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Sample records for reduced brain edema

  1. Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury.

    PubMed

    Huang, Lei; Woo, Wendy; Sherchan, Prativa; Khatibi, Nikan H; Krafft, Paul; Rolland, William; Applegate, Richard L; Martin, Robert D; Zhang, John

    2016-01-01

    Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI?+?vehicle, SBI?+?low dose (100 mg/kg) VA, and SBI?+?high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits. PMID:26463966

  2. 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

  3. Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood–brain barrier Na/H exchanger

    PubMed Central

    O'Donnell, Martha E; Chen, Yi-Je; Lam, Tina I; Taylor, Kelleen C; Walton, Jeffrey H; Anderson, Steven E

    2013-01-01

    Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood–brain barrier (BBB). Our previous studies provided evidence that the BBB Na–K–Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210?minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na–K–Cl cotransporter activity. PMID:23149557

  4. Src Family Kinases in Brain Edema After Acute Brain Injury.

    PubMed

    Liu, DaZhi; Zhang, Xiong; Hu, BeiLei; Ander, Bradley P

    2016-01-01

    Brain edema, the first stage of intracranial hypertension, has been associated with poor prognosis and increased mortality after acute brain injury such as ischemic stroke, intracranial hemorrhage (ICH), and traumatic brain injury (TBI). Acute brain injury often initiates release of many molecules, including glutamate, adenosine, thrombin, oxyhemoglobin, cytokines, reactive oxygen species (ROS), damage-associated molecular pattern molecules (DAMPs), and others. Most of these molecules activate Src family kinases (SFKs), a family of proto-oncogenic non-receptor tyrosine kinases, resulting in blood-brain barrier (BBB) disruption and brain edema at the acute stage after brain injury. However, SFKs also contribute to BBB self-repair and brain edema resolution in the chronic stage that follows brain injury. In this review, we summarize possible pathways through which SFKs are implicated in both brain edema formation and its eventual resolution. PMID:26463946

  5. Effects of Gender and Estrogen Receptors on Iron-Induced Brain Edema Formation.

    PubMed

    Xie, Qing; Xi, Guohua; Keep, Richard F; Hua, Ya

    2016-01-01

    Our previous studies have shown that female mice have less brain edema and better recovery in neurological deficits after intracerebral hemorrhage (ICH) and that 17?-estradiol treatment in male mice markedly reduces ICH-induced brain edema. In this study, we investigated the role of gender and the estrogen receptors (ERs) in iron-induced brain edema. There were three parts in this study: (1) either male or female mice received an injection of 10 ?L FeCl2 (1 mM) into the right caudate; (2) females received an intracaudate injection of FeCl2 or saline with 1 ?g of ICI 182,780 (antagonists of ERs) or vehicle; and (3) males were treated with the ER regulator tamoxifen (5 mg/kg subcutaneously) or vehicle 1 h after FeCl2 injection. Mice were euthanized 24 h later for brain edema determination. FeCl2 induced lower brain edema in females than in males. Co-injection of ICI 182,780 with FeCl2 aggravated iron-induced brain edema in female mice. ICI 182,780 itself did not induce brain edema at the dose of 1 ?g. Tamoxifen treatment reduced FeCl2-induced brain edema in male mice. In conclusion, iron induced less brain edema in female mice than in males. ER modification can affect iron-induced brain edema. PMID:26463972

  6. Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

    PubMed Central

    Michinaga, Shotaro; Koyama, Yutaka

    2015-01-01

    Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

  7. Local drug delivery for treatment of brain tumor associated edema

    E-print Network

    Ong, Qunya

    2014-01-01

    Brain tumor associated edema, a common feature of malignant brain neoplasms, is a significant cause of morbidity from brain tumor. Systemic administration of corticosteroids, the standard of care, is highly effective but ...

  8. Activation of NF-?B Mediates Astrocyte Swelling and Brain Edema in Traumatic Brain Injury

    PubMed Central

    Jayakumar, Arumugam R.; Tong, Xiao Y.; Ruiz-Cordero, Roberto; Bregy, Amade; Bethea, John R.; Bramlett, Helen M.

    2014-01-01

    Abstract Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury (TBI). While astrocyte swelling (cytotoxic edema) represents a major component of the brain edema in the early phase of TBI, its mechanisms are unclear. One factor known to be activated by trauma is nuclear factor-?B (NF-?B). Because this factor has been implicated in the mechanism of cell swelling/brain edema in other neurological conditions, we examined whether NF-?B might also be involved in the mediation of post-traumatic astrocyte swelling/brain edema. Here we show an increase in NF-?B activation in cultured astrocytes at 1 and 3?h after trauma (fluid percussion injury, FPI), and that BAY 11–7082, an inhibitor of NF-?B, significantly blocked the trauma-induced astrocyte swelling. Increased activities of nicotinamide adenine dinucleotide phosphate-oxidase and the Na+, K+, 2Cl- cotransporter were also observed in cultured astrocytes after trauma, and BAY 11–7082 reduced these effects. We also examined the role of NF-?B in the mechanism of cell swelling by using astrocyte cultures derived from transgenic (Tg) mice with a functional inactivation of astrocytic NF-?B. Exposure of cultured astrocytes from wild-type mice to in vitro trauma (3?h) caused a significant increase in cell swelling. By contrast, traumatized astrocyte cultures derived from NF-?B Tg mice showed no swelling. We also found increased astrocytic NF-?B activation and brain water content in rats after FPI, while BAY 11-7082 significantly reduced such effects. Our findings strongly suggest that activation of astrocytic NF-?B represents a key element in the process by which cytotoxic brain edema occurs after TBI. PMID:24471369

  9. 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.

  10. Hypertensive encephalopathy presenting with isolated brain stem and cerebellar edema.

    PubMed

    Bhagavati, Satyakam; Chum, Florence; Choi, Jai

    2008-10-01

    Hypertensive encephalopathy typically presents with headache and confusion and bilateral parietooccipital vasogenic edema. Brain stem and cerebellar edema in hypertensive encephalopathy usually occurs in association with these typical supratentorial changes and is usually asymptomatic. We report here an uncommon hypertensive patient with isolated, severe, and symptomatic brain stem and cerebellar edema with fourth ventricular obstruction and mild hydrocephalus. Rapid treatment of hypertension resulted in clinical and radiological improvement. Prompt recognition of the cause and aggressive treatment of hypertension in such patients are crucial to relieve edema and prevent life-threatening progression. PMID:18321248

  11. 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

  12. 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.

  13. Modern approach in therapy of brain edema in cerebral ischemia.

    PubMed

    An?eli?, Sla?ana

    2012-08-01

    Based on the national data register in Serbia, every 20 min a person develops acute stroke, and every 60 min one dies of the same disease. Studies have shown that during the first 24-40 hours patients develop cytotoxic brain edema and increased intracranial pressure. Up-to-date therapeutic concept must take into consideration possible pathophysiological processes, so that antiedematous therapy becomes an unavoidable segment of this program. The paper presents a female patient who had cerebral ischemia out-of- hospital to develop brain edema three years later. The diagnostic and therapeutic approach to this problem was in accordance with the National Guidelines for Brain Ischemic Disease. PMID:22926391

  14. Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury.

    PubMed

    Liu, Su; Liu, Ying; Deng, Shukun; Guo, Aisong; Wang, Xiubing; Shen, Guangyu

    2015-12-01

    Hyperbaric oxygen (HBO) therapy helps alleviate secondary injury following brain trauma [traumatic brain injury (TBI)], although the mechanisms remain unclear. In this study, we assessed recovery of post-TBI spatial learning and memory in rats using the Morris water maze (MWM) and measured changes in apparent diffusion coefficient in the hippocampus by diffusion-weighted imaging (DWI) to evaluate possible therapeutic effects of HBO on TBI-associated brain edema. DWIs were obtained 8, 24, 48 h, 7 days, and 14 days post-TBI. Daily HBO therapy significantly improved post-TBI MWM performance and reduced edema in the ipsilateral hippocampus, suggesting that the therapeutic efficacy of HBO is mediated, at least in part, by a reduction in brain edema. PMID:26267487

  15. Edema

    MedlinePLUS

    Edema means swelling caused by fluid in your body's tissues. It usually occurs in the feet, ankles ... it can involve your entire body. Causes of edema include Eating too much salt Sunburn Heart failure ...

  16. Edema

    MedlinePLUS

    MENU Return to Web version Edema Overview What is edema? Edema (say: “eh-dee-mah”) is swelling or puffiness of parts of the ... I make? Can you recommend any books or web sites where I can read about low-salt ...

  17. Brain edema in neurooncology: radiological assessment and management.

    PubMed

    Wick, W; Küker, W

    2004-06-01

    Vasogenic brain edema is a common diagnostic and management problem in brain tumor patients. Molecular mechanisms play a role in the pathophysiology, including abnormalities of tumor endothelium, vascular endothelial growth factor and leukotriene synthase. Edema diagnosis is facilitated by the development of neuroradiological imaging techniques, with diffusion-weighted imaging (DW-MRI) differentiating tumor grades or abscesses and tumors, and diffusion tensor imaging representing an advanced technique to potentially differentiate malignant glioma from metastasis or facilitate preoperative planning. Edema is a prognostic factor for meningioma and metastases but not for glioma. Therapy includes, amongst others, tumor-directed measures such as debulking surgery, radio- and chemotherapy. However, local therapeutic approaches might also induce or exacerbate edema formation. Peritumoral edema can usually be managed with corticosteroids. However, patients on corticosteroids are at greater risk of metabolic changes, Pneumocystis carinii pneumonia, and thromboembolism. More recently, inhibitors of cyclooxygenase-2 as well as boswellic acids have been explored as antiedema agents in patients with brain tumors. PMID:15249715

  18. Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors ? and ? following traumatic brain injury

    PubMed Central

    Naderi, Vida; Khaksari, Mohammad; Abbasi, Reza; Maghool, Fatemeh

    2015-01-01

    Objective(s): Estrogen (E2) has neuroprotective effects on blood-brain-barrier (BBB) after traumatic brain injury (TBI). In order to investigate the roles of estrogen receptors (ERs) in these effects, ER-? antagonist (MPP) and, ER-? antagonist (PHTPP), or non-selective estrogen receptors antagonist (ICI 182780) were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg) or oil were administered 30 min after TBI. 1 dose (150 µg/Kg) of each of MPP, PHTPP, and (4 mg/kg) ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content) and brain edema (brain water content) evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P<0.01). The brain edema in the MPP+E2 and PHTPP+E2 groups decreased compared to the vehicle (P<0.001). There was no significant difference in MPP+PHTPP+E2 and ICI+E2 compared to TBI. This parameter in MPP was similar to vehicle. Evans blue content in E2 group was lower than vehicle (P<0.05). The inhibitory effect of E2 on Evans blue was not reduced by MPP+E2 and PHTPP+E2 groups, but decreased by treatment with MPP+PHTPP or ICI. MPP had no effect on Evans blue content. Conclusion: A combined administration of MPP and PHTPP or ICI inhibited the E2-induced decrease in brain edema and BBB disruption; this may suggest that these effects were mediated via both receptors. PMID:25810887

  19. Assessment of the Correlations Between Brain Weight and Brain Edema in Experimental Subarachnoid Hemorrhage.

    PubMed

    Hasegawa, Yu; Suzuki, Hidenori; Nakagawa, Takashi; Uekawa, Ken; Koibuchi, Nobutaka; Kawano, Takayuki; Kim-Mitsuyama, Shokei

    2016-01-01

    Because brain edema is correlated with poor outcome in clinical subarachnoid hemorrhage (SAH), appropriate evaluation methods for brain edema are important in experimental SAH studies. Although brain water content (BWC) is widely used to evaluate brain edema in stroke research, the usefulness of brain weight is undetermined. In this study, we examined the role of brain weight in the evaluation of brain edema in experimental SAH. The endovascular perforation model of SAH was used, and rats were assessed by neurological scoring (NS). The brains were quickly removed at 24 h after the operation, and the weights of wet cerebrum (WWC) and dry cerebrum (WDC) were measured to determine the brain water content (BWC). The correlations of those values with each other and to body weight (BW) were then examined to reveal the significance of brain weight. The rats were assigned to sham-operated (n?=?8) and SAH (n?=?16) groups. There were no significant differences in WWC between the groups (p?=?0.61). WWC was correlated with BWC but not with NS in all rats. In addition, WWC was clearly correlated with BW and WDC, which is thought to substitute for the original brain weight. From these results, we suggest that the measurement of brain weight as an evaluation of brain edema is limited and that BW and original brain volume can be confounding factors in evaluation. PMID:26463928

  20. Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice.

    PubMed

    Jie, Pinghui; Tian, Yujing; Hong, Zhiwen; Li, Lin; Zhou, Libin; Chen, Lei; Chen, Ling

    2015-01-01

    Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema. Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO) mice. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047. The increased MMP-2/9 protein expression in hippocampi of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occludens-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein expression increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein expression was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein. PMID:25914628

  1. Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage

    PubMed Central

    Tait, Matthew J.; Saadoun, Samira; Bell, B. Anthony; Verkman, Alan S.; Papadopoulos, Marios C.

    2010-01-01

    We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid haemorrhage in which thirty microliters of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At six hours after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5 ± 0.1 vs. 0.5 ± 0.2 % (Mean ± Standard Error, P < 0.0005) and intracranial pressure by 36 ± 5 vs. 21 ± 3 mmHg (P < 0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P < 0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water. PMID:20132873

  2. Cerebral Edema Following Photodynamic Therapy Using Endogenous and Exogenous Photosensitizers in Normal Brain

    PubMed Central

    Mathews, Marlon S.; Chighvinadze, David; Gach, H. Michael; Uzal, Francisco A.; Madsen, Steen J.; Hirschberg, Henry

    2014-01-01

    Background and Objective Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy such as photodynamic therapy (PDT) could be of benefit. The increase in brain edema following PDT using endogenous and exogenous photosensitizers was compared in terms of animal survival, MR imaging, and histopathological changes in normal brain. Materials and Methods Fischer rats were exposed to increasing laser light treatment following intraperitoneal injection of either the photosensitizers 5-aminolevulinic acid (ALA) or aluminum phthalocyanine disulfonate (AlPcS2a). Light treatment was applied either via an optical fiber inserted directly into the brain parenchyma or through a fiber applied to the surface of the intact skull. Edema development was followed by T2-weighted MR imaging. Results ALA and AlPcS2a PDT resulted in a fluence dependent increase in cerebral edema and mortality. AlPcS2a PDT showed significant edema and mortality even at low fluences following interstitial light delivery, which was reduced with surface illumination. The mechanism of edema was determined to be vasogenic by response to steroid therapy and confirmed on histological images. Conclusions T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and noninvasive modality in following the development of the edema reaction and the degree and time course of blood–brain barrier dysfunction thus allowing the use of fewer animals. ALA mediated PDT induced a lower edema reaction than that observed with the photosensitizer AlPcS2a. PMID:22006731

  3. 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. PMID:24959845

  4. Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.

    PubMed

    Zhou, Qing-Bo; Jin, Yun-Ling; Jia, Qing; Zhang, Yuan; Li, Lu-Yang; Liu, Ping; Liu, Yuan-Tao

    2014-02-01

    Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on brain injury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-?B (NF-?B) protein expression was analyzed by western blotting. IL-1? and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reduced brain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-?B activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1? and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism. PMID:23974988

  5. Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?

    PubMed Central

    Laird, Melissa D.; SR, Sangeetha; Swift, Andrew E.B.; Meiler, Steffen E.; Vender, John R.; Dhandapani, Krishnan M.

