity of 6.8 km/s. Propagation and reflection of the shockwave was captured using a shadowgraph technique. Shockwave speeds ranging from 423.3 m/s to 680.3 m/s were recorded. The model demonstrated a two-stage response: a pressure dominant (overpressure) stage followed by kinematic dominant (blast wind) stage. Positive pressures in the brain simulant ranged from 75.1 kPa to 1095 kPa, and negative pressures ranged from -43.6 kPa to -646.0 kPa. High- and normal-speed videos did not reveal observable deformations in the brain simulant from the neutral density markers embedded in the midsagittal plane of the head model. Amplitudes of the internal positive and negative pressures were found to linearly correlate with external overpressure. Results from the current study suggested a pressure-dominant brain injury mechanism instead of strain injury mechanism under the blast severity of the current study. These quantitative results also served as the validation and calibration

  7. Dual-porosity poroviscoelasticity and quantitative hydromechanical characterization of the brain tissue with experimental hydrocephalus data.

    PubMed

    Mehrabian, Amin; Abousleiman, Younane N; Mapstone, Timothy B; El-Amm, Christian A

    2015-11-01

    Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time

  8. High-resolution ultrasound evaluation of experimental brain abscess evolution: comparison with computed tomography and neuropathology.

    PubMed

    Enzmann, D R; Britt, R H; Lyons, B; Carroll, B; Wilson, D A; Buxton, J

    1982-01-01

    Computed tomographic (CT) and high-resolution ultrasound (HRUS) imaging of experimental brain abscess were correlated with neuropathologic findings in nine mongrel dogs. The HRUS scan was more sensitive to different histologic features than the CT scan but both accurately delineated the evolution of the experimental brain abscess. All stages of abscess evolution were characterized by an appearance of an echogenic rim with a hypoechoic center. In the early stages the echogenicity of the abscess was related primarily to marked cellular infiltration, while in the late stages extensive collagen deposition correlated closely with the echo pattern. The size of the abscess in the cerebritis stages appeared smaller on the HRUS scan than on the CT scan because the latter modality detected the extensive cerebritis around the developing necrotic center whereas the HRUS scan did not. This discrepancy disappeared in the capsule stages. The HRUS scan provided a more accurate depiction of the neuropathologic characteristics of the necrotic than did the CT scan. Healing of the abscess, indicated by a decrease in size of the hypoechoic center, was accurately detected by the HRUS scan. PMID:7053556

  9. High-resolution ultrasound evaluation of experimental brain abscess evolution: comparison with computed tomography and neuropathology

    SciTech Connect

    Enzmann, D.R.; Britt, R.H.; Lyons, B.; Carroll, B.; Wilson, D.A.; Buxton, J.

    1982-01-01

    Computed tomographic (CT) and high-resolution ultrasound (HRUS) imaging of experimental brain abscess were correlated with neuropathologic findings in nine mongrel dogs. The HRUS scan was more sensitive to different histologic features than the CT scan but both accurately delineated the evolution of the experimental brain abscess. All stages of abscess evolution were characterized by an appearance of an echogenic rim with a hypoechoic center. In the early stages the echogenicity of the abscess was related primarily to marked cellular infiltration while in the late stages extensive collagen deposition correlated closely with the echo pattern. The size of the abscess in the cerebritis stages appeared smaller on the HRUS scan than on the CT scan because the latter modality detected the extensive cerebritis around the developing necrotic center whereas the HRUS scan did not. This discrepancy disappeared in the capsule stages. The HRUS scan provided a more accurate depiction of the neuropathologic characteristics of the necrotic center than did the CT scan. Healing of the abscess, indicated by a decrease in size of the hypoechoic center, was accurately detected by the HRUS scan.

  10. Environmental enrichment as a viable neurorehabilitation strategy for experimental traumatic brain injury.

    PubMed

    Bondi, Corina O; Klitsch, Kyle C; Leary, Jacob B; Kline, Anthony E

    2014-05-15

    Environmental enrichment (EE) emerged as a robust independent variable capable of influencing behavioral outcome in experimental studies after the fortuitous observation by renowned neuropsychologist Donald O. Hebb that rats raised as pets in his home performed markedly better on problem-solving tasks than those kept in the laboratory. In the subsequent years, numerous studies ensued demonstrating that EE was also capable of inducing neuroplasticity in normal (i.e., noninjured) rats. These behavioral and neural alterations provided the impetus for investigating EE as a potential therapy for traumatic brain injury (TBI), which, over the past two decades, has resulted in several reports. Hence, the aim of this review is to integrate the findings and present the current state of EE as a viable neurorehabilitation strategy for TBI. Using the specific key term searches "traumatic brain injury" and "environmental enrichment" or "enriched environment," 30 and 30 experimental TBI articles were identified by PubMed and Scopus, respectively. Of these, 27 articles were common to both search engines. An additional article was found on PubMed using the key terms "enriched environment" and "fluid percussion." A review of the bibliographies in the 34 articles did not yield additional citations. The overwhelming consensus of the 34 publications is that EE benefits behavioral and histological outcome after brain injury produced by various models. Further, the enhancements are observed in male and female as well as adult and pediatric rats and mice. Taken together, these cumulative findings provide strong support for EE as a generalized and robust preclinical model of neurorehabilitation. However, to further enhance the model and to more accurately mimic the clinic, future studies should continue to evaluate EE during more rehabilitation-relevant conditions, such as delayed and shorter time periods, as well as in combination with other therapeutic approaches, as we have been doing

  11. Downregulating hypoxia-inducible factor-1α expression with perfluorooctyl-bromide nanoparticles reduces early brain injury following experimental subarachnoid hemorrhage in rats

    PubMed Central

    Xu, Wei; Xu, Rui; Li, Xia; Zhang, Huan; Wang, Xin; Zhu, Ji

    2016-01-01

    The aim of the present study was to investigate the effects of perfluorooctyl-bromide (PFOB) nanoparticles on hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target genes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Healthy male Sprague Dawley rats (n=100) were randomly divided into five groups: Sham, SAH, SAH + vehicle, SAH + 5 mg/kg PFOB and SAH + 10 mg/kg PFOB. A rat model of SAH was created by endovascular perforation, and PFOB treatment (5 mg/kg or 10 mg/kg injected into the caudal vein) was initiated 1 h after SAH. All rats were subsequently sacrificed 24 h after surgery. Treatment with PFOB significantly alleviated EBI (including neurological dysfunction, brain edema, blood-brain barrier disruption (BBB), and neural cell apoptosis). In addition, it also suppressed the expression of HIF-1α, vascular endothelial growth factor (VEGF) and BNIP3 in the rat hippocampus. The effects of 10 g/kg PFOB were found to be more obvious than those of 5 g/kg PFOB. Our work demonstrated that PFOB treatment alleviated EBI after SAH, potentially through downregulation of the expression of HIF-1α and its target genes, which led to reduced cell apoptosis, BBB disruption and brain edema. PMID:27347319

  12. Macular edema. A complication of diabetic retinopathy.

    PubMed

    Ferris, F L; Patz, A

    1984-05-01

    Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.

  13. Acute pulmonary edema associated with naphazoline ingestion.

    PubMed

    Fukushima, Hidetada; Norimoto, Kazunobu; Seki, Tadahiko; Nishiguchi, Takashi; Nakamura, Tatsuya; Konobu, Toshifumi; Nishio, Kenji; Okuchi, Kazuo

    2008-03-01

    In published reports of naphazoline ingestion, clinical effects are hypertension, bradycardia, pallor, diaphoresis, and respiratory distress. We report three cases of acute pulmonary edema after the intentional ingestion of naphazoline-containing antiseptic first aid liquid. These cases presented with altered mental status, hypertension, bradycardia, and diaphoresis. Chest x-ray on admission revealed acute pulmonary edema. Two cases required mechanical ventilation. All of these clinical effects resolved within 24 hours and the patients were discharged with no sequelae. Since naphazoline stimulates the peripheral alpha-2 adrenergic receptor, we speculate that intense vasoconstriction may have elevated cardiac afterload and left atrial-ventricular blood volume and caused acute pulmonary edema.

  14. BOLD-based Techniques for Quantifying Brain Hemodynamic and Metabolic Properties – Theoretical Models and Experimental Approaches

    PubMed Central

    Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; He, Xiang

    2012-01-01

    Quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for understanding normal human brain operation as well as pathophysiology of neurological disorders. It can also be of great importance for evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and co-workers of the BOLD (Blood Oxygenation Level Dependent) contrast opened a possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require developing theoretical models connecting MRI signal to brain structure and functioning and designing experimental techniques allowing MR measurements of salient features of theoretical models. In our review we discuss several such theoretical models and experimental methods for quantification brain hemodynamic and metabolic properties. Our review aims mostly at methods for measuring oxygen extraction fraction, OEF, based on measuring blood oxygenation level. Combining measurement of OEF with measurement of CBF allows evaluation of oxygen consumption, CMRO2. We first consider in detail magnetic properties of blood – magnetic susceptibility, MR relaxation and theoretical models of intravascular contribution to MR signal under different experimental conditions. Then, we describe a “through-space” effect – the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the MR signal formation. Further we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry, and T2-based quantification of oxygen OEF – utilize intravascular MR signal. Another technique – qBOLD – evaluates OEF by making use of through-space effects. In this review we targeted both scientists just entering the MR field and more experienced MR researchers

  15. Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury.

    PubMed

    Moro, Nobuhiro; Ghavim, Sima S; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2016-07-01

    Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment. PMID:27059390

  16. High-speed documented experimental gunshot to a skull-brain model and radiologic virtual autopsy.

    PubMed

    Thali, Michael J; Kneubuehl, Beat P; Vock, Peter; Allmen, Gabriel v; Dirnhofer, Richard

    2002-09-01

    The authors documented and evaluated experimental gunshots to a skull-brain model with high-speed photography and subsequent radiographic examination for comparison of the morphologic findings in the model. The artificial skull was a polyurethane ball constructed in layers, with a porous diploe sandwiched between a tabula externa and a tabula interna. The brain itself was simulated with gelatin 10% at 4 degrees C, a material well known in wound ballistics. Gunshots were fired at the model from a distance of 10 m and documented with high-speed photography (up to 50 million frames/sec). Subsequently, a complete examination of the artificial skull was performed, including spiral computed tomography (with two-dimensional and three-dimensional reconstructions) and classic skull autopsy. The high-speed photographs clearly showed the dynamic development of the skull fracture system from an external perspective. The subsequent radiographic examination of the entire head volume created two-dimensional reformations in any plane and three-dimensional reconstructions of the gunshot injury of the polyurethane skull-brain model, especially the wound channel and the fracture system. Thanks to the model and high-speed photographs, the dynamic development of the morphology of a gunshot wound could be documented and studied. The data from computed tomography, using two-dimensional and three-dimensional postprocessing with a perspective view, were very similar to those from classic head autopsy, but derived in a hands-off and nondestructive manner. This examination method leads the way to radiographic digital autopsy or virtual autopsy.

  17. Experimental study and model validation of selective spinal cord and brain hypothermia induced by a simple torso-cooling pad.

    PubMed

    Smith, K D

    2011-06-01

    In vivo experiments have been performed to test the effectiveness of a torso-cooling pad to reduce the temperature in the spinal cord and brain in rats. Coolant was circulated through the cooling pad to provide either mild or moderate cooling. Temperatures in the brain tissue, on the head surface, and on the spine and back surfaces were measured. During mild cooling, the temperature on the back surface was 22.82 +/- 2.43 degrees C compared to 29.34 +/- 1.94 degrees C on the spine surface. The temperature on the back surface during moderate cooling was 13.66 +/- 1.28 degrees C compared to 24.12 +/- 5.7 degrees C on the spine surface. Although the temperature in the brain tissue did not drastically deviate from its baseline value during cooling, there was a difference between the rectal and brain temperatures during cooling, which suggests mild hypothermia in the brain tissue. Using experimental data, theoretical models of the rat head and torso were developed to predict the regional temperatures and to validate the rat models. There was good agreement between the theoretical and experimental temperatures in the torso region. Differences between the predicted and measured temperatures in the brain are likely to be the result of imperfect mixing between the cold spinal fluid and the warm cerebrospinal fluid that surrounds the brain. PMID:22034738

  18. Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue.

    PubMed

    Nakielski, Paweł; Kowalczyk, Tomasz; Zembrzycki, Krzysztof; Kowalewski, Tomasz A

    2015-02-01

    Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing.

  19. Experimental studies on brain hematoma detection and oxygenation monitoring using PRM/NIR sensors

    NASA Astrophysics Data System (ADS)

    Zheng, Liu; Lee, Hyo Sang; Wilson, David A.; Hanley, Daniel F.; Lokos, Sandor; Kim, Jin

    1997-08-01

    Real time noninvasive head injury detection is needed in critical care facilities and triage site with limited resources. One tool missing right now is a small and fast noninvasive sensor which can help urgent care workers to (1) diagnose the location and severity of the injury, (2) to perform on site pre-hospital treatment if necessary, and (3) to make a decision on what kind of further medical action is needed. On the other hand, continuous monitoring of cerebral blood oxygenation is also needed in intensive care unit and in operation rooms. Pseudo-random modulation/near infrared sensor (PRM/NIR sensor) is developed to address these issues. It relies on advanced techniques in diode laser cw modulation and time resolved spectroscopy to perform fast and noninvasive brain tissue diagnostics. Phantom experiments have been conducted to study the feasibility of the sensor. Brain's optical properties are simulated with solutions of intralipid and ink. Hematomas are simulated with bags of paint and hemoglobin immersed in the solution of varies sizes, depths, and orientations. Effects of human skull and hair are studied experimentally. In animal experiment, the sensor was used to monitor the cerebral oxygenation change due to hypercapnia, hypoxia, and hyperventilation. Good correlations were found between NIR measurement parameters and physiological changes induced to the animals.

  20. Numerical modeling of an experimental shock tube for traumatic brain injury studies

    NASA Astrophysics Data System (ADS)

    Phillips, Michael; Regele, Jonathan D.

    2015-11-01

    Unfortunately, Improvised Explosive Devices (IEDs) are encountered commonly by both civilians and military soldiers throughout the world. Over a decade of medical history suggests that traumatic brain injury (TBI) may result from exposure to the blast waves created by these explosions, even if the person does not experience any immediate injury or lose consciousness. Medical researchers study the exposure of mice and rats to blast waves created in specially designed shock tubes to understand the effect on brain tissue. A newly developed table-top shock tube with a short driver section has been developed for mice experiments to reduce the time necessary to administer the blast radiation and increase the amount of statistical information available. In this study, numerical simulations of this shock tube are performed to assess how the blast wave takes its shape. The pressure profiles obtained from the numerical results are compared with the pressure histories from the experimental pressure transducers. The results show differences in behavior from what was expected, but the blast wave may still be an effective means of studying TBI.

  1. Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model

    PubMed Central

    Wells, Adam J.; Vink, Robert; Helps, Stephen C.; Knox, Steven J.; Blumbergs, Peter C.; Turner, Renée J.

    2015-01-01

    Introduction Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model. Materials and Methods 30 adult female Merino sheep (n = 8–12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed. Results No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%. Conclusions Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies. PMID:26121036

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

    PubMed

    Masel, Brent E; Bell, Randy S; Brossart, Shawn; Grill, Raymond J; Hayes, Ronald L; Levin, Harvey S; Rasband, Matthew N; Ritzel, David V; Wade, Charles E; DeWitt, Douglas S

    2012-08-10

    Blast injury is the most prevalent source of mortality and morbidity among combatants in Operations Iraqi and Enduring Freedom. Blast-induced neurotrauma (BINT) is a common cause of mortality, and even mild BINT may be associated with chronic cognitive and emotional deficits. In addition to military personnel, the increasing use of explosives by terrorists has resulted in growing numbers of blast injuries in civilian populations. Since the medical and rehabilitative communities are likely to be faced with increasing numbers of patients suffering from blast injury, the 2010 Galveston Brain Injury Conference focused on topics related to the diagnosis, treatment, and mechanisms of BINT. Although past military actions have resulted in large numbers of blast casualties, BINT is considered the signature injury of the conflicts in Iraq and Afghanistan. The attention focused on BINT has led to increased financial support for research on blast effects, contributing to the development of better experimental models of blast injury and a clearer understanding of the mechanisms of BINT. This more thorough understanding of blast injury mechanisms will result in novel and more effective therapeutic and rehabilitative strategies designed to reduce injury and facilitate recovery, thereby improving long-term outcomes in patients suffering from the devastating and often lasting effects of BINT. The following is a summary of the 2010 Galveston Brain Injury Conference, that included presentations related to the diagnosis and treatment of acute BINT, the evaluation of the long-term neuropsychological effects of BINT, summaries of current experimental models of BINT, and a debate about the relative importance of primary blast effects on the acute and long-term consequences of blast exposure.

  3. Perspectives on edema in childhood nephrotic syndrome.

    PubMed

    Teoh, Chia Wei; Robinson, Lisa A; Noone, Damien

    2015-10-01

    There have been two major theories surrounding the development of edema in nephrotic syndrome (NS), namely, the under- and overfill hypotheses. Edema is one of the cardinal features of NS and remains one of the principal reasons for admission of children to the hospital. Recently, the discovery that proteases in the glomerular filtrate of patients with NS are activating the epithelial sodium channel (ENaC), resulting in intrarenal salt retention and thereby contributing to edema, might suggest that targeting ENaC with amiloride might be a suitable strategy to manage the edema of NS. Other potential agents, particularly urearetics and aquaretics, might also prove useful in NS. Recent evidence also suggests that there may be other areas involved in salt storage, especially the skin, and it will be intriguing to study the implications of this in NS.

  4. Transient Corneal Edema is a Predictive Factor for Pseudophakic Cystoid Macular Edema after Uncomplicated Cataract Surgery

    PubMed Central

    Do, Jae Rock; Oh, Jong-Hyun; Chuck, Roy S.

    2015-01-01

    Purpose To report transient corneal edema after phacoemulsification as a predictive factor for the development of pseudophakic cystoid macular edema (PCME). Methods A total of 150 eyes from 150 patients (59 men and 91 women; mean age, 68.0 ± 10.15 years) were analyzed using spectral domain optical coherence tomography 1 week and 5 weeks after routine phacoemulsification cataract surgery. Transient corneal edema detected 1 week after surgery was analyzed to reveal any significant relationship with the development of PCME 5 weeks after surgery. Results Transient corneal edema developed in 17 (11.3%) of 150 eyes 1 week after surgery. A history of diabetes mellitus was significantly associated with development of transient corneal edema (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.41 to 11.54; p = 0.011). Both diabetes mellitus and transient corneal edema were significantly associated with PCME development 5 weeks after surgery (OR, 4.58; 95% CI, 1.56 to 13.43; p = 0.007; and OR, 6.71; CI, 2.05 to 21.95; p = 0.003, respectively). In the 8 eyes with both diabetes mellitus and transient corneal edema, 4 (50%) developed PCME 5 weeks after surgery. Conclusions Transient corneal edema detected 1 week after routine cataract surgery is a predictive factor for development of PCME. Close postoperative observation and intervention is recommended in patients with transient corneal edema. PMID:25646056

  5. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI.

  6. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI. PMID:27602324

  7. Is there chaos in the brain? II. Experimental evidence and related models.

    PubMed

    Korn, Henri; Faure, Philippe

    2003-09-01

    The search for chaotic patterns has occupied numerous investigators in neuroscience, as in many other fields of science. Their results and main conclusions are reviewed in the light of the most recent criteria that need to be satisfied since the first descriptions of the surrogate strategy. The methods used in each of these studies have almost invariably combined the analysis of experimental data with simulations using formal models, often based on modified Huxley and Hodgkin equations and/or of the Hindmarsh and Rose models of bursting neurons. Due to technical limitations, the results of these simulations have prevailed over experimental ones in studies on the nonlinear properties of large cortical networks and higher brain functions. Yet, and although a convincing proof of chaos (as defined mathematically) has only been obtained at the level of axons, of single and coupled cells, convergent results can be interpreted as compatible with the notion that signals in the brain are distributed according to chaotic patterns at all levels of its various forms of hierarchy. This chronological account of the main landmarks of nonlinear neurosciences follows an earlier publication [Faure, Korn, C. R. Acad. Sci. Paris, Ser. III 324 (2001) 773-793] that was focused on the basic concepts of nonlinear dynamics and methods of investigations which allow chaotic processes to be distinguished from stochastic ones and on the rationale for envisioning their control using external perturbations. Here we present the data and main arguments that support the existence of chaos at all levels from the simplest to the most complex forms of organization of the nervous system. We first provide a short mathematical description of the models of excitable cells and of the different modes of firing of bursting neurons (Section 1). The deterministic behavior reported in giant axons (principally squid), in pacemaker cells, in isolated or in paired neurons of Invertebrates acting as coupled

  8. P2X7 Receptor Suppression Preserves Blood-Brain Barrier through Inhibiting RhoA Activation after Experimental Intracerebral Hemorrhage in Rats.

    PubMed

    Zhao, Hengli; Zhang, Xuan; Dai, Zhiqiang; Feng, Yang; Li, Qiang; Zhang, John H; Liu, Xin; Chen, Yujie; Feng, Hua

    2016-01-01

    Blockading P2X7 receptor(P2X7R) provides neuroprotection toward various neurological disorders, including stroke, traumatic brain injury, and subarachnoid hemorrhage. However, whether and how P2X7 receptor suppression protects blood-brain barrier(BBB) after intracerebral hemorrhage(ICH) remains unexplored. In present study, intrastriatal autologous-blood injection was used to mimic ICH in rats. Selective P2X7R inhibitor A438079, P2X7R agonist BzATP, and P2X7R siRNA were administrated to evaluate the effects of P2X7R suppression. Selective RhoA inhibitor C3 transferase was administered to clarify the involvement of RhoA. Post-assessments, including neurological deficits, Fluoro-Jade C staining, brain edema, Evans blue extravasation and fluorescence, western blot, RhoA activity assay and immunohistochemistry were performed. Then the key results were verified in collagenase induced ICH model. We found that endogenous P2X7R increased at 3 hrs after ICH with peak at 24 hrs, then returned to normal at 72 hrs after ICH. Enhanced immunoreactivity was observed on the neurovascular structure around hematoma at 24 hrs after ICH, along with perivascular astrocytes and endothelial cells. Both A438079 and P2X7R siRNA alleviated neurological deficits, brain edema, and BBB disruption after ICH, in association with RhoA activation and down-regulated endothelial junction proteins. However, BzATP abolished those effects. In addition, C3 transferase reduced brain injury and increased endothelial junction proteins' expression after ICH. These data indicated P2X7R suppression could preserve BBB integrity after ICH through inhibiting RhoA activation. PMID:26980524

  9. P2X7 Receptor Suppression Preserves Blood-Brain Barrier through Inhibiting RhoA Activation after Experimental Intracerebral Hemorrhage in Rats

    PubMed Central

    Zhao, Hengli; Zhang, Xuan; Dai, Zhiqiang; Feng, Yang; Li, Qiang; Zhang, John H.; Liu, Xin; Chen, Yujie; Feng, Hua

    2016-01-01

    Blockading P2X7 receptor(P2X7R) provides neuroprotection toward various neurological disorders, including stroke, traumatic brain injury, and subarachnoid hemorrhage. However, whether and how P2X7 receptor suppression protects blood-brain barrier(BBB) after intracerebral hemorrhage(ICH) remains unexplored. In present study, intrastriatal autologous-blood injection was used to mimic ICH in rats. Selective P2X7R inhibitor A438079, P2X7R agonist BzATP, and P2X7R siRNA were administrated to evaluate the effects of P2X7R suppression. Selective RhoA inhibitor C3 transferase was administered to clarify the involvement of RhoA. Post-assessments, including neurological deficits, Fluoro-Jade C staining, brain edema, Evans blue extravasation and fluorescence, western blot, RhoA activity assay and immunohistochemistry were performed. Then the key results were verified in collagenase induced ICH model. We found that endogenous P2X7R increased at 3 hrs after ICH with peak at 24 hrs, then returned to normal at 72 hrs after ICH. Enhanced immunoreactivity was observed on the neurovascular structure around hematoma at 24 hrs after ICH, along with perivascular astrocytes and endothelial cells. Both A438079 and P2X7R siRNA alleviated neurological deficits, brain edema, and BBB disruption after ICH, in association with RhoA activation and down-regulated endothelial junction proteins. However, BzATP abolished those effects. In addition, C3 transferase reduced brain injury and increased endothelial junction proteins’ expression after ICH. These data indicated P2X7R suppression could preserve BBB integrity after ICH through inhibiting RhoA activation. PMID:26980524

  10. A Ruptured Basilar Tip Aneurysm Showing Repeated Perianeurysmal Edema after Endovascular Coil Embolization: Case Report

    PubMed Central

    TAKESHITA, Tomonori; HORIE, Nobutaka; FUKUDA, Yutaka; SO, Gohei; HAYASHI, Kentaro; MORIKAWA, Minoru; SUYAMA, Kazuhiko; NAGATA, Izumi

    The authors present an extremely rare case of a 48-year-old female who developed repeated perianeurysmal edema at 2, 9, and 16 weeks after endovascular coil embolization for the ruptured intracranial aneurysm. Interestingly, the mechanism for this edema could be different at each time point in this case; acute thrombosis formation, chemical inflammation, and aneurysm recanalization. We have to be aware of this potential complication in the long term after endovascular coil embolization for the intracranial aneurysm, especially with large size or buried into the brain parenchyma. The clinical implications of this case are discussed with a review of the literature. PMID:24390180

  11. [Hyponatremic encephalopathy with non-cardiogenic pulmonary edema. Development following marathon run].

    PubMed

    Wellershoff, G

    2013-04-01

    This article presents the case of a 52-year-old woman who developed exercise-associated hyponatremia (EAH) complicated by non-cardiogenic pulmonary edema after a marathon run. The condition of EAH is a potentially life-threatening complication of endurance exercise. The main cause seems to be inadequate intake of free water during or following exercise with enduring antidiuresis due to nonosmotic stimulation of ADH secretion. Known risk factors are female gender, slow running pace and lack of weight loss. Emergency therapy is fluid restriction and bolus infusion of 3% NaCl solution to rapidly reduce brain edema. PMID:23381723

  12. Mechanics of blast loading on the head models in the study of traumatic brain injury using experimental and computational approaches.

    PubMed

    Ganpule, S; Alai, A; Plougonven, E; Chandra, N

    2013-06-01

    Blast waves generated by improvised explosive devices can cause mild, moderate to severe traumatic brain injury in soldiers and civilians. To understand the interactions of blast waves on the head and brain and to identify the mechanisms of injury, compression-driven air shock tubes are extensively used in laboratory settings to simulate the field conditions. The overall goal of this effort is to understand the mechanics of blast wave-head interactions as the blast wave traverses the head/brain continuum. Toward this goal, surrogate head model is subjected to well-controlled blast wave profile in the shock tube environment, and the results are analyzed using combined experimental and numerical approaches. The validated numerical models are then used to investigate the spatiotemporal distribution of stresses and pressure in the human skull and brain. By detailing the results from a series of careful experiments and numerical simulations, this paper demonstrates that: (1) Geometry of the head governs the flow dynamics around the head which in turn determines the net mechanical load on the head. (2) Biomechanical loading of the brain is governed by direct wave transmission, structural deformations, and wave reflections from tissue-material interfaces. (3) Deformation and stress analysis of the skull and brain show that skull flexure and tissue cavitation are possible mechanisms of blast-induced traumatic brain injury.

  13. Mechanics of blast loading on the head models in the study of traumatic brain injury using experimental and computational approaches.

    PubMed

    Ganpule, S; Alai, A; Plougonven, E; Chandra, N

    2013-06-01

    Blast waves generated by improvised explosive devices can cause mild, moderate to severe traumatic brain injury in soldiers and civilians. To understand the interactions of blast waves on the head and brain and to identify the mechanisms of injury, compression-driven air shock tubes are extensively used in laboratory settings to simulate the field conditions. The overall goal of this effort is to understand the mechanics of blast wave-head interactions as the blast wave traverses the head/brain continuum. Toward this goal, surrogate head model is subjected to well-controlled blast wave profile in the shock tube environment, and the results are analyzed using combined experimental and numerical approaches. The validated numerical models are then used to investigate the spatiotemporal distribution of stresses and pressure in the human skull and brain. By detailing the results from a series of careful experiments and numerical simulations, this paper demonstrates that: (1) Geometry of the head governs the flow dynamics around the head which in turn determines the net mechanical load on the head. (2) Biomechanical loading of the brain is governed by direct wave transmission, structural deformations, and wave reflections from tissue-material interfaces. (3) Deformation and stress analysis of the skull and brain show that skull flexure and tissue cavitation are possible mechanisms of blast-induced traumatic brain injury. PMID:22832705

  14. Bilateral leg edema in an older woman.

    PubMed

    Thaler, H W; Pienaar, S; Wirnsberger, G; Roller-Wirnsberger, R E

    2015-01-01

    Bilateral leg edema is a frequent symptom in older people and an important concern in geriatric medicine. Further evaluation is frequently not performed and simple therapy with diuretics is prescribed. Particularly in older patients, long-term use of diuretics can lead to severe electrolyte imbalances, volume depletion, and falls. In this case report we want to focus the physicians' attention on the necessity to determine the cause and show a correspondingly effective treatment for bilateral leg edema in older people. A thorough approach is required to recognize diseases and to avoid adverse drug events as geriatric patients often show an atypical presentation or minor symptoms. The cause of swollen legs is often multifactorial; therefore, the patient's individual history and an appropriate physical examination are important. Depending on the clinical symptoms, evaluation including basic laboratory tests, urinalysis, chest radiography, and echocardiogram may be indicated. The most probable cause of bilateral edema in older patients is chronic venous insufficiency. Heart failure is also a common cause. Other systemic causes such as renal disease or liver disease are much rarer. Antihypertensive and anti-inflammatory drugs can frequently cause leg edema, but the incidence of drug-induced leg swelling is unknown. With the help of this special case we tried to develop an approach to the diagnosis of symmetric leg edema in older patients, a problem frequently neglected in geriatric medicine.

  15. Spatiotemporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    NASA Astrophysics Data System (ADS)

    Kang, DongYel; Wang, Alex; Volgger, Veronika; Chen, Zhongping; Wong, Brian J. F.

    2015-07-01

    Detection of an early stage of subglottic edema is vital for airway management and prevention of stenosis, a life-threatening condition in critically ill neonates. As an observer for the task of diagnosing edema in vivo, we investigated spatiotemporal correlation (STC) of full-range optical coherence tomography (OCT) images acquired in the rabbit airway with experimentally simulated edema. Operating the STC observer on OCT images generates STC coefficients as test statistics for the statistical decision task. Resulting from this, the receiver operating characteristic (ROC) curves for the diagnosis of airway edema with full-range OCT in-vivo images were extracted and areas under ROC curves were calculated. These statistically quantified results demonstrated the potential clinical feasibility of the STC method as a means to identify early airway edema.

  16. Spatiotemporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    PubMed Central

    Kang, DongYel; Wang, Alex; Volgger, Veronika; Chen, Zhongping; Wong, Brian J. F.

    2015-01-01

    Abstract. Detection of an early stage of subglottic edema is vital for airway management and prevention of stenosis, a life-threatening condition in critically ill neonates. As an observer for the task of diagnosing edema in vivo, we investigated spatiotemporal correlation (STC) of full-range optical coherence tomography (OCT) images acquired in the rabbit airway with experimentally simulated edema. Operating the STC observer on OCT images generates STC coefficients as test statistics for the statistical decision task. Resulting from this, the receiver operating characteristic (ROC) curves for the diagnosis of airway edema with full-range OCT in-vivo images were extracted and areas under ROC curves were calculated. These statistically quantified results demonstrated the potential clinical feasibility of the STC method as a means to identify early airway edema. PMID:26222962

  17. Neuroprotective profile of dextromethorphan in an experimental model of penetrating ballistic-like brain injury.

    PubMed

    Shear, Deborah A; Williams, Anthony J; Sharrow, Keith; Lu, Xi-Chun M; Tortella, Frank C

    2009-11-01

    Dextromethorphan (DM) has been well-characterized as a neuroprotective agent in experimental models of CNS injury. The goal of this study was to determine the neuroprotective profile of DM in a military-relevant model of penetrating ballistic-like brain injury (PBBI). In an acute (3 day) dose-response study, anesthetized male Sprague-Dawley rats were exposed to a unilateral frontal PBBI with DM (0.156-10 mg/kg) or vehicle delivered as an i.v. bolus from 30 min to 48 h post-injury. In a follow-up (7 day) experiment, the 10-mg/kg bolus injections of DM were administered in conjunction with a 6-h infusion (5 mg/kg/h). DM bolus injections alone produced a dose-dependent improvement in motor recovery on a balance beam task at 3 days post-injury. However, more rapid recovery (24 h) was observed on this task when the bolus injections were combined with the 6-h infusion. Moreover, the DM bolus/infusion treatment regimen resulted in a significant (76%) improvement in cognitive performance in a novel object recognition (NOR) task at 7 days post-injury. Although post-injury administration of DM (all doses) failed to reduce core lesion size, the maximum dose of DM (10 mg/kg) was effective in reducing silver-stained axonal fiber degeneration in the cortical regions adjacent to the injury.

  18. Chronic administration of antipsychotics impede behavioral recovery after experimental traumatic brain injury.

    PubMed

    Kline, Anthony E; Hoffman, Ann N; Cheng, Jeffrey P; Zafonte, Ross D; Massucci, Jaime L

    2008-12-31

    Antipsychotics are often administered to traumatic brain injured (TBI) patients as a means of controlling agitation, albeit the rehabilitative consequences of this intervention are not well known. Hence, the goal of this study was to evaluate the effects of risperidone (RISP) and haloperidol (HAL) on behavioral outcome after experimental TBI. Anesthetized rats received either a cortical impact or sham injury and then were randomly assigned to five TBI (RISP 0.045mg/kg, RISP 0.45mg/kg, RISP 4.5mg/kg, HAL 0.5mg/kg and VEHicle 1mL/kg) and three Sham (RISP 4.5mg/kg, HAL 0.5mg/kg and VEH 1mL/kg) groups. Treatments began 24h after surgery and were provided once daily for 19 days. Behavior was assessed with established motor (beam-balance/walk) and cognitive (spatial learning/memory in a water maze) tasks on post-operative days 1-5 and 14-19, respectively. RISP and HAL delayed motor recovery, impaired the acquisition of spatial learning, and slowed swim speed relative to VEH in both TBI and sham groups. These data indicate that chronic administration of RISP and HAL impede behavioral recovery after TBI and impair performance in uninjured controls.

  19. Experimental studies with selected light sources for NIRS of brain tissue: quantifying tissue chromophore concentration

    NASA Astrophysics Data System (ADS)

    Myllylä, Teemu; Korhonen, Vesa; Kiviniemi, Vesa; Tuchin, Valery

    2015-03-01

    Near-infrared spectroscopy (NIRS) based techniques are utilised in quantifying changes of chromophore concentrations in tissue. Particularly, non-invasive in vivo measurements of tissue oxygenation in the cerebral cortex are of interest. The measurement method is based on illuminating tissue and measuring the back-scattered light at wavelengths of interest. Tissue illumination can be realised using different techniques and various light sources. Commonly, lasers and laser diodes (LD) are utilised, but also high-power light emitting diodes (HPLED) are becoming more common. At the moment, a wide range of available narrow-band light sources exists, covering basically the entire spectrum of interest in brain tissue NIRS measurements. In this paper, in the centre of our interest are LDs and HPLEDs, because of their affordability, efficiency in terms of radiant flux versus size and easiness to adopt in in vivo medical applications. We compare characteristics of LDs and HPLEDs at specific wavelengths and their suitability for in vivo quantifying of different tissue chromophore concentration, particularly in cerebral blood flow (CBF). A special focus is on shape and width of the wavelength bands of interest, generated by the LDs and HPLEDs. Moreover, we experimentally study such effects as, spectroscopy cross talk, separability and signal-to-noise ratio (SNR) when quantifying tissue chromophore concentration. Chromophores of our interest are cytochrome, haemoglobin and water. Various LDs and HPLEDs, producing narrow-band wavelengths in the range from 500 nm to 1000 nm are tested.

  20. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria

    PubMed Central

    Freeman, Brandi D.; Martins, Yuri C.; Akide-Ndunge, Oscar B.; Bruno, Fernando P.; Wang, Hua; Tanowitz, Herbert B.; Spray, David C.; Desruisseaux, Mahalia S.

    2016-01-01

    Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA) antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria. PMID:27031954

  1. Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

    PubMed

    Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin

    2015-12-10

    Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway.

  2. Serum cleaved Tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis.

    PubMed

    Irazuzta, J E; de Courten-Myers, G; Zemlan, F P; Bekkedal, M Y; Rossi, J

    2001-09-14

    Brain injury due to bacterial meningitis affects multiple areas of the brain with a heterogeneous distribution generating a challenge to assess severity. Tau proteins are microtubular binding proteins localized in the axonal compartment of neurons. Brain injury releases cleaved Tau proteins (C-tau) into the extracellular space where they are transported to the cerebral spinal fluid. We hypothesized that C-tau crosses the blood-brain barrier during inflammation and that it can be detected in serum. The correlation between serum C-tau levels and the extent of the meningitic insult was examined. Furthermore, we studied whether the use of a subset of neurobehavioral tasks can assess the extent of brain injury after meningitis. The tests were chosen primarily for their ability to detect deficits in the acoustic system, low brain, reflexive responding, as well as for impaired motor coordination and the higher brain functions of learning and memory. A rat model of group B streptococcal meningitis with variable severity was utilized. At five days after bacterial inoculation followed by antibiotic therapy neurobehavioral tests were performed and serum C-tau and histologic samples of the brain were obtained. Our study shows that during meningitis C-tau appears in serum and reflects the extent of neurologic damage. Neurobehavioral performance was altered after bacterial meningitis and could be correlated with histologic and biochemical markers of neurologic sequelae. We conclude that serum C-tau and a composite of neurobehavioral tests could become useful markers for assessing the severity of neurological damage in experimental bacterial meningitis.

  3. The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Lereim, Ragnhild Reehorst; Oveland, Eystein; Xiao, Yichuan; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Sun, Shao-Cong; Berven, Frode S

    2016-01-01

    The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences between Peli1 knock-out and wild-type mice were observed at the disease peak. In Peli1 knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogating Peli1 expression, underlining the importance of Peli1 as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710. PMID:27746629

  4. Heterogeneity of myocardial edema in isolated pig hearts after perfusion with different types of cardioprotective solutions.

    PubMed

    Vahl, C F; Albers, J; Makabe, M H; Meinzer, H P; Ilg, M; Fu, X; Szabo, G; Mühling, J; Hagl, S

    1998-10-01

    The extent and distribution of myocardial edema induced by perfusion with cardioprotective solutions is of great interest. Domestic pig hearts (n = 12) were perfused in situ after aortic cross clamping either with Bretschneider's cardioplegic solution (HTK, 4 degrees C, n = 3), with a heparinized Krebs-Henseleit solution containing 30 mmol/L 2,3 Butanedionemonoxime (BDM, 4 degrees C, n = 3) or with heparinized pig blood (HPB, 24 degrees C, n = 3). After a three-hours storage period, magnetic resonance tomography (MRI) was carried out. The acquired T1-weighted data were used for the subsequent three-dimensional reconstruction based on the "Heidelberg ray-tracing technique". The small myocardial tissue blocks (n = 216) were excised from these hearts for dry weight measurements for 9 preselected regions in duplicate including ventricular papillary muscle, ventricular free wall, ventricular septum, apex, and atrial tissue. In control hearts (n = 3), dry weight was measured immediately after explantation (no MRI). The results of dry-weight measurements and three dimensional visualization were compared. Dry-weight measurements revealed that considerable myocardial edema is induced by any of the experimental procedures. The effects were most pronounced after BDM perfusion. Regardless how the edema was induced, there were significant differences of the water content within the heart: the water content in the heads of the papillary muscles and in the interventricular septum was always smaller than that of the free left- and right-ventricular walls. The heterogeneity of myocardial edema and its spatial distribution pattern could be qualitatively visualized. The experimental data (biophysical data and 3D visualization) clearly show a heterogeneity of myocardial edema induced by different types of cardioprotective solutions. As the presence of myocardial edema represents one of the crucial events in the pathophysiology of myocardial dysfunction occurring during myocardial

  5. [GLUTATHIONE SYSTEM ACTIVITY IN RAT TISSUES UNDER PHENYLETHYL BIGUANIDE ACTION ON THE BACKGROUND OF EXPERIMENTAL BRAIN ISCHEMIA/REPERFUSION DEVELOPMENT].

    PubMed

    Safonova, O A; Popova, T N; Kryl'skii, D V

    2016-01-01

    It was studied the total antioxidant activity, content of primary lipid peroxidation (LPO) products and reduced glutathione, and the activity of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase in rat tissues under phenylethyl biguanide (phenfor- min) action on the background of experimental brain ischemia/reperfusion development. It is stablished the analyzed parameters, increasing under ischemia/reperfusion conditions in the brain and blood serum of animals, exhibit a decrease upon the introduction of this biguanide derivative. The obtained data can be explained by a decrease in degree of mobilization of the antioxidant system--in particular, of its glutathione chain--in the pathologic state. Hence, there is a need in NADPH supply for the system functioning compared with the pathology. Thus, phenylethyl biguanide demonstrates its antioxidant and protective properties under oxidative stress development that is accompanied by accumulation of the products of free radical oxidation of biomolecules during the ischemic brain injury. PMID:27159954

  6. Dysphagia Caused by Chronic Laryngeal Edema.

    PubMed

    Delides, Alexander; Sakagiannis, George; Maragoudakis, Pavlos; Gouloumi, Αlina-Roxani; Katsimbri, Pelagia; Giotakis, Ioannis; Panayiotides, John G

    2015-10-01

    A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

  7. An uncommon cause of acute pulmonary edema.

    PubMed

    Nepal, Santosh; Giri, Smith; Bhusal, Mohan; Siwakoti, Krishmita; Pathak, Ranjan

    2016-09-01

    Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment. PMID:27575897

  8. Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors

    PubMed Central

    Parker, Jacqueline N.; Gillespie, G. Yancey; Love, Cammy E.; Randall, Suzanne; Whitley, Richard J.; Markert, James M.

    2000-01-01

    Genetically engineered, neuroattenuated herpes simplex viruses (HSVs) expressing various cytokines can improve survival when used in the treatment of experimental brain tumors. These attenuated viruses have both copies of γ134.5 deleted. Recently, we demonstrated increased survival of C57BL/6 mice bearing syngeneic GL-261 gliomas when treated with an engineered HSV expressing IL-4, as compared with treatment with the parent construct (γ134.5−) alone or with a virus expressing IL-10. Herein, we report construction of a conditionally replication-competent mutant expressing both subunits of mIL-12 (M002) and its evaluation in a syngeneic neuroblastoma murine model. IL-12 induces a helper T cell subset type 1 response, which may induce more durable antitumor effects. In vitro studies showed that, when infected with M002, both Vero cells and murine Neuro-2a neuroblastoma cells produced physiologically relevant levels of IL-12 heterodimers, as determined by ELISA. M002 was cytotoxic for Neuro-2a cells and human glioma cell lines U251MG and D54MG. Neurotoxicity studies, as defined by plaque-forming units/LD50, performed in HSV-1-sensitive A/J strain mice found that M002 was not toxic even at high doses. When evaluated in an intracranial syngeneic neuroblastoma murine model, median survival of M002-treated animals was significantly longer than the median survival of animals treated with R3659, the parent γ134.5− mutant lacking any cytokine gene insert. Immunohistochemical analysis of M002-treated tumors identified a pronounced influx of CD4+ T cells and macrophages as well as CD8+ cells when compared with an analysis of R3659-treated tumors. We conclude that M002 produced a survival benefit via oncolytic effects combined with immunologic effects meditated by helper T cells of subset type 1. PMID:10681459

  9. Electromagnetic Controlled Cortical Impact Device for Precise, Graded Experimental Traumatic Brain Injury

    PubMed Central

    BRODY, DAVID L.; DONALD, CHRISTINE Mac; KESSENS, CHAD C.; YUEDE, CARLA; PARSADANIAN, MAIA; SPINNER, MIKE; KIM, EDDIE; SCHWETYE, KATHERINE E.; HOLTZMAN, DAVID M.; BAYLY, PHILIP V.

    2008-01-01

    Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice. PMID:17439349

  10. Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury.

    PubMed

    Brody, David L; Mac Donald, Christine; Kessens, Chad C; Yuede, Carla; Parsadanian, Maia; Spinner, Mike; Kim, Eddie; Schwetye, Katherine E; Holtzman, David M; Bayly, Philip V

    2007-04-01

    Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice.

  11. Systemic Inflammatory Effects of Traumatic Brain Injury, Femur Fracture, and Shock: An Experimental Murine Polytrauma Model

    PubMed Central

    Probst, C.; Mirzayan, M. J.; Mommsen, P.; Zeckey, C.; Tegeder, T.; Geerken, L.; Maegele, M.; Samii, A.; van Griensven, M.

    2012-01-01

    Objective. Despite broad research in neurotrauma and shock, little is known on systemic inflammatory effects of the clinically most relevant combined polytrauma. Experimental investigation in an animal model may provide relevant insight for therapeutic strategies. We describe the effects of a combined injury with respect to lymphocyte population and cytokine activation. Methods. 45 male C57BL/6J mice (mean weight 27 g) were anesthetized with ketamine/xylazine. Animals were subjected to a weight drop closed traumatic brain injury (WD-TBI), a femoral fracture and hemorrhagic shock (FX-SH). Animals were subdivided into WD-TBI, FX-SH and combined trauma (CO-TX) groups. Subjects were sacrificed at 96 h. Blood was analysed for cytokines and by flow cytometry for lymphocyte populations. Results. Mortality was 8%, 13% and 47% for FX-SH, WD-TBI and CO-TX groups (P < 0.05). TNFα (11/13/139 for FX-SH/WD-TBI/CO-TX; P < 0.05), CCL2 (78/96/227; P < 0.05) and IL-6 (16/48/281; P = 0.05) showed significant increases in the CO-TX group. Lymphocyte populations results for FX-SH, WD-TBI and CO-TX were: CD-4 (31/21/22; P = n.s.), CD-8 (7/28/34, P < 0.05), CD-4-CD-8 (11/12/18; P = n.s.), CD-56 (36/7/8; P < 0.05). Conclusion. This study shows that a combination of closed TBI and femur-fracture/ shock results in an increase of the humoral inflammation. More attention to combined injury models in inflammation research is indicated. PMID:22529516

  12. Wedge MUSIC: a novel approach to examine experimental differences of brain source connectivity patterns from EEG/MEG data.

    PubMed

    Ewald, Arne; Avarvand, Forooz Shahbazi; Nolte, Guido

    2014-11-01

    We introduce a novel method to estimate bivariate synchronization, i.e. interacting brain sources at a specific frequency or band, from MEG or EEG data robust to artifacts of volume conduction. The data driven calculation is solely based on the imaginary part of the cross-spectrum as opposed to the imaginary part of coherency. In principle, the method quantifies how strong a synchronization between a distinct pair of brain sources is present in the data. As an input of the method all pairs of pre-defined locations inside the brain can be used which is computationally exhaustive. In contrast to that, reference sources can be used that have been identified by any source reconstruction technique in a prior analysis step. We introduce different variants of the method and evaluate the performance in simulations. As a particular advantage of the proposed methodology, we demonstrate that the novel approach is capable of investigating differences in brain source interactions between experimental conditions or with respect to a certain baseline. For measured data, we first show the application on resting state MEG data where we find locally synchronized sources in the motor-cortex based on the sensorimotor idle rhythms. Finally, we show an example on EEG motor imagery data where we contrast hand and foot movements. Here, we also find local interactions in the expected brain areas.

  13. A New Method of Selective, Rapid Cooling of the Brain: An Experimental Study

    SciTech Connect

    Allers, Mats; Boris-Moeller, Fredrik; Lunderquist, Anders; Wieloch, Tadeusz

    2006-04-15

    Purpose. To determine whether retrograde perfusion of cooled blood into one internal jugular vein (IJV) in the pig can selectively reduce the brain temperature without affecting the core body temperature (CBT). Methods. In 7 domestic pigs, the left IJV was catheterized on one side and a catheter placed with the tip immediately below the rete mirabile. Thermistors were placed in both brain hemispheres and the brain temperature continuously registered. Thermistors placed in the rectum registered the CBT. From a catheter in the right femoral vein blood was aspirated with the aid of a roller pump, passed through a cooling device, and infused into the catheter in the left IJV at an initial rate of 200 ml/min. Results. Immediately after the start of the infusion of cooled blood (13.8 deg. C) into the IJV, the right brain temperature started to drop from its initial 37.9 deg. C and reached 32 deg. C within 5 min. By increasing the temperature of the perfusate a further drop in the brain temperature was avoided and the brain temperature could be kept around 32 deg. C during the experiment. In 4 of the animals a heating blanket was sufficient to compensate for the slight drop in CBT during the cooling period. Conclusions. We conclude that brain temperature can be reduced in the pig by retrograde perfusion of the internal jugular vein with cooled blood and that the core body temperature can be maintained with the aid of a heating blanket.

  14. Hereditary angioneurotic edema and HLA types in two Danish families.

    PubMed

    Eggert, J; Zachariae, H; Svejgaard, E; Svejgaard, A; Kissmeyer-Nielsen, F

    1982-01-01

    HLA types were determined in 19 patients and 9 healthy members of 2 Danish families with hereditary angioneurotic edema. The study revealed no connections between hereditary angioneurotic edema and the HLA system. PMID:7165360

  15. Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain.

    PubMed

    Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Okan Irfanoglu, M; Albert, Paul S; Pierpaoli, Carlo

    2015-04-01

    Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent inter-individual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different acquisition protocols. In this study we examined scans of 61 individuals (aged 4-22 years) from the NIH MRI study of normal brain development. Two scans were collected with different protocols (low and high resolution). Our goal was to separate the contributions of biological variability and experimental noise to the overall measured variance, as well as to assess potential systematic effects related to the use of different protocols. We analyzed FA and MD in seventeen regions of interest. We found that biological variability for both FA and MD varies widely across brain regions; biological variability is highest for FA in the lateral part of the splenium and body of the corpus callosum along with the cingulum and the superior longitudinal fasciculus, and for MD in the optic radiations and the lateral part of the splenium. These regions with high inter-individual biological variability are the most likely candidates for assessing genetic and environmental effects in the developing brain. With respect to protocol-related effects, the lower resolution acquisition resulted in higher MD and lower FA values for the majority of regions compared with the higher resolution protocol. However, the majority of the regions did not show any age-protocol interaction, indicating similar trajectories were obtained irrespective of the protocol used.

  16. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    PubMed Central

    Li, Shu-Hua; Wang, Yu; Gao, Hai-Bin; Zhao, Kun; Hou, Yu-Chen; Sun, Wei

    2015-01-01

    Objective: To determine whether Povidone-iodine was toxic to brain tissues by rinsing the cerebral cortex of New Zealand rabbits with Povidone-iodine Solution of different concentrations. Methods: 12 New Zealand rabbits were randomly divided into 4 groups (Group A, B, C and D, 3 rabbits each group). In each group, the left cerebral cortex of rabbits was rinsed with physiological saline after the craniotomy; in Group A and B, the right cerebral cortex of rabbits was also locally rinsed with Povidone-iodine Solution (0.01%), in Group C and D, the right cerebral cortex of rabbits was also locally rinsed with Povidone-iodine Solution (0.05%). In Group A and C, the rabbits were sacrificed at D3 after the operation, and the brain was taken out; and in Group B and D, the rabbits were sacrificed at D7 after the operation, and the brain was taken out. Under the optical and electron microscope, the change in micro-structure of brain tissues was observed in each group. Results: In each group, there was no epilepsy or paralysis during and after the operation. At the treatment side of physiological saline, there was no significant cell damage in the local brain tissues. At the treatment side of Povidone-iodine Solution, there was no cell apoptosis or degeneration in the local brain tissues. Conclusion: The Povidone-iodine Solution (0.05% and 0.01%) was toxic to brain tissues, with a more obvious damage of brain tissues for the former concentration. The histological sign was more serious at D7 than that at D3. PMID:26628968

  17. Penetration of intra-arterially administered vincristine in experimental brain tumor1,2

    PubMed Central

    Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

    2004-01-01

    Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan’s blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors. PMID:15494097

  18. Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats.

    PubMed

    Kondoh, Takashi; Uneyama, Hisayuki; Nishino, Hitoo; Torii, Kunio

    2002-12-20

    Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group (P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.

  19. [The effects of taurine on oxidative processes in brain edema].

    PubMed

    Hovsepyan, L M; Zakaryan, G V; Melkonyan, M M; Zakaryan, A V

    2015-01-01

    Цель исследования — изучение свободнорадикального окисления липидов, окислительной модификации белка, активности глутатионпероксидазы и глутатионредуктазы, а также конечного продукта оксида азота — нитрита в митохондриальной фракции головного мозга животных во время экспериментально вызванного отека мозга при лечении таурином. Материал и методы. Токсический отек головного мозга вызывали внутрибрюшинным введением крысам тетраэтилолова в дозе 10 мг на 1 кг массы животного. Интенсивность перекисного окисления липидов регистрировали по содержанию гидроперекисей и малонового диальдегида. Результаты и заключение. Анализ уровней окислительной модификации белков показал, что отек мозга характеризуется повышением содержания продуктов окислительной модификации белков и липидов, оксида азота, а также снижением содержания глутатиона и понижением активности глутатионсодержащих ферментов (глутатионпероксидаза и глутатионредуктаза). Исходя из этого, большой интерес вызывает использование препаратов, которые могут повышать содержание глутатиона и активизировать ферменты, содержащие его в своей структуре. К таким препаратам относится таурин. По нашим данным, введение таурина в течение 5 дней в дозе 50 мг/кг приводило к уменьшению содержания продуктов перекисного окисления липидов, нормализации окислительной модификации белков в митохондриальной фракции головного мозга крыс с экспериментальным отеком мозга.

  20. The evolution of scuba divers pulmonary edema.

    PubMed

    Edmonds, Carl

    2016-01-01

    The evolution of scuba divers pulmonary edema is described. When discovered in 1981, it was believed to be a cold-induced response in a submerged, otherwise healthy, scuba diver. The clinical features are described and discussed, as are the demographics. An alleged prevalence of 1.1% was complicated by problematic statistics and an apparent increase in reported cases. Recurrences both while diving and swimming or snorkeling were common. More recent case reports and surveys are described, identifying predisposing factors and associations, including cardiac pathology. Stress cardiomyopathies, reversible myocardial disorder or Takotsubo cardiomyopathy, may complicate the presentation, especially in older females. Relevant cardiac investigations and autopsy findings are reviewed. Disease severity and potential lethality of scuba divers pulmonary edema became more apparent early this century, and these influence our current recommendations to survivors. First aid and treatment are also discussed. PMID:27265985

  1. Influenza leaves a TRAIL to pulmonary edema.

    PubMed

    Brauer, Rena; Chen, Peter

    2016-04-01

    Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS. PMID:26999598

  2. Management of pseudophakic cystoid macular edema.

    PubMed

    Guo, Suqin; Patel, Shriji; Baumrind, Ben; Johnson, Keegan; Levinsohn, Daniel; Marcus, Edward; Tannen, Brad; Roy, Monique; Bhagat, Neelakshi; Zarbin, Marco

    2015-01-01

    Pseudophakic cystoid macular edema (PCME) is a common complication following cataract surgery. Acute PCME may resolve spontaneously, but some patients will develop chronic macular edema that affects vision and is difficult to treat. This disease was described more than 50 years ago, and there are multiple options for clinical management. We discuss mechanisms, clinical efficacy, and adverse effects of these treatment modalities. Topical non-steroidal anti-inflammatory agents and corticosteroids are widely used and, when combined, may have a synergistic effect. Intravitreal corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) agents have shown promise when topical medications either fail or have had limited effects. Randomized clinical studies evaluating anti-VEGF agents are needed to fully evaluate benefits and risks. When PCME is either refractory to medical therapy or is associated with significant vitreous involvement, pars plana vitrectomy has been shown to improve outcomes, though it is associated with additional risks.

  3. The evolution of scuba divers pulmonary edema.

    PubMed

    Edmonds, Carl

    2016-01-01

    The evolution of scuba divers pulmonary edema is described. When discovered in 1981, it was believed to be a cold-induced response in a submerged, otherwise healthy, scuba diver. The clinical features are described and discussed, as are the demographics. An alleged prevalence of 1.1% was complicated by problematic statistics and an apparent increase in reported cases. Recurrences both while diving and swimming or snorkeling were common. More recent case reports and surveys are described, identifying predisposing factors and associations, including cardiac pathology. Stress cardiomyopathies, reversible myocardial disorder or Takotsubo cardiomyopathy, may complicate the presentation, especially in older females. Relevant cardiac investigations and autopsy findings are reviewed. Disease severity and potential lethality of scuba divers pulmonary edema became more apparent early this century, and these influence our current recommendations to survivors. First aid and treatment are also discussed.

  4. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    PubMed Central

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole. PMID:24949209

  5. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    PubMed Central

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  6. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    PubMed

    Jugé, Lauriane; Pong, Alice C; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  7. Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation

    PubMed Central

    Oswal, Ashwini; Jha, Ashwani; Neal, Spencer; Reid, Alphonso; Bradbury, David; Aston, Peter; Limousin, Patricia; Foltynie, Tom; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

    2016-01-01

    Background Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. New method In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. Results Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. Comparison with existing approaches To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS. PMID:26698227

  8. Naturally occurring and experimentally induced beta-amyloid deposits in the brains of marmosets (Callithrix jacchus).

    PubMed

    Maclean, C J; Baker, H F; Ridley, R M; Mori, H

    2000-01-01

    Cerebral beta-amyloid occurs in elderly animals of some species and in Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally with brain tissue from a patient with Alzheimer's disease. Six years later, when the monkeys were middle aged, we found moderate numbers of intracerebral plaques and cerebrovascular deposits containing beta-amyloid. We have re-examined these brains and those of 10 other marmosets injected with brain homogenate containing beta-amyloid, and have found some beta-amyloid in animals injected more than 4 years previously. We have found beta-amyloid in 4 of 26 elderly control marmosets, but not in 9 young to middle-aged control marmosets. The beta-amyloid found in middle aged marmosets injected with Alzheimer brain tissue was, therefore, not a consequence of their age. Deposits in large cerebral vessels in elderly marmosets, and in marmosets previously injected with brain tissue containing beta-amyloid, reacted with antibodies to Abeta and Abeta1-40; plaques and microvessel deposits reacted with antibodies to Abeta and Abeta1-42.

  9. High altitude pulmonary edema in mountain climbers.

    PubMed

    Korzeniewski, Krzysztof; Nitsch-Osuch, Aneta; Guzek, Aneta; Juszczak, Dariusz

    2015-04-01

    Every year thousands of ski, trekking or climbing fans travel to the mountains where they stay at the altitude of more than 2500-3000m above sea level or climb mountain peaks, often exceeding 7000-8000m. High mountain climbers are at a serious risk from the effects of adverse environmental conditions prevailing at higher elevations. They may experience health problems resulting from hypotension, hypoxia or exposure to low temperatures; the severity of those conditions is largely dependent on elevation, time of exposure as well as the rate of ascent and descent. A disease which poses a direct threat to the lives of mountain climbers is high altitude pulmonary edema (HAPE). It is a non-cardiogenic pulmonary edema which typically occurs in rapidly climbing unacclimatized lowlanders usually within 2-4 days of ascent above 2500-3000m. It is the most common cause of death resulting from the exposure to high altitude. The risk of HAPE rises with increased altitude and faster ascent. HAPE incidence ranges from an estimated 0.01% to 15.5%. Climbers with a previous history of HAPE, who ascent rapidly above 4500m have a 60% chance of illness recurrence. The aim of this article was to present the relevant details concerning epidemiology, pathophysiology, clinical symptoms, prevention, and treatment of high altitude pulmonary edema among climbers in the mountain environment.

  10. [High-altitude pulmonary edema in Japan].

    PubMed

    Kobayashi, T

    1995-12-01

    To understand the pathophysiology of high-altitude pulmonary edema (HAPE), we examined the pathway of adaptation to high altitude in lifelong of Tibet. The Tibetan natives had higher exercise performance, but lower maximal oxygen uptake and lower blood lactate concentrations than did acclimatized Han newcomers. Clinical and basic studies done to determine the pathophysiologic characteristics of 47 patients with HAPE and of subjects susceptible to HAPE. The altitude of onset was 2,680 m to 3,190 m above sea level. Results of hemodynamic studies and the presence of protein-rich edema fluid indicated that HAPE is noncardiogenic and is a type of increased permeability edema. The levels of IL-1 beta, IL-6, IL-8, and TNF-alpha in bronchoalveolar lavage fluid from subjects with HAPE were high on admission. The subjects susceptible to HAPE had much greater increases in an index of pulmonary vascular resistance than did the controls, which resulted in much higher levels of pulmonary arterial pressure during both acute hypoxia and hypobaria. The subjects susceptible to HAPE also has blunted hypoxic ventilatory drives. We studied whether human leukocyte antigen DR-6 functions as a genetic predisposition to HAPE. The frequency of DR-6 was increased in the subjects susceptible to HAPE, which suggests that they have a constitutional abnormality in the pulmonary circulatory, and ventilatory responses to hypoxia and hypobaria, and that genetic factors may be involved in the development of HAPE.