    2010-01-01

    Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 minute post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1?, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1?-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of NF?B. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically-achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation. PMID:20132469

  6. 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. PMID:26463940

  7. 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

  8. Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage.

    PubMed

    Liu, Lei; Fujimoto, Masashi; Kawakita, Fumihiro; Ichikawa, Naoki; Suzuki, Hidenori

    2016-01-01

    Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of brain edema formation after experimental subarachnoid hemorrhage (SAH). In this study, we evaluated the effect of anti-VEGF antibody neutralization on brain edema formation after experimental SAH in mice. Mice underwent sham operation or filament puncture SAH and were assigned to sham, SAH?+?vehicle, or SAH?+?anti-VEGF antibody groups. Vehicle or anti-VEGF antibody was administrated by an intracerebroventricular injection at 30 min post-SAH. After 24 h of SAH modeling, neurological score was recorded to evaluate neurobehavioral functions, brain water content was calculated to assess the level of brain edema, and immunohistochemistry of immunoglobulin (Ig) G was performed to evaluate the permeability of the blood-brain barrier (BBB). Anti-VEGF antibody significantly ameliorated neurological score and brain edema after SAH compared with the SAH?+?vehicle group. Immunohistochemistry showed that post-SAH IgG extravasation in brain tissue was suppressed by anti-VEGF antibody. This study suggests that VEGF is involved in brain edema formation after SAH, and that anti-VEGF antibody can decrease BBB permeability, suppress brain edema formation, and improve functional outcome after 24 h of SAH. PMID:26463944

  9. The protective effect of HET0016 on brain edema and blood-brain barrier dysfunction after cerebral ischemia/reperfusion.

    PubMed

    Liu, Yu; Wang, Di; Wang, Huan; Qu, Youyang; Xiao, Xingjun; Zhu, Yulan

    2014-01-28

    N-hydroxy-N-(4-butyl-2-methylphenyl) formamidine (HET0016) is a specific 20-hydroxyeicosatetraenoic acid (20-HETE) inhibitor which was first synthesized in 2001. It has been demonstrated that HET0016 reduces cerebral infarction volume in rat middle cerebral artery occlusion (MCAO) models. However, little is known about the role of HET0016 in the blood-brain barrier (BBB) dysfunction after cerebral ischemia/reperfusion (I/R) injury. The present study was designed to examine the effect of HET0016 in a MCAO and reperfusion rat model to determine whether it protects against brain edema and BBB disruption. Rats were subjected to 90 min MCAO, followed by 4, 24, 48, and 72 h reperfusion. Brain edema was measured according to the wet and dry weight method. BBB permeability based on the extravasation of Evans blue and sodium fluorescein was detected. BBB ultrastructure alterations were presented through transmission electron microscope. Superoxide production in ischemic tissue was also measured by dihydroethidium fluorescent probe. Western blot was used to analyze the expression of Claudin-5, ZO-1, MMP-9, and JNK pathway. At 24h after reperfusion, HET0016 reduced brain edema and BBB leakage. Ultrastructural damage of BBB and the increase of superoxide production were attenuated by HET0016 treatment. Western blot showed that HET0016 suppressed the activation of MMP-9 and JNK pathway but restored the expression of Claudin-5 and ZO-1. In conclusion, these results suggest that HET0016 protects BBB dysfunction after I/R by regulating the expression of MMP-9 and tight junction proteins. Furthermore, inhibition of oxidative stress and JNK pathway may be involved in this protecting effect. PMID:24316243

  10. 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 (?s') and BWC. By recording ?s' 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.

  11. 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.

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

    PubMed

    Castejón, Orlando J

    2015-12-01

    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

  13. Absence of Glial ?-Dystrobrevin Causes Abnormalities of the Blood-Brain Barrier and Progressive Brain Edema*

    PubMed Central

    Lien, Chun Fu; Mohanta, Sarajo Kumar; Frontczak-Baniewicz, Malgorzata; Swinny, Jerome D.; Zablocka, Barbara; Górecki, Dariusz C.

    2012-01-01

    The blood-brain barrier (BBB) plays a key role in maintaining brain functionality. Although mammalian BBB is formed by endothelial cells, its function requires interactions between endotheliocytes and glia. To understand the molecular mechanisms involved in these interactions is currently a major challenge. We show here that ?-dystrobrevin (?-DB), a protein contributing to dystrophin-associated protein scaffolds in astrocytic endfeet, is essential for the formation and functioning of BBB. The absence of ?-DB in null brains resulted in abnormal brain capillary permeability, progressively escalating brain edema, and damage of the neurovascular unit. Analyses in situ and in two-dimensional and three-dimensional in vitro models of BBB containing ?-DB-null astrocytes demonstrated these abnormalities to be associated with loss of aquaporin-4 water and Kir4.1 potassium channels from glial endfeet, formation of intracellular vacuoles in ?-DB-null astrocytes, and defects of the astrocyte-endothelial interactions. These caused deregulation of tight junction proteins in the endothelia. Importantly, ?-DB but not dystrophins showed continuous expression throughout development in BBB models. Thus, ?-DB emerges as a central organizer of dystrophin-associated protein in glial endfeet and a rare example of a glial protein with a role in maintaining BBB function. Its abnormalities might therefore lead to BBB dysfunction. PMID:23043099

  14. Curcumin inhibits apoptosis and brain edema induced by hypoxia-hypercapnia brain damage in rat models.

    PubMed

    Yu, Linsheng; Fan, Yanyan; Ye, Guanghua; Li, Junli; Feng, Xiangping; Lin, Kezhi; Dong, Miuwu; Wang, Zhenyuan

    2015-06-01

    Curcumin, extracted from South Asian spice turmeric, has been determined to have the promising ability in antioxidation and anti-inflammation. However, the effect of curcumin on treating brain damage has been not reported. In this article, the aim was to evaluate the effect of curcumin on cell apoptosis in rats exposed to hypoxia-hypercapnia and explore the therapeutic potential of curcumin in hypoxia-hypercapnia brain damage (HHBD). Sprague Dawley rats were randomly assigned into 3 groups: control group, hypoxia-hypercapnia group and curcumin group. The Fas/FasL expressions in HHBD rats treated by curcumin were measured by immunohistochemical staining and western blotting. The pathological changes of brain cells were observed by transmission electron microscope. Rats with HHBD showed significant increase of Fas/FasL expression and ultrastructural changes in brain tissue cells. Curcumin intervention effectively reversed the Fas/FasL-mediated apoptosis and HHBD-induced brain edema. Curcumin may be a potential therapeutic alternative for HHBD. PMID:25867253

  15. Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia.

    PubMed

    Lee, Kyungjin; Lee, Jeong-Sook; Jang, Hyeung-Jin; Kim, Sung-Moo; Chang, Mun Seog; Park, Si Hyung; Kim, Kwan Su; Bae, Jinhyun; Park, Jae-Woo; Lee, Bumjun; Choi, Ho-Young; Jeong, Chang-Hyun; Bu, Youngmin

    2012-08-15

    Chlorogenic acid (CGA) has been reported to have various beneficial effects on the cardiovascular and central nervous systems. The purpose of the current study was to investigate whether CGA has protective effects against cerebral ischemia and whether these effects are due to modification of brain edema-related vascular factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h of occlusion followed by 22 h of reperfusion), we measured infarct volume and performed behavioral test to evaluate the effects of CGA on brain damage and sensory-motor functional deficits. Brain water content and Evans blue extravasation were measured to evaluate brain edema and blood brain barrier (BBB) damage. Lipid peroxidation (LPO) and the expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms of action. Intraperitoneal injection of CGA (3, 10, and 30 mg/kg) at 0 h and 2h after MCAo dose-dependently reduced infarct volume and sensory-motor functional deficits. It also reduced brain water content and Evans blue extravasation. Mechanistically, CGA reduced LPO and MMPs expressions and activities. These results suggest that CGA reduces brain damage, BBB damage and brain edema by radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9. PMID:22659584

  16. [Generalized brain edema and cerebral infarct in ergotamine abuse: imaging by computerized tomography, magnetic resonance tomography and angiography].

    PubMed

    Toedt, C; Hötzinger, H; Salbeck, R; Beyer, H K

    1989-09-01

    Abuse of ergotamine can release a generalised brain edema and brain infarctions. This can be visualized by CT, MR and angiography. The reason, however, can only be found in the patients history. PMID:2591142

  17. Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

    PubMed Central

    Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

    2012-01-01

    Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

  18. Effect of Polyphenols on Oxidative Stress and Mitochondrial Dysfunction in Neuronal Death and Brain Edema in Cerebral Ischemia

    PubMed Central

    Panickar, Kiran S.; Anderson, Richard A.

    2011-01-01

    Polyphenols are natural substances with variable phenolic structures and are elevated in vegetables, fruits, grains, bark, roots, tea, and wine. There are over 8000 polyphenolic structures identified in plants, but edible plants contain only several hundred polyphenolic structures. In addition to their well-known antioxidant effects, select polyphenols also have insulin-potentiating, anti-inflammatory, anti-carcinogenic, anti-viral, anti-ulcer, and anti-apoptotic properties. One important consequence of ischemia is neuronal death and oxidative stress plays a key role in neuronal viability. In addition, neuronal death may be initiated by the activation of mitochondria-associated cell death pathways. Another consequence of ischemia that is possibly mediated by oxidative stress and mitochondrial dysfunction is glial swelling, a component of cytotoxic brain edema. The purpose of this article is to review the current literature on the contribution of oxidative stress and mitochondrial dysfunction to neuronal death, cell swelling, and brain edema in ischemia. A review of currently known mechanisms underlying neuronal death and edema/cell swelling will be undertaken and the potential of dietary polyphenols to reduce such neural damage will be critically reviewed. PMID:22174658

  19. HIGH MOBILITY GROUP BOX PROTEIN-1 PROMOTES CEREBRAL EDEMA AFTER TRAUMATIC BRAIN INJURY VIA ACTIVATION OF TOLL-LIKE RECEPTOR 4

    PubMed Central

    Laird, Melissa D.; Shields, Jessica S.; Sukumari-Ramesh, Sangeetha; Kimbler, Donald E.; Fessler, R. David; Shakir, Basheer; Youssef, Patrick; Yanasak, Nathan; Vender, John R.; Dhandapani, Krishnan M.

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor-4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI. PMID:24166800

  20. 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.

  1. Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice.

    PubMed

    McBride, Devin W; Donovan, Virginia; Hsu, Mike S; Obenaus, Andre; Rodgers, V G J; Binder, Devin K

    2016-01-01

    Traumatic brain injury (TBI), the foremost cause of morbidity and mortality in persons under 45 years of age worldwide, leads to about 200,000 victims requiring hospitalization and approximately 52,000 deaths per year in the United States. TBI is characterized by cerebral edema leading to raised intracranial pressure, brain herniation, and subsequent death. Current therapies for TBI treatment are often ineffective, thus novel therapies are needed. Recent studies have shown that an osmotic transport device (OTD) is capable of reducing brain water content and improving survival in mice with severe cerebral edema. Here we compare the effects of a craniectomy and an OTD plus craniectomy on neurological function in mice after TBI. Animals treated with a craniectomy plus an OTD had significantly better neurological function 2 days after TBI compared with those treated with craniectomy only. This study suggests that an OTD for severe brain swelling may improve patient functional outcome. Future studies include a more comprehensive neurological examination, including long-term memory tests. PMID:26463962

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

    PubMed

    Demirhan, Ay?e; 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. PMID:25265636

  3. Occludin and connexin 43 expression contribute to the pathogenesis of traumatic brain edema

    PubMed Central

    Ren, Wanyin; Jing, Guojie; Shen, Qin; Yao, Xiaoteng; Jing, Yingchao; Lin, Feng; Pan, Weidong

    2013-01-01

    The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney's free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Changes in brain water content were determined using the wet and dry weights. Our results showed that water content of tissue significantly increased after traumatic brain injury, and reached minimum at 24 hours. Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury, particularly at 3 days, with nerve cell edema, degenera-tion, and necrosis observed, and the apoptotic rate significantly increased. Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually de-creased as injury time advanced and reached a minimum at 3 days after injury; the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after in-jury. The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema, and may reflect the pathogenesis of brain injury. PMID:25206581

  4. Whole Blood Cardioplegia (Minicardioplegia) Reduces Myocardial Edema After Ischemic Injury and Cardiopulmonary Bypass

    PubMed Central

    McCann, Ulysses G.; Lutz, Charles J.; Picone, Anthony L.; Searles, Bruce; Gatto, Louis A.; Dilip, Karikehalli A.; Nieman, Gary F.

    2006-01-01

    Abstract: While blood:crystalloid cardioplegia is the clinical standard for patients undergoing cardiopulmonary bypass (CPB), it has been postulated that whole blood minicardioplegia may benefit the severely injured heart by reducing cardioplegic volume, thereby reducing myocardial edema. To test this hypothesis, we compared the cardioprotection of a popular 4:1 blood:crystalloid cardioplegia to whole blood minicardioplegia (WB) in a porcine model of acute myocardial ischemia. Yorkshire pigs (n = 20) were placed on atriofemoral bypass and subjected to 30 minutes of global normothermic ischemia. Animals were randomized to receive either 4:1 cold cardioplegia (n = 10) or WB cold cardioplegia (n = 10) delivered antegrade continuously for 90 minutes. Baseline (BL) echocardiographic determination of left ventricular mass (LVM) was compared within groups for cardiac edema (%) measured by histologic morphometrics. All (100%) animals receiving WB were successfully weaned off CPB, whereas only 40% of animals receiving 4:1 were successfully weaned off CPB. Cardiac edema percentage (p < .004) and LVM (p < .05) were significantly decreased in the WB group compared with 4:1. WB cardioplegia increases the number of hearts successfully weaned from CPB and decreases cardiac edema in our porcine model of acute myocardial ischemia. This finding implies whole blood cardioplegia may be more protective in a select group of patients undergoing extended CPB time by decreasing myocardial edema. PMID:16637518

  5. Ability of eugenol to reduce tongue edema induced by Dieffenbachia picta Schott in mice.

    PubMed

    Dip, Etyene Castro; Pereira, Nuno Alvarez; Fernandes, Patricia Dias

    2004-05-01

    Dieffenbachia picta Schott (Araceae), known in Brazil as "comigo-ninguém-pode" is an ornamental plant with toxic properties. Its juice, when chewed, causes a painful edema of the oral mucous membranes, buccal ulcerations and tongue hypertrophy. This acute inflammation sometimes becomes severe enough to produce glottis obstruction, respiratory compromise and death. Eugenol (4-alil-2-metoxiphenol), the essential oil extracted from Caryophyllus aromaticus (Myrtaceae) is widely used in odontology. In this study, our objective was to standardize, in mice, a measurable methodology for the tongue edema induced by the topical application of the D. picta stem juice; evaluate the effects of eugenol in this model and compare the results with emergency treatment used in hospitals. Our results show that in spite of a small increase in edema a few minutes after administration, emergency treatment reduced by 70% the overall edema. When compared with the combination of the above drugs, eugenol, even at the smallest dose of 5 microg/kg, regardless of the chosen administration route, or the moment the treatment began, presents better results in the reduction and inhibition of the tongue edema induced by the D. picta juice. PMID:15109894

  6. Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases

    PubMed Central

    Leeman, Jonathan E.; Clump, David A.; Flickinger, John C.; Mintz, Arlan H.; Burton, Steven A.; Heron, Dwight E.

    2013-01-01

    Background Differentiation of tumor recurrence from radionecrosis is a critical step in the follow-up management of patients treated with stereotactic radiosurgery (SRS) for brain metastases. A method that can reliably differentiate tumor recurrence from radiation necrosis using standard MR sequences would be of significant value. Methods We analyzed the records of 49 patients with 52 brain metastases treated with SRS who subsequently underwent surgical resection of the same lesion. Forty-seven of the lesions had preoperative MRI available for review (90%), including T1 postcontrast, T2, and fluid attenuated inversion recovery sequences. Pre-SRS and preoperative lesion and edema volumes were manually contoured and measured in a blinded fashion using radiation treatment planning software. A neuropathologist analyzed samples for the presence of tumor and/or radiation necrosis. Results Longer time between SRS and resection (P < .001) and a larger edema/lesion volume ratio (high T2/T1c, P = .002) were found to be predictive of radionecrosis as opposed to tumor recurrence. Using a cutoff value of 10 for the edema/lesion volume ratio, we were able to predict the presence of tumor with a positive predictive value of 92%, which increased to 100% when looking only at patients who underwent resection <18 months following SRS. Conclusions On follow-up imaging, lesions with a high edema/lesion volume ratio and lesions that progress later after SRS are more likely to contain radionecrosis. These indices may help guide clinical decision making in the context of evolving lesions after SRS for brain metastases and thereby avoid unnecessary interventions. PMID:24243914

  7. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure.

    PubMed

    Butterworth, Roger F

    2015-03-01

    Neuropathologic investigations in acute liver failure (ALF) reveal significant alterations to neuroglia consisting of swelling of astrocytes leading to cytotoxic brain edema and intracranial hypertension as well as activation of microglia indicative of a central neuroinflammatory response. Increased arterial ammonia concentrations in patients with ALF are predictors of patients at risk for the development of brain herniation. Molecular and spectroscopic techniques in ALF reveal alterations in expression of an array of genes coding for neuroglial proteins involved in cell volume regulation and mitochondrial function as well as in the transport of neurotransmitter amino acids and in the synthesis of pro-inflammatory cytokines. Liver-brain pro-inflammatory signaling mechanisms involving transduction of systemically-derived cytokines, ammonia neurotoxicity and exposure to increased brain lactate have been proposed. Mild hypothermia and N-Acetyl cysteine have both hepato-protective and neuro-protective properties in ALF. Potentially effective anti-inflammatory agents aimed at control of encephalopathy and brain edema in ALF include etanercept and the antibiotic minocycline, a potent inhibitor of microglial activation. Translation of these potentially-interesting findings to the clinic is anxiously awaited. PMID:26041966

  8. 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.

  9. 3D multimodal MRI brain glioma tumor and edema segmentation: a graph cut distribution matching approach.

    PubMed

    Njeh, Ines; Sallemi, Lamia; Ayed, Ismail Ben; Chtourou, Khalil; Lehericy, Stephane; Galanaud, Damien; Hamida, Ahmed Ben

    2015-03-01

    This study investigates a fast distribution-matching, data-driven algorithm for 3D multimodal MRI brain glioma tumor and edema segmentation in different modalities. We learn non-parametric model distributions which characterize the normal regions in the current data. Then, we state our segmentation problems as the optimization of several cost functions of the same form, each containing two terms: (i) a distribution matching prior, which evaluates a global similarity between distributions, and (ii) a smoothness prior to avoid the occurrence of small, isolated regions in the solution. Obtained following recent bound-relaxation results, the optima of the cost functions yield the complement of the tumor region or edema region in nearly real-time. Based on global rather than pixel wise information, the proposed algorithm does not require an external learning from a large, manually-segmented training set, as is the case of the existing methods. Therefore, the ensuing results are independent of the choice of a training set. Quantitative evaluations over the publicly available training and testing data set from the MICCAI multimodal brain tumor segmentation challenge (BraTS 2012) demonstrated that our algorithm yields a highly competitive performance for complete edema and tumor segmentation, among nine existing competing methods, with an interesting computing execution time (less than 0.5s per image). PMID:25467804

  10. 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

  11. Relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma

    PubMed Central

    Peng, Yihua; Shao, Chunhong; Gong, Ye; Wu, Xuehai; Tang, Weijun; Shi, Shenxun

    2015-01-01

    Background The purpose of this study is to assess the relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma. Methods We enrolled 65 consecutive patients with meningioma and 31 normal controls matched for age, gender, and education. The patients were divided into frontal or non-frontal (NF) meningioma groups based on magnetic resonance imaging; the frontal group was then subdivided to dorsolateral frontal (DLF), medial frontal (MF), and ventral frontal (VF) groups. Tumor size and brain edema were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES). Assessments were carried out 1 week before and 3 months after surgery, respectively. Logistic regression analysis was performed to identify the predictive effect of tumor size, location, and brain edema on apathy. Analysis of variance and chi-square analysis were applied to compare apathy scores and apathy rates among the frontal, NF, and normal control groups, and all subgroups within the frontal group. Results Compared with the NF and control groups, the mean AES score was much higher in the frontal group (34.0±8.3 versus 28.63±6.0, P=0.008, and 26.8±4.2, P<0.001). Subgroup analysis showed that AES scores in the MF group (42.1±6.6) and VF group (34.7±8.0) were higher than in the DLF group (28.5±4.36), NF group, and control group (P<0.05). The apathy rate was 63.6% in the MF group and 25% in the VF group, and significantly higher than in the DLF (5.6%), NF (5.3%), and control (0%) groups (P<0.001). A moderate correlation was found between AES score and mean diameter of the meningioma in all patient groups. Further analysis demonstrated that the correlation existed in the DLF (r=0.52, P=0.032), MF (r=0.84, P<0.001), and VF (r=0.64, P=0.008) groups, but not in the NF group (r=0.19, P=0.448). The AES score was much higher in patients with brain edema than in those without brain edema (34.73±8.28 versus 28.77±4.20, t=3.545, P=0.001). In subgroups within frontal meningioma patients, the statistical significance above only existed in the MF group (43.50±5.26 versus 25.67±6.03, P=0.001). Also, we examined the effect of related factors, such as age, sex, education, tumor size, tumor location and edema on the occurrence of apathy. The binary logistic regression analysis showed that MF [P=0.023, Exp(B) =145.6] and size [P=0.012, Exp(B) =1.20] got into the regression equation. Thirty-two patients underwent follow-up post-surgery. A significant reduction in AES was found in the MF group (AES1 – AES2 =6.86±6.82, t=2.68, P=0.04), but not in any of the other groups. Conclusion Apathy occurs frequently in patients with frontal meningioma, and is more severe, especially in the MF region. Apathy is probably correlated with tumor location and size. Brain edema might increase the severity of apathy. PMID:26203250

  12. The Effects of Estrogen Receptors' Antagonist on Brain Edema, Intracranial Pressure and Neurological Outcomes after Traumatic Brain Injury in Rat

    PubMed Central

    Dehghan, Fatemeh; Khaksari, Mohammad; Abbasloo, Elham; Shahrokhi, Nader

    2015-01-01

    Background: In previous studies, the neuroprotective effect of 17?-estradiol in diffuse traumatic brain injury has been shown. This study used ICI 182,780, a non-selective estrogen receptor antagonist, to test the hypothesis that the neuroprotective effect of 17?-estradiol in traumatic brain injury is mediated by the estrogen receptors. Methods: The ovariectomized rats were divided into eight groups. Brain injury was induced by Marmarou’s method. Estrogen was injected 30 minutes after traumatic brain injury, and ICI 182,780 was injected before traumatic brain injury and also before estrogen treatment. In one group only ICI 182,780 was injected. The brain water content and Evans blue dye content were measured 24 and 5 hours after traumatic brain injury, respectively. The neurologic outcomes and intracranial pressure were assessed before, 4, and 24 hours after traumatic brain injury. Results: Brain water content and Evans blue content were less in estrogen-treated group comparison to vehicle group. ICI 182,780 eliminated the effects of estrogen on brain edema and brain blood barrier permeability. Intracranial pressure was increased significantly after trauma, and estrogen decreased intracranial pressure at 4 and 24 hours after traumatic brain injury in comparison to vehicle. This inhibitory effect was also eliminated by treatment with ICI182,780. ICI 182,780 also inhibited the estrogen induced increase in neurologic outcomes following traumatic brain injury. However, the use of ICI 182,780 alone had no neuroprotective effect after traumatic brain injury. Conclusion: The results suggest that classical estrogen receptors have probably a role in the neuroprotective function of estrogen following traumatic brain injury. PMID:26024665

  13. Tumor-associated edema in brain cancer patients: pathogenesis and management.

    PubMed

    Roth, Patrick; Regli, Luca; Tonder, Michaela; Weller, Michael

    2013-11-01

    The long-term treatment of peritumoral edema remains a major challenge in clinical neuro-oncology. Steroids have been and will remain the backbone of any anti-edematous therapy because of their striking activity, convenient oral administration and also because of their cost-effectiveness. Their side effects, however, can compromise quality of life, particularly upon continuous administration. Therapeutic alternatives which may replace or - at least - help to reduce the steroid dose are limited. However, with the development of new agents such as corticorelin acetate, there is a hope that steroid-induced side effects can be delayed and reduced. The administration of anti-angiogenic agents with steroid-sparing effects, for example, bevacizumab, is limited due to their costs. Increased knowledge on boswellic acids and cyclooxygenase-2 inhibitors which are available for clinical application may help to exploit their anti-edema activity more efficiently in the future. PMID:24152171

  14. 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. PMID:25000290

  15. Amelioration of Cold Injury-Induced Cortical Brain Edema Formation by Selective Endothelin ETB Receptor Antagonists in Mice

    PubMed Central

    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. PMID:25000290

  16. A new method for the early diagnosis of brain edema/brain swelling. An experimental study in rabbits.

    PubMed

    Kostopoulos, V; Douzinas, E E; Kypriades, E M; Pappas, Y Z

    2006-01-01

    The aim of the present work is to develop a non-destructive, non-invasive technique for the early diagnosis of an oncoming brain edema based on the variation of vibration characteristics of the head system (i.e. eigenfrequency spectrum and modal damping). Besides the theoretical model that supports the basic principle, the proposed technique has been verified experimentally in animal tests. The advantage of such an approach is that the relative information is available well in advance an increase of intracranial pressure is detected. The uncontrolled intracranial hypertension is associated with increased mortality or vegetative state in head trauma. Traumatic lesions located on temporal lobe render particularly impeding the transtendorial herniation. From the medical point of view, intracranial pressure (ICP) monitoring represents an effective way for early consideration of neurological decompensation in various neurosurgical conditions particularly in the head-injured setting. However, the use of ICP monitoring is not an effective way of brain edema detection, since ICP increase very often causes irreversible problems to the patient's brain. Therefore, the determination of an earlier, less invasive and more sensitive indicator of the oncoming intracranial hypertension and of the impeding neurological deterioration is of profound importance. The present work aims at experimental verification of both eigenfrequency shifting and modal damping increase of the spectral response of the head system of rabbits, wherever a mass increase in the content of cranial shell appears. The conducted analysis concludes that the eigenfrequency spectrum and its modal damping characteristics are sufficiently sensitive parameters in order to characterize mass increase in the cranial shell. Therefore the combination of both the above parameters could be used with confidence for the early diagnosis of brain edema. PMID:16413930

  17. Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN

    NASA Astrophysics Data System (ADS)

    Pradhan, Nandita; Sinha, A. K.

    2008-03-01

    This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels. The k-means algorithm is used to cluster the image based on the feature vectors of blocks forming different classes representing different regions in the whole image. With the knowledge of the feature vectors of different segmented regions, supervised technique is used to train Artificial Neural Network using fuzzy back propagation algorithm (FBPA). Segmentation for detecting healthy tissues and tumors has been reported by several researchers by using conventional MRI sequences like T1, T2 and PD weighted sequences. This work successfully presents segmentation of healthy and pathological tissues (both Tumors and Edema) using FLAIR images. At the end pseudo coloring of segmented and classified regions are done for better human visualization.

  18. A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation

    PubMed Central

    Finsterwalder, Richard; Friedl, Heinz P.; Rauscher, Sabine; Gröger, Marion; Kocher, Alfred; Wagner, Christine; Wagner, Stephan N.; Fischer, Gottfried; Schultz, Marcus J.; Wiedemann, Dominik; Petzelbauer, Peter

    2015-01-01

    Background Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself. Methods We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting. Results XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host. Conclusions In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation. PMID:26536466

  19. Anti-edema action of thyroid hormone in MCAO model of ischemic brain stroke: Possible association with AQP4 modulation.

    PubMed

    Sadana, Prabodh; Coughlin, Lucy; Burke, Jamie; Woods, Robert; Mdzinarishvili, Alexander

    2015-07-15

    The use of neuroprotective strategies to mitigate the fatal consequences of ischemic brain stroke is a focus of robust research activity. We have previously demonstrated that thyroid hormone (T3; 3,3',5-triiodo-l-thyronine) possesses neuroprotective and anti-edema activity in pre-stroke treatment regimens when administered as a solution or as a nanoparticle formulation. In this study we have extended our evaluation of thyroid hormone use in animal models of brain stroke. We have used both transient middle cerebral artery occlusion (t-MCAO) and permanent (p-MCAO) models of ischemic brain stroke. A significant reduction of tissue infarction and a concurrent decrease in edema were observed in the t-MCAO model of brain stroke. However, no benefit of T3 was observed in p-MCAO stroke setting. Significant improvement of neurological outcomes was observed upon T3 treatment in t-MCAO mice. Further, we tested T2 (3,5-diiodo-l-thyronine) a natural deiodination metabolite of T3 in MCAO model of brain stroke. T2 potently decreased infarct size as well as edema formation. Additionally, we report here that T3 suppresses the expression of aquaporin-4 (AQP4) water channels which could be a likely mechanism of its anti-edema activity. Our studies provide evidence to stimulate clinical development of thyroid hormones for use in ischemic brain stroke. PMID:25963308

  20. Peritumoral Brain Edema after Stereotactic Radiosurgery for Asymptomatic Intracranial Meningiomas: Risks and Pattern of Evolution

    PubMed Central

    Hoe, Yeon; Choi, Young Jae; Kim, Jeong Hoon; Kwon, Do Hoon; Kim, Chang Jin

    2015-01-01

    Objective To investigate the risks and pattern of evolution of peritumoral brain edema (PTE) after stereotactic radiosurgery (SRS) for asymptomatic intracranial meningiomas. Methods A retrospective study was conducted on 320 patients (median age 56 years, range 24-87 years) who underwent primary Gamma Knife radiosurgery for asymptomatic meningiomas between 1998 and 2012. The median tumor volume was 2.7 cc (range 0.2-10.5 cc) and the median follow-up was 48 months (range 24-168 months). Volumetric data sets for tumors and PTE on serial MRIs were analyzed. The edema index (EI) was defined as the ratio of the volume of PTE including tumor to the tumor volume, and the relative edema indices (rEIs) were calculated from serial EIs normalized against the baseline EI. Risk factors for PTE were analyzed using logistic regression. Results Newly developed or increased PTE was noted in 49 patients (15.3%), among whom it was symptomatic in 28 patients (8.8%). Tumor volume larger than 4.2 cc (p<0.001), hemispheric tumor location (p=0.005), and pre-treatment PTE (p<0.001) were associated with an increased risk of PTE. rEI reached its maximum value at 11 months after SRS and decreased thereafter, and symptoms resolved within 24 months in most patients (85.7%). Conclusion Caution should be exercised in decision-making on SRS for asymptomatic meningiomas of large volume (>4.2 cc), of hemispheric location, or with pre-treatment PTE. PTE usually develops within months, reaches its maximum degree until a year, and resolves within 2 years after SRS. PMID:26587194

  1. 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. PMID:26285064

  2. Effect of propofol post-treatment on blood-brain barrier integrity and cerebral edema after transient cerebral ischemia in rats.