  11. Isosmotic media prevent edema in amphibian larvae without cardiac function.

    PubMed

    Smith, S C

    2000-03-01

    The absence of cardiac and circulatory function causes severe edema in amphibian embryos. Analyzing the roles of embryonic and larval circulation in respiration may thus be confounded by the increased diffusion distance and decreased surface area/volume ratio caused by edema. Similarly, detailed morphological analyses of embryos/larvae with defective circulatory or renal function is difficult or impossible due to the gross morphological anomalies engendered by edematous swelling. To circumvent these problems, two media have been developed which are isosmotic with the plasma of a common experimental amphibian species (Ambystoma mexicanun). These media are remarkably effective in preventing fluid accumulation in embryos and larvae lacking heart function and, when used in slightly lower concentrations, cause no apparent harm to embryos and larvae with normal circulation for periods up to 3 weeks. These media should prove useful for a variety of studies on the developmental physiology of the circulatory system and possibly also when examining the development of renal function and ionoregulation. PMID:10764226

  12. Regulation of brain aquaporins.

    PubMed

    Zelenina, Marina

    2010-11-01

    Three aquaporins are expressed in the brain. AQP4, the predominant brain water channel, is expressed in astrocyte endfeet facing brain capillaries, perisynaptic spaces, and nodes of Ranvier. It is implicated in brain edema formation and resolution. It is also believed to assist clearance of K(+) released during neuronal activity. AQP1 is expressed in epithelial cells of choroid plexus and is implicated in cerebrospinal fluid formation. AQP9, which has been reported to be present in astrocytes and in subpopulations of neurons, is implicated in the brain energy metabolism. All three brain AQPs are strongly upregulated in brain tumors and in injured brain tissue. Water and solute transport via AQPs depends on concentration gradients across the membrane, but the magnitude of the transport is to a large extent determined by the single channel permeability of AQPs and by their abundance in the cell membrane. The future therapies will have to address not only the forces driving the water and solute transport (e.g. as mannitol infusion does in the treatment of brain edema), but also the regulation of AQPs, which provide the means for water entry to the brain, for water exit from the brain, and for redistribution of water and solutes within the brain compartments. This review summarizes the data concerning structure, permeability, role in the brain, short-term and long-term regulation of the three AQPs.

  13. T-Tau and P-Tau in Brain and Blood from Natural and Experimental Prion Diseases.

    PubMed

    Rubenstein, Richard; Chang, Binggong; Petersen, Robert; Chiu, Allen; Davies, Peter

    2015-01-01

    Synaptic abnormalities are prominent in prion disease pathogenesis and are responsible for functional deficits. The microtubule associated protein, Tau, binds to and stabilizes microtubules in axons ensuring axonal transport of synaptic components. Tau phosphorylation reduces its affinity for microtubules leading to their instability and resulting in disrupted axonal transport and synaptic dysfunction. We report on the levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau), measured by highly sensitive laser-based immunoassays, in the central nervous system and biofluids from experimentally transmitted prion disease in mice and natural cases of sporadic Creutzfeldt-Jakob Disease (sCJD) in humans. We found that, in contrast to sCJD where only the levels of T-Tau in brain are increased, both T-Tau and P-Tau are increased in the brains of symptomatic mice experimentally infected with the ME7, 139A and 22L mouse-adapted scrapie strains. The increased levels of T-Tau in sCJD brain, compared to control samples, were also observed in patient plasma. In contrast, there was no detectable increase in T-Tau and P-Tau in plasma from symptomatic experimentally infected mice. Furthermore, our data suggests that in mice showing clinical signs of prion disease the levels and/or ratios of T-Tau and P-Tau are only a useful parameter for differentiating the mouse-adapted scrapie strains that differ in the extent of disease. We conclude that the neuropathogenesis associated with P-Tau and synaptic dysfunction is similar for at least two of the mouse-adapted scrapie strains tested but may differ between sporadic and experimentally transmitted prion diseases. PMID:26630676

  14. T-Tau and P-Tau in Brain and Blood from Natural and Experimental Prion Diseases

    PubMed Central

    Rubenstein, Richard; Chang, Binggong; Petersen, Robert; Chiu, Allen; Davies, Peter

    2015-01-01

    Synaptic abnormalities are prominent in prion disease pathogenesis and are responsible for functional deficits. The microtubule associated protein, Tau, binds to and stabilizes microtubules in axons ensuring axonal transport of synaptic components. Tau phosphorylation reduces its affinity for microtubules leading to their instability and resulting in disrupted axonal transport and synaptic dysfunction. We report on the levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau), measured by highly sensitive laser-based immunoassays, in the central nervous system and biofluids from experimentally transmitted prion disease in mice and natural cases of sporadic Creutzfeldt-Jakob Disease (sCJD) in humans. We found that, in contrast to sCJD where only the levels of T-Tau in brain are increased, both T-Tau and P-Tau are increased in the brains of symptomatic mice experimentally infected with the ME7, 139A and 22L mouse-adapted scrapie strains. The increased levels of T-Tau in sCJD brain, compared to control samples, were also observed in patient plasma. In contrast, there was no detectable increase in T-Tau and P-Tau in plasma from symptomatic experimentally infected mice. Furthermore, our data suggests that in mice showing clinical signs of prion disease the levels and/or ratios of T-Tau and P-Tau are only a useful parameter for differentiating the mouse-adapted scrapie strains that differ in the extent of disease. We conclude that the neuropathogenesis associated with P-Tau and synaptic dysfunction is similar for at least two of the mouse-adapted scrapie strains tested but may differ between sporadic and experimentally transmitted prion diseases. PMID:26630676

  15. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    PubMed

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect.

  16. Laparoscopic Surgery Can Reduce Postoperative Edema Compared with Open Surgery

    PubMed Central

    Guo, Dong; Gong, Jianfeng; Cao, Lei; Wei, Yao; Guo, Zhen

    2016-01-01

    Aim. The study aimed to investigate the impact of laparoscopic surgery and open surgery on postoperative edema in Crohn's disease. Methods. Patients who required enterectomy were divided into open group (Group O) and laparoscopic group (Group L). Edema was measured using bioelectrical impedance analysis preoperatively (PRE) and on postoperative day 3 (POD3) and postoperative day 5 (POD5). The postoperative edema was divided into slight edema and edema by an edema index, defined as the ratio of total extracellular water to total body water. Results. Patients who underwent laparoscopic surgery had better clinical outcomes and lower levels of inflammatory and stress markers. A total of 31 patients (26.05%) developed slight edema and 53 patients (44.54%) developed edema on POD3. More patients developed postoperative edema in Group O than in Group L on POD3 (p = 0.006). The value of the edema index of Group O was higher than that of Group L on POD3 and POD5 (0.402 ± 0.010 versus 0.397 ± 0.008, p = 0.001; 0.401 ± 0.009 versus 0.395 ± 0.007, p = 0.039, resp.). Conclusions. Compared with open surgery, laparoscopic surgery can reduce postoperative edema, which may contribute to the better outcomes of laparoscopic surgery over open surgery. PMID:27777583

  17. Combined Neurotrauma Models: Experimental Models Combining Traumatic Brain Injury and Secondary Insults.

    PubMed

    Simon, Dennis W; Vagni, Vincent M; Kochanek, Patrick M; Clark, Robert S B

    2016-01-01

    Patients with severe traumatic brain injury (TBI) frequently present with concomitant injuries that may cause secondary brain injury and impact outcomes. Animal models have been developed that combine contemporary models of TBI with a secondary neurologic insult such as hypoxia, shock, long bone fracture, and radiation exposure. Combined injury models may be particularly useful when modeling treatment strategies and in efforts to map basic research to a heterogeneous patient population. Here, we review these models and their collective contribution to the literature on TBI. In addition, we provide protocols and notes for two well-characterized models of TBI plus hemorrhagic shock. PMID:27604730

  18. The effect of short-term corticosteroid treatment on the CT appearance of experimental brain abscesses. [Dogs

    SciTech Connect

    Enzmann, D.R.; Britt, R.H.; Placone, R.C. Jr.; Obana, W.; Lyons, B.; Yeager, A.S.

    1982-10-01

    The effect of short-term corticosteroid treatment on contrast enhancement was investigated in an experimental brain abscess model. The degree of enhancement was reduced in the cerebritis stage, unaffected in the capsule stage, and intermediate in the transitional stage. The area and pattern of enhancement were also altered in the cerebritis stage. Although the magnitude of the entire cerebritis time-density curve (extended for 60 minutes) was decreased by the steroids, its configuration was unchanged. Prior to steroid administration, the 10- and 60-minute components of the curve discriminated between cerebritis and capsule stages, with the latter exhibiting a far lower 60-minute value. Implications for treatment of brain abscesses are discussed.

  19. In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses

    PubMed Central

    Bonifazi, Paolo; Difato, Francesco; Massobrio, Paolo; Breschi, Gian L.; Pasquale, Valentina; Levi, Timothée; Goldin, Miri; Bornat, Yannick; Tedesco, Mariateresa; Bisio, Marta; Kanner, Sivan; Galron, Ronit; Tessadori, Jacopo; Taverna, Stefano; Chiappalone, Michela

    2013-01-01

    Brain-machine interfaces (BMI) were born to control “actions from thoughts” in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI—a neuromorphic chip for brain repair—to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary “bottom-up” approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of “finite size networks” which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented. PMID:23503997

  20. Blood-Brain Barrier Permeability and Monocyte Infiltration in Experimental Allergic Encephalomyelitis

    ERIC Educational Resources Information Center

    Floris, S.; Blezer, E. L. A.; Schreibelt, G.; Dopp, E.; van der Pol, S. M. A.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E.

    2004-01-01

    Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive…

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

    PubMed Central

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

    2016-01-01

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

  2. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  3. Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

    PubMed

    Abou-Abbass, Hussein; Bahmad, Hisham; Abou-El-Hassan, Hadi; Zhu, Rui; Zhou, Shiyue; Dong, Xue; Hamade, Eva; Mallah, Khalil; Zebian, Abir; Ramadan, Naify; Mondello, Stefania; Fares, Jawad; Comair, Youssef; Atweh, Samir; Darwish, Hala; Zibara, Kazem; Mechref, Yehia; Kobeissy, Firas

    2016-06-01

    As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings. PMID:27249377

  4. Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

    SciTech Connect

    Testylier, Guy . E-mail: guytestylier@crssa.net; Lahrech, Hana; Montigon, Olivier; Foquin, Annie; Delacour, Claire; Bernabe, Denis; Segebarth, Christoph; Dorandeu, Frederic; Carpentier, Pierre

    2007-04-15

    Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.

  5. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  6. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases

  7. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI. PMID:27648146

  8. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI.

  9. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway.

    PubMed

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI. PMID:27648146

  10. Graft derived cells with double nuclei in the penumbral region of experimental brain trauma.

    PubMed

    Horváth, Eszter M; Lacza, Zsombor; Csordás, Attila; Szabó, Csaba; Kollai, Márk; Busija, David W

    2006-04-01

    Recent in vitro studies showed that stem cells might fuse with mature cells or each other; however, there is no in vivo evidence for this phenomenon in the cerebral cortex. Our goal was to find evidence for cell fusion in a model of traumatic brain injury followed by grafting of embryonic cortical cells. Cold lesion protocol was applied to induce lesion of the motor cortex in adult male rats. Six days later we grafted a suspension of freshly isolated rat brain cortical cells of early embryonic stage (E14) into the penumbra area of the lesion. The grafted cell nuclei were labelled with bromodeoxyuridine (BrDU). Six days after transplantation 4,328 BrDU positive cells were observed in nine animals. 89.5% of these cells had cytoplasmic staining probably representing dead or phagocyted grafted cells. Ten percent of surviving BrDU positive cells had only one BrDU positive nucleus and negative cytoplasm, while 0.5% had two distinct nuclei, one was unlabelled and one was BrDU positive. These cells were similar in appearance and size to the astrocytes in the vicinity and expressed the astocyte specific glial fibrillaly acidic protein. Thus, these cells showed a possible sign of cell fusion in the penumbral region of the injured brain. PMID:16377084

  11. Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): Lethal brain concentrations

    USGS Publications Warehouse

    Clark, D.R.; Kroll, J.C.

    1977-01-01

    Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.

  12. Effects of hydroxysafflor yellow A on the experimental traumatic brain injury in rats.

    PubMed

    Bie, Xiao-Dong; Han, Jue; Dai, Hai-Bin

    2010-03-01

    This paper explores the effects of hydroxysafflor yellow A (HSYA) on traumatic brain injury (TBI). Rats were divided into four groups: control, TBI, TBI combined with HSYA, and TBI combined with nimodipine. Saline, HSYA, or nimodipine was i.v. injected at 30 min before and 6 h after the onset of TBI. The contusion volume of brain, mitochondrial ATPase activity, brain malondialdehyde (MDA) content, and the concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in the blood plasma were investigated. The results showed that the inhibitory rate of HSYA at a dose of 4 mg/kg was 59.2% compared with the TBI group. After the insult by TBI for 48 h, the activity of Na(+), K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase decreased to 31, 35, and 38% of control group. HSYA increased these ATPase activities by 162, 96, and 131% of TBI group. HSYA also increased superoxide dismutase activity and decreased MDA content in the right parietal lobe adjacent to contusion foci in TBI rats. HSYA enhanced the t-PA activity by 64.64%, decreased the PAI-1 activity by 71.88%, and decreased the MMP-9 expression to 49.11% in the hippocampus of the TBI group at 12 h. In conclusion, HSYA may exert a potential therapeutic strategy to improve the outcome following TBI injury.

  13. Variability of human brain and muscle optical pathlength in different experimental conditions

    NASA Astrophysics Data System (ADS)

    Ferrari, Marco; Wei, Qingnong; De Blasi, Roberto A.; Quaresima, Valentina; Zaccanti, Giovanni

    1993-09-01

    Pathlength can be evaluated by measuring the time taken from a picosecond (psec) near infrared (IR) laser pulse to cross tissue. Differential pathlength factor (DPF) is calculated by dividing the mean pathlength by the inter-fiber distance. Data on DPF variability on humans are scarce. We investigated the forehead and forearm DPF in resting conditions and dynamically during brain hypoxic hypoxia, muscle ischemia and voluntary isometric exercise. At 3 cm inter optode spacing DPF at 800 nm was 4.3 +/- 0.2 (n equals 14, mean +/- SD) on the forearm, and 6.5 +/- 0.5 (n equals 8) on the forehead. Brain, muscle, and breast DPF values were almost constant over the inter optode spacing 2.5 - 4 cm. DPF was roughly constant in the central region of forehead. DPF drastically decreased under the fronto- temporal junction for the presence of muscle in the optical field. DPF decreased 5 - 10% during forearm ischemia with and without maximal voluntary contraction and during brain hypoxic hypoxia.

  14. Aquaporins and Brain Tumors

    PubMed Central

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  15. Subclinical pulmonary edema in endurance athletes.

    PubMed

    Bussotti, M; Di Marco, S; Marchese, G; Agostoni, P G

    2012-06-01

    Strenuous exercise may cause progressive and proportional haemodynamic overload damage to the alveolar membrane, even in athletes. Despite the high incidence of arterial desaturation reported in endurance athletes has been attributed, into other factors, also to the damage of the alveolar-capillary membrane this evidence is equivocal. Some studies demonstrated flood of the interstitial space and consequent increase in pulmonary water content, but most of them were able to show this through indirect signs of interstitial oedema. The present review illustrates the literature's data in favour or against pulmonary interstitial edema due to intense exercise in athletes.

  16. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    PubMed

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation.

  17. [Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

    PubMed

    Titov, E A; Sosedova, L M; Novikov, M A

    2015-01-01

    The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum. PMID:27116877

  18. [Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

    PubMed

    Titov, E A; Sosedova, L M; Novikov, M A

    2015-01-01

    The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum.

  19. Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging.

    PubMed

    Sakamaki, Masanori; Igarashi, Hironaka; Nishiyama, Yutaka; Hagiwara, Hiroshi; Ando, Jun; Chishiki, Tetsurou; Curran, Brian C; Katayama, Yasuo

    2003-05-15

    The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction. PMID:12686405

  20. Diffusion tensor-based tumor infiltration index cannot discriminate vasogenic edema from tumor-infiltrated edema.

    PubMed

    Kinoshita, Manabu; Goto, Tetsu; Okita, Yoshiko; Kagawa, Naoki; Kishima, Haruhiko; Hashimoto, Naoya; Yoshimine, Toshiki

    2010-02-01

    Diffusion tensor imaging (DTI) by magnetic resonance imaging (MRI) is now used not only for delineating white matter fiber tracts, but also for assessing the histological characteristics of pathological tissues. Among these uses, predicting the extent or existence of tumor cell invasion into white matter by DTI is under extensive investigation. The previously reported tumor infiltration index (TII) holds great potential for the discrimination of pure vasogenic edema from tumor-infiltrated edema. However, conflicting data are being reported questioning the clinical value of TII. The present investigation reevaluated the utility of TII in patients with meningioma or glioma. We found that TII was unable to discriminate vasogenic from tumor-infiltrated edema. Conversely, detailed voxel-by-voxel comparison of TII and (11)C-methionie PET in the T2-hyperintense area of gliomas showed that TII and (11)C-methionie PET has a positive correlation, suggesting that, although TII is unable to discriminate the cause of edema, the extent of tumor cell invasion into white matter is depicted in gliomas by TII. These data suggest that TII involves both vasogenic and tumor-infiltrated factors, rather than only a single factor. A more intensive investigation is required to reach a complete understanding of TII.

  1. Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

    PubMed

    Mazzone, P; Arena, P; Cantelli, L; Spampinato, G; Sposato, S; Cozzolino, S; Demarinis, P; Muscato, G

    2016-07-01

    The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery. PMID:27194228

  2. Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

    PubMed

    Mazzone, P; Arena, P; Cantelli, L; Spampinato, G; Sposato, S; Cozzolino, S; Demarinis, P; Muscato, G

    2016-07-01

    The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery.

  3. Macular edema in branch retinal vein occlusion: types and treatment.

    PubMed

    Jalkh, A E; Trempe, C L

    1989-01-01

    In this study of branch retinal vein occlusion, we distinguished between cystoid macular edema caused by increased capillary pressure and noncystoid edema due to hard exudates in the macula caused by chronic leakage from vascular abnormalities in the posterior pole or midperiphery. We performed laser photocoagulation in 51 eyes with cystoid macular edema to achieve focal narrowing of the retinal arterioles perfusing the macular area affected by the cystoid edema; good anatomic and functional results were achieved in 40 of these eyes (78%). In 25 of the five eyes, the treated segment of the retinal arteriole was outside the area of macular edema; results were successful in 19 of these eyes (76%). In 14 eyes with noncystoid exudative macular edema, we performed laser photocoagulation to the vascular abnormalities; good anatomic and functional results were obtained in 12 of these (86%). PMID:2927879

  4. Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    PubMed

    Eisele, Yvonne S; Duyckaerts, Charles

    2016-01-01

    In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

  5. Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    PubMed

    Eisele, Yvonne S; Duyckaerts, Charles

    2016-01-01

    In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology. PMID:26715565

  6. Observational study of subclinical diabetic macular edema

    PubMed Central

    Bressler, N M; Miller, K M; Beck, R W; Bressler, S B; Glassman, A R; Kitchens, J W; Melia, M; Schlossman, D K

    2012-01-01

    Purpose To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. Methods In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 μm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME (performed at the discretion of the investigator). Results The cumulative probability of meeting an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. Conclusions Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification. PMID:22441027

  7. New Compton densitometer for measuring pulmonary edema

    SciTech Connect

    Loo, B.W.; Goulding, F.S.; Simon, D.S.

    1985-10-01

    Pulmonary edema is the pathological increase of extravascular lung water found most often in patients with congestive heart failure and other critically ill patients who suffer from intravenous fluid overload. A non-invasive lung density monitor that is accurate, easily portable, safe and inexpensive is needed for clinical evaluation of pulmonary edema. Other researchers who have employed Compton scattering techniques generally used systems of extended size and detectors with poor energy resolution. This has resulted in significant systematic biases from multiply-scattered photons and larger errors in counting statistics at a given radiation dose to the patient. We are proposing a patented approach in which only backscattered photons are measured with a high-resolution HPGe detector in a compact system geometry. By proper design and a unique data extraction scheme, effects of the variable chest wall on lung density measurements are minimized. Preliminary test results indicate that with a radioactive source of under 30 GBq, it should be possible to make an accurate lung density measurement in one minute, with a risk of radiation exposure to the patient a thousand times smaller than that from a typical chest x-ray. The ability to make safe, frequent lung density measurements could be very helpful for monitoring the course of P.E. at the hospital bedside or outpatient clinics, and for evaluating the efficacy of therapy in clinical research. 6 refs., 5 figs.

  8. Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria.

    PubMed

    Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen A L

    2014-07-01

    We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested that glycocalyx disruption preceded cerebral manifestations. The contribution of this loss to pathogenesis should be studied further.

  9. [Effect of prostaglandin synthesis inhibitors of diabetic cystoid macular edema].

    PubMed

    Kieselbach, G; Juen, S

    1990-01-01

    In most cases, diabetic macular edema is treated successfully with central laser photocoagulation. However, only few studies report such favorable results in cystoid macular edema, which has a poor visual prognosis. In the present prospective study on diabetics with cystoid macular edema, aged less than 40 years, a better visual outcome was obtained in patients treated with prostaglandin synthesis inhibitors than in an untreated group. PMID:2345629

  10. Behavioral, blood, and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury.

    PubMed

    Wright, David K; Trezise, Jack; Kamnaksh, Alaa; Bekdash, Ramsey; Johnston, Leigh A; Ordidge, Roger; Semple, Bridgette D; Gardner, Andrew J; Stanwell, Peter; O'Brien, Terence J; Agoston, Denes V; Shultz, Sandy R

    2016-01-01

    Repeated mild traumatic brain injuries (mTBI) may lead to serious neurological consequences, especially if re-injury occurs within the period of increased cerebral vulnerability (ICV) triggered by the initial insult. MRI and blood proteomics might provide objective measures of pathophysiological changes in mTBI, and indicate when the brain is no longer in a state of ICV. This study assessed behavioral, MRI, and blood-based markers in a rat model of mTBI. Rats were given a sham or mild fluid percussion injury (mFPI), and behavioral testing, MRI, and blood collections were conducted up to 30 days post-injury. There were cognitive impairments for three days post-mFPI, before normalizing by day 5 post-injury. In contrast, advanced MRI (i.e., tractography) and blood proteomics (i.e., vascular endothelial growth factor) detected a number of abnormalities, some of which were still present 30 days post-mFPI. These findings suggest that MRI and blood proteomics are sensitive measures of the molecular and subtle structural changes following mTBI. Of particular significance, this study identified novel tractography measures that are able to detect mTBI and may be more sensitive than traditional diffusion-tensor measures. Furthermore, the blood and MRI findings may have important implications in understanding ICV and are translatable to the clinical setting. PMID:27349514

  11. The Molecular Mechanisms Affecting N-Acetylaspartate Homeostasis Following Experimental Graded Traumatic Brain Injury

    PubMed Central

    Di Pietro, Valentina; Amorini, Angela Maria; Tavazzi, Barbara; Vagnozzi, Roberto; Logan, Ann; Lazzarino, Giacomo; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio

    2014-01-01

    To characterize the molecular mechanisms of N-acetylaspartate (NAA) metabolism following traumatic brain injury (TBI), we measured the NAA, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentrations and calculated the ATP/ADP ratio at different times from impact, concomitantly evaluating the gene and protein expressions controlling NAA homeostasis (the NAA synthesizing and degrading enzymes N-acetyltransferase 8-like and aspartoacylase, respectively) in rats receiving either mild or severe TBI. The reversible changes in NAA induced by mild TBI were due to a combination of transient mitochondrial malfunctioning with energy crisis (decrease in ATP and in the ATP/ADP ratio) and modulation in the gene and protein levels of N-acetyltransferase 8-like and increase of aspartoacylase levels. The irreversible decrease in NAA following severe TBI, was instead characterized by profound mitochondrial malfunctioning (constant 65% decrease of the ATP/ADP indicating permanent impairment of the mitochondrial phosphorylating capacity), dramatic repression of the N-acetyltransferase 8-like gene and concomitant remarkable increase in the aspartoacylase gene and protein levels. The mechanisms underlying changes in NAA homeostasis following graded TBI might be of note for possible new therapeutic approaches and will help in understanding the effects of repeat concussions occurring during particular periods of the complex NAA recovery process, coincident with the so called window of brain vulnerability. PMID:24515258

  12. Assessment of an experimental rodent model of pediatric mild traumatic brain injury.

    PubMed

    Mychasiuk, Richelle; Farran, Allyson; Esser, Michael J

    2014-04-15

    Childhood is one the highest risk periods for experiencing a mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls. In addition, many children experience lingering symptomology (post-concussion syndrome) from these closed head injuries. Although the negative sequel of mTBI has been described, a clinically reliable animal model of mild pediatric brain injury has not. The purpose of this study was to examine the validity of a modified weight-drop technique as a model for the induction of mTBI/concussion in juvenile rats following a single impact. Male and female rats (P30) were exposed to a single mTBI or a sham injury followed by a behavioral test battery. Juvenile rats who experienced a single mTBI displayed significant motor/balance impairments when tested on the beam walking task and in the open field, as well as deficits of executive functioning as measured with the novel context mismatch task and the probe trial of the Morris water task. In addition, both male and female rats showed depression-like behavior in the forced swim task, with male rats also exhibiting decreased anxiety-related behaviors in the elevated plus maze. The results from this study suggest that the modified weight-drop technique induces a clinically relevant behavioral phenotype in juvenile rats, and may provide researchers with a reliable animal model of mTBI/concussion from which clinical therapeutic strategies could be developed.

  13. Global Metabolomic Profiling of Mice Brains following Experimental Infection with the Cyst-Forming Toxoplasma gondii

    PubMed Central

    Elsheikha, Hany M.; Liu, Guang-Xue; Suo, Xun; Zhu, Xing-Quan

    2015-01-01

    The interplay between the Apicomplexan parasite Toxoplasma gondii and its host has been largely studied. However, molecular changes at the metabolic level in the host central nervous system and pathogenesis-associated metabolites during brain infection are largely unexplored. We used a global metabolomics strategy to identify differentially regulated metabolites and affected metabolic pathways in BALB/c mice during infection with T. gondii Pru strain at 7, 14 and 21 days post-infection (DPI). The non-targeted Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics analysis detected approximately 2,755 retention time-exact mass pairs, of which more than 60 had significantly differential profiles at different stages of infection. These include amino acids, organic acids, carbohydrates, fatty acids, and vitamins. The biological significance of these metabolites is discussed. Principal Component Analysis and Orthogonal Partial Least Square-Discriminant Analysis showed the metabolites’ profile to change over time with the most significant changes occurring at 14 DPI. Correlated metabolic pathway imbalances were observed in carbohydrate metabolism, lipid metabolism, energetic metabolism and fatty acid oxidation. Eight metabolites correlated with the physical recovery from infection-caused illness were identified. These findings indicate that global metabolomics adopted in this study is a sensitive approach for detecting metabolic alterations in T. gondii-infected mice and generated a comparative metabolic profile of brain tissue distinguishing infected from non-infected host. PMID:26431205

  14. Assessment of an experimental rodent model of pediatric mild traumatic brain injury.

    PubMed

    Mychasiuk, Richelle; Farran, Allyson; Esser, Michael J

    2014-04-15

    Childhood is one the highest risk periods for experiencing a mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls. In addition, many children experience lingering symptomology (post-concussion syndrome) from these closed head injuries. Although the negative sequel of mTBI has been described, a clinically reliable animal model of mild pediatric brain injury has not. The purpose of this study was to examine the validity of a modified weight-drop technique as a model for the induction of mTBI/concussion in juvenile rats following a single impact. Male and female rats (P30) were exposed to a single mTBI or a sham injury followed by a behavioral test battery. Juvenile rats who experienced a single mTBI displayed significant motor/balance impairments when tested on the beam walking task and in the open field, as well as deficits of executive functioning as measured with the novel context mismatch task and the probe trial of the Morris water task. In addition, both male and female rats showed depression-like behavior in the forced swim task, with male rats also exhibiting decreased anxiety-related behaviors in the elevated plus maze. The results from this study suggest that the modified weight-drop technique induces a clinically relevant behavioral phenotype in juvenile rats, and may provide researchers with a reliable animal model of mTBI/concussion from which clinical therapeutic strategies could be developed. PMID:24283269

  15. Behavioral, blood, and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury

    PubMed Central

    Wright, David K.; Trezise, Jack; Kamnaksh, Alaa; Bekdash, Ramsey; Johnston, Leigh A.; Ordidge, Roger; Semple, Bridgette D.; Gardner, Andrew J.; Stanwell, Peter; O’Brien, Terence J.; Agoston, Denes V.; Shultz, Sandy R.

    2016-01-01

    Repeated mild traumatic brain injuries (mTBI) may lead to serious neurological consequences, especially if re-injury occurs within the period of increased cerebral vulnerability (ICV) triggered by the initial insult. MRI and blood proteomics might provide objective measures of pathophysiological changes in mTBI, and indicate when the brain is no longer in a state of ICV. This study assessed behavioral, MRI, and blood-based markers in a rat model of mTBI. Rats were given a sham or mild fluid percussion injury (mFPI), and behavioral testing, MRI, and blood collections were conducted up to 30 days post-injury. There were cognitive impairments for three days post-mFPI, before normalizing by day 5 post-injury. In contrast, advanced MRI (i.e., tractography) and blood proteomics (i.e., vascular endothelial growth factor) detected a number of abnormalities, some of which were still present 30 days post-mFPI. These findings suggest that MRI and blood proteomics are sensitive measures of the molecular and subtle structural changes following mTBI. Of particular significance, this study identified novel tractography measures that are able to detect mTBI and may be more sensitive than traditional diffusion-tensor measures. Furthermore, the blood and MRI findings may have important implications in understanding ICV and are translatable to the clinical setting. PMID:27349514

  16. Global Metabolomic Profiling of Mice Brains following Experimental Infection with the Cyst-Forming Toxoplasma gondii.