    PubMed

    Lee, Jae Hoon; Cui, Hui Song; Shin, Seo Kyung; Kim, Jeong Min; Kim, So Yeon; Lee, Jong Eun; Koo, Bon-Nyeo

    2013-11-01

    Although propofol has been reported to offer neuroprotection against cerebral ischemia injury, its impact on cerebral edema following ischemia is not clear. The objective of this investigation is to evaluate the effects of propofol post-treatment on blood-brain barrier (BBB) integrity and cerebral edema after transient cerebral ischemia and its mechanism of action, focusing on modulation of aquaporins (AQPs), matrix metalloproteinases (MMPs), and hypoxia inducible factor (HIF)-1?. Cerebral ischemia was induced in male Sprague-Dawley rats (n = 78) by occlusion of the right middle cerebral artery for 1 h. For post-treatment with propofol, 1 mg kg(-1) min(-1) of propofol was administered for 1 h from the start of reperfusion. Nineteen rats undergoing sham surgery were also included in the investigation. Edema and BBB integrity were assessed by quantification of cerebral water content and extravasation of Evans blue, respectively, following 24 h of reperfusion. In addition, the expression of AQP-1, AQP-4, MMP-2, and MMP-9 was determined 24 h after reperfusion and the expression of HIF-1? was determined 8 h after reperfusion. Propofol post-treatment significantly reduced cerebral edema (P < 0.05) and BBB disruption (P < 0.05) compared with the saline-treated control. The expression of AQP-1, AQP-4, MMP-2, and MMP-9 at 24 h and of HIF-1? at 8 h following ischemia/reperfusion was significantly suppressed in the propofol post-treatment group (P < 0.05). Propofol post-treatment attenuated cerebral edema after transient cerebral ischemia, in association with reduced expression of AQP-1, AQP-4, MMP-2, and MMP-9. The decreased expression of AQPs and MMPs after propofol post-treatment might result from suppression of HIF-1? expression. PMID:23990224

  3. Oxidative Damage is Present in the Fatal Brain Edema of Diabetic Ketoacidosis

    PubMed Central

    Hoffman, William H.; Siedlak, Sandra L.; Wang, Yang; Castellani, Rudy J.; Smith, Mark A.

    2011-01-01

    Oxidative stress is implicated as a pathogenic factor in a spectrum of chronic diseases, notably, neurodegenerative disease. Noteworthy in this regard is that type 1 diabetes mellitus (T1DM) results in oxidative stress, leading to systemic complications of T1DM. We hypothesized that oxidative stress associated with diabetic ketoacidosis (DKA) of T1DM might have measurable brain sequelae. Consistent with this hypothesis are neurohistology and neuroradiologic studies of T1DM that suggest that oxidative insults are involved in the chronic complications of diabetic encephalopathy. To further address the role of oxidative stress in an acute setting, specifically in fatal brain edema (BE) associated with DKA, we studied neuronal localization and levels of oxidative stress markers reported to be increased in other neurodegenerative conditions. We demonstrated increased levels of 8-hydroxyguansine (8OHG), 4-hydroxynonenal (HNE) and hemeoxygenase-1 (HO-1) in the pyramidal neurons of the hippocampus of DKA BE in comparison to controls. However, in the cerebellum, only 8OHG was increased in the Purkinje cells and other cells of the molecular layer. These results indicate a role for oxidative stress in the pathogenesis of T1DM encephalopathy. PMID:21040714

  4. Brain edema formation correlates with perfusion deficit during the first six hours after experimental subarachnoid hemorrhage in rats

    PubMed Central

    2012-01-01

    Background Severe brain edema is observed in a number of patients suffering from subarachnoid hemorrhage (SAH). Little is known about its pathogenesis and time-course in the first hours after SAH. This study was performed to investigate the development of brain edema and its correlation with brain perfusion after experimental SAH. Methods Male Sprague–Dawley rats, randomly assigned to one of six groups (n = 8), were subjected to SAH using the endovascular filament model or underwent a sham operation. Animals were sacrificed 15, 30, 60, 180 or 360 minutes after SAH. Intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and bilateral local cerebral blood flow (LCBF) were continuously measured. Brain water content (BWC) was determined by the wet/dry-weight method. Results After SAH, CPP and LCBF rapidly decreased. The decline of LCBF markedly exceeded the decline of CPP and persisted until the end of the observation period. BWC continuously increased. A significant correlation was observed between the BWC and the extent of the perfusion deficit in animals sacrificed after 180 and 360 minutes. Conclusions The significant correlation with the perfusion deficit after SAH suggests that the development of brain edema is related to the extent of ischemia and acute vasoconstriction in the first hours after SAH. PMID:22551223

  5. Progesterone attenuates cerebral edema in neonatal rats with hypoxic-ischemic brain damage by inhibiting the expression of matrix metalloproteinase-9 and aquaporin-4

    PubMed Central

    WANG, XIAOYIN; ZHANG, JUNHE; YANG, YUXIN; DONG, WEIHUA; WANG, FANG; WANG, LI; LI, XIAOJUAN

    2013-01-01

    The aim of this study was to investigate the effects of progesterone (PROG) on blood-brain barrier (BBB) permeability, cerebral edema and the expression of matrix metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore the mechanism of its neuroprotective effect. Sixty 7-day-old Wistar rats were divided into sham surgery, hypoxic ischemia (HI) and drug prophylaxis (PROG) groups. HIBD animal models were established. All the animals were sacrificed after 24 h. The BBB was assessed using Evans blue. Cerebral moisture capacity was determined using the dry-wet method. MMP-9 was detected in the brain tissues using enzyme-linked immunosorbent assay. The expression of AQP-4 and MMP-9 in the cerebral cortex was observed using immunohistochemistry and real-time polymerase chain reaction. The MMP-9 levels in the cortex, BBB permeability, cerebral moisture capacity and expression of AQP-4 and MMP-9 in the HI group were significantly higher compared with those in the sham surgery group (P<0.01), and they were significantly lower in the drug prophylaxis group compared with those in the HI group (P<0.05). In conclusion, PROG reduces BBB damage and cerebral edema and inhibits MMP-9 generation to protect rat brains against HIBD. The protective effect of PROG may be correlated with downregulated expression of AQP-4 and MMP-9 in the cerebral cortex. PMID:23935758

  6. 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 ?g) or IRL-2500 (10 ?g) (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. PMID:26174228

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

    PubMed Central

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

    2015-01-01

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

  8. PGJ2 Provides Prolonged CNS Stroke Protection by Reducing White Matter Edema

    PubMed Central

    Nicholson, James D.; Puche, Adam C.; Guo, Yan; Weinreich, Daniel; Slater, Bernard J.; Bernstein, Steven L.

    2012-01-01

    Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NF?B-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-?12,14-prostaglandin J2 (PGJ2), an analog of the metabolically active PGD2 metabolite. We evaluated PGJ2's effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION); an in vivo white matter ischemia model. PGJ2 administration systemically administered either acutely or 5 hours post-insult results in significant neuroprotection, with stereologic evaluation showing improved neuronal survival 30 days post-infarct. Quantitative capillary vascular analysis reveals that PGJ2 improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ2 acts by reducing NF?B signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ2 showed no in vivo toxicity structurally as measured by optic nerve (ON) myelin thickness, functionally by ON-compound action potentials, on a cellular basis by oligodendrocyte precursor survival or changes in ON-myelin gene expression. PGJ2 may be a clinically useful neuroprotective agent for ON and other CNS infarcts involving white matter, with mechanisms of action enabling effective treatment beyond the currently considered maximal time for intervention. PMID:23284631

  9. Radiation brain injury is reduced by the polyamine inhibitor [alpha]-difluoromethylornithine

    SciTech Connect

    Fike, J.R.; Seilhan, T.M.; Gobbel, G.T. ); Marton, L.J. )

    1994-04-01

    [alpha]-difluoromethylornithine (DFMO) was used to reduce [sup 125]I-induced brain injury in normal beagle dogs. Different DFMO doses and administration schedules were used to determine if the reduction in brain injury was dependent on dose and/or dependent upon when the drug was administered relative to the radiation treatment. Doses of DMFO of 75 mg/kg/day and 37.5 mg/kg/day given 2 days before, during and for 14 days after irradiation reduced levels of putrescine (PU) in the cerebrospinal fluid relative to controls. Volume of edema was significantly reduced by 75 mg/kg/day of DFMO before, during and after irradiation and by the same dose when the drug was started immediately after irradiation. A reduction in edema volume after 37.5 mg/kg/day of DFMO before, during and after irradiation was very near significance. Ultrafast CT studies performed on dogs that received a DFMO dose of 75 mg/kg/day before, during and after irradiation suggested that the reduce edema volume was associated with reduced vascular permeability. Volume of necrosis and volume of contrast enhancement (breakdown of the blood-brain barrier) were significantly lower than controls only after a DFMO dose of 75 mg/kg/day before, during and after irradiation. These latter data, coupled with the findings relative to edema, suggest that different mechanisms may be involved with respect to the effects of DFMO on brain injury, or that the extents of edema, necrosis and breakdown of the blood-brain barrier may depend upon different levels of polyamine depletion. The precise mechanisms by which DFMO exerts the effects observed here need to be determined. 41 refs., 5 figs.

  10. Mildly Reduced Brain Swelling and Improved Neurological Outcome in Aquaporin-4 Knockout Mice following Controlled Cortical Impact Brain Injury.

    PubMed

    Yao, Xiaoming; Uchida, Kazuyoshi; Papadopoulos, Marios C; Zador, Zsolt; Manley, Geoffrey T; Verkman, Alan S

    2015-10-01

    Brain edema following traumatic brain injury (TBI) is associated with considerable morbidity and mortality. Prior indirect evidence has suggested the involvement of astrocyte water channel aquaporin-4 (AQP4) in the pathogenesis of TBI. Here, focal TBI was produced in wild type (AQP4(+/+)) and knockout (AQP4(-/-)) mice by controlled cortical impact injury (CCI) following craniotomy with dura intact (parameters: velocity 4.5?m/sec, depth 1.7?mm, dwell time 150 msec). AQP4-deficient mice showed a small but significant reduction in injury volume in the first week after CCI, with a small improvement in neurological outcome. Mechanistic studies showed reduced intracranial pressure at 6?h after CCI in AQP4(-/-) mice, compared with AQP4(+/+) control mice (11 vs. 19?mm Hg), with reduced local brain water accumulation as assessed gravimetrically. Transmission electron microscopy showed reduced astrocyte foot-process area in AQP4(-/-) mice at 24?h after CCI, with greater capillary lumen area. Blood-brain barrier disruption assessed by Evans blue dye extravasation was similar in AQP4(+/+) and AQP4(-/-) mice. We conclude that the mildly improved outcome in AQP4(-/-) mice following CCI results from reduced cytotoxic brain water accumulation, though concurrent cytotoxic and vasogenic mechanisms in TBI make the differences small compared to those seen in disorders where cytotoxic edema predominates. PMID:25790314

  11. Analysis of animal models of macular edema.

    PubMed

    Bellhorn, R W

    1984-05-01

    Various models of macular edema have been studied; however, frank development of a prototypical cystoid macular edema has not been observed. In humans, cystoid edema is frequently observed in association with other disturbances of the retina. Thus, a basic drawback of the animal models may be that an otherwise healthy retina is capable of resolving the experimentally produced edema, thereby preventing chronic cystoid maculopathy. A review of macular edema models and of experimental retinal and brain edema investigations suggests that blood-retinal (blood-brain) barrier permeability abnormalities need to be accompanied by ineffective edema resolving mechanisms for the production of a chronic edema. Intraglial uptake of extravasated serum proteins has been hypothesized to be an edema-resolving mechanism in brain edema. As such, the hypothesis that the Müller cell may be important to edema resolution appears attractive. Future animal model studies should include methodologies whereby edema resolution mechanisms are impaired. PMID:6379949

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

    PubMed Central

    Zhang, Bo; Wang, Bing; Cao, Shuhua

    2015-01-01

    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-1? and TNF-? 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 p47phox 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

  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 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

  14. Acute administration of 3,4-methylenedioxymethamphetamine induces profound hyperthermia, blood-brain barrier disruption, brain edema formation, and cell injury.

    PubMed

    Sharma, Hari Shanker; Ali, Syed F

    2008-10-01

    The psychostimulant 3,4-,ethylenedioxymethamphetamine (MDMA, "ecstasy") is known to induce hyperthermia and alterations in neurochemical metabolism in the CNS. However, the detailed cellular or molecular mechanisms behind MDMA-induced neurotoxicity are still not well known. Since MDMA induces profound hyperthermia that could lead to intense cellular stress and cause disruption of the blood-brain barrier (BBB), this investigation examined the effects of acute MDMA on BBB dysfunction, brain edema, and cell injury in rats and mice. When MDMA (40 mg/kg, i.p.) was administered to rats or mice, these animals exhibited profound behavioral disturbances (hyperactivity and hyperlocomotion) and hyperthermia (>40 to 41 degrees C) at 4 h. At this time, the leakage of Evans blue dye was evident, particularly in the cerebellum, hippocampus, cortex, thalamus, and hypothalamus. This effect was most pronounced in mice compared to rats. Marked increase in brain water along with Na(+), K(+), and Cl(-) content was also seen in the aforementioned brain regions. Presence of distorted neuronal and glial cells in brain regions associated with leakage of Evans blue is quite common in MDMA-treated animals. Increased albumin immunoreactivity, indicating breakdown of the BBB, and upregulation of glial fibrillary acidic protein (GFAP), suggesting activation of astrocytes, were seen in most brain regions showing edematous changes. Upregulation of heat-shock protein (HSP72) immunoreactivity in the nuclei and cell cytoplasm of the neurons located in the edematous brain regions are quite common. Taken together, these observations are the first to show that MDMA has the capacity to disrupt BBB permeability to proteins and to induce the formation of edema, probably by inducing hyperthermia and cellular stress, as evident with HSP overexpression leading to cell injury. PMID:18991870

  15. Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation.

    PubMed

    Su, Wei-Shen; Tsai, Min-Lan; Huang, Sin-Luo; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-12-01

    It has been shown that the blood-brain barrier (BBB) can be locally disrupted by focused ultrasound (FUS) in the presence of microbubbles (MB) while sustaining little damage to the brain tissue. Thus, the safety issue associated with FUS-induced BBB disruption (BBBD) needs to be investigated for future clinical applications. This study demonstrated the neuroprotective effects induced by low-intensity pulsed ultrasound (LIPUS) against brain injury in the sonicated brain. Rats subjected to a BBB disruption injury received LIPUS exposure for 5 min after FUS/MB application. Measurements of BBB permeability, brain water content, and histological analysis were then carried out to evaluate the effects of LIPUS. The permeability and time window of FUS-induced BBBD can be effectively modulated with LIPUS. LIPUS also significantly reduced brain edema, neuronal death, and apoptosis in the sonicated brain. Our results show that brain injury in the FUS-induced BBBD model could be ameliorated by LIPUS and that LIPUS may be proposed as a novel treatment modality for controllable release of drugs into the brain. PMID:26517350

  16. CEREBRAL ISCHEMIA-REPERFUSION INJURY IN RATS – A 3 T MRI STUDY ON BIPHASIC BLOOD-BRAIN BARRIER OPENING AND THE DYNAMICS OF EDEMA FORMATION

    PubMed Central

    Pillai, Deepu R.; Dittmar, Michael S.; Baldaranov, Dobri; Heidemann, Robin M.; Henning, Erica C.; Schuierer, Gerhard; Bogdahn, Ulrich; Schlachetzki, Felix

    2010-01-01

    Serial magnetic resonance imaging (MRI) was performed to investigate the temporal and spatial relationship between the biphasic nature of blood-brain barrier (BBB) opening and in parallel, edema formation following ischemia-reperfusion (I/R) injury in rats. T2-weighted imaging combined with T2-relaxometry mainly for edema assessment was performed at 1 hour post-ischemia, following reperfusion, and at 4, 24, and 48 hours post-reperfusion. T1-weighted imaging was performed pre/post-gadolinium contrast at the last three time points to assess BBB integrity. The biphasic course of BBB opening with significant reduction in BBB permeability at 24 hours post-reperfusion associated with progressive expansion of leaky BBB volume was accompanied by a peak ipsilateral edema formation. In addition, at 4 hours post-reperfusion, edema formation could also be detected at the contralateral striatum as determined by the elevated T2 values that persisted to varying degrees indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in mechanisms responsible for bi-phasic BBB permeability changes with complex relations to edema formation. Stroke therapy aimed at vasogenic edema and drug delivery for neuroprotection may also be guided according to the functional status of the BBB and these findings should be confirmed in human stroke. PMID:19654585

  17. Pulmonary edema

    MedlinePLUS

    Pulmonary edema is an abnormal buildup of fluid in the lungs. This buildup of fluid leads to shortness of ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  18. Symmetrical Curvilinear Cytotoxic Edema Along the Surface of the Brain Stem: A Probable New Magnetic Resonance Imaging Finding of Leptomeningeal Carcinomatosis

    PubMed Central

    Khil, Eun Kyung; Lee, A Leum; Chang, Kee-Hyun; Yun, Tae Jin; Hong, Hyun Sook

    2015-01-01

    Abstract Lung cancer is one of the most common neoplasms to appear leptomeningeal metastasis (LM). Contrast-enhanced magnetic resonance imaging (MRI) is better diagnostic choice for LM and usually shows focal nodular or diffuse linear enhancement on the leptomeninges along the sulci and tentorium in the brain. We experienced atypical 2 cases of lung cancer in patients who showed unusual brain MRI finding of symmetrical curvilinear or band-like, nonenhancing cytotoxic edema along the surface of the brain stem. This finding is unique and different from the general findings of leptomeningeal metastasis. This unique imaging finding of symmetric curvilinear nonenhancing cytotoxic edema along the brainstem is extremely rare and represents a new presentation of leptomeningeal carcinomatosis. PMID:26200611

  19. Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15.

    PubMed

    Streffer, J R; Bitzer, M; Schabet, M; Dichgans, J; Weller, M

    2001-05-01

    Twelve patients with brain tumors and progressive edema caused by tumor progression or radiochemotherapy-related leukoencephalopathy were treated with H15, a phytotherapeutic anti-inflammatory agent. Edema was reduced in two of seven patients with glioblastoma with tumor progression and in three of five patients with treatment-related leukoencephalopathy. All patients with leukoencephalopathy improved clinically for several months. PMID:11342692

  20. Deep brain stimulation to reduce sexual drive

    PubMed Central

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  1. Deep brain stimulation to reduce sexual drive.

    PubMed

    Fuss, Johannes; Auer, Matthias K; Biedermann, Sarah V; Briken, Peer; Hacke, Werner

    2015-11-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  2. An aqueous extract of Ilex paraguariensis reduces carrageenan-induced edema and inhibits the expression of cyclooxygenase-2 and inducible nitric oxide synthase in animal models of inflammation.

    PubMed

    Schinella, Guillermo; Neyret, Elisa; Cónsole, Gloria; Tournier, Horacio; Prieto, José M; Ríos, José-Luis; Giner, Rosa María

    2014-08-01

    Mate (Ilex paraguariensis) is a highly popular herbal beverage in South America due to its high content of caffeine. Its hypolipidemic and antioxidant properties are of increasing interest in the treatment of cardiovascular disorders and for weight control. In the present study, we show for the first time both the local and systemic anti-inflammatory effects of an aqueous extract of mate in three classic in vivo models, namely acute and chronic 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema and acute carrageenan-induced mouse paw edema. Caffeine, rutin, chlorogenic acid, 3,5-dicafeoyl quinic acid, and 4,5-dicafeoyl quinic acid, accompanied by a complex mixture of other simple phenolic acids, were identified in the extract by HPLC-UV analyses. In the acute edema model, mate extract applied topically (1?mg/ear) halved the 12-O-tetradecanoylphorbol 13-acetate-induced acute edema (50?%) and almost suppressed neutrophil infiltration (93?%), while in the 12-O-tetradecanoylphorbol 13-acetate-induced subchronic inflammation, the edema was significantly reduced by 62?% (1?mg/ear/day × seven doses). The oral administration of the mate extract (250?mg/kg) significantly reduced the carrageenan-induced edema at all time points, an effect which was accompanied by a 43?% and 53?% reduction of the expression of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Histological analyses confirmed a reduction of epithelium thickness, dermis with mild inflammation, hair follicles with some secretory cells of sebaceous glands, and hypodermic adipocytes. In conclusion, mate is endowed with in vivo preventative or therapeutic anti-inflammatory effects in both local and systemic inflammatory processes. PMID:25089736

  3. Progesterone is neuroprotective by inhibiting cerebral edema after ischemia

    PubMed Central

    Zhao, Yuan-zheng; Zhang, Min; Liu, Heng-fang; Wang, Jian-ping

    2015-01-01

    Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema. PMID:26330829

  4. Diabetic macular edema.

    PubMed

    Stefánsson, Einar

    2009-07-01

    A variety of treatment options are available for the treatment of diabetic macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal steroids, and vitrectomy with or without release of vitreoretinal traction. A full understanding of the physiological mechanisms of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and thereby decreases leakage of plasma proteins from capillaries into the tissue. In addition, vitrectomy allows faster clearance of cytokines, such as VEGF, from the retina into the vitreous cavity. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary permeability. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF-induced vascular permeability causes plasma protein to leak into the tissue interstitial space, thus decreasing the osmotic pressure gradient between vessel and tissue, resulting in water accumulation, i.e. edema. This is reversed by reducing VEGF production, which is achieved with laser treatment; or by removing VEGF with antibodies or vitrectomy; or by reducing the permeability effect with steroids. At the same time, Starling's law takes into account hemodynamic changes that affect the hydrostatic gradient. High arterial blood pressure and hypoxic vasodilatation increase the hydrostatic pressure in the microcirculation, which increases water flux from vessel to tissue and induce edema. Treatment of arterial hypertension or reversal of retinal hypoxia with laser reverses this pathophysiology and reduces edema. Newton's third law explains, that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient between vessel and tissue, and stimulates water fluxes from vessel into tissue, leading to edema. Release of vitreoretinal traction reverses this mechanism and reduces edema. PMID:23960851

  5. Medulla oblongata edema associated with neurogenic pulmonary edema. Case report.

    PubMed

    Brown, R H; Beyerl, B D; Iseke, R; Lavyne, M H

    1986-03-01

    Neurogenic pulmonary edema (NPE) occurs in association with central nervous system disease without underlying cardiopulmonary problems. It is characterized by profound pulmonary vascular congestion and a fulminant clinical course. Although several reports document a role for experimental brain-stem lesions in the production of NPE, there have been only two studies in man correlating specific brain-stem lesions with NPE. The authors report a case of NPE occurring in a patient with von Hippel-Lindau disease and a dorsal medullary syrinx with postoperative dorsal medullary edema. The anatomical location of this patient's lesion is reviewed in the context of alternative theories of the pathogenesis of NPE. PMID:3950726

  6. Over-expression of laminin correlates to recovery of vasogenic edema following status epilepticus.

    PubMed

    Kim, Y-J; Kim, J-Y; Ko, A-R; Kang, T-C

    2014-09-01

    In the present study, we addressed the question of whether the up-regulation of laminin expression represents the astroglio-vascular responses to status epilepticus (SE) in the rat brain to better understand the role of vasogenic edema in epileptogenic insult. In the hippocampus, vasogenic edema was observed in the hippocampus 12h after SE when astroglial degeneration was undetected. Vasogenic edema in the hippocampus was more severe in the CA1 region where astroglial loss was absent than in the dentate gyrus showing astroglial degeneration. In the piriform cortex (PC), vasogenic edema was accompanied by appearance of astroglial degeneration 12h after SE. Laminin expression in the hippocampus and the PC was increased 3 days and 4 days after SE, respectively. Laminin expression was up-regulated in the hippocampus and the PC with concomitant reduction of SMI-71 (the endothelial barrier antigen) expression. Four weeks after SE, laminin expression was reduced in vessels showing strong SMI-71 expression within vasogenic edema lesion. Inhibition of SE-induced vasogenic edema formation by BQ788 effectively prevented laminin over-expression. Therefore, our findings indicate that laminin over-expression may be one of consequences from vasogenic edema rather than astroglial loss, and that laminin over-expression may promote migration of astrocytes to damaged or newly generated vessels to repair brain-blood barrier (BBB) disruption accompanied by the reconstruction of endothelial barrier. PMID:24931765

  7. Reducing Test Anxiety: A Right Brain Approach.

    ERIC Educational Resources Information Center

    Cohen, Ruth I.

    Methods of helping students reduce test anxiety are discussed, including guided fantasy which leads students to imagine a setting in which they feel competent and relaxed. Catastrophic-anastrophic expectations teach that different expectations create different feelings and make students aware that they are in charge of their own attitudes. Anxiety…

  8. A single dose of PPAR? agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.

    PubMed

    Pilipovi?, Kristina; Župan, Željko; Dolenec, Petra; Mrši?-Pel?i?, Jasenka; Župan, Gordana

    2015-06-01

    Neuroprotective actions of the peroxisome proliferator-activated receptor-? (PPAR?) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPAR? agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI. PMID:25579788

  9. Extent of Contrast Enhancement on Non-Enhanced Computed Tomography after Intra-Arterial Thrombectomy for Acute Infarction on Anterior Circulation: As a Predictive Value for Malignant Brain Edema

    PubMed Central

    Song, Seung Yoon; Rhee, Jong Ju; Lee, Jong Won; Hur, Jin Woo; Lee, Hyun Koo

    2015-01-01

    Objective To determine whether the use of contrast enhancement (especially its extent) predicts malignant brain edema after intra-arterial thrombectomy (IAT) in patients with acute ischemic stroke. Methods We reviewed the records of patients with acute ischemic stroke who underwent IAT for occlusion of the internal carotid artery or the middle cerebral artery between January 2012 and March 2015. To estimate the extent of contrast enhancement (CE), we used the contrast enhancement area ratio (CEAR)-i.e., the ratio of the CE to the area of the hemisphere, as noted on immediate non-enhanced brain computed tomography (NECT) post-IAT. Patients were categorized into two groups based on the CEAR values being either greater than or less than 0.2. Results A total of 39 patients were included. Contrast enhancement was found in 26 patients (66.7%). In this subgroup, the CEAR was greater than 0.2 in 7 patients (18%) and less than 0.2 in the other 19 patients (48.7%). On univariate analysis, both CEAR ?0.2 and the presence of subarachnoid hemorrhage were significantly associated with progression to malignant brain edema (p<0.001 and p=0.004), but on multivariate analysis, only CEAR ?0.2 showed a statistically significant association (p=0.019). In the group with CEAR ?0.2, the time to malignant brain edema was shorter (p=0.039) than in the group with CEAR <0.2. Clinical functional outcomes, based on the modified Rankin scale, were also significantly worse in patients with CEAR ?0.2 (p=0.003) Conclusion The extent of contrast enhancement as noted on NECT scans obtained immediately after IAT could be predictive of malignant brain edema and a poor clinical outcome. PMID:26587184

  10. Immunization of rats reduces nicotine distribution to brain.

    PubMed

    Hieda, Y; Keyler, D E; VanDeVoort, J T; Niedbala, R S; Raphael, D E; Ross, C A; Pentel, P R

    1999-04-01

    The effect of active immunization against nicotine on the initial distribution of nicotine to brain was studied in anesthetized rats. Animals received nicotine 0.03 mg/kg nicotine (equivalent to the nicotine dose absorbed by a human smoking two cigarettes) as a rapid injection in the jugular vein. In control animals, the arterial serum nicotine concentration initially exceeded the venous concentration 4.6-fold, similar to the initial arteriovenous difference produced by cigarette smoking in humans. Animals immunized with the nicotine analog CMUNic maintained this arteriovenous gradient, but with both arterial and venous nicotine concentrations several times higher than in controls. The arterial nicotine concentration was higher in immunized animals even at the first (7.5 s) sampling time. The brain nicotine concentration at 3 min was 36% lower in the immunized animals. The time course of nicotine distribution to brain was studied in a second group of animals. Brain nicotine concentration was reduced in rats immunized with CMUNic over the entire 6-min sampling period immediately following nicotine dosing (mean reduction 38%). A reduction was found at the earliest sampling time (30 s) and was maximal at 1 min (48%). Nicotine protein binding in serum was markedly increased in animals immunized with CMUNic compared to controls (91.2 versus 10.9%), and the unbound nicotine concentration in serum was lower (10.0 versus 13.4 ng/ml). The reduction in brain nicotine concentration correlated with antibody affinity for nicotine, and the percentage of nicotine bound in serum. These data demonstrate that nicotine-specific antibodies produced by active immunization rapidly bind nicotine in arterial blood, reduce the unbound nicotine concentration, and reduce the early distribution of nicotine to brain. Effects were observed using a clinically relevant nicotine dose and route of administration. These data suggest that the use of immunization to modify the behavioral effects of nicotine may be possible. PMID:10326777

  11. Reducing proactive aggression through non-invasive brain stimulation.

    PubMed

    Dambacher, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T

    2015-10-01

    Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders. PMID:25680991

  12. FTY720 Reduces Post-Ischemic Brain Lymphocyte Influx but Does Not Improve Outcome in Permanent Murine Cerebral Ischemia

    PubMed Central

    Liesz, Arthur; Sun, Li; Zhou, Wei; Schwarting, Sönke; Mracsko, Eva; Zorn, Markus; Bauer, Henrike; Sommer, Clemens; Veltkamp, Roland

    2011-01-01

    Background The contribution of neuroinflammation and specifically brain lymphocyte invasion is increasingly recognised as a substantial pathophysiological mechanism after stroke. FTY720 is a potent treatment for primary neuroinflammatory diseases by inhibiting lymphocyte circulation and brain immigration. Previous studies using transient focal ischemia models showed a protective effect of FTY720 but did only partially characterize the involved pathways. We tested the neuroprotective properties of FTY720 in permanent and transient cortical ischemia and analyzed the underlying neuroimmunological mechanisms. Methodology/Principal Findings FTY720 treatment resulted in substantial reduction of circulating lymphocytes while blood monocyte counts were significantly increased. The number of histologically and flow cytometrically analyzed brain invading T- and B lymphocytes was significantly reduced in FTY720 treated mice. However, despite testing a variety of treatment protocols, infarct volume and behavioural dysfunction were not reduced 7d after permanent occlusion of the distal middle cerebral artery (MCAO). Additionally, we did not measure a significant reduction in infarct volume at 24h after 60 min filament-induced MCAO, and did not see differences in brain edema between PBS and FTY720 treatment. Analysis of brain cytokine expression revealed complex effects of FTY720 on postischemic neuroinflammation comprising a substantial reduction of delayed proinflammatory cytokine expression at 3d but an early increase of IL-1? and IFN-? at 24 h after MCAO. Also, serum cytokine levels of IL-6 and TNF-? were increased in FTY720 treated animals compared to controls. Conclusions/Significance In the present study we were able to detect a reduction of lymphocyte brain invasion by FTY720 but could not achieve a significant reduction of infarct volumes and behavioural dysfunction. This lack of neuroprotection despite effective lymphopenia might be attributed to a divergent impact of FTY720 on cytokine expression and possible activation of innate immune cells after brain ischemia. PMID:21701599

  13. Cytotoxic edema: mechanisms of pathological cell swelling

    PubMed Central

    Liang, Danny; Bhatta, Sergei; Gerzanich, Volodymyr; Simard, J. Marc

    2009-01-01

    Cerebral edema is caused by a variety of pathological conditions that affect the brain. It is associated with two separate pathophysiological processes with distinct molecular and physiological antecedents: those related to cytotoxic (cellular) edema of neurons and astrocytes, and those related to transcapillary flux of Na+ and other ions, water, and serum macromolecules. In this review, the authors focus exclusively on the first of these two processes. Cytotoxic edema results from unchecked or uncompensated influx of cations, mainly Na+, through cation channels. The authors review the different cation channels that have been implicated in the formation of cytotoxic edema of astrocytes and neurons in different pathological states. A better understanding of these molecular mechanisms holds the promise of improved treatments of cerebral edema and of the secondary injury produced by this pathological process. PMID:17613233

  14. Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?