    PubMed

    Zhou, Chun-Xue; Zhou, Dong-Hui; Elsheikha, Hany M; Liu, Guang-Xue; Suo, Xun; Zhu, Xing-Quan

    2015-01-01

    The interplay between the Apicomplexan parasite Toxoplasma gondii and its host has been largely studied. However, molecular changes at the metabolic level in the host central nervous system and pathogenesis-associated metabolites during brain infection are largely unexplored. We used a global metabolomics strategy to identify differentially regulated metabolites and affected metabolic pathways in BALB/c mice during infection with T. gondii Pru strain at 7, 14 and 21 days post-infection (DPI). The non-targeted Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics analysis detected approximately 2,755 retention time-exact mass pairs, of which more than 60 had significantly differential profiles at different stages of infection. These include amino acids, organic acids, carbohydrates, fatty acids, and vitamins. The biological significance of these metabolites is discussed. Principal Component Analysis and Orthogonal Partial Least Square-Discriminant Analysis showed the metabolites' profile to change over time with the most significant changes occurring at 14 DPI. Correlated metabolic pathway imbalances were observed in carbohydrate metabolism, lipid metabolism, energetic metabolism and fatty acid oxidation. Eight metabolites correlated with the physical recovery from infection-caused illness were identified. These findings indicate that global metabolomics adopted in this study is a sensitive approach for detecting metabolic alterations in T. gondii-infected mice and generated a comparative metabolic profile of brain tissue distinguishing infected from non-infected host. PMID:26431205

  17. Scuba diving-induced pulmonary edema in a swimming pool.

    PubMed

    Gnadinger, C A; Colwell, C B; Knaut, A L

    2001-11-01

    SCUBA diving-induced pulmonary edema is a rare syndrome that has been previously reported to occur in cold water. We present a case of SCUBA diving-induced pulmonary edema in a 52-year-old man diving in a warm swimming pool. The pathophysiology of this syndrome is unclear, but it is unrelated to either barotrauma or decompression illness. This patient developed frank pulmonary edema while submerged, which resolved after surfacing. As with other patients who have had this syndrome, he did not have any cardiorespiratory disease. The presentation and pathophysiology of SCUBA diving-induced pulmonary edema are discussed.

  18. The Curious Question of Exercise-Induced Pulmonary Edema

    PubMed Central

    Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

    2011-01-01

    The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

  19. Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    PubMed

    Uchihara, Toshiki; Giasson, Benoit I

    2016-01-01

    Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac

  20. The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol.

    PubMed

    Osier, Nicole; Dixon, C Edward

    2016-01-01

    Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details-that should be reported in CCI studies-will be noted. PMID:27604719

  1. Chronic Decrease in Wakefulness and Disruption of Sleep-Wake Behavior after Experimental Traumatic Brain Injury

    PubMed Central

    Skopin, Mark D.; Kabadi, Shruti V.; Viechweg, Shaun S.; Mong, Jessica A.

    2015-01-01

    Abstract Traumatic brain injury (TBI) can cause sleep-wake disturbances and excessive daytime sleepiness. The pathobiology of sleep disorders in TBI, however, is not well understood, and animal models have been underused in studying such changes and potential underlying mechanisms. We used the rat lateral fluid percussion (LFP) model to analyze sleep-wake patterns as a function of time after injury. Rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wake bouts during light and dark phases were measured with electroencephalography and electromyography at an early as well as chronic time points after LFP. Moderate TBI caused disturbances in the ability to maintain consolidated wake bouts during the active phase and chronic loss of wakefulness. Further, TBI resulted in cognitive impairments and depressive-like symptoms, and reduced the number of orexin-A-positive neurons in the lateral hypothalamus. PMID:25242371

  2. Chronic decrease in wakefulness and disruption of sleep-wake behavior after experimental traumatic brain injury.

    PubMed

    Skopin, Mark D; Kabadi, Shruti V; Viechweg, Shaun S; Mong, Jessica A; Faden, Alan I

    2015-03-01

    Traumatic brain injury (TBI) can cause sleep-wake disturbances and excessive daytime sleepiness. The pathobiology of sleep disorders in TBI, however, is not well understood, and animal models have been underused in studying such changes and potential underlying mechanisms. We used the rat lateral fluid percussion (LFP) model to analyze sleep-wake patterns as a function of time after injury. Rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wake bouts during light and dark phases were measured with electroencephalography and electromyography at an early as well as chronic time points after LFP. Moderate TBI caused disturbances in the ability to maintain consolidated wake bouts during the active phase and chronic loss of wakefulness. Further, TBI resulted in cognitive impairments and depressive-like symptoms, and reduced the number of orexin-A-positive neurons in the lateral hypothalamus.

  3. Experimental evidence that ornithine and homocitrulline disrupt energy metabolism in brain of young rats.

    PubMed

    Viegas, Carolina Maso; Zanatta, Angela; Knebel, Lisiane Aurélio; Schuck, Patrícia Fernanda; Tonin, Anelise Miotti; Ferreira, Gustavo da Costa; Amaral, Alexandre Umpierrez; Dutra Filho, Carlos Severo; Wannmacher, Clovis Milton Duval; Wajner, Moacir

    2009-09-29

    Tissue accumulation of ornithine (Orn), homocitrulline (Hcit), ammonia and orotic acid (Oro) is the biochemical hallmark of patients affected by hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a disorder clinically characterized by neurological symptoms, whose pathophysiology is practically unknown. In the present study, we investigated the in vitro effect of Orn, Hcit and Oro on important parameters of energy metabolism in brain of 30-day-old Wistar rats since mitochondrial abnormalities have been observed in the affected patients. We first verified that Orn and Hcit significantly inhibited the citric acid cycle (inhibition of CO(2) synthesis from [1-(14)C] acetate, as well as aconitase and alpha-ketoglutarate dehydrogenase activities), the aerobic glycolytic pathway (reduced CO(2) production from [U-(14)C] glucose) and moderately the electron transfer flow (inhibitory effect on complex I-III). Hcit, but not Orn, was also able to significantly inhibit the mitochondrial creatine kinase activity. Furthermore, this inhibition was prevented by GSH, suggesting a possible role of reactive species oxidizing critical thiol groups of the enzyme. In contrast, the other enzyme activities of the citric acid cycle and of the electron transfer chain, as well as synaptic Na(+),K(+)-ATPase were not altered by either Orn or Hcit at concentrations as high as 5.0 mM. Similarly, Oro did not interfere with any of the tested parameters. Taken together, these data strongly indicate that Orn and Hcit compromise brain energy metabolism homeostasis and Hcit also interferes with cellular ATP transfer and buffering. It is therefore suggested that Orn and especially Hcit may be involved in the neurological damage found in patients affected by HHH syndrome. PMID:19616520

  4. Bystander effect-mediated therapy of experimental brain tumor by genetically engineered tumor cells.

    PubMed

    Namba, H; Tagawa, M; Iwadate, Y; Kimura, M; Sueyoshi, K; Sakiyama, S

    1998-01-01

    Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, followed by administration of ganciclovir (GCV), generates the "bystander effect," in which HSV-tk-negative wild-type cells, as well as HSV-tk-expressing cells, are killed by GCV. To eradicate an intracranial tumor by this bystander effect, we injected the tumor cells transduced with the HSV-tk gene (TK cells) in the vicinity of the preimplanted wild-type tumor and then administered GCV. Wild-type 9L-gliosarcoma cells (1 x 10[5]) were implanted into the brain of syngeneic Fisher rats. On the next day, rats were injected with TK cells (1 x 10(5) or 3 x 10[5]) or medium alone at the same brain coordinate and then treated with GCV or saline. Administration of GCV significantly prolonged the survival of the rats injected with TK cells compared with that injected with medium alone (p < 0.01). Reduction in tumor size and retardation of tumor growth were observed by serial magnetic resonance imaging in the rats that received the combination of TK cells and GCV. The results show that the bystander effect is also achieved in vivo even when TK cells and wild-type cells are not simultaneously implanted. This treatment modality circumvents potential risks accompanied with in vivo gene transfer. Because there remained substantially no HSV-tk-positive cells in the recurrent tumors, this modality offers a "safe" therapeutic strategy against human malignant gliomas. PMID:9458237

  5. Update on corticosteroids for diabetic macular edema.

    PubMed

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. PMID:27660409

  6. Update on corticosteroids for diabetic macular edema

    PubMed Central

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. PMID:27660409

  7. Update on corticosteroids for diabetic macular edema

    PubMed Central

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME.

  8. Serotonin syndrome presenting as pulmonary edema

    PubMed Central

    Shah, Nilima Deepak; Jain, Ajay B.

    2016-01-01

    Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive central and peripheral serotonergic activity. Clinically, it is a triad of mental-status changes, neuromuscular abnormalities, and autonomic disturbances. It can be caused by intentional self-poisoning, overdose, or inadvertent drug interactions. We report the case of a 58-year-old male with type 2 diabetes mellitus and obsessive compulsive disorder who developed pulmonary edema as a possible complication of SS. SS was caused by a combination of three specific serotonin re-uptake inhibitors (fluoxetine, fluvoxamine, and sertraline), linezolid, and fentanyl. The hospital course was further complicated by difficult weaning from the ventilator. SS was identified and successfully treated with cyproheptadine and lorazepam. The case highlights the importance of effective consultation-liaison and prompt recognition of SS as the presentation may be complex in the presence of co-morbid medical illness. PMID:26997733

  9. Nonproliferative diabetic retinopathy and macular edema.

    PubMed

    Smith, S C

    1999-01-01

    As previously noted, although visual loss usually does not fall below 20/200 in the presence of ME, it may nevertheless be a significant disability. Additional interventions may include referral to low vision clinics, home health agencies, visual loss support groups, and local or regional blindness agencies to aid the patient's occupational rehabilitation, coping mechanisms, and adaptation responses in the presence of this potentially debilitating process. Control of blood sugar, blood pressure, and the intervention of focal/grid laser treatments to seal leaks and prevent further edema provide the best chance of maintaining useful vision throughout life. Patient education is paramount to improve comprehension of the condition, recommended treatment modalities, and compliance with prescribed regimens. Assessments and interventions related to knowledge and sensory deficits, anxiety, discomfort, ineffective coping mechanisms, and health maintenance behaviors add a quality link in the multidisciplinary approach surrounding the delivery of care to patients with NPDR and clinically significant ME. PMID:11907881

  10. Pseudophakic cystoid macular edema: update 2016

    PubMed Central

    Grzybowski, Andrzej; Sikorski, Bartosz L; Ascaso, Francisco J; Huerva, Valentín

    2016-01-01

    Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice.

  11. Pseudophakic cystoid macular edema: update 2016

    PubMed Central

    Grzybowski, Andrzej; Sikorski, Bartosz L; Ascaso, Francisco J; Huerva, Valentín

    2016-01-01

    Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice. PMID:27672316

  12. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study.

    PubMed

    Hansen, Tine Maria; Olesen, Anne Estrup; Graversen, Carina; Drewes, Asbjørn Mohr; Frøkjaer, Jens Brøndum

    2015-11-01

    Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 ± 2.6 years) in a randomized, double-blind, placebo-controlled, cross-over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain-specific areas decreased (n = 20). Reduced pain-induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain-induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the 'pain matrix' and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics.

  13. [Repressional effects of the glutamate antibodies on expression of Dffb gene in the brain of rats with experimental Alzheimer's disease].

    PubMed

    Kolobov, V V; Davydova, T V; Zakharova, I A; Gorbatov, V Iu; Fomina, V G

    2012-01-01

    The intranasal administration of glutamate antibodies in the dose of 300 microg/kg one hour after damage on the level of mRNA expression of Dffb gene which codes caspase-activated DNase which participates in intranucleosome fragmentation of genome DNA in apoptosis was investigated in experimental Alzheimer's disease induced by injection of neurotoxic fragment of beta-amyloid protein Abeta25-35 in Meynert basal magnocellular nuclei on rats. On the Day 3 after Abeta25-35 injection is observed significant decrease of the level of mRNA expression of Dffb gene in prefrontal cortex in 37%, and in hippocampus in 62% in the experiment group versus the control group. These differences were not found in the hypothalamus when comparing the experimental and control animals. It was suggested that repressive effect of glutamate antibodies on the level of mRNA expression of Dffb gene reflects stabilization of processes taking place in brain cells in experimental Alzheimer's disease, and in its turn the intensiveness of nerve and glial cells apoptotic death is decreased.

  14. Smoke aldehyde component influences pulmonary edema

    SciTech Connect

    Hales, C.A.; Musto, S.W.; Janssens, S.; Jung, W.; Quinn, D.A.; Witten, M. , Massachusetts General Hospital, Boston )

    1992-02-01

    The pulmonary edema of smoke inhalation is caused by the toxins of smoke and not the heat. We investigated the potential of smoke consisting of carbon in combination with either acrolein or formaldehyde (both common components of smoke) to cause pulmonary edema in anesthetized sheep. Seven animals received acrolein smoke, seven animals received a low-dose formaldehyde smoke, and five animals received a high-dose formaldehyde smoke. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were not affected by smoke in any group. Peak airway pressure increased after acrolein (14 +/- 1 to 21 +/- 2 mmHg; P less than 0.05) and after low- and high-dose formaldehyde (14 +/- 1 to 21 +/- 1 and 20 +/- 1 mmHg, respectively; both P less than 0.05). The partial pressure of O2 in arterial blood fell sharply after acrolein (219 +/- 29 to 86 +/- 9 (SE) Torr; P less than 0.05) but not after formaldehyde. Only acrolein resulted in a rise in lung lymph flow (6.5 +/- 2.2 to 17.9 +/- 2.6 ml/h; P less than 0.05). Lung lymph-to-plasma protein ratio was unchanged for all three groups, but clearance of lymph protein was increased after acrolein. After acrolein, the blood-free extravascular lung water-to-lung dry weight ratio was elevated (P less than 0.05) compared with both low- and high-dose formaldehyde groups (4.8 +/- 0.4 to 3.3 +/- 0.2 and 3.6 +/- 0.2, respectively). Lymph clearance (ng/h) of thromboxane B2, leukotriene B4, and the sulfidopeptide leukotrienes was elevated after acrolein but not formaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study

    PubMed Central

    Shi, Yu; Liu, Ziping; Zhang, Shanshan; Li, Qiang; Guo, Shigui; Yang, Jiangming; Wu, Wen

    2015-01-01

    Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP. PMID:26161117

  16. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study.

    PubMed

    Shi, Yu; Liu, Ziping; Zhang, Shanshan; Li, Qiang; Guo, Shigui; Yang, Jiangming; Wu, Wen

    2015-01-01

    Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP. PMID:26161117

  17. Massive vulvar edema in 2 prepartum dairy cows.

    PubMed

    Cheong, Soon Hon; Gilbert, Robert O

    2014-05-01

    Two late gestation Holstein cows about to begin the third lactation developed massive vulvar edema. These were the only affected animals in the herd of 500 milking cows. The vulvar edema spontaneously regressed postpartum for both cows. Massive vulvar swelling is seldom observed in dairy cows in advanced pregnancy and is not described in the literature.

  18. Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better?

    PubMed

    Kline, Anthony E; Leary, Jacob B; Radabaugh, Hannah L; Cheng, Jeffrey P; Bondi, Corina O

    2016-07-01

    Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the bench, similar results have not translated to the clinic. One reason for the lack of successful translation may be due to the fact that TBI is a heterogeneous disease that affects multiple mechanisms, thus requiring a therapeutic approach that can act on complementary, rather than single, targets. Hence, the use of combination therapies (i.e., polytherapy) has emerged as a viable approach. Stringent criteria, such as verification of each individual treatment plus the combination, a focus on behavioral outcome, and post-injury vs. pre-injury treatments, were employed to determine which studies were appropriate for review. The selection process resulted in 37 papers that fit the specifications. The review, which is the first to comprehensively assess the effects of combination therapies on behavioral outcomes after TBI, encompasses five broad categories (inflammation, oxidative stress, neurotransmitter dysregulation, neurotrophins, and stem cells, with and without rehabilitative therapies). Overall, the findings suggest that combination therapies can be more beneficial than monotherapies as indicated by 46% of the studies exhibiting an additive or synergistic positive effect versus on 19% reporting a negative interaction. These encouraging findings serve as an impetus for continued combination studies after TBI and ultimately for the development of successful clinically relevant therapies.

  19. Lipocalin 2 and Blood-Brain Barrier Disruption in White Matter after Experimental Subarachnoid Hemorrhage.

    PubMed

    Egashira, Yusuke; Hua, Ya; Keep, Richard F; Iwama, Toru; Xi, Guohua

    2016-01-01

    We reported previously that subarachnoid hemorrhage (SAH) causes acute white matter injury in mice. In this study, we investigated lipocalin 2 (LCN2) mediated blood-brain barrier (BBB) disruption in white matter, which may lead to subsequent injury. SAH was induced by endovascular perforation in wild-type (WT) and LCN2-knockout (LCN2(-/-)) mice. Sham mice underwent the same procedure without perforation. Mice underwent magnetic resonance imaging (MRI) 24 h after SAH to confirm the development of T2-hyperintensity in white matter. Western blotting and immunohistochemistry were performed to elucidate the mechanisms of LCN2-mediated white matter injury and BBB disruption. It was confirmed that LCN2 expression was significantly increased in white matter of WT mice after SAH by Western blotting (versus sham; p < 0.05). Immunohistochemistry showed that LCN2 receptor 24p3R was expressed in oligodendrocytes, astrocytes, endothelial cells, and pericytes in the white matter. In WT mice with SAH, albumin leakage along the white matter was prominently observed and was consistent with T2-hyperintensity on MRI. As with our previous report, LCN2(-/-) mice scarcely developed T2-hyperintensity on MRI or albumin leakage in white matter. Our results suggest that BBB leakage occurs in white matter after SAH and that LCN2 contributes to SAH-induced BBB disruption.

  20. Role of Mitochondrial Calcium Uniporter in Early Brain Injury After Experimental Subarachnoid Hemorrhage.

    PubMed

    Yan, Huiying; Zhang, Dingding; Hao, Shuangying; Li, Kuanyu; Hang, Chun-Hua

    2015-12-01

    Previous studies have shown that mitochondrial Ca(2+) is undertaken by mitochondrial calcium uniporter (MCU), and its accumulation is associated with the development of many diseases. However, little was known about the role of MCU in early brain injury (EBI) after subarachnoid hemorrhage (SAH). MCU can be opened by spermine under a physiological condition and inhibited by ruthenium red (RR). Herein, we investigated the effects of RR and spermine to reveal the role of MCU in SAH animal model. The data obtained with biochemical and histological assays showed that mitochondrial Ca(2+) concentration was significantly increased in the temporal cortex of rats 1, 2, and 3 days after SAH, consistent with constant high levels of cellular Ca(2+) concentration. In agreement with the observation in the acute phase, SAH rats showed an obvious increase of reactive oxygen species (ROS) level and decrease of ATP production. Blockage of MCU prevented Ca(2+) accumulation, abated the level of oxidative stress, and improved the energy supply. Translocation of cytochrome c, increased cleaved caspase-3, and a large amount of apoptotic cells after SAH were reversed by RR administration. Surprisingly, exogenous spermine did not increase cellular Ca(2+) concentration, but lessened the Ca(2+) accumulation after SAH to benefit the rats. Taken together, our results demonstrated that blockage of MCU or prevention of Ca(2+) accumulation after SAH is essential in EBI after SAH. These findings suggest that MCU is considered to be a therapeutic target for patients suffering from SAH.

  1. Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice.

    PubMed

    Shein, Steven L; Shellington, David K; Exo, Jennifer L; Jackson, Travis C; Wisniewski, Stephen R; Jackson, Edwin K; Vagni, Vincent A; Bayır, Hülya; Clark, Robert S B; Dixon, C Edward; Janesko-Feldman, Keri L; Kochanek, Patrick M

    2014-08-15

    Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition of HS on the inflammatory response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; TBI (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; and CCI+HS. All non-naïve mice underwent identical monitoring and anesthesia. HS and CCI+HS underwent a 35-min period of pressure-controlled hemorrhage (target mean arterial pressure, 25-27 mm Hg) and a 90-min resuscitation with lactated Ringer's injection and autologous blood transfusion. Mice were sacrificed at 2 or 24 h after injury. Levels of 13 cytokines, six chemokines, and three growth factors were measured in serum and in five brain tissue regions. Serum levels of several proinflammatory mediators (eotaxin, interferon-inducible protein 10 [IP-10], keratinocyte chemoattractant [KC], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1alpha [MIP-1α], interleukin [IL]-5, IL-6, tumor necrosis factor alpha, and granulocyte colony-stimulating factor [G-CSF]) were increased after CCI alone. Serum levels of fewer proinflammatory mediators (IL-5, IL-6, regulated upon activation, normal T-cell expressed, and secreted, and G-CSF) were increased after CCI+HS. Serum level of anti-inflammatory IL-10 was significantly increased after CCI+HS versus CCI alone. Brain tissue levels of eotaxin, IP-10, KC, MCP-1, MIP-1α, IL-6, and G-CSF were increased after both CCI and CCI+HS. There were no significant differences between levels after CCI alone and CCI+HS in any mediator. Addition of HS to experimental TBI led to a shift toward an anti-inflammatory serum profile--specifically, a marked increase in IL-10 levels. The brain cytokine and chemokine profile after TBI was minimally affected by the addition of HS.

  2. Temporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    NASA Astrophysics Data System (ADS)

    Kang, DongYel; Wang, Alex; Tjoa, Tjoson; Volgger, Veronika; Hamamoto, Ashley; Su, Erica; Jing, Joseph; Chen, Zhongping; Wong, Brian J. F.

    2014-03-01

    Recently, full-range optical coherence tomography (OCT) systems have been developed to image the human airway. These novel systems utilize a fiber-based OCT probe which acquires three-dimensional (3-D) images with micrometer resolution. Following an airway injury, mucosal edema is the first step in the body's inflammatory response, which occasionally leads to airway stenosis, a life-threatening condition for critically ill newborns. Therefore, early detection of edema is vital for airway management and prevention of stenosis. In order to examine the potential of the full-range OCT to diagnose edema, we investigated temporal correlation of OCT images obtained from the subglottic airway of live rabbits. Temporally correlated OCT images were acquired at fixed locations in the rabbit subglottis of either artificially induced edema or normal tissues. Edematous tissue was experimentally modeled by injecting saline beneath the epithelial layer of the subglottic mucosa. The calculated cross temporal correlations between OCT images of normal airway regions show periodicity that correlates with the respiratory motion of the airway. However, the temporal correlation functions calculated from OCT images of the edematous regions show randomness without the periodic characteristic. These in-vivo experimental results of temporal correlations between OCT images show the potential of a computer-based or -aided diagnosis of edema in the human respiratory mucosa with a full-range OCT system.

  3. [Effect of cinnarizine on the brain mitochondrial oxidative system, antioxidant blood activity, and the rat behavior in hypoxia].

    PubMed

    Belostotskaia, L I; Chaĭka, L A; Gomon, O N

    2003-01-01

    The effect of cinnarizine on the functional state of brain mitochondria, the activity of blood antioxidant system, and the behavior of rats was studied under model hypoxic hypoxia conditions. A four-day treatments with cinnarizine (50 mg/kg, twice per day via a gastric tube) prevents the hypoxic brain edema development, restores NAD+ dependent oxidation of a succinate substrate, normalizes emotional-exploratory activity, and causes hyperlocomotion of the experimental animals, while not influencing a high level of activity of the blood antioxidant system. PMID:14743704

  4. Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    PubMed

    Lewis, Jada; Dickson, Dennis W

    2016-01-01

    Tau is a microtubule-associated protein and a key regulator of microtubule stabilization as well as the main component of neurofibrillary tangles-a principle neuropathological hallmark of Alzheimer's disease (AD)-as well as pleomorphic neuronal and glial inclusions in neurodegenerative tauopathies. Cross-sectional studies of neurofibrillary pathology in AD reveal a stereotypic spatiotemporal pattern of neuronal vulnerability that correlates with disease severity; however, the relationship of this pattern to disease progression is less certain and exceptions to the typical pattern have been described in a subset of AD patients. The basis for the selective vulnerability of specific populations of neurons to tau pathology and cell death is largely unknown, although there have been a number of hypotheses based upon shared properties of vulnerable neurons (e.g., degree of axonal myelination or synaptic plasticity). A recent hypothesis for selective vulnerability takes into account the emerging science of functional connectivity based upon resting state functional magnetic resonance imaging, where subsets of neurons that fire synchronously define patterns of degeneration similar to specific neurodegenerative disorders, including various tauopathies. In the past 6 years, the concept of tau propagation has emerged from numerous studies in cell and animal models suggesting that tau moves from cell-to-cell and that this may trigger aggregation and region-to-region spread of tau pathology within the brain. How the spread of tau pathology relates to functional connectivity is an area of active investigation. Observations of templated folding and propagation of tau have prompted comparisons of tau to prions, the pathogenic proteins in transmissible spongiform encephalopathies. In this review, we discuss the most compelling studies in the field, discuss their shortcomings and consider their implications with respect to human tauopathies as well as the controversy that

  5. Alternations of 14-3-3 θ and β protein levels in brain during experimental sepsis.

    PubMed

    Memos, Nikolaos; Kataki, Agapi; Chatziganni, Emmy; Nikolopoulou, Marilena; Skoulakis, Euthimios; Consoulas, Christos; Zografos, George; Konstadoulakis, Manousos

    2011-09-01

    The 14-3-3 family members play a crucial role in the determination of cell fate, exerting their antiapoptotic activity through directly interfering with the critical function of the mitochondrial core proapoptotic machinery. Dimerization of 14-3-3 is vital for the interaction with many of its client proteins and is regulated by phosphorylation. In a previous study, we observed time-dependent neuronal apoptosis during sepsis. Therefore, in the present study, we sought to evaluate the expression of 14-3-3 θ and β isoforms in septic brain and their association with apoptosis. Sepsis was induced by a CLP model in Wistar rats that were sacrificed at predefined time points. Flow cytometric analysis showed a sepsis-induced, time-dependent alteration of 14-3-3 θ and β isoforms in both Neun(+) and GFAP(+) cells. 14-3-3 θ was linearly correlated with apoptosis, and stratified analysis for alive and apoptotic neuronal cells demonstrated a gradual down-regulation of θ isoform in alive neurons and astrocytes. The phospho-P38 (pP38) MAP kinase levels were altered in a time-dependent manner during sepsis, presenting a peak at 6 hr post-CLP. A significant correlation between the two isoforms of 14-3-3 was observed in septic rats, with the θ isoform predominant at all time points. The hippocampus, Purkinje cells, and glia-like cells showed intense immunohistochemical reactivity for 14-3-3 θ isoform, whereas the choroid plexus showed constantly increased β isoform expression. Our results showed that sepsis alters the expression of both 14-3-3 θ and β isoforms in a time-, cell-, and topography-dependent manner. PMID:21618583

  6. Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream

    PubMed Central

    Hoffmann, Angelika; Pfeil, Johannes; Alfonso, Julieta; Kurz, Felix T.; Sahm, Felix; Heiland, Sabine; Monyer, Hannah; Bendszus, Martin; Mueller, Ann-Kristin; Helluy, Xavier; Pham, Mirko

    2016-01-01

    It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal

  7. Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream.

    PubMed

    Hoffmann, Angelika; Pfeil, Johannes; Alfonso, Julieta; Kurz, Felix T; Sahm, Felix; Heiland, Sabine; Monyer, Hannah; Bendszus, Martin; Mueller, Ann-Kristin; Helluy, Xavier; Pham, Mirko

    2016-03-01

    It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal

  8. Edema surrounding calcified intracranial cysticerci: clinical manifestations, natural history, and treatment

    PubMed Central

    Nash, Theodore

    2012-01-01

    Calcified granulomas are the most common radiological finding in neurocysticercosis (10–20% of endemic populations). A small proportion serves as foci of seizure activity, which results in large numbers of persons with epilepsy. Calcified granulomas are not all the same. Some demonstrate blood–brain barrier dysfunction (magnetic resonance imaging enhancement) most likely due to the presence of inflammation, visualizable scolices, and/or gliosis. About half the patients with a recent history of seizures, positive serology, and only calcified lesions develop perilesional edema at the time of a seizure recurrence. The natural history, treatment, and pathophysiology of this phenomenon are not well studied. Episodes are usually associated with seizures or other neurological manifestations, resolve by 4–6 weeks, sometimes occur repeatedly, and usually involve a subset of the same calcifications. Treatment is supportive. Histopathological examination of one calcification associated with multiple perilesional edema episodes revealed significant inflammation and supports the concept that perilesional edema is inflammatory in nature. This most likely is due to host responses to released or newly recognized parasite antigen and/or upregulation of the host immune response. Immunosuppressive and anti-inflammatory agents may be useful in prevention and/or treatment of this phenomenon. PMID:23265551

  9. Why standard brain-computer interface (BCI) training protocols should be changed: an experimental study

    NASA Astrophysics Data System (ADS)

    Jeunet, Camille; Jahanpour, Emilie; Lotte, Fabien

    2016-06-01

    Objective. While promising, electroencephaloraphy based brain-computer interfaces (BCIs) are barely used due to their lack of reliability: 15% to 30% of users are unable to control a BCI. Standard training protocols may be partly responsible as they do not satisfy recommendations from psychology. Our main objective was to determine in practice to what extent standard training protocols impact users’ motor imagery based BCI (MI-BCI) control performance. Approach. We performed two experiments. The first consisted in evaluating the efficiency of a standard BCI training protocol for the acquisition of non-BCI related skills in a BCI-free context, which enabled us to rule out the possible impact of BCIs on the training outcome. Thus, participants (N = 54) were asked to perform simple motor tasks. The second experiment was aimed at measuring the correlations between motor tasks and MI-BCI performance. The ten best and ten worst performers of the first study were recruited for an MI-BCI experiment during which they had to learn to perform two MI tasks. We also assessed users’ spatial ability and pre-training μ rhythm amplitude, as both have been related to MI-BCI performance in the literature. Main results. Around 17% of the participants were unable to learn to perform the motor tasks, which is close to the BCI illiteracy rate. This suggests that standard training protocols are suboptimal for skill teaching. No correlation was found between motor tasks and MI-BCI performance. However, spatial ability played an important role in MI-BCI performance. In addition, once the spatial ability covariable had been controlled for, using an ANCOVA, it appeared that participants who faced difficulty during the first experiment improved during the second while the others did not. Significance. These studies suggest that (1) standard MI-BCI training protocols are suboptimal for skill teaching, (2) spatial ability is confirmed as impacting on MI-BCI performance, and (3) when faced

  10. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies.