    PubMed Central

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

    2014-01-01

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

  15. Brainstem edema caused by traumatic carotid-cavernous fistula: A case report and review of the literature

    PubMed Central

    YU, JINLU; GUO, YUNBAO; ZHAO, SHUJIE; XU, KAN

    2015-01-01

    Brainstem edema caused by traumatic carotid-cavernous fistula (TCCF) is rare, and there is little information available regarding its clinical characteristics. The present report describes the case of a 51-year-old man with TCCF, who presented with right exophthalmos and intracranial bruit for 1 week. One month prior to admission at hospital, he fractured the frontal and ethmoid sinuses. Digital subtraction angiography confirmed the diagnosis of TCCF, and magnetic resonance imaging (MRI) suggested edema on the right side of the pons. Five days after admission, the patient exhibited left hemiparesis, and MRI revealed aggravation of the brainstem edema. Following treatment with transarterial balloon embolization, the clinical symptoms, including hemiparesis, were relieved; at the 1-month follow-up, the brain edema had disappeared. The patient was normal at the 6-month follow-up. Following the report of the present case, we reviewed six additional cases previously reported in the literature and discussed the potential mechanisms of TCCF-associated brainstem edema. We conclude that occlusion of the superior petrosal sinus may contribute to brainstem edema caused by TCCF. Relief of the brainstem edema and brainstem edema-associated clinical symptoms can be achieved with transarterial coil or balloon embolization of the TCCF to reduce the drainage pressure in the brainstem veins.

  16. High Delta-Like Ligand 4 (DLL4) Is Correlated With Peritumoral Brain Edema and Predicts Poor Prognosis in Primary Glioblastoma

    PubMed Central

    Qiu, Xian-xin; Chen, Long; Wang, Chen-hong; Lin, Zhi-xiong; Zhou, Chang-fu; Liu, Shui-yuan; Wang, Xing-fu; Chen, Yu-peng

    2014-01-01

    Abstract Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated. Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan–Meier survival and the Cox proportional hazard model. The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P?

  17. Reduced predictable information in brain signals in autism spectrum disorder

    PubMed Central

    Gómez, Carlos; Lizier, Joseph T.; Schaum, Michael; Wollstadt, Patricia; Grützner, Christine; Uhlhaas, Peter; Freitag, Christine M.; Schlitt, Sabine; Bölte, Sven; Hornero, Roberto; Wibral, Michael

    2014-01-01

    Autism spectrum disorder (ASD) is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS)—a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the past state of a process and its next measurement. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG) signals in 10 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, 12 task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD. PMID:24592235

  18. Restoring blood-brain barrier P-glycoprotein reduces brain amyloid-beta in a mouse model of Alzheimer's disease.

    PubMed

    Hartz, Anika M S; Miller, David S; Bauer, Björn

    2010-05-01

    Reduced clearance of amyloid-beta (Abeta) from brain partly underlies increased Abeta brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of Abeta from mouse brain capillaries into the vascular space, thus identifying a critical component of the Abeta brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type control mice, suggesting a mechanism by which Abeta accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16alpha-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain Abeta levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase Abeta clearance from the brain and reduce Abeta brain accumulation. This mechanism suggests a new therapeutic strategy in AD. PMID:20101004

  19. Restoring Blood-Brain Barrier P-Glycoprotein Reduces Brain Amyloid-? in a Mouse Model of Alzheimer's DiseaseS?

    PubMed Central

    Hartz, Anika M. S.; Miller, David S.

    2010-01-01

    Reduced clearance of amyloid-? (A?) from brain partly underlies increased A? brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of A? from mouse brain capillaries into the vascular space, thus identifying a critical component of the A? brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type control mice, suggesting a mechanism by which A? accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16?-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain A? levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase A? clearance from the brain and reduce A? brain accumulation. This mechanism suggests a new therapeutic strategy in AD. PMID:20101004

  20. Melatonin lowers edema after spinal cord injury

    PubMed Central

    Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

    2014-01-01

    Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein. PMID:25657743

  1. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour

    PubMed Central

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats. PMID:22666534

  2. Reduced Regional Brain Cortical Thickness in Patients with Heart Failure

    PubMed Central

    Kumar, Rajesh; Yadav, Santosh K.; Palomares, Jose A.; Park, Bumhee; Joshi, Shantanu H.; Ogren, Jennifer A.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Woo, Mary A.

    2015-01-01

    Aims Autonomic, cognitive, and neuropsychologic deficits appear in heart failure (HF) subjects, and these compromised functions depend on cerebral cortex integrity in addition to that of subcortical and brainstem sites. Impaired autoregulation, low cardiac output, sleep-disordered-breathing, hypertension, and diabetic conditions in HF offer considerable potential to affect cortical areas by loss of neurons and glia, which would be expressed as reduced cortical thicknesses. However, except for gross descriptions of cortical volume loss/injury, regional cortical thickness integrity in HF is unknown. Our goal was to assess regional cortical thicknesses across the brain in HF, compared to control subjects. Methods and Results We examined localized cortical thicknesses in 35 HF and 61 control subjects with high-resolution T1-weighted images (3.0-Tesla MRI) using FreeSurfer software, and assessed group differences with analysis-of-covariance (covariates; age, gender; p<0.05; FDR). Significantly-reduced cortical thicknesses appeared in HF over controls in multiple areas, including the frontal, parietal, temporal, and occipital lobes, more markedly on the left side, within areas that control autonomic, cognitive, affective, language, and visual functions. Conclusion Heart failure subjects show reduced regional cortical thicknesses in sites that control autonomic, cognitive, affective, language, and visual functions that are deficient in the condition. The findings suggest chronic tissue alterations, with regional changes reflecting loss of neurons and glia, and presumably are related to earlier-described axonal changes. The pathological mechanisms contributing to reduced cortical thicknesses likely include hypoxia/ischemia, accompanying impaired cerebral perfusion from reduced cardiac output and sleep-disordered-breathing and other comorbidities in HF. PMID:25962164

  3. Selective Brain Cooling Reduces Water Turnover in Dehydrated Sheep

    PubMed Central

    Strauss, W. Maartin; Hetem, Robyn S.; Mitchell, Duncan; Maloney, Shane K.; Meyer, Leith C. R.; Fuller, Andrea

    2015-01-01

    In artiodactyls, arterial blood destined for the brain can be cooled through counter-current heat exchange within the cavernous sinus via a process called selective brain cooling. We test the hypothesis that selective brain cooling, which results in lowered hypothalamic temperature, contributes to water conservation in sheep. Nine Dorper sheep, instrumented to provide measurements of carotid blood and brain temperature, were dosed with deuterium oxide (D2O), exposed to heat for 8 days (40?C for 6-h per day) and deprived of water for the last five days (days 3 to 8). Plasma osmolality increased and the body water fraction decreased over the five days of water deprivation, with the sheep losing 16.7% of their body mass. Following water deprivation, both the mean 24h carotid blood temperature and the mean 24h brain temperature increased, but carotid blood temperature increased more than did brain temperature resulting in increased selective brain cooling. There was considerable inter-individual variation in the degree to which individual sheep used selective brain cooling. In general, sheep spent more time using selective brain cooling, and it was of greater magnitude, when dehydrated compared to when they were euhydrated. We found a significant positive correlation between selective brain cooling magnitude and osmolality (an index of hydration state). Both the magnitude of selective brain cooling and the proportion of time that sheep spent selective brain cooling were negatively correlated with water turnover. Sheep that used selective brain cooling more frequently, and with greater magnitude, lost less water than did conspecifics using selective brain cooling less efficiently. Our results show that a 50kg sheep can save 2.6L of water per day (~60% of daily water intake) when it employs selective brain cooling for 50% of the day during heat exposure. We conclude that selective brain cooling has a water conservation function in artiodactyls. PMID:25675092

  4. Neurogenic pulmonary edema in subarachnoid hemorrage.

    PubMed

    Piazza, O; Venditto, A; Tufano, R

    2011-09-01

    Aneurysmal subarachnoid hemorrhage (SAH), in addition to the direct effects of the initial hemorrhage and secondary neurological complications, predisposes to medical complications. The proportion of deaths caused by non-neurological medical complications (cardiac, pulmonary, gastrointestinal, renal, hematological) equals that from neurological complications. In particular, pulmonary complications are responsible for 50% of all deaths from medical complications. Neurogenic pulmonary edema (NPE) is an increase of interstitial and alveolar fluid occurring as direct consequence of any acute central nervous system injury. Two different pathogenetic mechanisms of NPE have been hypothesized: i) hemodynamic (an increase of pulmonary vascular pressure due to an ?-adrenergic response produces hydrostatic edema) and ii) inflammatory mechanism (brain cytokines and chemokines determinates an increase in the permeability of pulmonary capillaries causing exudative edema). Recent studies postulate that both mechanisms may be implicated in the pathogenesis of NPE. Brain injury is known to determine increased levels of S100B, a Ca- binding protein, in cerebrospinal fluid and in blood. Moreover, amine precursor uptake and decarboxylation (APUD) cells located in the respiratory tract produce and release S100B. This protein may contribute to the pathogenesis of NPE binding RAGE receptors in alveolar epithelial type I pneumocytes and amplifying the immune and inflammatory response causing lung injury. S100B can be the link between the brain and the lung and may be among the multiple pathological pathways that determine the development of pulmonary edema after bleeding. PMID:21775947

  5. Inhibiting mitochondrial ?-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain

    PubMed Central

    Chen, Chuck T; Trépanier, Marc-Olivier; Hopperton, Kathryn E; Domenichiello, Anthony F; Masoodi, Mojgan; Bazinet, Richard P

    2014-01-01

    Schönfeld and Reiser recently hypothesized that fatty acid ?-oxidation is a source of oxidative stress in the brain. To test this hypothesis, we inhibited brain mitochondrial ?-oxidation with methyl palmoxirate (MEP) and measured oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites were reduced with few effects on enzymatically derived metabolites. Our finding confirms the hypothesis that reduced fatty acid ?-oxidation decreases oxidative stress in the brain and ?-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress. PMID:24326387

  6. Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

    PubMed

    Min, Jia-Wei; Hu, Jiang-Jian; He, Miao; Sanchez, Russell M; Huang, Wen-Xian; Liu, Yu-Qiang; Bsoul, Najeeb Bassam; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2015-12-01

    Previous studies have demonstrated that the early suppression of HIF-1? after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1? inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1? and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1? by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1? and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1? inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury. PMID:26187393

  7. Chronic oral or intraarticular administration of docosahexaenoic acid reduces nociception and knee edema and improves functional outcomes in a mouse model of Complete Freund’s Adjuvant–induced knee arthritis

    PubMed Central

    2014-01-01

    Introduction Clinical and preclinical studies have shown that supplementation with ?-3 polyunsaturated fatty acids (?-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ?-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ?-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis. Methods Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 ?g/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection. Results The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA. Conclusions To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and anti-inflammatory effects as individual ?-3 PUFAs following sustained systemic and intraarticular administration in a mouse model of CFA-induced knee arthritis. The results suggest that DHA treatment may offer a new therapeutic approach to alleviate inflammation as well as a beneficial effect on pain-related functional disabilities in RA patients. PMID:24612981

  8. An Attempt to Experimentally Produce Edema Disease in Swine by Oral Administration of Escherichia Coli Serotype 0139:K82:H1*

    PubMed Central

    Pickrell, J. A.; Simon, J.; Link, R. P.; Rhoades, H. E.; Gossling, J.

    1969-01-01

    Diarrhea, reduced appetite, and nervousness were observed following oral exposure of six pigs to freeze-thaw extract and living culture of E. coli strain 0139:K82:H1. The most significance gross change was the appearance of subserosal edema of the mesentry, especially of the mesocolon. Histological findings included perivascular edema of the brain and reticulum cells as well as lymphocytic aggregates in the renal cortex simulating early neoplasia. Edema of the submucosa of gallbladder, the duodenum, the spiral colon and the fundic stomach as well as the lymph nodes was also observed. The syndrome which was produced resembled, in many aspects, edema disease although some complicating factors were ob- ImagesFig. 1.Fig. 2.Fig. 3. PMID:4237301

  9. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    PubMed Central

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

    2012-01-01

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

  10. 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.

  11. Thioperamide reduces intracellular calcium in mouse brain synaptosomes.

    PubMed

    Vohora, Divya; Pal, Shanthi N; Pillai, K K

    2007-04-01

    Intracellular calcium regulation is vital for cells, especially for neurons; raised levels are associated with cytotoxicity and neuronal death. In this report, we present the first experimental evidence showing a concentration-dependent reduction of free calcium in the mouse brain synaptosomes by thioperamide (THP), an H3 receptor antagonist. This is interesting in view of the recent reports on the anticonvulsant and cognition facilitating effects of THP. A neuroprotective potential of THP is suggested. PMID:16996723

  12. Reperfusion pulmonary edema

    SciTech Connect

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. )

    1989-02-17

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B{sub 4} and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

  13. Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system.