    PubMed

    Canazza, Alessandra; Minati, Ludovico; Boffano, Carlo; Parati, Eugenio; Binks, Sophie

    2014-01-01

    Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment, and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

  11. [Perioperative management of a patient complicated with Quincke's edema].

    PubMed

    Nakaigawa, Naoko; Kamata, Kotoe; Komatsu, Ryu; Ozaki, Makoto

    2010-04-01

    We experienced perioperative management of a patient with Quincke's edema who underwent clipping of ruptured intracranial aneurysm. At the time of presentation, he complained of lip and tongue swelling. We administered dl-chlorpheniramine malate and tranexamic acid perioperatively to prevent further edema. Intraoperatively, we avoided contact of objects to the face and the oral cavity which might have caused mechanical stimuli, and infused albumin to maintain plasma osmotic pressure. The patient was kept intubated postoperatively because of significant tongue edema at the end of the procedure. On postoperative day 1, we extubated the trachea after prophylactic administration of methylpredonisolone. Significant upper airway edema was denied by flexible laryngoscopy. Pathophysiological cause of Quincke's edema is increased permeability of capillary vessels due to vasoactive substances. Aside from anti-histaminergic agents and steroids, tranexamic acid, which reduces production of kinin, is specifically effective for this condition. Although there is a reported case of Quincke's edema, eventually diagnosed after development of postoperative upper airway obstruction, there have been no reports of planned perioperative management of this condition. We demonstrated that Quincke's edema could be managed without life-threatening airway compromise by employing adequate pharmacologic interventions and sensible determination of the timing of extubation.

  12. Synthetic smoke with acrolein but not HCl produces pulmonary edema

    SciTech Connect

    Hales, C.A.; Barkin, P.W.; Jung, W.; Trautman, E.; Lamborghini, D.; Herrig, N.; Burke, J.

    1988-03-01

    The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 +/- 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 +/- 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.

  13. Exercise-Induced Pulmonary Edema in a Triathlon.

    PubMed

    Yamanashi, Hirotomo; Koyamatsu, Jun; Nobuyoshi, Masaharu; Murase, Kunihiko; Maeda, Takahiro

    2015-01-01

    Introduction. Family physicians have more opportunities to attend athletic competitions as medical staff at first-aid centers because of the increasing popularity of endurance sports. Case. A 38-year-old man who participated in a triathlon race experienced difficulty in breathing after swimming and was moved to a first-aid center. His initial oxygen saturation was 82% and a thoracic computed tomography scan showed bilateral ground glass opacity in the peripheral lungs. His diagnosis was noncardiogenic pulmonary edema associated with exercise or swimming: exercise-induced pulmonary edema (EIPE) or swimming-induced pulmonary edema (SIPE). Treatment with furosemide and corticosteroid relieved his symptoms of pulmonary edema. Discussion. Noncardiogenic pulmonary edema associated with endurance sports is not common, but knowledge about EIPE/SIPE or neurogenic pulmonary edema associated with hyponatremia, which is called Ayus-Arieff syndrome, is crucial. Knowledge and caution for possible risk factors, such as exposure to cold water or overhydration, are essential for both medical staff and endurance athletes. Conclusion. To determine the presence of pulmonary edema associated with strenuous exercise, oxygen saturation should be used as a screening tool at a first-aid center. To avoid risks for EIPE/SIPE, knowledge about these diseases is essential for medical staff and for athletes who perform extreme exercise.

  14. Exercise-Induced Pulmonary Edema in a Triathlon

    PubMed Central

    Yamanashi, Hirotomo; Koyamatsu, Jun; Nobuyoshi, Masaharu; Murase, Kunihiko; Maeda, Takahiro

    2015-01-01

    Introduction. Family physicians have more opportunities to attend athletic competitions as medical staff at first-aid centers because of the increasing popularity of endurance sports. Case. A 38-year-old man who participated in a triathlon race experienced difficulty in breathing after swimming and was moved to a first-aid center. His initial oxygen saturation was 82% and a thoracic computed tomography scan showed bilateral ground glass opacity in the peripheral lungs. His diagnosis was noncardiogenic pulmonary edema associated with exercise or swimming: exercise-induced pulmonary edema (EIPE) or swimming-induced pulmonary edema (SIPE). Treatment with furosemide and corticosteroid relieved his symptoms of pulmonary edema. Discussion. Noncardiogenic pulmonary edema associated with endurance sports is not common, but knowledge about EIPE/SIPE or neurogenic pulmonary edema associated with hyponatremia, which is called Ayus-Arieff syndrome, is crucial. Knowledge and caution for possible risk factors, such as exposure to cold water or overhydration, are essential for both medical staff and endurance athletes. Conclusion. To determine the presence of pulmonary edema associated with strenuous exercise, oxygen saturation should be used as a screening tool at a first-aid center. To avoid risks for EIPE/SIPE, knowledge about these diseases is essential for medical staff and for athletes who perform extreme exercise. PMID:26229538

  15. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory

    PubMed Central

    Baget-Bernaldiz, Marc; Pareja-Rios, Alicia; Lopez-Galvez, Maribel; Navarro-Gil, Raul; Verges, Raquel

    2016-01-01

    Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug. PMID:27761468

  16. Glyphosate poisoning with acute pulmonary edema.

    PubMed

    Thakur, Darshana Sudip; Khot, Rajashree; Joshi, P P; Pandharipande, Madhuri; Nagpure, Keshav

    2014-01-01

    GlySH-surfactant herbicide (GlySH), one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The US Environmental Protection Agency (EPA) states that 'GlySH' is of relatively low oral and acute dermal toxicity. It does not have anticholinesterase effect and no organophosphate-like central nervous system (CNS) effects. The clinical features range from skin and throat irritation to hypotension and death. Severe GlySH-surfactant poisoning is manifested by gastroenteritis, respiratory disturbances, altered mental status, hypotension refractory to the treatment, renal failure, and shock.[1] GlySH intoxication has a case fatality rate 3.2-29.3%. Pulmonary toxicity and renal toxicity seem to be responsible for mortality. Metabolic acidosis, abnormal chest X-ray, arrhythmias, and elevated serum creatinine levels are useful prognostic factors for predicting GlySH mortality.[2] There is no antidote and the mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. We report a case of acute pulmonary edema, which is a rare but severe manifestation of oral GlySH poisoning, where patient survived with aggressive supportive therapy. PMID:25948977

  17. Temporal-spatial pathological changes in the brains of permissive and non-permissive hosts experimentally infected with Angiostrongylus cantonensis.

    PubMed

    Wang, Lian-Chen; Jung, Shih-Ming; Chen, Kuang-Yao; Wang, Tzu-Yi; Li, Chung-Han

    2015-10-01

    Human cerebral angiostrongyliasis becomes an emerging disease in many parts of the world. By postmortem examination, Angiostrongylus cantonensis have been reported to cause severe pathological changes in the central nervous system. The present study was designed to determine the temporal-spatial pathological changes through experimental infections and histopathological examination of permissive (SD rats) and non-permissive (ICR mice) hosts. After infecting SD rats with 25, 50, or 100 third-stage larvae (L3) and ICR mice with 25 L3, one animal from each group was sacrificed daily from day 1 to day 30 post-infection. Each rat brain was cut into six sections and mouse brain into five sections. These sections were stained with haematoxylin and eosin and examined microscopically. Eosinophilic meningitis was found to be the most commonly pathological change and occurred on day 17 post-infection in rats with 25 L3, day 9 in the 50- or 100-L3 groups, and day 12 in infected mice. Thickness of the meninges increased 9-24 folds in infected rats and 89 folds in an infected mouse on day 28. Encephalitis, congestion, perivascular cuffing, and haemorrhage were revealed in infected mice and rats with 100 L3. Fifth-stage larvae were frequently observed in the meninges but occasionally in the parenchyma. Significant correlations between meningitis and presence of larvae in the meninges were found in the three infected rat groups but not in the infected mice. The results indicate that the clinical course of A. cantonensis infection is not self-limited but becomes more severe with the intensity of infection.

  18. Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4.

    PubMed

    Chen, Zhihong; Jalabi, Walid; Shpargel, Karl B; Farabaugh, Kenneth T; Dutta, Ranjan; Yin, Xinghua; Kidd, Grahame J; Bergmann, Cornelia C; Stohlman, Stephen A; Trapp, Bruce D

    2012-08-22

    Intraperitoneal injection of the Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a rapid innate immune response. While this systemic inflammatory response can be destructive, tolerable low doses of LPS render the brain transiently resistant to subsequent injuries. However, the mechanism by which microglia respond to LPS stimulation and participate in subsequent neuroprotection has not been documented. In this study, we first established a novel LPS treatment paradigm where mice were injected intraperitoneally with 1.0 mg/kg LPS for four consecutive days to globally activate CNS microglia. By using a reciprocal bone marrow transplantation procedure between wild-type and Toll-like receptor 4 (TLR4) mutant mice, we demonstrated that the presence of LPS receptor (TLR4) is not required on hematogenous immune cells but is required on cells that are not replaced by bone marrow transplantation, such as vascular endothelia and microglia, to transduce microglial activation and neuroprotection. Furthermore, we showed that activated microglia physically ensheathe cortical projection neurons, which have reduced axosomatic inhibitory synapses from the neuronal perikarya. In line with previous reports that inhibitory synapse reduction protects neurons from degeneration and injury, we show here that neuronal cell death and lesion volumes are significantly reduced in LPS-treated animals following experimental brain injury. Together, our results suggest that activated microglia participate in neuroprotection and that this neuroprotection is likely achieved through reduction of inhibitory axosomatic synapses. The therapeutic significance of these findings rests not only in identifying neuroprotective functions of microglia, but also in establishing the CNS location of TLR4 activation. PMID:22915113

  19. Temporal-spatial pathological changes in the brains of permissive and non-permissive hosts experimentally infected with Angiostrongylus cantonensis.

    PubMed

    Wang, Lian-Chen; Jung, Shih-Ming; Chen, Kuang-Yao; Wang, Tzu-Yi; Li, Chung-Han

    2015-10-01

    Human cerebral angiostrongyliasis becomes an emerging disease in many parts of the world. By postmortem examination, Angiostrongylus cantonensis have been reported to cause severe pathological changes in the central nervous system. The present study was designed to determine the temporal-spatial pathological changes through experimental infections and histopathological examination of permissive (SD rats) and non-permissive (ICR mice) hosts. After infecting SD rats with 25, 50, or 100 third-stage larvae (L3) and ICR mice with 25 L3, one animal from each group was sacrificed daily from day 1 to day 30 post-infection. Each rat brain was cut into six sections and mouse brain into five sections. These sections were stained with haematoxylin and eosin and examined microscopically. Eosinophilic meningitis was found to be the most commonly pathological change and occurred on day 17 post-infection in rats with 25 L3, day 9 in the 50- or 100-L3 groups, and day 12 in infected mice. Thickness of the meninges increased 9-24 folds in infected rats and 89 folds in an infected mouse on day 28. Encephalitis, congestion, perivascular cuffing, and haemorrhage were revealed in infected mice and rats with 100 L3. Fifth-stage larvae were frequently observed in the meninges but occasionally in the parenchyma. Significant correlations between meningitis and presence of larvae in the meninges were found in the three infected rat groups but not in the infected mice. The results indicate that the clinical course of A. cantonensis infection is not self-limited but becomes more severe with the intensity of infection. PMID:26299243

  20. Brain Cooling With Ventilation of Cold Air Over Respiratory Tract in Newborn Piglets: An Experimental and Numerical Study

    PubMed Central

    Bakhsheshi, Mohammad Fazel; Moradi, Hadi Vafadar; Stewart, Errol E.; Keenliside, Lynn; Lee, Ting-Yim

    2015-01-01

    We investigate thermal effects of pulmonary cooling which was induced by cold air through an endotracheal tube via a ventilator on newborn piglets. A mathematical model was initially employed to compare the thermal impact of two different gas mixtures, O2-medical air (1:2) and O2-Xe (1:2), across the respiratory tract and within the brain. Following mathematical simulations, we examined the theoretical predictions with O2-medical air condition on nine anesthetized piglets which were randomized to two treatment groups: 1) control group (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$n = 4$ \\end{document}) and 2) pulmonary cooling group (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$n = 5$ \\end{document}). Numerical and experimental results using O2-medical air mixture show that brain temperature fell from 38.5 °C and 38.3 °C ± 0.3 °C to 35.7 °C ± 0.9 °C and 36.5 °C ± 0.6 °C during 3 h cooling which corresponded to a mean cooling rate of 0.9 °C/h ± 0.2 °C/h and 0.6 °C/h ± 0.1 °C/h, respectively. According to the numerical results, decreasing the metabolic rate and increasing air velocity are helpful to maximize the cooling effect. We demonstrated that pulmonary cooling by cooling of inhalation gases immediately before they enter the trachea can slowly reduce brain and core body temperature of newborn piglets. Numerical simulations show no significant differences between two different inhaled conditions, i.e., O2-medical air (1:2) and O2-Xe (1:2) with respect to cooling rate. PMID:27170888

  1. New Perspectives in Edema Control via Electrical Stimulation

    PubMed Central

    Mendel, Frank C.; Fish, Dale R.

    1993-01-01

    Clinicians commonly use electrical stimulation (ES) to control acute edema. But, except for anecdotal reports, there is little evidence to support that practice. We recently conducted a series of controlled, blinded studies on several nonhuman animal models to determine the efficacy of several forms of ES, but high-voltage pulsed current (HVPC) in particular, in controlling acute posttraumatic edema. We observed that acute posttraumatic edema is curbed by HVPC when certain protocols are used. Results of these studies suggest to us that wave form, polarity, treatment schedule, intensity and frequency of pulses all influence ES, and that clinical protocols need revision. PMID:16558209

  2. Blockage of the Upregulation of Voltage-Gated Sodium Channel Nav1.3 Improves Outcomes after Experimental Traumatic Brain Injury

    PubMed Central

    Huang, Xian-jian; Li, Wei-ping; Lin, Yong; Feng, Jun-feng; Jia, Feng

    2014-01-01

    Abstract Excessive active voltage-gated sodium channels are responsible for the cellular abnormalities associated with secondary brain injury following traumatic brain injury (TBI). We previously presented evidence that significant upregulation of Nav1.3 expression occurs in the rat cortex at 2 h and 12 h post-TBI and is correlated with TBI severity. In our current study, we tested the hypothesis that blocking upregulation of Nav1.3 expression in vivo in the acute stage post-TBI attenuates the secondary brain injury associated with TBI. We administered either antisense oligodeoxynucleotides (ODN) targeting Nav1.3 or artificial cerebrospinal fluid (aCSF) at 2 h, 4 h, 6 h, and 8 h following TBI. Control sham animals received aCSF administration at the same time points. At 12 h post-TBI, Nav1.3 messenger ribonucleic acid (mRNA) levels in bilateral hippocampi of the aCSF group were significantly elevated, compared with the sham and ODN groups (p<0.01). However, the Nav1.3 mRNA levels in the uninjured contralateral hippocampus of the ODN group were significantly lowered, compared with the sham group (p<0.01). Treatment with antisense ODN significantly decreased the number of degenerating neurons in the ipsilateral hippocampal CA3 and hilar region (p<0.01). A set of left-to-right ratio value analyzed by magnetic resonance imaging T2 image on one day, three days, and seven days post-TBI showed marked edema in the ipsilateral hemisphere of the aCSF group, compared with that of the ODN group (p<0.05). The Morris water maze memory retention test showed that both the aCSF and ODN groups took longer to find a hidden platform, compared with the sham group (p<0.01). However, latency in the aCSF group was significantly higher than in the ODN group (p<0.05). Our in vivo Nav1.3 inhibition studies suggest that therapeutic strategies to block upregulation of Nav1.3 expression in the brain may improve outcomes following TBI. PMID:24313291

  3. Scalp edema: don't forget sunburn in children.

    PubMed

    Shah, Binod; Yavuz, Süleyman Tolga; Tekşam, Ozlem

    2012-01-01

    Scalp edema is an uncommon and striking finding in children that may alarm both parents and physicians. The objectives of this case report were to raise awareness among pediatric emergency physicians of the unusual presentation of sunburn as scalp edema. We present the case of an eight-year-old boy with sunburn of the head, presenting with scalp and face edema. Pitting edema and erythema were dominant on the forehead. Shaving of the boy's head the day before the symptoms was the most striking issue, and the sunburn healed gradually without any complications. Healthcare professionals should be aware of this condition, and the diagnosis of sunburn must be kept in mind in otherwise healthy-looking patients with a unique history.

  4. Visual Priming Enhances the Effects of Non-Spatial Cognitive Rehabilitation Training on Spatial Learning after Experimental Traumatic Brain Injury

    PubMed Central

    Edwards, Clarice M.; Kumar, Krishma; Koesarie, Kathleen; Brough, Elizabeth; Ritter, Anne C.; Brayer, Samuel W.; Thiels, Edda; Skidmore, Elizabeth R.; Wagner, Amy K.

    2015-01-01

    Previous work demonstrates that spatial (explicit) and non-spatial (implicit) elements of place learning in the Morris water maze (MWM) task can be dissociated and examined in the context of experimental traumatic brain injury (TBI). Providing non-spatial cognitive training (CT) after injury can improve place learning compared to untrained controls. In the present study, we hypothesized that brief exposure to extra-maze cues, in conjunction with CT, may further improve MWM performance and extra-maze cue utilization compared to CT alone. Adult male Sprague-Dawley rats (n=66) received controlled cortical impact (CCI) injury or sham surgery. Beginning D8 post-surgery, CCI and Sham rats received 6 days to no training (NT) or cognitive training with/without brief, non-contextualized exposure to extra-maze cues (BE and CT, respectively). Acquisition (D14-D18), Visible Platform (VP; D19), Carryover (CO; D20-D26), and periodic probe trials were performed. Platform latencies, peripheral and target zone time allocation, and search strategies were assessed. CCI/BE rats had shorter acquisition trial latencies than CCI/NT (p<0.001) and tended to have shorter latencies than CCI/CT rats (p<0.10). Both BE and CT reduced peripheral zone swimming for CCI rats vs. CCI/NT. CCI/BE animals increased spatial swim strategies from D14 to D18 relative to CCI/CT and showed similar swim strategy selection to the Sham/NT group. These data suggest that visual priming improves initial place learning in the MWM. These results support the visual priming response as another clinically relevant experimental rehabilitation construct, to use when assessing injury and treatment effects of behavioral and pharmacological therapies on cognition after TBI. PMID:25665829

  5. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke

    PubMed Central

    Frankowski, Jan C.; DeMars, Kelly M.; Ahmad, Abdullah S.; Hawkins, Kimberly E.; Yang, Changjun; Leclerc, Jenna L.; Doré, Sylvain; Candelario-Jalil, Eduardo

    2015-01-01

    Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs). This study aimed to investigate the role of PGE2 EP1 receptor in neurovascular injury in stroke. We hypothesized that pharmacological blockade or genetic deletion of EP1 protects against BBB damage and hemorrhagic transformation by decreasing the levels and activity of MMP-3 and MMP-9. We found that post-ischemic treatment with the EP1 antagonist, SC-51089, or EP1 genetic deletion results in a significant reduction in BBB disruption and reduced hemorrhagic transformation in an experimental model of transient focal cerebral ischemia. These neurovascular protective effects of EP1 inactivation are associated with a significant reduction in MMP-9/-3, less peripheral neutrophil infiltration, and a preservation of tight junction proteins (ZO-1 and occludin) composing the BBB. Our study identifies the EP1 signaling pathway as an important link between neuroinflammation and MMP-mediated BBB breakdown in ischemic stroke. Targeting the EP1 receptor could represent a novel approach to diminish the devastating consequences of stroke-induced neurovascular damage. PMID:26648273

  6. Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis

    PubMed Central

    Flierl, Michael A; Stahel, Philip F; Rittirsch, Daniel; Huber-Lang, Markus; Niederbichler, Andreas D; Hoesel, L Marco; Touban, Basel M; Morgan, Steven J; Smith, Wade R; Ward, Peter A; Ipaktchi, Kyros

    2009-01-01

    Introduction Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. Methods Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. Results Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. Conclusions Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis. PMID:19196477

  7. Angioneurotic edema: a rare case of hypersensitivity to metoclopramide

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

    The case of a 30-year-old woman who had already experienced two incidents of angioneurotic edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found. PMID:24278059

  8. Local fluid shifts and edema in humans during simulated microgravity

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R.

    1991-01-01

    Local fluid shifts and edema in humans during simulated microgravity is studied. Recent results and significance and future plans on the following research topics are discussed: mechanisms of headward edema formation during head-down tilt; postural responses of head and foot microcirculations and their sensitivity to bed rest; and transcapillary fluid transport associated with lower body negative pressure (LBNP) with and without saline ingestion.

  9. Blood pressure, edema and proteinuria in pregnancy. 7. Edema-plus-proteinuria relationships.

    PubMed

    Sellmann, A H

    1976-01-01

    1. A total of 488 pregnancies had the combination of two-plus or more proteinuria and edema of the hands and face. Of these, 208 were white and 280 were black gravidas. In the white gravidas, 8 fetal and neonatal deaths occurred with a perinatal mortality of 38.5 per 1,000. There were 13 perinatal deaths in the black subgroup with a perinatal mortality rate of 46.4 per 1,000. The overall perinatal mortality rate was 43.0 per 1,000, which could be compared to the overall perinatal mortality rate of 32.8 per 1,000 for the segment of the study population without edema or proteinuria. This underscored the implication of increased hazard to fetal outcome of these clinical signs in combination. 2. The analysis of the matrix data showed scattered rates throughout gestation in white median-age nulliparas. Their black counterparts had comparable increased mortality rates. In the white multiparas of ages 20 to 34 years, the highest rates were found at relatively low blood pressure levels. The black median-age multiparas had rates associated with higher pressure readings, especially at or above 125/75. In teenage mulliparas with edema and proteinuria, perinatal mortality rates were similar for both subgroups and were found in somewhat lower blood pressures. 3. The incremental analysis was remarkable in that rates were scattered widely in the white subgroups, but tightly clustered in the black subgroups. The black median-age nulliparas had perinatal mortality concentrated about 115 to 134 mm. Hg systolic and 65 to 84 mm. Hg diastolic. The overall mortality rates of this subgroup were the highest of the subgroups studied. The black 20 to 34 year old multiparas had highest coassociated deaths in the 134-154 mm. Hg systolic levels throughout pregnancy. The clustering effect was most pronounced in black teenage nulliparas in both systolic and diastolic blood pressure groups at much lower levels. 4. The use of a critical cut-off blood pressure level of 125 mm. Hg systolic and 75 mm

  10. Protective actions of PJ34, a poly(ADP-ribose)polymerase inhibitor, on the blood-brain barrier after traumatic brain injury in mice.

    PubMed

    Tao, X; Chen, X; Hao, S; Hou, Z; Lu, T; Sun, M; Liu, B

    2015-04-16

    Poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays an important role in traumatic brain injury (TBI). The objective of this study was to investigate whether PARP activation participated in the blood-brain barrier (BBB) disruption and edema formation in a mouse model of controlled cortical impact (CCI). N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally at 5 min and 8 h after experimental CCI. After 6 h and 24 h of CCI, the permeability of the cortical BBB was determined after Evans Blue administration. The water content of the brain was also measured. Treatment with PJ34 markedly attenuated the permeability of the BBB and decreased the brain edema at 6 h and 24 h after CCI. Our data showed the up-regulation of nuclear factor-κB in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by PJ34. Moreover, PJ34 significantly lessened the activities of myeloperoxidase and the levels of matrix metalloproteinase-9, enhanced the levels of occludin, laminin, collagen IV and integrin β1, reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death. These data suggest the protective effects of PJ34 on BBB integrity and cell death during acute TBI. PMID:25668593

  11. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome

    PubMed Central

    Ellis, Demetrius

    2016-01-01

    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

  12. [Migraine with prolonged eyelid edema: a series of 10 cases].

    PubMed

    Toribio-Díaz, M E; Cuadrado-Pérez, M L; Peláez, A; Aledo-Serrano, Angel; Pedraza, M Isabel; Porta-Etessam, Jesús; Guerrero-Peral, Angel L

    2014-05-01

    Introduccion. La migraña puede cursar con sintomas autonomicos craneales propios de las cefaleas trigeminoautonomicas, lo que plantea dificultades en el diagnostico. Objetivo. Describir una serie de diez pacientes con edema palpebral asociado a la migraña. Pacientes y metodos. Diez pacientes atendidos en la consulta de cefaleas de tres hospitales (nueve mujeres, un varon; edad: 26-53 años), con edema palpebral recurrente asociado a la migraña. Resultados. Segun los criterios diagnosticos de la Clasificacion Internacional de las Cefaleas (ICHD-III, version beta), ocho pacientes presentaban migraña sin aura, una tenia migraña con aura y otra, migraña cronica. El edema palpebral aparecia durante las crisis de migraña mas intensas, y tenia mayor duracion que la cefalea. Se descartaron causas farmacologicas o sistemicas del edema en todos los casos. Otros sintomas autonomicos asociados fueron la inyeccion conjuntival (n = 3), el lagrimeo (n = 2) y la rinorrea (n = 1). Tanto el dolor como el edema asociado respondieron a los tratamientos sintomaticos y preventivos de la migraña. Conclusiones. El edema palpebral es un posible acompañante de la migraña. Aparece en algunos pacientes con los episodios de mayor intensidad, y responde al tratamiento sintomatico y preventivo de la migraña.

  13. Cerebral embolism: local CFBF and edema measured by CT scanning and Xe inhalation. [Baboons

    SciTech Connect

    Meyer, J.S.; Yamamoto, M.; Hayman, L.A.; Sakai, F.; Nakajima, S.; Armstrong, D.

    1980-01-01

    Serial CT scans were made in baboons after cerebral embolization during stable Xe inhalation for measuring local values for CBF and lambda (brain-blood partition or solubility coefficients), followed by iodine infusion for detecting blood-brain barrier (BBB) damage. Persistent zones of zero flow surrounded by reduced flow were measured predominantly in subcortical regions, which showed gross and microscopic evidence of infarction at necropsy. Overlying cortex was relatively spared. Reduced lambda values attributed to edema appeared within 3 to 5 minutes and progressed up to 60 minutes. Damage to BBB with visible transvascular seepage of iodine began to appear 1 to 1 1/2 hours after embolism. In chronic animals, lambda values were persistently reduced in areas showing histologic infarction. Contralateral hemispheric CBF increased for the first 15 minutes after embolism, followed by progressive reduction after 30 minutes (diaschisis).

  14. Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties - theoretical models and experimental approaches.

    PubMed

    Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; He, Xiang

    2013-08-01

    The quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for the understanding of normal human brain operation, as well as the pathophysiology of neurological disorders. It can also be of great importance for the evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and coworkers of the blood oxygenation level-dependent (BOLD) contrast opened up the possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require the development of theoretical models connecting the MRI signal to brain structure and function, and the design of experimental techniques allowing MR measurements to be made of the salient features of theoretical models. In this review, we discuss several such theoretical models and experimental methods for the quantification of brain hemodynamic and metabolic properties. The review's main focus is on methods for the evaluation of the oxygen extraction fraction (OEF) based on the measurement of the blood oxygenation level. A combination of the measurement of OEF and the cerebral blood flow (CBF) allows an evaluation to be made of the cerebral metabolic rate of oxygen consumption (CMRO2 ). We first consider in detail the magnetic properties of blood - magnetic susceptibility, MR relaxation and theoretical models of the intravascular contribution to the MR signal under different experimental conditions. We then describe a 'through-space' effect - the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the formation of the MR signal. Further, we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry and T2 -based quantification of OEF - utilize the intravascular MR signal. Another technique

  15. Effect of meta-chlorobenzhydryl urea (m-ClBHU) on benzodiazepine receptor system in rat brain during experimental alcoholism.

    PubMed

    Shushpanova, T V; Solonskii, A V; Novozheeva, T P; Udut, V V

    2014-04-01

    Chronic alcohol intake induces neuroadaptive changes in benzodiazepine receptors modulating GABAA receptors that promote alcohol addiction. Analysis of benzodiazepine receptors in the brain of Wistar rats differing by alcohol preference has demonstrated that affinity of [(3)H]flunitrazepam and [(3)H]Ro5-4864 binding with membrane fraction was reduced, while the density of specific binding sites in the brain cortex of heavy drinking and low drinking rats was increased in comparison with rats nonpreferring alcohol. Administration of anticonvulsant meta-chlorobenzhydryl urea increased affinity of benzodiazepine receptors in the brain cortex of heavy drinking rats, which improved GABA neurotransmission in the brain of these animals and reduced alcohol consumption.