  14. Omega-3 Fatty Acid Deficiency during Brain Maturation Reduces Neuronal and Behavioral Plasticity in Adulthood

    PubMed Central

    Sharma, Sandeep; Huo, Yi-Xin; Ying, Zhe; Gomez-Pinilla, Fernando

    2011-01-01

    Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3 deficient diets for 15 weeks. Results showed that the n-3 deficiency increased parameters of anxiety-like behavior using open field and elevated plus maze tests in the male offspring. Behavioral changes were accompanied by a level reduction in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the anxiogenic-related glucocorticoid receptor in the cognitive related frontal cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of docosahexaenoic acid (DHA) and increased the ratio n-6/n-3 assessed by gas chromatography. The n-3 deficiency reduced the levels of BDNF and signaling through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced the activation of the BDNF-related signaling molecule CREB in selected brain regions. The n-3 deficiency also disrupted the insulin signaling pathways as evidenced by changes in insulin receptor (IR) and insulin receptor substrate (IRS). DHA deficiency during brain maturation reduces plasticity and compromises brain function in adulthood. Adequate levels of dietary DHA seem crucial for building long-term neuronal resilience for optimal brain performance and aiding in the battle against neurological disorders. PMID:22163304

  15. Reduced reward processing in the brains of Parkinsonian patients.

    PubMed

    Künig, G; Leenders, K L; Martin-Sölch, C; Missimer, J; Magyar, S; Schultz, W

    2000-11-27

    Regional cerebral blood flow (rCBF) in healthy controls and non-demented, non-depressed Parkinsonian patients was measured using H2(15)O PET while subjects performed a prelearned pattern recognition task with delayed response. To investigate differences between the two groups in response to reward, the experimental design consisted of three reinforcement conditions: no reinforcement consisting of nonsense feedback, positive symbolic reinforcement and monetary reward. In the controls, monetary reward activated bilaterally the striatum and anterior cingulate gyrus, as well as unilaterally the left cerebellum, midbrain and medial frontal gyrus. Symbolic reinforcement revealed a similar pattern of activation, except that the striatum and left midbrain showed no activation. The Parkinsonian patients responded to monetary reward with increased activation bilaterally in the cerebellum, medial frontal gyrus, and anterior cingulate gyrus as well as unilaterally in the right fusiform gyrus and midbrain and left caudate nucleus and precentral gyrus. Symbolic reinforcement induced significantly increased rCBF in the right cerebellum only. Compared with symbolic reinforcement, monetary reward produced extended activation of temporoparietal association cortex. The pattern observed in the controls demonstrates the role in reward processing of dopaminergic mesolimbic pathways in the healthy human brain, whereas the pattern in the Parkinsonian patients suggests the involvement of compensatory cortical loops in the diseased brain. PMID:11117472

  16. Brain-computer interfaces and disability: extending embodiment, reducing stigma?

    PubMed

    Aas, Sean; Wasserman, David

    2016-01-01

    Brain-Computer Interfaces (BCIs) now enable an individual without limb function to "move" a detached mechanical arm to perform simple actions, such as feeding herself. This technology may eventually offer almost everyone a way to move objects at a distance, by exercising cognitive control of a mechanical device. At that point, BCIs may be seen less as an assistive technology for disabled people, and more as a tool, like the internet, which can benefit all users. We will argue that BCIs will have a significant but uncertain impact on attitudes toward disabilities and on norms of bodily form and function. It may be liberating, oppressive, or both. Its impact, we argue, will depend - though not in any simple way - on whether BCIs come to be seen as parts of the body itself or as external tools. PMID:26336895

  17. 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.

  18. Neurogenic pulmonary edema following Cryptococcal meningoencephalitis associated with HIV infection.

    PubMed

    Kondo, Reiichiro; Sugita, Yasuo; Arakawa, Kenji; Nakashima, Shinji; Umeno, Yumi; Todoroki, Keita; Yoshida, Tomoko; Takase, Yorihiko; Kage, Masayoshi; Oshima, Koichi; Yano, Hirohisa

    2015-08-01

    Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. Only a few cases of NPE after Cryptococcal meningitis have been reported. We report a case of NPE following Cryptococcal meningoencephalitis. A 40-year-old man with no medical history was hospitalized for disturbance of consciousness. Blood glucose level was 124?mg/dL. Non-contrast head computed tomography showed no abnormalities. Lumbar puncture revealed a pressure of over 300?mm H2 O and cerebrospinal fluid (CSF) confirmed a white blood cell count of 65/mm(3) . The CSF glucose level was 0?mg/dL. The patient was empirically started on treatment for presumptive bacterial and viral meningitis. Four days after, the patient died in a sudden severe pulmonary edema. Autopsy was performed. We found at autopsy a brain edema with small hemorrhage of the right basal ganglia, severe pulmonary edema and mild cardiomegaly. Histologically, dilated Virchow-Robin spaces, crowded with Cryptococci were observed. In the right basal ganglia, Virchow-Robin spaces were destroyed with hemorrhage and Cryptococci spread to parenchyma of the brain. No inflammatory reaction of the lung was seen. Finally, acute pulmonary edema in this case was diagnosed as NPE following Cryptococcal meningoencephalitis. After autopsy, we found that he was positive for serum antibodies to human immunodeficiency virus. PMID:25955768

  19. 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).

  20. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

    PubMed

    Shultz, Sandy R; Wright, David K; Zheng, Ping; Stuchbery, Ryan; Liu, Shi-Jie; Sashindranath, Maithili; Medcalf, Robert L; Johnston, Leigh A; Hovens, Christopher M; Jones, Nigel C; O'Brien, Terence J

    2015-05-01

    Traumatic brain injury is a common and serious neurodegenerative condition that lacks a pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau is implicated in some of the consequences of traumatic brain injury and is a potential pharmacological target. Protein phosphatase 2A is a heterotrimeric protein that regulates key signalling pathways, and protein phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major tau phosphatase in the brain. Here we investigated whether traumatic brain injury in rats and humans would induce changes in protein phosphatase 2A and phosphorylated tau, and whether treatment with sodium selenate-a potent PR55 activator-would reduce phosphorylated tau and improve traumatic brain injury outcomes in rats. Ninety young adult male Long-Evans rats were administered either a fluid percussion injury or sham-injury. A proportion of rats were killed at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A and tau. Other rats were given either sodium selenate or saline-vehicle treatment that was continuously administered via subcutaneous osmotic pump for 12 weeks. Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12 weeks post-injury to assess evolving structural brain damage and axonal injury. Behavioural impairments were assessed at 12 weeks post-injury. The results showed that traumatic brain injury in rats acutely reduced PR55 expression and protein phosphatase 2A activity, and increased the expression of phosphorylated tau and the ratio of phosphorylated tau to total tau. Similar findings were seen in post-mortem brain samples from acute human traumatic brain injury patients, although many did not reach statistical significance. Continuous sodium selenate treatment for 12 weeks after sham or fluid percussion injury in rats increased protein phosphatase 2A activity and PR55 expression, and reduced the ratio of phosphorylated tau to total tau, attenuated brain damage, and improved behavioural outcomes in rats given a fluid percussion injury. Notably, total tau levels were decreased in rats 12 weeks after fluid percussion injury, and several other factors, including the use of anaesthetic, the length of recovery time, and that some brain injury and behavioural dysfunction still occurred in rats treated with sodium selenate must be considered in the interpretation of this study. However, taken together these data suggest protein phosphatase 2A and hyperphosphorylated tau may be involved in the neurodegenerative cascade of traumatic brain injury, and support the potential use of sodium selenate as a novel traumatic brain injury therapy. PMID:25771151

  1. Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury

    PubMed Central

    Schaible, Eva-Verena; Timaru-Kast, Ralph; Hedrich, Jana; Luhmann, Heiko J.; Engelhard, Kristin

    2012-01-01

    Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema. PMID:23251381

  2. Antenatal Allopurinol Reduces Hippocampal Brain Damage After Acute Birth Asphyxia in Late Gestation Fetal Sheep

    PubMed Central

    Kaandorp, Joepe J.; Derks, Jan B.; Oudijk, Martijn A.; Torrance, Helen L.; Harmsen, Marline G.; Nikkels, Peter G. J.; van Bel, Frank; Visser, Gerard H. A.

    2014-01-01

    Free radical–induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia–reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia. PMID:23793473

  3. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.

    PubMed

    Ostrowski, Robert P; Schulte, Reinhard W; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S; Zhang, John H

    2012-12-01

    Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. PMID:23956805

  4. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV.

    PubMed

    Grishchuk, Yulia; Peña, Karina A; Coblentz, Jessica; King, Victoria E; Humphrey, Daniel M; Wang, Shirley L; Kiselyov, Kirill I; Slaugenhaupt, Susan A

    2015-12-01

    Mucolipidosis type IV (MLIV) is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1). MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1(-/-) mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1(-/-) mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1(-/-) brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development. PMID:26398942

  5. Evaluation & design of a novel drug delivery device for treating tumor-related cerebral edema

    E-print Network

    Shair, Kamal A. (Kamal Abdo)

    2010-01-01

    Tumor-related cerebral edema is a debilitating medical condition that afflicts tens of thousands of newly diagnosed brain cancer patients in the U.S. each year, where the standard care of treatment indicates the systemic ...

  6. Compliant intracortical implants reduce strains and strain rates in brain tissue in vivo

    NASA Astrophysics Data System (ADS)

    Sridharan, Arati; Nguyen, Jessica K.; Capadona, Jeffrey R.; Muthuswamy, Jit

    2015-06-01

    Objective. The objective of this research is to characterize the mechanical interactions of (1) soft, compliant and (2) non-compliant implants with the surrounding brain tissue in a rodent brain. Understanding such interactions will enable the engineering of novel materials that will improve stability and reliability of brain implants. Approach. Acute force measurements were made using a load cell in n = 3 live rats, each with 4 craniotomies. Using an indentation method, brain tissue was tested for changes in force using established protocols. A total of 4 non-compliant, bare silicon microshanks, 3 non-compliant polyvinyl acetate (PVAc)-coated silicon microshanks, and 6 compliant, nanocomposite microshanks were tested. Stress values were calculated by dividing the force by surface area and strain was estimated using a linear stress-strain relationship. Micromotion effects from breathing and vascular pulsatility on tissue stress were estimated from a 5 s interval of steady-state measurements. Viscoelastic properties were estimated using a second-order Prony series expansion of stress-displacement curves for each shank. Main results. The distribution of strain values imposed on brain tissue for both compliant nanocomposite microshanks and PVAc-coated, non-compliant silicon microshanks were significantly lower compared to non-compliant bare silicon shanks. Interestingly, step-indentation experiments also showed that compliant, nanocomposite materials significantly decreased stress relaxation rates in the brain tissue at the interface (p < 0.05) compared to non-compliant silicon and PVAc-coated silicon materials. Furthermore, both PVAc-coated non-compliant silicon and compliant nanocomposite shanks showed significantly reduced (by 4-5 fold) stresses due to tissue micromotion at the interface. Significance. The results of this study showed that soft, adaptive materials reduce strains and strain rates and micromotion induced stresses in the surrounding brain tissue. Understanding the material behavior at the site of tissue contact will help to improve neural implant design.

  7. Pulmonary Edema in Myasthenic Crisis

    PubMed Central

    Anand, Uttara Swati; Arulneyam, Jayanthi

    2013-01-01

    We report a previously asymptomatic 50-year-old lady who came with myasthenic crisis as initial presentation of myasthenia gravis. She developed pulmonary edema following intravenous immunoglobulin administration and had ischemic changes in ECG and left ventricular dysfunction on echocardiography. She improved with diuretics, dobutamine, and fluid restriction alone. This is the first report in English-language medical literature describing the association between myasthenic crisis and likely takotsubo cardiomyopathy-related pulmonary edema following intravenous immunoglobulin administration. PMID:24829832

  8. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

    PubMed Central

    de Hemptinne, Coralie; Swann, Nicole; Ostrem, Jill L.; Ryapolova-Webb, Elena S.; Luciano, Marta San; Galifianakis, Nicholas; Starr, Philip A.

    2015-01-01

    Deep brain stimulation (DBS) is increasingly applied to the treatment of brain disorders, but its mechanism of action remains unknown. Here, we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the ? rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive ? phase locking of motor cortex neurons. PMID:25867121

  9. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

    PubMed Central

    Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

    2015-01-01

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

  10. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice

    PubMed Central

    Cooper, J Mark; Wiklander, PB Oscar; Nordin, Joel Z; Al-Shawi, Raya; Wood, Matthew J; Vithlani, Mansi; Schapira, Anthony H V; Simons, J Paul; El-Andaloussi, Samir; Alvarez-Erviti, Lydia

    2014-01-01

    Alpha-synuclein (?-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that ?-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing ?-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used ?-Syn small interfering RNA (siRNA) to reduce total and aggregated ?-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease ?-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D ?-Syn, which exhibits aggregation. In normal mice we detected significantly reduced ?-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to ?-Syn. In S129D ?-Syn transgenic mice we found a decreased ?-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain ?-Syn pathological conditions. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:25112864

  11. Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain

    PubMed Central

    Kozi?, Duško B.; Petrovi?, Igor; Svetel, Marina; Pekmezovi?, Tatjana; Ragaji, Aleksandar; Kosti?, Vladimir S.

    2014-01-01

    The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ? 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity. PMID:25558242

  12. Effect of hyperbaric oxygen preconditioning on peri-hemorrhagic focal edema and aquaporin-4 expression

    PubMed Central

    FANG, JINYONG; LI, HONGLING; LI, GUANGLEI; WANG, LICHUN

    2015-01-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen preconditioning (HBO-PC) on peri-hemorrhagic focal edema and aquaporin-4 (AQP-4) expression in an experimental intracerebral hemorrhage (ICH) rat model. Sixty-six Sprague Dawley® rats were divided into three groups: The sham-surgery group (SHG; n=6); the control group (A-ICH; n=30), in which the rats were injected with autologous blood; and the experimental HBO-PC group (P-HBO; n=30). The rats underwent brain edema and AQP-4 detection at 5 postoperative time-points (24, 48 and 72 h and 5 and 7 days). The water content in the brain tissues of the A-ICH animals was higher than that in the brain tissues of the SHG rats at each time-point (P<0.05), and the edema in the P-HBO was significantly more severe 24 and 48 h postoperatively than that at 7 days postoperatively (P<0.05). The difference between the P-HBO and A-ICH was significant at 48 and 72 h postoperatively (P<0.05). AQP-4 was expressed in the post-hemorrhagic rat brains of all groups; the SHG animals exhibited low expression, while the A-ICH animals exhibited an increased expression 24 h postoperatively. In the A-ICH, expression peaked at 48 h postoperatively and began to decrease gradually after 72 h. At the 7-day time-point, the expression level in the A-ICH was closer to but still higher than that of the SHG animals (P<0.05). The differences between the P-HBO and A-ICH animals at the postoperative 24-h, 48-h and 7-day time-points were statistically significant (P<0.05). In conclusion, HBO-PC may downregulate AQP-4 expression to reduce the intracerebral edema, thus strengthening tolerance to ICH and protecting the nerves. PMID:26622378

  13. A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats.

    PubMed

    Li, Lin; Tao, Yihao; Tang, Jun; Chen, Qianwei; Yang, Yang; Feng, Zhou; Chen, Yujie; Yang, Liming; Yang, Yunfeng; Zhu, Gang; Feng, Hua; Chen, Zhi

    2015-12-01

    Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH). We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH). We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved. A total of 144 Sprague-Dawley (S-D) rats received a thrombin (20 U) injection in the right basal ganglia. JWH-133 (1.5 mg/kg) or SR-144528 (3.0 mg/kg) and vehicle were intraperitoneally (i.p.) injected 1 h after surgery. Brain water content measurement, Evans blue (EB) extravasation, Western blot, and immunofluorescence were used to study the effects of a CB2R agonist 24 h after surgery. The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia. JWH-133 also decreased the number of P44/P42(+)/Iba-1(+) microglia, lowered Evans blue extravasation, and inhibited the elevated matrix metallopeptidase (MMP)-9 and matrix metallopeptidase (MMP)-12 activities. However, a selective CB2R antagonist (SR-144528) reversed these effects. We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage. We also found that matrix metalloproteinase suppression may be partially involved in these processes. PMID:26376816

  14. 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.

  15. Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography

    PubMed Central

    Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra J.; O'Donnell, Lauren J.