  16. Thromboxane A2 exacerbates acute lung injury via promoting edema formation.

    PubMed

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca(2+) channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca(2+)- and Rho kinase-dependent signaling. PMID:27562142

  17. A Simple Luminescent Adenylate-Cyclase Functional Assay for Evaluation of Bacillus anthracis Edema Factor Activity

    PubMed Central

    Israeli, Ma’ayan; Rotem, Shahar; Elia, Uri; Bar-Haim, Erez; Cohen, Ofer; Chitlaru, Theodor

    2016-01-01

    Edema Factor (EF), the toxic sub-unit of the Bacillus anthracis Edema Toxin (ET) is a calmodulin-dependent adenylate cyclase whose detrimental activity in the infected host results in severe edema. EF is therefore a major virulence factor of B. anthracis. We describe a simple, rapid and reliable functional adenylate-cyclase assay based on inhibition of a luciferase-mediated luminescence reaction. The assay exploits the efficient adenylate cyclase-mediated depletion of adenosine tri-phosphate (ATP), and the strict dependence on ATP of the light-emitting luciferase-catalyzed luciferin-conversion to oxyluciferin, which can be easily visualized. The assay exhibits a robust EF-dose response decrease in luminescence, which may be specifically reverted by anti-EF antibodies. The application of the assay is exemplified in: (a) determining the presence of EF in B. anthracis cultures, or its absence in cultures of EF-defective strains; (b) evaluating the anti-EF humoral response in experimental animals infected/vaccinated with B. anthracis; and (c) rapid discrimination between EF producing and non-producing bacterial colonies. Furthermore, the assay may be amenable with high-throughput screening for EF inhibitory molecules. PMID:27548219

  18. Thromboxane A2 exacerbates acute lung injury via promoting edema formation

    PubMed Central

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca2+ channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca2+- and Rho kinase-dependent signaling. PMID:27562142

  19. Local brain hypothermia for neuroprotection in stroke treatment and aneurysm repair.

    PubMed

    Wagner, Kenneth R; Zuccarello, Mario

    2005-04-01

    Hypothermia is well known to provide neuroprotection following various brain insults in experimental animals. Two recently completed clinical trials of whole body hypothermia in out-of-hospital cardiac arrest patients' demonstrated significantly improved survival rates and neurologic outcomes. These results provide new excitement and encouragement for clinical application of hypothermia in cerebrovascular disease. However, the intensive care challenges and adverse events (e.g. prolonged times to target temperatures, shivering and sedation, pneumonia) during the management of hypothermia, dampen enthusiasm for widespread application especially in elderly stroke patients. In this manuscript, we review recent hypothermia trials for stroke. We describe an alternate approach, i.e. local brain cooling, and discuss this new technique with reference to the extensive literature on the marked efficacy of hypothermia. We describe a new technology, the ChillerPad(TM) and ChillerStrip(TM) Systems developed by Seacoast Technologies, Inc. (Portsmouth, NH, USA). The latter device has received FDA approval and will be employed in a trial of local hypothermia for cerebral aneurysm repair. We present our experimental findings that profound local hypothermia does not damage cortical neurons. We also report that local hypothermia protects the blood-brain barrier and markedly reduces vasogenic edema development in an experimental intracerebral hemorrhage model. Lastly, we review potential mechanisms through which hypothermia provides blood-brain barrier protection and reduces edema formation. Clearly, hypothermia has a bright future for cerebrovascular disease treatment if brain cooling can be delivered in a manner that does not compromise the patient or the neurosurgical and intensive care settings. Local brain cooling may be just that new treatment approach.

  20. Cerebral Lactate Metabolism After Traumatic Brain Injury.

    PubMed

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

    2016-04-01

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

  1. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  2. Fumonisin toxicosis in swine: an overview of porcine pulmonary edema and current perspectives.

    PubMed Central

    Haschek, W M; Gumprecht, L A; Smith, G; Tumbleson, M E; Constable, P D

    2001-01-01

    Fumonisin toxicosis in swine was named porcine pulmonary edema (PPE) after outbreaks of a fatal disease in pigs fed Fusarium verticillioides (F. moniliforme)-contaminated corn screenings from the 1989 corn crop in Iowa, Illinois, and Georgia. Pigs that died had severe pulmonary edema, which has not been identified in other species after exposure to fumonisins. The disease has been reproduced experimentally by feeding of naturally contaminated corn, F. verticillioides culture material, and by intravenous administration of fumonisin B1 (FB1). Hepatic lesions consisting of apoptosis, necrosis, and hepatocyte proliferation also are observed. As in other species, alterations in clinical pathology reflect hepatic injury as well as elevated serum cholesterol concentration. In chronic studies, esophageal plaques, hyperplastic hepatic nodules, and right ventricular hypertrophy were found. In pigs, as in other species, fumonisin alters sphingolipid biosynthesis, with the greatest alterations in sphingosine and sphinganine concentrations in kidney, liver, lung, and heart. Our recent studies on fumonisin toxicosis in pigs have focused on immune effects and the pathogenesis of pulmonary edema. The specific immune system was not affected; however, FB1 inhibited phagocytosis and sphingolipid biosynthesis in pulmonary macrophages. Fumonisin induced an accumulation of membranous material in pulmonary capillary endothelial cells; this change appears specific to this cell type and to swine. In short-term cardiovascular studies, fumonisin decreased left ventricular dP/dt(max) (an index of cardiac contractility), mean systemic arterial pressure, heart rate, and cardiac output, and increased mean pulmonary artery pressure and pulmonary artery wedge pressure. These changes are compatible with the inhibition of L-type calcium channels by increased sphingosine and/or sphinganine concentration. Therefore, fumonisin-induced pulmonary edema in swine appears to result from acute left

  3. Mechanics of the brain: perspectives, challenges, and opportunities.

    PubMed

    Goriely, Alain; Geers, Marc G D; Holzapfel, Gerhard A; Jayamohan, Jayaratnam; Jérusalem, Antoine; Sivaloganathan, Sivabal; Squier, Waney; van Dommelen, Johannes A W; Waters, Sarah; Kuhl, Ellen

    2015-10-01

    The human brain is the continuous subject of extensive investigation aimed at understanding its behavior and function. Despite a clear evidence that mechanical factors play an important role in regulating brain activity, current research efforts focus mainly on the biochemical or electrophysiological activity of the brain. Here, we show that classical mechanical concepts including deformations, stretch, strain, strain rate, pressure, and stress play a crucial role in modulating both brain form and brain function. This opinion piece synthesizes expertise in applied mathematics, solid and fluid mechanics, biomechanics, experimentation, material sciences, neuropathology, and neurosurgery to address today's open questions at the forefront of neuromechanics. We critically review the current literature and discuss challenges related to neurodevelopment, cerebral edema, lissencephaly, polymicrogyria, hydrocephaly, craniectomy, spinal cord injury, tumor growth, traumatic brain injury, and shaken baby syndrome. The multi-disciplinary analysis of these various phenomena and pathologies presents new opportunities and suggests that mechanical modeling is a central tool to bridge the scales by synthesizing information from the molecular via the cellular and tissue all the way to the organ level.

  4. A relatively brief exposure to environmental enrichment after experimental traumatic brain injury confers long-term cognitive benefits.

    PubMed

    Cheng, Jeffrey P; Shaw, Kaitlyn E; Monaco, Christina M; Hoffman, Ann N; Sozda, Christopher N; Olsen, Adam S; Kline, Anthony E

    2012-11-20

    It is well established that a relatively brief exposure to environmental enrichment (EE) enhances motor and cognitive performance after experimental traumatic brain injury (TBI), but it is not known whether the benefits can be sustained after EE is discontinued. To address this important rehabilitation-relevant concern, anesthetized rats received a controlled cortical impact (CCI) or sham injury, and for phase 1 of the experiment were randomly assigned to either 3 weeks of EE or standard (STD) housing. Neurobehavioral outcome was assessed by established motor and cognitive tests on postoperative days 1-5 and 14-18, respectively. Beam-balance and spatial learning were facilitated in the TBI + EE more than the TBI + STD group (p<0.0001). In phase 2 of the experiment, half of the rats in EE were transferred to STD conditions (TBI + EE + STD and sham + EE + STD), and neurobehavior was re-assessed once per month for 6 months. The TBI + EE and TBI + EE + STD groups performed markedly better in the water maze than the TBI + STD group (p<0.0001), and did not differ from one another (p=0.53). These data replicate those of several studies from our laboratory showing that EE enhances recovery after CCI injury, and extend those findings by demonstrating that the cognitive benefits are maintained for at least 6 months post-rehabilitation. The persistent benefits shown with this paradigm provide further support for EE as a pre-clinical model of rehabilitation that can be further explored, either alone or in combination with pharmacotherapies, for optimal neurorehabilitation after TBI.

  5. Acute hemorrhagic edema of infancy and common mimics.

    PubMed

    Homme, James L; Block, Jason M

    2016-05-01

    Acute hemorrhagic edema of infancy (AHEI) is a rare acute benign cutaneous leukocytoclastic vasculitis affecting children younger than 24 months of age. Its presentation can be confused with those of urticaria, erythema multiforme, Henoch-Schönlein purpura, idiopathic thrombocytopenia,meningococcemia, Kawasaki disease, and drug rash. We present 2 cases of acute hemorrhagic edema of infancy, discuss the characteristics of AHEI, and compare and contrast AHEI with similar dermatologic presentations. This review provides emergency physicians with the basic knowledge necessary to easily recognize AHEI as a distinct clinical entity. The patients were 19- and 23-month-old females who presented to the pediatric emergency department at St Mary's Hospital,Mayo Clinic in Rochester, Minnesota, with impressive purpuric rashes and edema of the hands and feet after preceding upper respiratory tract infections. Both children had benign courses with complete resolution of clinical findings. These 2 cases typify the presentation of AHEI.Acute hemorrhagic edema of infancy presents with characteristic purpuric lesions and extremity edema. The emergency physician's recognition of these presenting characteristics will help diagnose AHEI, avoid unnecessary procedures and tests, and aid in counseling the patient's parents.

  6. Photoacoustic diagnosis of edema in rat burned skin

    NASA Astrophysics Data System (ADS)

    Yoshida, Ken; Sato, Shunichi; Hatanaka, Kosuke; Saitoh, Daizoh; Ashida, Hiroshi; Sakamoto, Toshihisa; Obara, Minoru

    2010-02-01

    Diagnosis of edema, abnormal accumulation of water in tissue, is important for managing various traumatic injuries and diseases. However, there is no established method for real-time, noninvasive monitoring of edema. In severe extensive burn injuries, edema develops both topically and systemically due to the increased permeability of blood vessels. In this study, we examined photoacoustic (PA) monitoring of edema formed in rat burn models. Deep dermal burn with a 20% total body surface area was made in the dorsal skin of rats. Burn and its adjacent nonburn tissues were irradiated with 6-ns light pulses at 1430 nm, which is one of the absorption peak wavelengths of water in the near infrared. The PA signal amplitude increased until 12 - 24 hr postburn, and thereafter it gradually decreased to its initial level; the latter phase (after 24 hr postburn) coincided with a diuretic phase in the rats. There was a significant correlation between the PA signal amplitudes and water contents in the tissue measured by wet/dry weight method. These findings demonstrate the validity of PA measurement for real-time, noninvasive monitoring of edema.

  7. High altitude pulmonary edema. Epidemiologic observations in Peru.

    PubMed

    Hultgren, H N; Marticorena, E A

    1978-10-01

    The incidence of high altitude pulmonary edema was examined by a survey (via questionnaire) of residents living at 3,750 meters (12,303 feet) in the mining community of La Oroya, Peru. Ninety-seven subjects made a total of 1,157 ascents to high altitude after a stay at sea level of longer than 14 days. Sixty-four subjects experienced at least one episode of high-altitude pulmonary edema. The incidence was higher in subjects aged 13 to 20 years, where 17 percent (15) of 90 ascents resulted in episodes of high-altitude pulmonary edema, than in subjects 21 years or older (3 percent; 18/686 ascents). Young subjects (2 to 12 years old) had more severe episodes of high-altitude pulmonary edema (81 percent; 30/37 episodes) than adults (22 percent; 4/18 episodes). No episodes were observed in children under two years old. Five subjects under 21 years of age experienced recurrent episodes. Our estimated incidence of severe episodes of high altitude pulmonary edema per ascent in adults (0.6 percent; 4/686) is similar to that reported by other workers (incidence of 0.15 to 0.57 percent) in various parts of the world. PMID:699645

  8. Finger stiffness or edema as presenting symptoms of eosinophilic fasciitis.

    PubMed

    Suzuki, Shingo; Noda, Kazutaka; Ohira, Yoshiyuki; Shikino, Kiyoshi; Ikusaka, Masatomi

    2015-10-01

    To investigate the clinical features and finger symptoms of eosinophilic fasciitis (EF), we reviewed five patients with EF. The chief complaint was pain, edema and/or stiffness of the extremities. The distal extremities were affected in all patients, and there was also proximal involvement in one patient. One patient had asymmetrical symptoms. All four patients with upper limb involvement had limited range of motion of the wrist joints, and three of them complained of finger symptoms. Two of these three patients showed slight non-pitting edema of the hands, and the other one had subcutaneous induration of the forearm. All four patients with lower limb symptoms had limited range of motion of the ankle joints, and two showed edema or induration of the legs. Inflammatory changes in the joints were not detected in any of the patients. Two patients displayed neither objective induration nor edema, and two patients had muscle tenderness. In conclusion, finger symptoms of patients with EF might be caused by fasciitis of the forearms, which leads to dysfunction of the long finger flexors and extensors as well as slight edema of hands. Limited range of motion of wrist and/or ankle joints indicates sensitively distal muscle dysfunction caused by fasciitis.

  9. Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood-brain barrier integrity during experimental cerebral ischemia-reperfusion injury.

    PubMed

    Li, Haiying; Gao, Anju; Feng, Dongxia; Wang, Yang; Zhang, Li; Cui, Yonghua; Li, Bo; Wang, Zhong; Chen, Gang

    2014-10-01

    Brain microvascular endothelial cell (BMVEC) injury induced by ischemia-reperfusion (I/R) is the initial phase of blood-brain barrier (BBB) disruption, which results in a poor prognosis for ischemic stroke patients. Autophagy occurs in ischemic brain and has been shown to exhibit protective effects on endothelial cell against stress. However, the potential effects of BMVEC autophagy on BBB permeability during I/R and the mechanisms underlying these effects have yet to be elucidated. In the current study, we answered these questions by using chemical modulators of autophagy, including rapamycin and lithium carbonate acting, respectively, as mammalian target of rapamycin (mTOR)-dependent and mTOR-independent autophagy inducers and 3-methyladenine (3-MA) as an autophagy inhibitor. To mimic I/R injury, BMVECs were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), and a rat transient middle cerebral artery occlusion/reperfusion (MCAO/R) model was performed. All the drugs were given at 0.5 h before OGD/R or MCAO/R. First, enhancement of autophagy by rapamycin and lithium carbonate attenuated, whereas suppression of autophagy by 3-MA intensified BMVEC apoptosis and the high level of ROS induced by OGD/R. In addition, rapamycin and lithium carbonate pretreatments significantly reversed the decreased level of tight junction protein zonula occludens-1 (ZO-1) induced by OGD/R and promoted the distribution of ZO-1 on cell membranes. Finally, pretreatments with rapamycin and lithium carbonate reduced evans blue extravasation and brain water content in the ischemic hemisphere of the rat. In contrast, 3-MA pretreatment exerted opposite effects both in vitro and in vivo. These results may indicate a beneficial effect of BMVEC autophagy on BBB integrity during I/R injury. PMID:25070048

  10. Design and experimental evaluation of a 256-channel dual-frequency ultrasound phased-array system for transcranial blood-brain barrier opening and brain drug delivery.

    PubMed

    Liu, Hao-Li; Jan, Chen-Kai; Chu, Po-Chun; Hong, Jhong-Cing; Lee, Pei-Yun; Hsu, Jyh-Duen; Lin, Chung-Chih; Huang, Chiung-Ying; Chen, Pin-Yuan; Wei, Kuo-Chen

    2014-04-01

    Focused ultrasound (FUS) in the presence of microbubbles can bring about transcranial and local opening of the blood-brain barrier (BBB) for potential noninvasive delivery of drugs to the brain. A phased-array ultrasound system is essential for FUS-BBB opening to enable electronic steering and correction of the focal beam which is distorted by cranial bone. Here, we demonstrate our prototype design of a 256-channel ultrasound phased-array system for large-region transcranial BBB opening in the brains of large animals. One of the unique features of this system is the capability of generating concurrent dual-frequency ultrasound signals from the driving system for potential enhancement of BBB opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2 MHz) with controllable driving burst patterns. Precise output power can be controlled for individual channels via 8-bit duty-cycle control of transistor-transistor logic signals and the 8-bit microcontroller-controlled buck converter power supply output voltage. The prototype system was found to be in compliance with the electromagnetic compatibility standard. Moreover, large animal experiments confirmed the phase switching effectiveness of this system, and induction of either a precise spot or large region of BBB opening through fast focal-beam switching. We also demonstrated the capability of dual-frequency exposure to potentially enhance the BBB-opening effect. This study contributes to the design of ultrasound phased arrays for future clinical applications, and provides a new direction toward optimizing FUS brain drug delivery.

  11. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  12. Negative pressure pulmonary edema following choking on a cookie.

    PubMed

    Toukan, Yazeed; Gur, Michal; Bentur, Lea

    2016-07-01

    A 12-year-old boy developed severe acute respiratory distress during a school break requiring resuscitative measures. The episode started shortly after a short choking episode with a cookie. History, physical examination, laboratory results, chest X-ray, and clinical course supported the diagnosis of negative pressure pulmonary edema (NPPE). NPPE occurring outside a hospital setting, especially following a short episode of choking on a cookie, is rarely reported in children. Understanding the pathophysiological mechanisms contributing to pulmonary edema can help in distinguishing NPPE from other causes of fulminant respiratory distress, and especially from other causes of noncardiogenic pulmonary edema. Pediatr Pulmonol. 2016;51:E25-E27. © 2016 Wiley Periodicals, Inc.

  13. Kawasaki Disease with Retropharyngeal Edema following a Blackfly Bite

    PubMed Central

    Watanabe, Toru

    2014-01-01

    We describe a patient with Kawasaki disease (KD) and retropharyngeal edema following a blackfly bite. An 8-year-old boy was referred to our hospital because of a 3-day-history of fever and left neck swelling and redness after a blackfly bite. Computed tomography of the neck revealed left cervical lymph nodes swelling with edema, increased density of the adjacent subcutaneous tissue layer, and low density of the retropharyngeum. The patient was initially presumed to have cervical cellulitis, lymphadenitis, and retropharyngeal abscess. He was administered antibiotics intravenously, which did not improve his condition. The patient subsequently exhibited other signs of KD and was diagnosed with KD and retropharyngeal edema. Intravenous immunoglobulin therapy and oral flurbiprofen completely resolved the symptoms and signs. A blackfly bite sometimes incites a systemic reaction in humans due to a hypersensitive reaction to salivary secretions, which may have contributed to the development of KD in our patient. PMID:25349761

  14. Bone marrow edema syndrome in postpartal women: treatment with iloprost.

    PubMed

    Aigner, Nicholas; Meizer, Roland; Meraner, Dominik; Becker, Stephan; Meizer, Elizabeth; Landsiedl, Franz

    2009-04-01

    Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing. Relief from pain, restoration of functional capacity, and normalization of the MRI signal pattern were rapidly achieved, thus avoiding the need for surgical intervention. As the substance is contraindicated in pregnancy, therapy may begin only some days after parturition, with a short discontinuation in breastfeeding.

  15. Pulmonary edema associated with scuba diving : case reports and review.

    PubMed

    Slade, J B; Hattori, T; Ray, C S; Bove, A A; Cianci, P

    2001-11-01

    Acute pulmonary edema has been associated with cold-water immersion in swimmers and divers. We report on eight divers using a self-contained underwater breathing apparatus (scuba) who developed acute pulmonary edema manifested by dyspnea, hypoxemia, and characteristic chest radiographic findings. All cases occurred in cold water. All scuba divers were treated with complete resolution, and three have returned to diving without further episodes. Mechanisms that would contribute to a raised capillary transmural pressure or to a reduced blood-gas barrier function or integrity are discussed. Pulmonary edema in scuba divers is multifactorial, and constitutional factors may play a role. Physicians should be aware of this potential, likely underreported, problem in scuba divers.

  16. [Literature review: Diabetic macular edema. Repercussions and treatment].

    PubMed

    Carmona-Moxica, Luis Roberto; Hernández-Núñez, Fabiola

    2015-01-01

    In our country there is a report of prevalence of Diabetes Mellitus in the adult population of a 10%, occupying one of the first causes of morbidity-mortality, also visual and labor incapacity. Macular edema is the first cause of lost vision in the diabetic patient. There are classic methods to detect it, as the examination with biomicroscope, indirect ophthalmoscopy, fluorangiography (FAR), and the new and gold standard method for diagnostic and sequence examination, Ocular Coherence Tomography (OCT). With OCT had been possible the study of distinct types of macular edema, that could represent distinct clinical states, with specific treatments. The protocol of treatment of macular edema, continues changing. The traditional methods as metabolic control and fotocoagulation with Laser now have more options as intravitreal injection of triamcinolone, or antiangiogenic substances, even surgical treatment with vitrectomy. There are many prospective and randomized studies evaluating this methods, so until now is difficult to determine which treatment is the best.

  17. Prediction of visual acuity recovery in cystoid macular edema.

    PubMed

    McDonnell, P J; Ryan, S J; Walonker, A F; Miller-Scholte, A

    1992-05-01

    Three consecutive patients participated in a prospective evaluation of pseudophakic cystoid macular edema. The duration of the macular edema ranged from 6 to 8 months. On the initial visit, the best corrected acuity with spectacles was determined and a potential acuity meter reading was obtained; this test suggested potential for visual recovery in two of the three patients. Sub-tenon's injections of methylprednisolone acetate (20 mg) were administered along with topical 1% prednisolone acetate and 1% atropine. One month later, visual acuity was improved by more than 2 Snellen lines in all three of the patients. A visual acuity measurement with the potential acuity meter that is better than the best corrected acuity with spectacles may reflect the presence of intact, but dysfunctional photoreceptors that are capable of restoring visual acuity upon resolution of the edema.

  18. Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus.

    PubMed

    Todo, T; Rabkin, S D; Sundaresan, P; Wu, A; Meehan, K R; Herscowitz, H B; Martuza, R L

    1999-11-20

    Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells were used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response. Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated by the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.

  19. Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

    PubMed

    Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

    2014-04-01

    Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage.

  20. Treatment of Acute Low Pressure Pulmonary Edema in Dogs

    PubMed Central

    Prewitt, R. M.; McCarthy, J.; Wood, L. D. H.

    1981-01-01

    Severe pulmonary edema sometimes develops despite normal pulmonary capillary wedge pressure (Ppw). The equation describing net transvascular flux of lung liquid predicts decreased edema when hydrostatic pressure is reduced or when colloid osmotic pressure is increased in the pulmonary vessels. We tested these predictions in a model of pulmonary capillary leak produced in 35 dogs by intravenous oleic acid. 1 h later, the dogs were divided into five equal groups and treated for 4 h in different ways: (a) not treated, to serve as the control group (Ppw = 11.1 mm Hg); (b) given albumin to increase colloid osmotic pressure by 5 mm Hg (Ppw = 10.6 mm Hg); (c) ventilated with 10 cm H2O positive end-expiratory pressure (Peep) (transmural Ppw = 10.4 mm Hg); (d) phlebotomized to reduce Ppw to 6 mm Hg; (e) infused with nitroprusside, which also reduced Ppw to 6 mm Hg. Phlebotomy and nitroprusside reduced the edema in excised lungs by 50% (P< 0.001), but Peep and albumin did not affect the edema. Pulmonary shunt decreased on Peep and increased on nitroprusside, and lung compliance was not different among the treatment groups, demonstrating that these variables are poor indicators of changes in edema. Cardiac output decreased during the treatment period in all but the nitroprusside group, where Ppw decreased and cardiac output did not. We conclude that canine oleic acid pulmonary edema is reduced by small reductions in hydrostatic pressure, but not by increased colloid osmotic pressure, because the vascular permeability to liquid and protein is increased. These results suggest that low pressure pulmonary edema may be reduced by seeking the lowest Ppw consistent with adequate cardiac output enhanced by vasoactive agents like nitroprusside. Further, colloid infusions and Peep are not helpful in reducing edema, so they may be used in the lowest amount that provides adequate circulating volume and arterial O2 saturation on nontoxic inspired O2. Until these therapeutic principles

  1. Iris angiography in cystoid macular edema after cataract extraction.

    PubMed

    Kottow, M; Hendrickson, P

    1975-07-01

    Iris angiography was performed on eight patients (nine eyes), who had cystoid macular edema postcataract extraction. The fundus fluorescein angiographies showed typical star-shaped, multiloculated staining of the macular area. The iris angiographies demonstrated moderate to massive leakage of dye from the iris, and possibly leakage of ciliary body vessels into the anterior chamber, thus evidencing the until now suspected but undocumented fact that fluorescein leakage is not restricted to the fundus vessels. These data tend to support the idea that this type of macular edema is due to a vascular abnormality, and not to altered vitreous mechanics.

  2. Experimental evaluation of electrical conductivity imaging of anisotropic brain tissues using a combination of diffusion tensor imaging and magnetic resonance electrical impedance tomography

    NASA Astrophysics Data System (ADS)

    Sajib, Saurav Z. K.; Jeong, Woo Chul; Kyung, Eun Jung; Kim, Hyun Bum; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2016-06-01

    Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

  3. Apparent target size of rat brain benzodiazepine receptor, acetylcholinesterase, and pyruvate kinase is highly influenced by experimental conditions

    SciTech Connect

    Nielsen, M.; Braestrup, C.

    1988-08-25

    Radiation inactivation is a method to determine the apparent target size of molecules. In this report we examined whether radiation inactivation of various enzymes and brain receptors is influenced by the preparation of samples preceding irradiation. The apparent target sizes of endogenous acetylcholinesterase and pyruvate kinase from rat brain and from rabbit muscle and benzodiazepine receptor from rat brain were investigated in some detail. In addition the target sizes of alcohol dehydrogenase (from yeast and horse liver), beta-galactosidase (from Escherichia coli), lactate dehydrogenase (endogenous from rat brain), and 5-HT2 receptors, acetylcholine muscarine receptors, and (/sup 35/S) butyl bicyclophosphorothionate tertiary binding sites from rat brain were determined. The results show that apparent target sizes are highly influenced by the procedure applied for sample preparation before irradiation. The data indicate that irradiation of frozen whole tissue as opposed to lyophilized tissue or frozen tissue homogenates will estimate the smallest and most relevant functional target size of a receptor or an enzyme.

  4. Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels.

    PubMed

    Chen, Zhi-Jian; Broaddus, William C; Viswanathan, Raju R; Raghavan, Raghu; Gillies, George T

    2002-02-01

    We have used agarose gel to develop a robust model of the intraparenchymal brain tissues for the purpose of simulating positive-pressure infusion of therapeutic agents directly into the brain. In parallel with that effort, we have synthesized a mathematical description of the infusion process on the basis of a poroelastic theory for the swelling of the tissues under the influence of the infusate's penetration into the interstitial space. Infusion line pressure measurements and video microscopy determinations of infusate volume of distribution within the gel demonstrate a good match between theory and experiment over a wide range of flow rates (0.5-10.0 microliters/min) and have clinical relevance for the convection-enhanced delivery of drugs into the brain without hindrance by the blood-brain barrier. We have put the brain phantom gel and the infusion measurement system into routine use in determining performance characteristics of novel types of neurosurgical catheters. This approach simplifies the catheter design process and helps to avoid some of the costs of in vivo testing. It also will allow validation of the elementary aspects of treatment planning systems that predict infusion distribution volumes on the basis of theoretical descriptions such as those derived from the poroelastic model. PMID:12066887

  5. [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. PMID:26810405

  6. Protective effects of Ephedra sinica extract on blood-brain barrier integrity and neurological function correlate with complement C3 reduction after subarachnoid hemorrhage in rats.

    PubMed

    Zuo, Shilun; Li, Wenyan; Li, Qiang; Zhao, Hengli; Tang, Jun; Chen, Qianwei; Liu, Xin; Zhang, John H; Chen, Yujie; Feng, Hua

    2015-11-16

    Early brain injury, which is associated with brain cell death, blood-brain barrier disruption, brain edema, and other pathophysiological events, is thought to be the main target in the prevention of poor outcomes after subarachnoid hemorrhage (SAH). Emerging evidences indicates that complement system, especially complement C3 is detrimental to neurological outcomes of SAH patients. Recently, Ephedra sinica extract was extracted and purified, which exhibits ability to block the activity of the classical and alternative pathways of complement, and improve neurological outcomes after spinal cord injury and ischemic brain injury. However, it is still unclear whether Ephedra sinica extract could attenuate early brain injury after SAH. In the present study, a standard endovascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. Ephedra sinica extract (15mg/kg) was orally administrated daily and evaluated for effects on modified Garcia score, brain water content, Evans blue extravasation and fluorescence, cortex cell death by TUNEL staining, and the expressions of complement C3/C3b, activated C3, sonic hedgehog, osteopontin and matrix metalloproteinase-9 by western bolt and immunofluorescence staining. We founded that the Ephedra sinica extract alleviated the blood-brain barrier disruption and brain edema, eventually improved neurological functions after SAH in rats. These neuroprotective effects was associated with the inhibition of complement C3, possibly via upregulating sonic hedgehog and osteopontin signal, and reducing the expressions of matrix metalloproteinase-9. Taking together, these observations suggested complement C3 inhibition by the Ephedra sinica extract may be a protective factor against early brain injury after SAH. PMID:26518242

  7. Balanoposthitis and Penile Edema: Atypical Manifestations of Primary Syphilis.

    PubMed

    Rovira-López, Roger; García-Martínez, Pablo; Martín-Ezquerra, Gemma; Pujol, Ramon M; Aventín, Daniel López

    2015-09-01

    The typical finding in primary syphilis stage is a unique, painless chancre with indurated borders. We report a case of primary syphilis presenting as erosive and crusted balanoposthitis with an underlying chancre, penile edema, and bilateral inguinal lymphadenopathy in a heterosexual man.

  8. Pulmonary tissue volume in dogs during pulmonary edema.

    PubMed

    Peterson, B T; Petrini, M F; Hyde, R W; Schreiner, B F

    1978-05-01

    Pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) were measured in anesthetized dogs by analyzing end-expiratory concentrations of dimethyl ether (DME), acetylene (C2H2), and sulfur hexafluoride during a 30-s rebreathing maneuver. Vt was compared to the postmortem lung weight of control dogs and dogs with hemodynamic and nonhemodynamic (alloxan) pulmonary edema. Qc was compared to the cardiac output measured by dye dilution. A 100-ml increase in alveolar volume (VA) in the range of 1-2 liters resulted in a 9 +/- 3 ml increase in Vt. Vt measured at a VA of 1.9 liters measures 114 +/- 18% of the postmortem lung weight in 20 control dogs and in 6 dogs with moderate edema (lung weight < 250% of predicted). Vt measured only 53 +/- 14% of the lung weight in 11 dogs with more severe edema. DME and C2H2 gave the smae mean values of Vt, but the reproducibility of a series of 3-7 measurements was greater with DME (coefficient of variation was 5% with DME and 8% C2H2). Qc measured 96 +/ 15% of the cardiac output during the rebreathing maneuver, but the maneuver caused a 4-40% fall in the cardiac output. These data show that Vt determined by rebreathing DME is between 86% and 135% of the lung weight in dogs with pulmonary edema until the lung weight is greater than 250% of the predicted value.

  9. Hemoptysis and pulmonary edema in a scuba diver using diclofenac.

    PubMed

    Van Renterghem, Dirk; Depuydt, Charlotte

    2012-01-01

    Hemoptysis and pulmonary edema associated with nonsteroidal anti-inflammatory drug use is a known condition, but is probably underreported. The mechanisms of induction of pulmonary toxicity are still not well understood. We describe a case of hemoptysis and dyspnea in a scuba diver who was taking diclofenac.

  10. Flt1/VEGFR1 heterozygosity causes transient embryonic edema

    PubMed Central

    Otowa, Yasunori; Moriwaki, Kazumasa; Sano, Keigo; Shirakabe, Masanori; Yonemura, Shigenobu; Shibuya, Masabumi; Rossant, Janet; Suda, Toshio; Kakeji, Yoshihiro; Hirashima, Masanori

    2016-01-01

    Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1+/−) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1+/− capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1+/− embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1−/− mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1+/−; Aspp1−/− mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype. PMID:27251772

  11. MRI of brain disease in veterinary patients part 1: Basic principles and congenital brain disorders.

    PubMed

    Hecht, Silke; Adams, William H

    2010-01-01

    Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis of central nervous system disorders in veterinary patients and is quickly becoming the imaging modality of choice in evaluation of brain and intracranial disease. This article provides an overview of the basic principles of MRI, a description of sequences and their applications in brain imaging, and an approach to interpretation of brain MRI. A detailed discussion of imaging findings in general intracranial disorders including hydrocephalus, vasogenic edema, brain herniation, and seizure-associated changes, and the MR diagnosis of congenital brain disorders is provided. MRI evaluation of acquired brain disorders is described in a second companion article.

  12. A neurovascular blood-brain barrier in vitro model.

    PubMed

    Zehendner, Christoph M; White, Robin; Hedrich, Jana; Luhmann, Heiko J

    2014-01-01

    The cerebral microvasculature possesses certain cellular features that constitute the blood-brain barrier (BBB) (Abbott et al., Neurobiol Dis 37:13-25, 2010). This dynamic barrier separates the brain parenchyma from peripheral blood flow and is of tremendous clinical importance: for example, BBB breakdown as in stroke is associated with the development of brain edema (Rosenberg and Yang, Neurosurg Focus 22:E4, 2007), inflammation (Kuhlmann et al., Neurosci Lett 449:168-172, 2009; Coisne and Engelhardt, Antioxid Redox Signal 15:1285-1303, 2011), and increased mortality. In vivo, the BBB consists of brain endothelial cells (BEC) that are embedded within a precisely regulated environment containing astrocytes, pericytes, smooth muscle cells, and glial cells. These cells experience modulation by various pathways of intercellular communication and by pathophysiological processes, e.g., through neurovascular coupling (Attwell et al., Nature 468:232-243, 2010), cortical spreading depression (Gursoy-Ozdemir et al., J Clin Invest 113:1447-1455, 2004), or formation of oxidative stress (Yemisci et al., Nat Med 15:1031-1037, 2009). Hence, this interdependent assembly of cells is referred to as the neurovascular unit (NVU) (Zlokovic, Nat Med 16:1370-1371, 2010; Zlokovic, Neuron 57:178-201, 2008). Experimental approaches to investigate the BBB in vitro are highly desirable to study the cerebral endothelium in health and disease. However, due to the complex interactions taking place within the NVU in vivo, it is difficult to mimic this interplay in vitro.Here, we describe a murine blood-brain barrier coculture model consisting of cortical organotypic slice cultures and brain endothelial cells that includes most of the cellular components of the NVU including neurons, astrocytes, and brain endothelial cells. This model allows the experimental analysis of several crucial BBB parameters such as transendothelial electrical resistance or tight junction protein localization by

  13. Inflammatory mediators and modulation of blood-brain barrier permeability.

    PubMed

    Abbott, N J

    2000-04-01

    1. Unlike some interfaces between the blood and the nervous system (e.g., nerve perineurium), the brain endothelium forming the blood-brain barrier can be modulated by a range of inflammatory mediators. The mechanisms underlying this modulation are reviewed, and the implications for therapy of the brain discussed. 2. Methods for measuring blood-brain barrier permeability in situ include the use of radiolabeled tracers in parenchymal vessels and measurements of transendothelial resistance and rate of loss of fluorescent dye in single pial microvessels. In vitro studies on culture models provide details of the signal transduction mechanisms involved. 3. Routes for penetration of polar solutes across the brain endothelium include the paracellular tight junctional pathway (usually very tight) and vesicular mechanisms. Inflammatory mediators have been reported to influence both pathways, but the clearest evidence is for modulation of tight junctions. 4. In addition to the brain endothelium, cell types involved in inflammatory reactions include several closely associated cells including pericytes, astrocytes, smooth muscle, microglia, mast cells, and neurons. In situ it is often difficult to identify the site of action of a vasoactive agent. In vitro models of brain endothelium are experimentally simpler but may also lack important features generated in situ by cell:cell interaction (e.g. induction, signaling). 5. Many inflammatory agents increase both endothelial permeability and vessel diameter, together contributing to significant leak across the blood-brain barrier and cerebral edema. This review concentrates on changes in endothelial permeability by focusing on studies in which changes in vessel diameter are minimized. 6. Bradykinin (Bk) increases blood-brain barrier permeability by acting on B2 receptors. The downstream events reported include elevation of [Ca2+]i, activation of phospholipase A2, release of arachidonic acid, and production of free radicals, with

  14. Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice.

    PubMed

    Hasan, M; Seo, J-E; Rahaman, K A; Kang, M-J; Jung, B-H; Kwon, O-S

    2016-04-01

    The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high-performance liquid chromatography. The plasma and tissue NADPH oxidase and matrix metalloproteinases (MMP)-9 activities were analyzed by fluorescence spectrophotometry. The cumulative disease index and disease peaks were significantly higher in HFD-EAE compared with those in ND-EAE. Significantly higher 5-HT levels and lower 5-HT turnovers 5-hydroxyindole acetic acid ((5-HIAA)/5-HT) were found in the brains of HFD-EAE mice compared with those found in the HFD-CON and ND-EAE mice brains. Moreover, increased DA levels were observed in the caudate nucleus of the HFD-EAE mice compared with the control and ND-EAE mice. The NADPH oxidase and MMP-9 activities in the plasma and tissues were significantly higher in both the ND-EAE and HFD-EAE groups than in their respective controls. The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice. PMID:26820599

  15. Effects of DDE and PCB (Aroclor 1260) on experimentally poisoned little brown bats (Myotis lucifugus): Lethal brain concentrations

    USGS Publications Warehouse

    Clark, D.R.; Stafford, C.J.

    1981-01-01

    Adult female little brown bats (Myotis lucifugus) were collected in a church attic in North East, Cecil County, Md. Mealworms (Tenebrio molitor) containing organochlorine pollutants were fed to the bats as follows: 5 bats were dosed at 480 ppm DDE, 12 at 150 ppm DDE, 5 at 1000 ppm polychlorinated biphenyl (PCB; Aroclor 1260), and 12 at 15 ppm PCB. Seven other bats were fed untreated mealworms. The objective was to elevate brain levels of DDE and PCB to lethality and measure these concentrations. During 40 d of dosage, one DDE-dosed bat and two PCB-dosed bats died after exhibiting the prolonged tremor that characterizes organochlorine poisoning. After dosage, surviving bats were starved to elevate brain levels of toxicants, and three additional DDE-dosed bats had tremors before dying. The mean brain concentration of DDE diagnostic of death was estimated as 603 ppm, range 540-670 ppm. This mean is 16-18% higher than means for Mexican free-tailed bats (Tadarida brasiliensis) and common grackles (Quiscalus quiscula), and may indicate less sensitivity. Lethal brain concentrations of Aroclor 1260 were 1300 and 1500 ppm. Such values appear to be higher than values (Aroclor 1254) for brown-headed cowbirds (Molothrus ater). During starvation, DDE-dosed bats lost weight about 24% faster than controls. If smaller amounts of stored DDE cause increases in metabolic rates of nonfeeding bats, as during hibernation or migration, the result could be premature energy depletion and increased mortality.

  16. Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia

    PubMed Central

    Selb, Juliette; Boas, David A.; Chan, Suk-Tak; Evans, Karleyton C.; Buckley, Erin M.; Carp, Stefan A.

    2014-01-01

    Abstract. Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are two diffuse optical technologies for brain imaging that are sensitive to changes in hemoglobin concentrations and blood flow, respectively. Measurements for both modalities are acquired on the scalp, and therefore hemodynamic processes in the extracerebral vasculature confound the interpretation of cortical hemodynamic signals. The sensitivity of NIRS to the brain versus the extracerebral tissue and the contrast-to-noise ratio (CNR) of NIRS to cerebral hemodynamic responses have been well characterized, but the same has not been evaluated for DCS. This is important to assess in order to understand their relative capabilities in measuring cerebral physiological changes. We present Monte Carlo simulations on a head model that demonstrate that the relative brain-to-scalp sensitivity is about three times higher for DCS (0.3 at 3 cm) than for NIRS (0.1 at 3 cm). However, because DCS has higher levels of noise due to photon-counting detection, the CNR is similar for both modalities in response to a physiologically realistic simulation of brain activation. Even so, we also observed higher CNR of the hemodynamic response during graded hypercapnia in adult subjects with DCS than with NIRS. PMID:25453036

  17. Embryonic stem cell transplantation after experimental traumatic brain injury dramatically improves neurological outcome, but may cause tumors.

    PubMed

    Riess, Peter; Molcanyi, Marek; Bentz, Kristine; Maegele, Mark; Simanski, Christian; Carlitscheck, Christoph; Schneider, Annette; Hescheler, Jürgen; Bouillon, Bertil; Schäfer, Ute; Neugebauer, Edmund

    2007-01-01

    Transplantation of embryonic stem (ES) cells may provide cures for the damaged nervous system. Pre-differentiated ES or neuronal precursor cells have been investigated in various animal models of neurodegenerative diseases including traumatic brain injury (TBI). To our knowledge, no study has yet examined the effects of undifferentiated, murine ES cells on functional recovery and tumorigenity following implantation into injured rat brains. We evaluated the effect of transplantation of undifferentiated, murine embryonic cells on the recovery of motor function following lateral fluid percussion brain injury in Sprague-Dawley rats. At 3 days post-injury, animals received stereotactic injections of either embryonic stem cell suspension or injections of phosphate buffered saline without cells (control) into the injured cortex. Neurological motor function assessments were performed before injury, 72 h, 1, 3, and 6 weeks after transplantation using a Rotatrod and a Composite Neuroscore test. During this time period brain injured animals receiving ES cell transplantation showed a significant improvement in the Rotarod Test and in the Composite Neuroscore Test as compared to phosphate buffered saline (PBS)-treated animals. At 1 week post-transplantation, ES cells were detectable in 100% of transplanted animals. At 7 weeks following transplantation, EScells were detectable in only one animal. Two of 10 xenotransplanted animals revealed tumor formation over the observation period. These findings provide evidence for therapeutic potency of embryonic stem cell transplantation after TBI in rat, but also raise serious safety concerns about the use of such cells in human.

  18. Using Drawings of the Brain Cell to Exhibit Expertise in Neuroscience: Exploring the Boundaries of Experimental Culture

    ERIC Educational Resources Information Center

    Hay, David B.; Williams, Darren; Stahl, Daniel; Wingate, Richard J.

    2013-01-01

    This paper explores the research perspective of neuroscience by documenting the brain cell (neuron) drawings of undergraduates, trainee scientists, and leading neuroscience researchers in a single research-intensive university. Qualitative analysis, drawing-sorting exercises, and hierarchical cluster analysis are used to answer two related…

  19. Experimental in-vivo study of laser-tissue interaction on the brain: influence of gaseous environment

    NASA Astrophysics Data System (ADS)

    Chavantes, Maria C.; Zamorano, Lucia J.; Vinas, Federico; Dujovny, Manuel; Dragovic, Ljubisa

    1990-06-01

    The present study attempted to assess the in vivo effects of Nd-YAG laser irradiation in different gaseous environments on liver and brain. Such an investigation is critical for determining the extent of injury under such conditions for improving further clinical applications. We intended to define the influence on laser-tissue interaction of Room Air, 30% Oxygen, Helium, and Nitrogen. The anesthetized rats were placed in a special chamber and kept breathtng via a tracheostomy tube to the outside, and craniotomy or laparotomy was performed. Nd-YAG laser fiber was directed with a fixed distance at the exposed brain/liver. The staining drug for brain study was 2,3,5 triphenyltetrazolium chloride, which was injected into the aorta before sacrificing the animals. The 44 rats studied were divided into: liver and brain groups. The resulting lesions were photographed macroscopically. In the liver group, statistical analysis showed that laser-liver tissue interaction in helium and nitrogen created a well defined and less hemorrhagic lesions. Macroscopically, in the brain group, we found that the target zones were well delineated with Nitrogen concentration. Moreover, we observed smaller lesions and more sharply defined areas with Helium concentration. In Room Air and Oxygen concentrations, more carbonized and bloodish lesions were found. Laser-tissue interaction in Helium and Nitrogen environments produces more sharply defined lesions with less involvement of the sorrounding tissue, less hemorrhagic lesions to the target, and reduce smoke production. This effect may be of benefit in clinical application of Nd YAG laser, where a more specific target-laser interaction could be achieved avoiding undesired complications due to penetration on the surrounding healthy tissue.

  20. Proliferative events experimentally induced by transient cold shock in the brain of adult terrestrial heterothermic vertebrates: preliminary analysis of PCNA expression in Triturus carnifex.

    PubMed

    Chimenti, Claudio; Margotta, Vito

    2013-01-01

    Experimental procedures used to investigate the persistence, location and abundance of scattered ("matrix cells") and/or clustered ("matrix areas") stem cells in the brain, responsible for proliferation in adult terrestrial heterothermic vertebrates have included an induced transient drop in body temperature in specimens subsequently deprived of encephalic areas. In a set of coordinated investigations focused on the influence of an exposure to a drastic thermally environment on these activities, we gave priority to Triturus carnifex, since there is a much larger amount of detailed, unequivocal experimental evidence available for this species than for other vertebrates of the same evolutionary level. In the present study, cold-shocked newts were examined after a stay at external temperature (the most suitable one based on previous experience) to allow the maximal expression of cerebral proliferation. In a qualitative evaluation, the brain of experimental specimens compared with that of normal individuals seemed not to show, contrary to expectations, more pronounced cell proliferation as assessed by Proliferating Cell Nuclear Antigen immunolabelling of neural-like cells in the S phase of cell cycle. This discrepancy with previous reports from other authors may depend on having used cold stress alone, while other traumatic stimuli (operatory shock, encephalic injury) administered by the previous authors might have induced a greater number of cells to move from a stand-by condition to proliferation, allowing for reparative and/or regenerative phenomena.

  1. Curcumin reduces brain-infiltrating T lymphocytes after intracerebral hemorrhage in mice.

    PubMed

    Liu, Wei; Yuan, Jichao; Zhu, Haitao; Zhang, Xuan; Li, Lan; Liao, Xiaojun; Wen, Zexian; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

    2016-05-01

    T lymphocytes contribute to inflammation, thereby exacerbating neuronal injury after cerebral ischemia. An increasing amount of evidence indicates that inflammation is a key contributor to intracerebral hemorrhage (ICH)-induced secondary brain injury. Curcumin, a low-molecular-weight curry spice that is derived from the Curcuma longa plant, suppresses T lymphocyte proliferation and migration. Based on these findings, we investigated whether treatment with curcumin would reduce the number of cerebral T lymphocytes in mice with experimentally induced ICH. We found that a large number of T lymphocytes infiltrated the brain at 3days post-ICH. Curcumin significantly improved neurological scores and reduced brain edema in mice with ICH, consistent with a role in reducing neuroinflammation and neurovascular injury. Using flow cytometry, we observed significantly fewer T lymphocytes in brain samples obtained from the curcumin-treated group than in samples obtained from the vehicle-treated group. Moreover, Western blot analysis and immunostaining indicated that treatment with curcumin significantly reduced the expression of a vascular cell adhesion molecule-1 (VCAM-1), interferon-γ (INF-γ) and interleukin-17 (IL-17) in the mouse brain at 72h post-ICH. Our results suggest that administering curcumin may alleviate cerebral inflammation resulting from ICH, at least in part by reducing the infiltration of T lymphocytes into the brain. Therefore, preventing T lymphocytes from infiltrating the brain may become a new strategy for treating clinical ICH. PMID:27026486

  2. Physiological abnormalities in experimental allergic encephalomyelitis (EAE): II. Correlation between clinical signs and vestibular hyperreactivity and other signs of brain-stem dysfunction in rats with EAE.

    PubMed

    Brinkman, C J; Huygen, P L

    1984-09-01

    12 Lewis rats were inoculated with a guinea pig spinal cord tissue preparation. They developed experimental allergic encephalomyelitis (EAE) after 12-14 days manifested by weight loss, tail flaccidity, ataxia, hind limb paresis or paralysis and urinary incontinence. Concomitantly with EAE, all animals developed vestibular hyperreactivity (VH) of canal and otolith reflexes. Other signs of brain-stem dysfunction were also observed: abducens paralysis, facial weakness, tachypnoe and mydriasis with defective pupillary light reflex. The vestibular and other abnormalities subsided with some delay after recovery from clinical EAE, whilst histological abnormalities were still present in the CNS.

  3. Cool-Water Immersion and High-Voltage Electric Stimulation Curb Edema Formation in Rats.

    PubMed

    Dolan, Michael G.; Mychaskiw, Anna M.; Mendel, Frank C.

    2003-09-01

    OBJECTIVE: Although cryotherapy and high-voltage electric stimulation, both alone and in combination, are commonly applied to curb acute edema, little evidence from randomized controlled studies supports these procedures. Our purpose was to examine the effects of cool-water immersion (CWI) at 12.8 degrees C (55 degrees F), cathodal high-voltage pulsed current (CHVPC) at 120 pulses per second and 90% of visible motor threshold, and the combination of CWI and CHVPC (CWI + CHVPC) on edema formation after impact injury to the hind limbs of rats. DESIGN AND SETTING: Both feet of 34 rats were traumatized after hind-limb volumes were determined. Animals were randomly assigned to 1 of 3 groups: CWI (n = 10), CHVPC (n = 10), or CWI + CHVPC (n = 14). One randomly selected hind limb of each rat was exposed to four 30-minute treatments, interspersed with four 30-minute rest periods beginning immediately after posttraumatic limb volumes were determined. Contralateral limbs served as controls. Limbs remained dependent during all treatments, rest periods, and volumetric measurements. SUBJECTS: We used 34 anesthetized Zucker Lean rats in this study. MEASUREMENTS: We measured limb volumes immediately before and after trauma and after each of 4 treatment and rest periods. RESULTS: Volumes of treated limbs of all 3 experimental groups were smaller (P <.05) than those of untreated limbs. No treatment was more effective than another. CONCLUSIONS: Cool-water immersion, cathodal high-voltage electric stimulation, and simultaneous application of these treatments were effective in curbing edema after blunt injury. Combining CWI and CHVPC was not more effective than either CWI or CHVPC alone.

  4. 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. PMID:27161367

  5. Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence.

    PubMed

    Rimes, Ridson Rosa; de Souza Moura, Antonio Marcos; Lamego, Murilo Khede; de Sá Filho, Alberto Souza; Manochio, João; Paes, Flávia; Carta, Mauro Giovanni; Mura, Gioia; Wegner, Mirko; Budde, Henning; Ferreira Rocha, Nuno Barbosa; Rocha, Joana; Tavares, João Manuel R S; Arias-Carrión, Oscar; Nardi, Antonio Egidio; Yuan, Ti-Fei; Machado, Sergio

    2015-01-01

    Exercise promotes several health benefits, such as cardiovascular, musculoskeletal and cardiorespiratory improvements. It is believed that the practice of exercise in individuals with psychiatric disorders, e.g. schizophrenia, can cause significant changes. Schizophrenic patients have problematic lifestyle habits compared with general population; this may cause a high mortality rate, mainly caused by cardiovascular and metabolic diseases. Thus, the aim of this study is to investigate changes in physical and mental health, cognitive and brain functioning due to the practice of exercise in patients with schizophrenia. Although still little is known about the benefits of exercise on mental health, cognitive and brain functioning of schizophrenic patients, exercise training has been shown to be a beneficial intervention in the control and reduction of disease severity. Type of training, form of execution, duration and intensity need to be better studied as the effects on physical and mental health, cognition and brain activity depend exclusively of interconnected factors, such as the combination of exercise and medication. However, one should understand that exercise is not only an effective nondrug alternative, but also acts as a supporting linking up interventions to promote improvements in process performance optimization. In general, the positive effects on mental health, cognition and brain activity as a result of an exercise program are quite evident. Few studies have been published correlating effects of exercise in patients with schizophrenia, but there is increasing evidence that positive and negative symptoms can be improved. Therefore, it is important that further studies be undertaken to expand the knowledge of physical exercise on mental health in people with schizophrenia, as well as its dose-response and the most effective type of exercise. PMID:26556069

  6. Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence.

    PubMed

    Rimes, Ridson Rosa; de Souza Moura, Antonio Marcos; Lamego, Murilo Khede; de Sá Filho, Alberto Souza; Manochio, João; Paes, Flávia; Carta, Mauro Giovanni; Mura, Gioia; Wegner, Mirko; Budde, Henning; Ferreira Rocha, Nuno Barbosa; Rocha, Joana; Tavares, João Manuel R S; Arias-Carrión, Oscar; Nardi, Antonio Egidio; Yuan, Ti-Fei; Machado, Sergio

    2015-01-01

    Exercise promotes several health benefits, such as cardiovascular, musculoskeletal and cardiorespiratory improvements. It is believed that the practice of exercise in individuals with psychiatric disorders, e.g. schizophrenia, can cause significant changes. Schizophrenic patients have problematic lifestyle habits compared with general population; this may cause a high mortality rate, mainly caused by cardiovascular and metabolic diseases. Thus, the aim of this study is to investigate changes in physical and mental health, cognitive and brain functioning due to the practice of exercise in patients with schizophrenia. Although still little is known about the benefits of exercise on mental health, cognitive and brain functioning of schizophrenic patients, exercise training has been shown to be a beneficial intervention in the control and reduction of disease severity. Type of training, form of execution, duration and intensity need to be better studied as the effects on physical and mental health, cognition and brain activity depend exclusively of interconnected factors, such as the combination of exercise and medication. However, one should understand that exercise is not only an effective nondrug alternative, but also acts as a supporting linking up interventions to promote improvements in process performance optimization. In general, the positive effects on mental health, cognition and brain activity as a result of an exercise program are quite evident. Few studies have been published correlating effects of exercise in patients with schizophrenia, but there is increasing evidence that positive and negative symptoms can be improved. Therefore, it is important that further studies be undertaken to expand the knowledge of physical exercise on mental health in people with schizophrenia, as well as its dose-response and the most effective type of exercise.

  7. An Experimental Study of the Potential Biological Effects Associated with 2-D Shear Wave Elastography on the Neonatal Brain.

    PubMed

    Li, Changtian; Zhang, Changsheng; Li, Junlai; Cao, Xiaolin; Song, Danfei

    2016-07-01

    2-D Shear wave elastography (SWE) imaging is widely used in clinical practice, and some researchers have applied this technique in the evaluation of neonatal brains. However, the immediate and long-term impacts of dynamic radiation force exposure on the neonatal central nervous system remain unknown. In this study, we exposed neonatal mice to 2-D SWE scanning for 10 min, 20 min and 30 min under diagnostic mode (mechanical index [MI]: 1.3; thermal index [TI]: 0.5), respectively. For the control group, the neonatal mice were sham irradiated for 30 min with the machine powered off. Their brains were collected and analyzed using histologic staining and western blot analysis at 24 h and 3 mo after the 2-D SWE scanning. The Morris water maze (MWM) test was used to assess learning and memory function of the mice at 3 mo of age. The results indicated that using 2-D SWE in evaluating brains of neonatal mice does not cause detectable histologic changes, nor does it have long-term effects on their learning and memory abilities. However, the PI3 K/AKT/mTOR pathway was disturbed when the 2-D SWE scanning lasted for more than 30 min, and the expression of p-PKCa was suppressed by 10 min or more in 2-D SWE scanning. Although these injuries may be self-repaired as the mice grow, more attention should be paid to the scanning duration when applying 2-D-SWE elastography in the assessment of neonatal brains.

  8. Feasibility and Utility of Telephone-Based Psychological Support for People with Brain Tumor: A Single-Case Experimental Study

    PubMed Central

    Jones, Stephanie; Ownsworth, Tamara; Shum, David H. K.

    2015-01-01

    Rates of psychological distress are high following diagnosis and treatment of brain tumor. There can be multiple barriers to accessing psychological support, including physical and cognitive impairments and geographical limitations. Tele-based support could provide an effective and more flexible option for delivering psychological interventions. The present study aimed to investigate the feasibility and utility of a telephone-based psychotherapy intervention for people with brain tumor. A single-case multiple-baseline design was employed with a 4–7-week baseline phase, 10-week treatment phase, and 5-week maintenance phase including a booster session. Four participants with a benign or malignant brain tumor (three males and one female; aged 34–49 years), received 10 sessions of tele-based therapy and a booster session at 4 weeks post-treatment. Levels of depression, anxiety, and illness cognitions were monitored on a weekly basis throughout each phase whilst measures of quality of life, stress, and self-concept were administered at the start and end of each phase. Weekly measures were analyzed using a combination of both visual analysis and Tau-U statistics. Of the four participants, two of them demonstrated significant gains in mental health (depression and/or anxiety) and a significant decrease in their levels of helplessness (p < 0.05). The other two participants did not show gains in mental health or change in illness cognitions. All participants reported improvement in quality of life post-treatment. The results of the study provide preliminary support concerning the feasibility and utility of tele-based therapy for some people with brain tumor. Further research examining factors influencing the outcomes of tele-based psychological support is needed. PMID:25859430

  9. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses

    PubMed Central

    Ilievski, Vladimir; Kinchen, Jason M; Prabhu, Ramya; Rim, Fadi; Leoni, Lara; Unterman, Terry G.; Watanabe, Keiko

    2016-01-01

    Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the

  10. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    PubMed Central

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

  11. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... anasarca or generalized edema. 311.8 Section 311.8 Animals and Animal Products FOOD SAFETY AND INSPECTION... ADULTERATED CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a... characterized by an extensive or well-marked generalized edema shall be condemned. (b) Carcasses of...

  12. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... anasarca or generalized edema. 311.8 Section 311.8 Animals and Animal Products FOOD SAFETY AND INSPECTION... ADULTERATED CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a... characterized by an extensive or well-marked generalized edema shall be condemned. (b) Carcasses of...

  13. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... anasarca or generalized edema. 311.8 Section 311.8 Animals and Animal Products FOOD SAFETY AND INSPECTION... ADULTERATED CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a... characterized by an extensive or well-marked generalized edema shall be condemned. (b) Carcasses of...

  14. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... generalized edema. 309.8 Section 309.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... anasarca and generalized edema. All cattle found on ante-mortem inspection to be affected with anasarca in advanced stages and characterized by an extensive and generalized edema shall be identified as...

  15. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... generalized edema. 309.8 Section 309.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... anasarca and generalized edema. All cattle found on ante-mortem inspection to be affected with anasarca in advanced stages and characterized by an extensive and generalized edema shall be identified as...

  16. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... anasarca or generalized edema. 311.8 Section 311.8 Animals and Animal Products FOOD SAFETY AND INSPECTION... ADULTERATED CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a... characterized by an extensive or well-marked generalized edema shall be condemned. (b) Carcasses of...

  17. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... anasarca or generalized edema. 311.8 Section 311.8 Animals and Animal Products FOOD SAFETY AND INSPECTION... ADULTERATED CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a... characterized by an extensive or well-marked generalized edema shall be condemned. (b) Carcasses of...

  18. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... generalized edema. 309.8 Section 309.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... anasarca and generalized edema. All cattle found on ante-mortem inspection to be affected with anasarca in advanced stages and characterized by an extensive and generalized edema shall be identified as...

  19. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... generalized edema. 309.8 Section 309.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... anasarca and generalized edema. All cattle found on ante-mortem inspection to be affected with anasarca in advanced stages and characterized by an extensive and generalized edema shall be identified as...

  20. Use of the Gamow Bag by EMT-basic park rangers for treatment of high-altitude pulmonary edema and high-altitude cerebral edema.

    PubMed

    Freeman, Kimberly; Shalit, Marc; Stroh, Geoffrey

    2004-01-01

    As part of an emergency medical system protocol, national park service rangers certified at the level of an emergency medical technician-basic (EMT-B) are taught to recognize and treat high-altitude pulmonary edema and high-altitude cerebral edema. In Sequoia and Kings Canyon National Parks, this is done with the assistance of physician on-line medical control as a backup. High-altitude pulmonary edema and high-altitude cerebral edema are both potentially fatal altitude illnesses that can be particularly problematic in the backcountry, where evacuation may be delayed. We report a case of high-altitude pulmonary edema and high-altitude cerebral edema occurring at moderate altitude that was successfully treated by park rangers with the Gamow Bag.

  1. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata).

    PubMed

    Potvin, Dominique A; Curcio, Michael T; Swaddle, John P; MacDougall-Shackleton, Scott A

    2016-01-01

    Recently, numerous studies have observed changes in bird vocalizations-especially song-in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers' songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats. PMID:27602270

  2. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata)

    PubMed Central

    Curcio, Michael T.; Swaddle, John P.; MacDougall-Shackleton, Scott A.

    2016-01-01

    Recently, numerous studies have observed changes in bird vocalizations—especially song—in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers’ songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats. PMID:27602270

  3. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata).

    PubMed

    Potvin, Dominique A; Curcio, Michael T; Swaddle, John P; MacDougall-Shackleton, Scott A

    2016-01-01

    Recently, numerous studies have observed changes in bird vocalizations-especially song-in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers' songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats.

  4. Transient blood-brain barrier permeability following profound temporary global ischemia: an experimental study using /sup 14/C-AIB

    SciTech Connect

    Dobbin, J.; Crockard, H.A.; Ross-Russell, R.

    1989-02-01

    The influence of reperfusion after profound incomplete forebrain ischemia on blood-brain barrier (BBB) permeability to a small protein tracer was studied in male Sprague-Dawley rats. The mean cortical blood to brain transfer constant (Ki) for /sup 14/C-amino isobutyric acid (AIB) was significantly greater at 3 and 6 h of reperfusion, 2.5 times the mean values of controls (p less than 0.05) (2.5 microliter g-1 min-1 and 1.0 microliters g-1 min-1 respectively), but had returned to control values after reperfusion for 24 h. Analysis of distribution of Ki values showed that following 15 min and 30 min of profound ischemia, there was a significant increase in transfer of AIB across the blood-brain barrier (BBB) after recirculation for up to 6 h, though there was no evidence of protein extravasation as assessed by Evans Blue (EB) dye. After 24 h of reperfusion, the BBB to AIB was restored, and Ki values had returned to control values. It is concluded that following transient global ischemia, the BBB may recover rapidly.

  5. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata)

    PubMed Central

    Curcio, Michael T.; Swaddle, John P.; MacDougall-Shackleton, Scott A.

    2016-01-01

    Recently, numerous studies have observed changes in bird vocalizations—especially song—in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers’ songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats.

  6. 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

  7. Acyclovir treatment of experimentally induced herpes simplex virus encephalitis: monitoring the changes in immunologic NO synthase expression and viral load within brain tissue of SJL mice.

    PubMed

    Haas, J; Meyding-Lamadé, U; Fäth, A; Stingele, K; Storch-Hagenlocher, B; Wildemann, B

    1999-04-01

    The effect of acyclovir treatment on viral burden and the expression of immunologic nitric oxide synthase (iNOS) within brains of 42 HSV-1 F infected mice was studied by using a titration PCR assay for HSV-1 DNA and a semiquantitative RT-PCR for iNOS mRNA. iNOS mediated NO-production may possibly be involved in secondary mechanisms of brain injury following virus infection, which may account for treatment failures in human herpes simplex virus encephalitis (HSVE). Following infection, a parallel increase of iNOS mRNA and HSV-1F-DNA occurred with peaks after 7 days that were both significantly lower under acyclovir treatment. Six months post infection viral load had declined, but iNOS mRNA expression in both treated and untreated mice was still enhanced as compared with mock infected controls. This suggests that acyclovir decreases iNOS expression via inhibition of viral replication shortly after infection but fails to influence elevated iNOS within the brain late in the course of experimental HSVE.

  8. Experimental scrapie in golden Syrian hamsters: temporal comparison of in vitro cell-fusing activity with brain infectivity and histopathological changes.

    PubMed Central

    Moreau-Dubois, M C; Brown, P; Rohwer, R G; Masters, C L; Franko, M; Gajdusek, D C

    1982-01-01

    Golden Syrain hamsters were inoculated intracerebrally with the hamster-adapted 263K strain of scrapie virus, and the evolution of in vitro cell fusing activity induced by brain suspensions was compared with brain infectivity titers and histological changes. Cell-fusing activity abruptly appeared 4 weeks after inoculation, 1 week before the earliest detectable histopathological changes, at an infectivity level of 7.6 log 50% lethal doses per g of brain. Cell-fusing activity was sustained throughout the remaining 4 weeks of the incubation period and the subsequent 1- to 3-week stage of clinical illness but did not increase with the logarithmic progression of infectivity, which reached a level of 11 log 50% lethal doses per g in the agonal stage of disease. Gliosis was most sensitively detected by a monoclonal antibody reacting with astrocyte intermediate filaments in an indirect immunofluorescence test, anticipating histological recognition of gliosis and spongiform change by 1 to 2 weeks. In vitro cell-fusing activity is thus one of the earliest known biological markers (apart from infectivity itself) of experimental scrapie infection. PMID:6809626

  9. dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis

    PubMed Central

    Lim, Sangho; Kim, Won-Ju; Kim, Yeon-Ho; Lee, Sohee; Koo, Ja-Hyun; Lee, Jung-Ah; Yoon, Heeseok; Kim, Do-Hyun; Park, Hong-Jai; Kim, Hye-Mi; Lee, Hong-Gyun; Yun Kim, Ji; Lee, Jae-Ung; Hun Shin, Jae; Kyun Kim, Lark; Doh, Junsang; Kim, Hongtae; Lee, Sang-Kyou; Bothwell, Alfred L. M.; Suh, Minah; Choi, Je-Min

    2015-01-01

    Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS. PMID:26372309

  10. Transient isolated ocular motor abnormality related to perilesional edema of an acute medullary microbleed: A case report and review of the literatures.

    PubMed

    Lee, Woo-Jin; Lee, Jee-Young; Lim, Jae-Sung; Kwon, Hyung-Min; Lee, Yong-Seok

    2015-11-01

    We report a case of transient isolated gaze-evoked nystagmus with ocular lateropulsion in a patient with an acute medullary microbleed which was detected by brain magnetic resonance imaging. Considering the correlation between the neural structures involved by the lesion and the ocular motor symptoms of this patient, we suggest that the perilesional edema of the acute medullary microbleed is responsible for this transient ocular motor abnormality.

  11. Aripiprazole induced non-cardiogenic pulmonary edema: a case report.

    PubMed

    Cetin, Mustafa; Celik, Mustafa; Cakıcı, Musa; Polat, Mustafa; Suner, Arif

    2014-01-01

    Aripiprazole is a second-generation antipsychotic drug with partial dopamine agonistic activity. Although the adverse cardiovascular effects of both typical and atypical antipsychotics are well known, similar data on aripiprazole, which was recently introduced, are scarce. Herein we report a 35-year-old female that presented to our emergency department with non-cardiogenic pulmonary edema. Chest X-ray and thoracic CT showed pulmonary edema and bilateral pleural effusion. Anamnesis showed that she had been taking sertraline 200 mg d-1 for obsessive-compulsive disorder for a long time and that aripiprazole10 mg d-1 was added for augmentation 2 months prior to presentation. We think that the CYP 2D6 inhibitor sertraline might have played a role in increasing the plasma concentration and toxicity of aripiprazole in the presented patient. PMID:25487626

  12. Pulmonary edema in scuba divers: recurrence and fatal outcome.

    PubMed

    Cochard, G; Arvieux, J; Lacour, J M; Madouas, G; Mongredien, H; Arvieux, C C

    2005-01-01

    Pulmonary edema occurring in divers using a self-contained underwater breathing apparatus (scuba) is an uncommon, probably under-reported, but potentially life-threatening and recurrent condition. We report six episodes of pulmonary edema in five scuba divers seen during a period of 15 months. The four men and one woman ranged in age from 37 to 56 years and two were treated for hypertension. Symptoms were mostly dyspnea onset at depth, cough, hemoptysis and hypoxemia, which in the recurrent case led to cardiac arrest and death. All cases occurred in rather cold water. Findings on thoracic computed tomography (CT) scanning ranged from pleural effusion to ground-glass opacities restricted to a few areas of the lung. The complex underlying mechanisms that would contribute to a raised transalveolar pressure or to a disruption of the blood-gas barrier are discussed. It is important for emergency care providers to be aware of this syndrome for prompt recognition and optimal treatment.

  13. Emma Kohman and the early history of nutritional edema.

    PubMed

    Bing, F C

    1983-06-01

    Nutritional edema is a generalized edematous condition that afflicted whole populations of central European countries during World War 1--and other areas since that time--with a mortality rate of about 50%. An analogous condition in white rats was produced by Emma Kohman as a graduate student in Chicago (1916 to 1919). She fed the rats a diet similar to that consumed by human subjects but prevented or cured nutritional edema in the animals by feeding them good quality protein in suitable amounts. Her work, verified by others, was of immense practical significance and helped establish the value of animal experiments in the study of human diseases. Ms. Kohman gave up a scientific career to be a homemaker when she married in 1919.

  14. Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema.

    PubMed

    Sharma, R K; Choudhary, R C; Reddy, M K; Ray, A; Ravi, K

    2015-01-01

    To investigate the role of posterior hypothalamus and central neurotransmitters in the pulmonary edema due to hypobaric hypoxia, rats were placed in a high altitude simulation chamber (barometric pressure-294.4 mmHg) for 24 h. Exposure to hypobaric hypoxia resulted in increases in mean arterial blood pressure, renal sympathetic nerve activity, right ventricular systolic pressure, lung wet to dry weight ratio and Evans blue dye leakage. There was a significant attenuation in these responses to hypobaric hypoxia (a) after lesioning posterior hypothalamus and (b) after chronic infusion of GABAA receptor agonist muscimol into posterior hypothalamus. No such attenuation was evident with the chronic infusion of the nitric oxide donor SNAP into the posterior hypothalamus. It is concluded that in hypobaric hypoxia, there is over-activity of posterior hypothalamic neurons probably due to a local decrease in GABA-ergic inhibition which increases the sympathetic drive causing pulmonary hypertension and edema. PMID:25448396

  15. Acute hemorrhagic edema of infancy after MMR vaccine.

    PubMed

    Binamer, Yousef

    2015-01-01

    Acute hemorrhagic edema of infancy (AHEI) is a rare type of leuckocytoclastic vasculitis. It affects mainly children less than two years of age. Many precipitating factors have been reported, including infectious etiology and vaccination. We are reporting a two-year-old boy with AHEI after measles, mumps, and rubella (MMR) vaccine. To our knowledge this is the second reported case after an MMR vaccine.

  16. Intractable bone marrow edema syndrome of the hip.

    PubMed

    Gao, Fuqiang; Sun, Wei; Li, Zirong; Guo, Wanshou; Kush, Nepali; Ozaki, Koji

    2015-04-01

    There is a need for an effective and noninvasive treatment for intractable bone marrow edema syndrome of the hip. Forty-six patients with intractable bone marrow edema syndrome of the hip were retrospectively studied to compare the short-term clinical effects of treatment with high-energy extracorporeal shock wave therapy vs femoral head core decompression. The postoperative visual analog scale score decreased significantly more in the extracorporeal shock wave therapy group compared with the femoral head core decompression group (P<.05). For unilateral lesions, postoperative Harris Hip Scores for all hips in the extracorporeal shock wave therapy group were more significantly improved than Harris Hip Scores for all hips in the femoral head core decompression group (P<.05). Patients who underwent extracorporeal shock wave therapy also resumed daily activities significantly earlier. Average overall operative time was similar in both groups. Symptoms disappeared significantly sooner in the extracorporeal shock wave therapy group in patients with both unilateral (P<.01) and bilateral lesions (P<.05). Hospital costs were significantly lower with extracorporeal shock wave therapy compared with femoral head core decompression. The intraoperative fluoroscopy radiation dose was lower in extracorporeal shock wave therapy than in femoral head core decompression for both unilateral (P<.05) and bilateral lesions (P<.01). On magnetic resonance imaging (MRI), bone marrow edema improved in all patients during the follow-up period. After extracorporeal shock wave therapy, all patients remained pain-free and had normal findings on posttreatment radiographs and MRI scans. Extracorporeal shock wave therapy appears to be a valid, reliable, and noninvasive tool for rapidly resolving intractable bone marrow edema syndrome of the hip, and it has a low complication rate and relatively low cost compared with other conservative and surgical treatment approaches.

  17. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis

    PubMed Central

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Warczyńska, Agnieszka; Kwiatkowska, Brygida

    2013-01-01

    Summary Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a “herald” of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted PMID:23493495

  18. Acute hemorrhagic edema of infancy after MMR vaccine.

    PubMed

    Binamer, Yousef

    2015-01-01

    Acute hemorrhagic edema of infancy (AHEI) is a rare type of leuckocytoclastic vasculitis. It affects mainly children less than two years of age. Many precipitating factors have been reported, including infectious etiology and vaccination. We are reporting a two-year-old boy with AHEI after measles, mumps, and rubella (MMR) vaccine. To our knowledge this is the second reported case after an MMR vaccine. PMID:26409801

  19. Movement, Function, Pain, and Postoperative Edema in Axillary Web Syndrome

    PubMed Central

    Blaes, Anne H.; Haddad, Tuffia C.; Hunter, David W.; Hirsch, Alan T.; Ludewig, Paula M.

    2015-01-01

    Background Axillary web syndrome (AWS) is a condition that may develop following breast cancer surgery and that presents as a palpable axillary cord of tissue. Objective The purposes of this study were: (1) to determine the clinical characteristics of AWS related to movement, function, pain, and postoperative edema and (2) to define the incidence of and risk factors for AWS within the first 3 months following breast cancer surgery. Design This was a prospective cohort study with a repeated-measures design. Methods Women who underwent breast cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36) were assessed for AWS, shoulder range of motion, function, pain, and postoperative edema (using girth measurements, bioimpedance, and tissue dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used for risk analysis. Results Seventeen women (47.2%) developed AWS, and AWS persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was significantly lower in the AWS group compared with the non-AWS group at 2 and 4 weeks. There were no differences between groups in measurements of function, pain, or edema at any time point. Trunk edema measured by dielectric constant was present in both groups, with an incidence of 55%. Multivariate analysis determined lower body mass index as being significantly associated with AWS (odds ratio=0.86; 95% confidence interval=0.74, 1.00). Limitations Limitations included a short follow-up time and a small sample size. Conclusion Axillary web syndrome is prevalent following breast/axilla surgery for early-stage breast cancer and may persist beyond 12 weeks. The early consequences include movement restriction, but the long-term effects of persistent AWS cords are yet unknown. Low body mass index is considered a risk factor for AWS. PMID:25977305

  20. The pathogenesis of pulmonary edema in acute pancreatitis.

    PubMed Central

    Warshaw, A L; Lesser, P B; Rie, M; Cullen, D J

    1975-01-01

    Acute pulmonary edema appeared 3 or more days after the onset of acute pancreatitis in 7 patients, an approximate incidence of 8%. The severity of pancreatitis in these patients was characterized by massive requirements for intravenous colloid and by marked hypocalcemia. In addition, at least 5 of the 7 patients had very high serum levels of triglycerides at the time of hospital admission. Hemodynamic studies during pulmonary edema showed normal central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. Cardiac index was appropriately elevated. Respiratory treatment, consisting of endotracheal intubation and controlled ventilation with PEEP, was successful in allowing reversal of the pulmonary injury and recovery of respiratory function within 1-2 weeks in all cases. Two patients died later from pancreatic abscesses. The findings indicate that a distinct form of pulmonary injury may occur in acute pancreatitis, characterized by loss of integrity of the alveolar-capilllary membrane, leading to pulmonary edema. The mechanism of injury is not known but may be caused by circulating free fatty acids, phospholipase A, or vasoactive substances. The pulmonary membrane lesion appears to heal during the period of intensive respiratory support. Images Fig. 1. PMID:1101836

  1. High-altitude cerebral edema with absence of headache.

    PubMed

    Thomassen, Oyvind; Skaiaa, Sven Chr

    2007-01-01

    Headache is the cardinal symptom of acute mountain sickness (AMS). The headache normally worsens, with increased cerebral affection and the development of high-altitude cerebral edema (HACE). A Norwegian expedition aimed to climb Baruntse (7129 m) in Nepal in 2003. At 5400 m a 35-year-old man felt exhausted. The next day he aborted his attempt at further climbing as a result of extreme fatigue. Over the next 24 hours he developed cough, dyspnea, and severe hypoxia before progressing to ataxia and blurred vision. At no point did he experience headache or nausea. The patient was evacuated by helicopter. He improved immediately after descent and recovered completely within a week. The speed of progression from AMS to HACE varies. Abrupt onset of HACE is occasionally reported. High-altitude pulmonary edema (HAPE) may induce severe hypoxia that can lead to rapid development of HACE. High-altitude cerebral edema in the setting of HAPE was the most likely diagnosis despite the unusual lack of headache. Rapid onset of HAPE with subsequent severe desaturation should raise awareness of the development of HACE, even in the absence of headache. PMID:17447714

  2. An accurate and simple method for measurement of paw edema.

    PubMed

    Fereidoni, M; Ahmadiani, A; Semnanian, S; Javan, M

    2000-01-01

    Several methods for measuring inflammation are available that rely on the parameters changing during inflammation. The most commonly used methods estimate the volume of edema formed. In this study, we present a novel method for measuring the volume of pathologically or artificially induced edema. In this model, a liquid column is placed on a balance. When an object is immersed, the liquid applies a force F to attempt its expulsion. Physically, F is the weight (W) of the volume of liquid displaced by that part of the object inserted into the liquid. A balance is used to measure this force (F=W).Therefore, the partial or entire volume of any object, for example, the inflamed hind paw of a rat, can be calculated thus, using the specific gravity of the immersion liquid, at equilibrium mass/specific gravity=volume (V). The extent of edema at time t (measured as V) will be V(t)-V(o). This method is easy to use, materials are of low cost and readily available. It is important that the rat paw (or any object whose volume is being measured) is kept from contacting the wall of the column containing the fluid whilst the value on the balance is read.

  3. [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

    PubMed

    Sánchez Marteles, Marta; Urrutia, Agustín

    2014-03-01

    Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

  4. [Retinal vein occlusion management algorithm. Part 2. Macular edema].

    PubMed

    Budzinskaya, M V; Mazurina, N K; Egorov, A E; Kuroedov, A V; Loskutov, I A; Plyukhova, A A; Razik, S; Ryabtseva, A A; Simonova, S V

    2015-01-01

    Macular edema (ME) is the most common complication of both ischemic and nonischemic retinal vein occlusion (RVO). If the main trunk of the central retinal vein is involved, ME occurs in 100% of cases. According to the Central Vein Occlusion Study, in 65% of RVO and ME patients with baseline visual acuity (VA) of at least 0.5 (Golovin-Sivtsev chart) or higher, ME may resolve itself without treatment with subsequent VA improvement. Therefore, we recommend a 3-month treatment-free follow-up of nonischemic central RVO (CRVO) and ME patients with VA of 0.5 or higher. If no improvement is noted within this period, treatment is initiated. Immediate treatment is required in patients with cystic ME revealed by optical coherence tomography (OCT) and VA below 0.5. Ischemic maculopathy is extremely unpromising. Modified grid laser photocoagulation should not be used as monotherapy for macular edema. Repeated corticosteroid (Ozurdex) and/or anti-VEGF (ranibizumab, aflibercept) intravitreal injections are considered the first choice treatment for ME in CRVO patients. Efficiency assessments should include monthly OCT. For persistent ME, intravitreal therapy can be supplemented by laser retinal photocoagulation (panretinal or modified grid). Anti-VEGF treatment schemes should be adjusted in BRVO patients as most of their edemas are self-limiting. Of laser photocoagulation techniques, only modified grid is used. PMID:26977728

  5. Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats

    PubMed Central

    Quan, Fu-Shi; Chen, Jian; Zhong, Yuan; Ren, Wen-Zhi

    2016-01-01

    The present study evaluated the comparative effect of stereotaxically transplanted immature neuronal or glial cells in brain on motor functional recovery and cytokine expression after cold-induced traumatic brain injury (TBI) in adult rats. A total of 60 rats were divided into four groups (n=15/group): Sham group; TBI only group; TBI plus neuronal cells-transplanted group (NC-G); and TBI plus glial cells-transplanted group (GC-G). Cortical lesions were induced by a touching metal stamp, frozen with liquid nitrogen, to the dura mater over the motor cortex of adult rats. Neuronal and glial cells were isolated from rat embryonic and newborn cortices, respectively, and cultured in culture flasks. Rats received neurons or glia grafts (~1×106 cells) 5 days after TBI was induced. Motor functional evaluation was performed with the rotarod test prior to and following glial and neural cell grafts. Five rats from each group were sacrificed at 2, 4 and 6 weeks post-cell transplantation. Immunofluorescence staining was performed on brain section to identify the transplanted neuronal or glial cells using neural and astrocytic markers. The expression levels of cytokines, including transforming growth factor-β, glial cell-derived neurotrophic factor and vascular endothelial growth factor, which have key roles in the proliferation, differentiation and survival of neural cells, were analyzed by immunohistochemistry and western blotting. A localized cortical lesion was evoked in all injured rats, resulting in significant motor deficits. Transplanted cells successfully migrated and survived in the injured brain lesion, and the expression of neuronal and astrocyte markers were detected in the NC-G and GC-G groups, respectively. Rats in the NC-G and GC-G cell-transplanted groups exhibited significant motor functional recovery and reduced histopathologic lesions, as compared with the TBI-G rats that did not receive neural cells (P<0.05, respectively). Furthermore, GC-G treatment

  6. Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats

    PubMed Central

    Quan, Fu-Shi; Chen, Jian; Zhong, Yuan; Ren, Wen-Zhi

    2016-01-01

    The present study evaluated the comparative effect of stereotaxically transplanted immature neuronal or glial cells in brain on motor functional recovery and cytokine expression after cold-induced traumatic brain injury (TBI) in adult rats. A total of 60 rats were divided into four groups (n=15/group): Sham group; TBI only group; TBI plus neuronal cells-transplanted group (NC-G); and TBI plus glial cells-transplanted group (GC-G). Cortical lesions were induced by a touching metal stamp, frozen with liquid nitrogen, to the dura mater over the motor cortex of adult rats. Neuronal and glial cells were isolated from rat embryonic and newborn cortices, respectively, and cultured in culture flasks. Rats received neurons or glia grafts (~1×106 cells) 5 days after TBI was induced. Motor functional evaluation was performed with the rotarod test prior to and following glial and neural cell grafts. Five rats from each group were sacrificed at 2, 4 and 6 weeks post-cell transplantation. Immunofluorescence staining was performed on brain section to identify the transplanted neuronal or glial cells using neural and astrocytic markers. The expression levels of cytokines, including transforming growth factor-β, glial cell-derived neurotrophic factor and vascular endothelial growth factor, which have key roles in the proliferation, differentiation and survival of neural cells, were analyzed by immunohistochemistry and western blotting. A localized cortical lesion was evoked in all injured rats, resulting in significant motor deficits. Transplanted cells successfully migrated and survived in the injured brain lesion, and the expression of neuronal and astrocyte markers were detected in the NC-G and GC-G groups, respectively. Rats in the NC-G and GC-G cell-transplanted groups exhibited significant motor functional recovery and reduced histopathologic lesions, as compared with the TBI-G rats that did not receive neural cells (P<0.05, respectively). Furthermore, GC-G treatment

  7. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    PubMed

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity.

  8. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  9. A reward-modulated Hebbian learning rule can explain experimentally observed network reorganization in a brain control task

    PubMed Central

    Legenstein, Robert; Chase, Steven M.; Schwartz, Andrew B.; Maass, Wolfgang

    2010-01-01

    It has recently been shown in a brain-computer interface experiment that motor cortical neurons change their tuning properties selectively to compensate for errors induced by displaced decoding parameters. In particular, it was shown that the 3D tuning curves of neurons whose decoding parameters were re-assigned changed more than those of neurons whose decoding parameters had not been re-assigned. In this article, we propose a simple learning rule that can reproduce this effect. Our learning rule uses Hebbian weight updates driven by a global reward signal and neuronal noise. In contrast to most previously proposed learning rules, this approach does not require extrinsic information to separate noise from signal. The learning rule is able to optimize the performance of a model system within biologically realistic periods of time under high noise levels. Furthermore, when the model parameters are matched to data recorded during the brain-computer interface learning experiments described above, the model produces learning effects strikingly similar to those found in the experiments. PMID:20573887

  10. Interactions Between Dyspnea and the Brain Processing of Nociceptive Stimuli: Experimental Air Hunger Attenuates Laser-Evoked Brain Potentials in Humans

    PubMed Central

    Dangers, Laurence; Laviolette, Louis; Similowski, Thomas; Morélot-Panzini, Capucine

    2015-01-01

    Dyspnea and pain share several characteristics and certain neural networks and interact with each other. Dyspnea-pain counter-irritation consists of attenuation of preexisting pain by intercurrent dyspnea and has been shown to have neurophysiological correlates in the form of inhibition of the nociceptive spinal reflex RIII and laser-evoked potentials (LEPs). Experimentally induced exertional dyspnea inhibits RIII and LEPs, while “air hunger” dyspnea does not inhibit RIII despite its documented analgesic effects. We hypothesized that air hunger may act centrally and inhibit LEPs. LEPs were obtained in 12 healthy volunteers (age: 21–29) during spontaneous breathing (FB), ventilator-controlled breathing (VC) tailored to FB, after inducing air hunger by increasing the inspired fraction of carbon dioxide -FiCO2- (VCCO2), and during ventilator-controlled breathing recovery (VCR). VCCO2 induced intense dyspnea (visual analog scale = 63% ± 6% of full scale, p < 0.001 vs. VC), predominantly of the air hunger type. VC alone reduced the amplitude of the N2-P2 component of LEPs (Δ = 24.0% ± 21.1%, p < 0.05, effect-size = 0.74) predominantly through a reduction in P2, and the amplitude of this inhibition was further reduced by inducting air hunger (Δ = 22.6% ± 17.9%, p < 0.05, effect-size = 0.53), predominantly through a reduction in N2. Somatosensory-evoked potentials (SEPs) were not affected by VC or VCCO2, suggesting that the observed effects are specific to pain transmission. We conclude that air hunger interferes with the cortical mechanisms responsible for the cortical response to painful laser skin stimulation, which provides a neurophysiological substrate to the central nature of its otherwise documented analgesic effects. PMID:26648875

  11. Interactions Between Dyspnea and the Brain Processing of Nociceptive Stimuli: Experimental Air Hunger Attenuates Laser-Evoked Brain Potentials in Humans.

    PubMed

    Dangers, Laurence; Laviolette, Louis; Similowski, Thomas; Morélot-Panzini, Capucine

    2015-01-01

    Dyspnea and pain share several characteristics and certain neural networks and interact with each other. Dyspnea-pain counter-irritation consists of attenuation of preexisting pain by intercurrent dyspnea and has been shown to have neurophysiological correlates in the form of inhibition of the nociceptive spinal reflex RIII and laser-evoked potentials (LEPs). Experimentally induced exertional dyspnea inhibits RIII and LEPs, while "air hunger" dyspnea does not inhibit RIII despite its documented analgesic effects. We hypothesized that air hunger may act centrally and inhibit LEPs. LEPs were obtained in 12 healthy volunteers (age: 21-29) during spontaneous breathing (FB), ventilator-controlled breathing (VC) tailored to FB, after inducing air hunger by increasing the inspired fraction of carbon dioxide -FiCO2- (VCCO2), and during ventilator-controlled breathing recovery (VCR). VCCO2 induced intense dyspnea (visual analog scale = 63% ± 6% of full scale, p < 0.001 vs. VC), predominantly of the air hunger type. VC alone reduced the amplitude of the N2-P2 component of LEPs (Δ = 24.0% ± 21.1%, p < 0.05, effect-size = 0.74) predominantly through a reduction in P2, and the amplitude of this inhibition was further reduced by inducting air hunger (Δ = 22.6% ± 17.9%, p < 0.05, effect-size = 0.53), predominantly through a reduction in N2. Somatosensory-evoked potentials (SEPs) were not affected by VC or VCCO2, suggesting that the observed effects are specific to pain transmission. We conclude that air hunger interferes with the cortical mechanisms responsible for the cortical response to painful laser skin stimulation, which provides a neurophysiological substrate to the central nature of its otherwise documented analgesic effects. PMID:26648875

  12. Pharmacological characterization of the rat paw edema induced by Bothrops lanceolatus (Fer de lance) venom.

    PubMed

    de Faria L; Antunes, E; Bon, C; de Araújo, A L

    2001-06-01

    The inflammatory response induced by Bothrops lanceolatus venom (BLV) in the rat hind-paw was studied measuring paw edema. Non-heated BLV (75microg/paw) caused a marked paw edema accompanied by intense haemorrhage whereas heated venom (97 degrees C, 30s; 12.5-100microg/paw) produced a dose- and time-dependent non-haemorrhagic edema. The response with heated BLV was maximal within 15min disappearing over 24h. Heated venom was then routinely used at the dose of 75microg/paw. The prostacyclin analogue iloprost (0.1microg/paw) potentiated by 125% the venom-induced edema. The histamine H(1) receptor antagonist mepyramine (6mg/kg) or the serotonin/histamine receptor antagonist cyproheptadine (6mg/kg) partially inhibited BLV-induced edema whereas the combination of both compounds virtually abolished the edema. The lipoxygenase inhibitor BWA4C (10mg/kg), but not the cyclooxygenase inhibitor indomethacin (10mg/kg), significantly inhibited the edema (35% reduction; P<0.05). Dexamethasone (1mg/kg) also markedly (P<0.001) reduced venom-induced edema. The bradykinin B(2) receptor antagonist Hoe 140 (0.6mg/kg) reduced by 30% (P<0.05) the venom induced edema, whereas the angiotensin-converting enzyme inhibitor captopril (300microg/paw) potentiated by 42% (P<0.05) the edema. Bothrops lanceolatus antivenon (anti-BLV) reduced by 28% (P<0.05) the venom-induced edema while intravenous administration of antivenom failed to affect the edema. In conclusion, BLV-induced rat paw edema involves mast cell degranulation causing local release of histamine and serotonin, a phenomenon mediated mainly by kinins and lipoxygenase metabolites. Additionally, the use of a specific Bothrops lanceolatus antivenom, given subplantarily or intravenously, revealed to be little effective to prevent BLV-induced edema. PMID:11137542

  13. Respiratory mechanics in brain injury: A review

    PubMed Central

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

    2016-01-01

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

  14. Experimental assessment of thermal effects of high power density light stimulation for optogenetics control of deep brain structures (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Senova, Suhan; Scisniak, Ilona; Chiang, Chih Chieh; Doignon, Isabelle; Martin, Claire; Palfi, Stephane; Chaillet, Antoine; Pain, Frederic

    2016-03-01

    2D surface maps of light distribution and temperature increase were recorded in wild type anesthetized rats brains during 90s light stimulation at 478nm (blue) and 638nm (red) with continuous or pulsed optical stimulations with corresponding power ranging from 100 up to 1200 mW/mm² at the output of an optical fiber. Post mortem maps were recorded in the same animals to assess the cooling effect of blood flow. Post mortem histological analysis were carried out to assess whether high power light stimulations had phototoxic effects or could trigger non physiological functional activation. Temperature increase remains below physiological changes (0,5 -1°) for stimulations up to 400mW/mm² at 40Hz. . Histology did not show significant irreversible modifications or damage to the tissues. The spatial profile of light distribution and heat were correlated and demonstrate as expected a rapid attenuation with diatnce to the fiber.

  15. Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

    PubMed

    Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

    2011-05-01

    Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p<0.05), none of these variables (nor hematocrit) correlated significantly with CA1 cell counts in the malnourished group exposed to 2-VO (p>0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor.

  16. Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Black, Joel A.; Dib-Hajj, Sulayman; Baker, David; Newcombe, Jia; Cuzner, M. Louise; Waxman, Stephen G.

    2000-10-01

    Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been considered. Sensory Neuron-Specific sodium channel SNS displays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" sodium channels. SNS is selectively expressed in spinal sensory and trigeminal ganglion neurons within the peripheral nervous system and is not expressed within the normal brain. Here we show that sodium channel SNS mRNA and protein, which are not present within the cerebellum of control mice, are expressed within cerebellar Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. We also demonstrate SNS mRNA and protein expression within Purkinje cells from tissue obtained postmortem from patients with MS, but not in cont