    2015-01-01

    Background Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Methods Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Results Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Conclusions Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients. PMID:26082890

  16. Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

    PubMed Central

    Babaee, Abdolreza; Eftekhar-Vaghefi, Seyed Hassan; Asadi-shekaari, Majid; Shahrokhi, Nader; Soltani, Samereh Dehghani; Malekpour-Afshar, Reza; Basiri, Mohsen

    2015-01-01

    Objective(s): Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis) in several models of brain injury. Secondary injury following the primary traumatic brain injury (TBI) results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis), as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline) and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg). All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP) marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P<0.05) in melatonin- treated groups (no dose dependent) compared to the vehicle group. Furthermore, based on TUNEL results, melatonin treatment considerably reduced the number of apoptotic cells (P<0.05). Conclusion: In total, the present findings suggest that melatonin treatment following TBI diminishes astrocyte reactivity and neuronal cells apoptosis in brain cortex in the rat model. PMID:26523219

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

    PubMed

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

    2014-10-01

    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

  18. 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

  19. Reducing Traumatic Brain Injuries in Youth Sports: Youth Sports Traumatic Brain Injury State Laws, January 2009–December 2012

    PubMed Central

    2013-01-01

    Objectives. I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. Methods. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Results. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state’s youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches’ and parents’ ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Conclusions. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution. PMID:23678903

  20. The cellular mechanisms of neuronal swelling underlying cytotoxic edema.

    PubMed

    Rungta, Ravi L; Choi, Hyun B; Tyson, John R; Malik, Aqsa; Dissing-Olesen, Lasse; Lin, Paulo J C; Cain, Stuart M; Cullis, Pieter R; Snutch, Terrance P; MacVicar, Brian A

    2015-04-23

    Cytotoxic brain edema triggered by neuronal swelling is the chief cause of mortality following brain trauma and cerebral infarct. Using fluorescence lifetime imaging to analyze contributions of intracellular ionic changes in brain slices, we find that intense Na(+) entry triggers a secondary increase in intracellular Cl(-) that is required for neuronal swelling and death. Pharmacological and siRNA-mediated knockdown screening identified the ion exchanger SLC26A11 unexpectedly acting as a voltage-gated Cl(-) channel that is activated upon neuronal depolarization to membrane potentials lower than -20 mV. Blockade of SLC26A11 activity attenuates both neuronal swelling and cell death. Therefore cytotoxic neuronal edema occurs when sufficient Na(+) influx and depolarization is followed by Cl(-) entry via SLC26A11. The resultant NaCl accumulation causes subsequent neuronal swelling leading to neuronal death. These findings shed light on unique elements of volume control in excitable cells and lay the ground for the development of specific treatments for brain edema. PMID:25910210

  1. Effect of arginine vasopressin on the cortex edema in the ischemic stroke of Mongolian gerbils.

    PubMed

    Zhao, Xue-Yan; Wu, Chun-Fang; Yang, Jun; Gao, Yang; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; Lin, Bao-Cheng

    2015-06-01

    Brain edema formation is one of the most important mechanisms of ischemia-evoked cerebral edema. It has been demonstrated that arginine vasopressin (AVP) receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. In a well-characterized animal model of ischemic stroke of Mongolian gerbils, the present study was undertaken to clear the effect of AVP on cortex edema in cerebral ischemia. The results showed that (1) occluding the left carotid artery of Mongolian gerbils not only decreased the cortex specific gravity (cortex edema) but also increased AVP levels in the ipsilateral cortex (ischemic area) including left prefrontal lobe, left parietal lobe, left temporal lobe, left occipital lobe and left hippocampus for the first 6 hours, and did not change of the cortex specific gravity and AVP concentration in the right cortex (non-ischemic area); (2) there were many negative relationships between the specific gravity and AVP levels in the ischemic cortex; (3) intranasal AVP (50 ng or 200 ng), which could pass through the blood-brain barrier to the brain, aggravated the focal cortex edema, whereas intranasal AVP receptor antagonist-D(CH2)5Tyr(ET)DAVP (2 µg) mitigated the cortex edema in the ischemic area after occluding the left carotid artery of Mongolian gerbils; and (4) either intranasal AVP or AVP receptor antagonist did not evoke that edema in the non-ischemic cortex. The data indicated that AVP participated in the process of ischemia-evoked cortex edema, and the cerebral AVP receptor might serve as an important therapeutic target for the ischemia-evoked cortex edema. PMID:25843346

  2. S100B inhibition reduces behavioral and pathologic changes in experimental traumatic brain injury.

    PubMed

    Kabadi, Shruti V; Stoica, Bogdan A; Zimmer, Danna B; Afanador, Lauriaselle; Duffy, Kara B; Loane, David J; Faden, Alan I

    2015-12-01

    Neuroinflammation following traumatic brain injury (TBI) is increasingly recognized to contribute to chronic tissue loss and neurologic dysfunction. Circulating levels of S100B increase after TBI and have been used as a biomarker. S100B is produced by activated astrocytes and can promote microglial activation; signaling by S100B through interaction with the multiligand advanced glycation end product-specific receptor (AGER) has been implicated in brain injury and microglial activation during chronic neurodegeneration. We examined the effects of S100B inhibition in a controlled cortical impact model, using S100B knockout mice or administration of neutralizing S100B antibody. Both interventions significantly reduced TBI-induced lesion volume, improved retention memory function, and attenuated microglial activation. The neutralizing antibody also significantly reduced sensorimotor deficits and improved neuronal survival in the cortex. However, S100B did not alter microglial activation in BV2 cells or primary microglial cultures stimulated by lipopolysaccharide or interferon gamma. Further, proximity ligation assays did not support direct interaction in the brain between S100B and AGER following TBI. Future studies are needed to elucidate specific pathways underlying S100B-mediated neuroinflammatory actions after TBI. Our results strongly implicate S100B in TBI-induced neuroinflammation, cell loss, and neurologic dysfunction, thereby indicating that it is a potential therapeutic target for TBI. PMID:26154869

  3. 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 ...

  4. Bexarotene Reduces Blood-Brain Barrier Permeability in Cerebral Ischemia-Reperfusion Injured Rats

    PubMed Central

    Xu, Lu; Cao, Fang; Xu, Feng; He, Baicheng; Dong, Zhi

    2015-01-01

    Background Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood-brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction. Methods A total of 180 rats were randomized into three groups (n = 60 each): (i) a sham-operation group, (ii) a cerebral ischemia-reperfusion (I/R) group, and (iii) an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE), claudin-5, and occludin expression were analyzed by Western blotting. Results After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i) brain water content and BBB permeability were significantly reduced; (ii) MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii) claudin-5 and occludin expression were significantly increased; and (iv) apoE expression was significantly increased. Conclusions Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene’s upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients. PMID:25844636

  5. Action expertise reduces brain activity for audiovisual matching actions: An fMRI study with expert drummers

    E-print Network

    Avanzini, Federico

    Action expertise reduces brain activity for audiovisual matching actions: An fMRI study with expert Rocchesso d , Carl Haakon Waadeland e , Scott Love a , Federico Avanzini f , Aina Puce g a Department, University of Padua, Padua, Italy g Department of Psychological and Brain Sciences, Indiana University

  6. Edema (Swelling) (Beyond the Basics)

    MedlinePLUS

    ... a result of a blood clot in the deep veins of the lower leg (called deep vein thrombosis [DVT]). In this case, the edema ... cause swelling of both legs. (See "Patient information: Deep vein thrombosis (DVT) (Beyond the Basics)" .) Pregnancy — Pregnant ...

  7. Exendin-4 reduces tau hyperphosphorylation in type 2 diabetic rats via increasing brain insulin level.

    PubMed

    Yang, Yan; Ma, Delin; Xu, Weijie; Chen, Fuqiong; Du, Tingting; Yue, Wenzhu; Shao, Shiying; Yuan, Gang

    2016-01-01

    Type 2 diabetes (T2D) is a high risk factor for Alzheimer's disease (AD). Our previous study identified that hyperphosphorylation of tau protein, which is one of the pathophysiologic hallmarks of AD, also occurred in T2D rats' brain; while glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, could decrease the phosphorylation of tau, probably via augmenting insulin signaling pathway. The purpose of this study was to further explore the mechanisms that underlie the effect of exendin-4 (ex-4, a GLP-1 receptor agonist) in reducing tau phosphorylation. We found that peripheral ex-4 injection in T2D rats reduced hyperphosphorylation of tau protein in rat hippocampus, probably via increasing hippocampal insulin which activated insulin signaling. Furthermore, we found that ex-4 could neither activate insulin signaling, nor reduce tau phosphorylation in HT22 neuronal cells in the absence of insulin. These results suggested that insulin is required in reduction of tau hyperphosphorylation by ex-4 in brain rats with T2D. PMID:26640240

  8. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, ?-7-nicotinic acetylcholine receptors (?7nAChRs) modulate effects of ?(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of ?7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of ?7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  9. 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.

  10. Efficient Multilevel Brain Tumor Segmentation with Integrated Bayesian Model Classification

    E-print Network

    Krovi, Venkat

    algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema are the tumor itself, comprising a necrotic (dead) part and an active part, the edema or swelling in the nearby. On the right, we outline the different heterogeneous regions of the brain tumor and label them as edema, active

  11. Aprepitant Reduces Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients with Brain Tumors

    PubMed Central

    Duggin, Kelly; Tickle, Kelly; Norman, Gina; Yang, Jie; Wang, Chong; Cross, Shane J.; Gajjar, Amar; Mandrell, Belinda

    2015-01-01

    Purpose Chemotherapy-induced nausea and vomiting (CINV) are common and distressing side effects in patients with brain tumors and may be associated with radiation and the administration of highly emetogenic chemotherapy (HEC). Pediatric antiemetic guidelines recommend administration of a 5-hydroxytryptamine-3 (5HT3) receptor antagonists and the addition of aprepitant, a neurokinin 1 (NK1) antagonist with corticosteroids for the treatment of HEC. However, challenges persist in treating CINV in patients with brain tumors as corticosteroids are contraindicated due to potential impairment of the blood brain barrier permeability. Our objective was to determine whether a 5HT3 receptor antagonist and the addition of aprepitant, a neurokinin 1 (NK1) antagonist without a corticosteroid, were effective in reducing HEC vomiting in pediatric brain tumors. Methods A retrospective review found that 18 patients with a history of high-grade vomiting during radiation were prescribed a 5HT3 receptor antagonist and aprepitant without a corticosteroid during their first course of HEC. To determine the efficacy of aprepitant without a corticosteroid, each recipient was matched with two controls that did not received aprepitant. Results During HEC, controls without aprepitant were more likely to have grade 2 or higher vomiting than the aprepitant recipients (p = 0.03; odds ratio = 4.15; 95% confidence interval [1.59, 10.82]), after controlling for radiation-associated vomiting toxicity. Discussion Significantly less vomiting was identified in children receiving HEC and prescribed a 5HT3 receptor antagonist and aprepitant. Findings suggest that the addition of a NK1 antagonist may be beneficial to emetic control in this highly vulnerable population. PMID:24972782

  12. Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress.

    PubMed

    Xia, Huijing; de Queiroz, Thyago Moreira; Sriramula, Srinivas; Feng, Yumei; Johnson, Tanya; Mungrue, Imran N; Lazartigues, Eric

    2015-03-01

    Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress. PMID:25519733

  13. 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 raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. PMID:26453995

  14. Pharmaco-modulations of induced edema and vascular permeability changes by Vipera lebetina venom: inflammatory mechanisms.

    PubMed

    Sebia-Amrane, Fatima; Laraba-Djebari, Fatima

    2013-04-01

    The inflammatory response induced by Vipera lebetina venom (VLV) in the mice hind paw was evaluated by paw edema value and vascular permeability changes. The edema was produced in a dose- and time-dependent manner. This response was maximal within 2 h and disappeared after 24 h The minimum edema-forming dose was estimated at 0.8 ?g/20 g body weight. Microscopic examination confirmed that VLV also induces skin structure alterations with collagen fiber dissociation and polynuclear infiltration, which is characteristic of edema formation. The induced edema with VLV (1 ?g/paw) could be due to the release of pharmacological active substances at the site of injection. Histamine, serotonine, and arachidonate metabolites may play important roles in the vasoactive and edematic effect of VLV since pretreatment of mice with cromoglycate, cyproheptadine, ibuprofen, loratidine, and indomethacin significantly reduced the edema formation (77, 63, 57, 45, and 43 %, respectively). The obtained results demonstrate that the induced edema and vasodilatation by this venom may be triggered and maintained by different pharmacological mechanisms, since cromoglycate and cyproheptadine were the most active inhibitors of the edema. The relationships between histamine and serotonin release from mast cells and arachidonate metabolites activation could be the main step in edema-forming and the induced vasodilatation by the venom. PMID:23108954

  15. TNF? siRNA Reduces Brain TNF and EEG Delta Wave Activity in Rats

    PubMed Central

    Taishi, Ping; Churchill, Lynn; Wang, Mingxiang; Kay, Daniel; Davis, Christopher J.; Guan, Xin; De, Alok; Yasuda, Tadanobu; Liao, Fan; Krueger, James M.

    2007-01-01

    Tumor necrosis factor alpha (TNF?) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNF? were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNF? siRNA treatment specifically reduced TNF? mRNA by 45% in vitro without affecting interleukin-6 or gluR1-4 mRNA levels. In vivo the TNF? siRNA? reduced TNF? mRNA, interleukin-6 mRNA and gluR1 mRNA levels compared to treatment with a scrambled control siRNA. After in vivo microinjection, the density of TNF?-immunoreactive cells in layer V of the SSctx was also reduced. Electroencephalogram (EEG) delta wave power was decreased on days 2 and 3 on the side of the brain that received the TNF? siRNA microinjection relative to the side receiving the control siRNA. These findings support the hypothesis that TNF? siRNA attenuates TNF? mRNA and TNF? protein in the rat cortex and that those reductions reduce cortical EEG delta power. Results also are consistent with the notion that TNF? is involved in CNS physiology including sleep regulation. PMID:17531209

  16. Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

    PubMed

    Fang, Qing; Yan, Xu; Li, Shaowu; Sun, Yilin; Xu, Lixin; Shi, Zhongfang; Wu, Min; Lu, Yi; Dong, Liping; Liu, Ran; Yuan, Fang; Yang, Shao-Hua

    2016-01-01

    The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented. PMID:26463954

  17. Reduced de novo synthesis of 5-methyltetrahydrofolate and reduced taurine levels in ethanol-treated chick brains.

    PubMed

    Berlin, Kelsey N; Cameron, Lauren M; Gatt, Meredith; Miller, Robert R

    2010-09-01

    In previous studies, exogenous ethanol (3 mmol EtOH/kg egg) caused a 1.6-fold increase in chick brain homocysteine (HoCys) levels at 11 days of development and the mixture of 3 mmol EtOH/kg egg and 34 micromol folic acid/kg egg attenuated EtOH-induced increases in chick brain HoCys levels. Because HoCys is converted to methionine utilizing the methyl donor, 5-methyltetrahydrofolate (5-methyl THF), we studied whether exogenous ethanol (3 mmol EtOH/kg egg) or the mixture of 3 mmol EtOH/kg egg and 34 micromol 5-methyl THF/kg egg inhibited chick brain 10-formyltetrahydrofolate dehydrogenase (10-FTHF DH; EC 1.5.1.6) activities and brain N5, N10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) activities at 11 days of development. Three daily dosages of 3 mmol EtOH/kg egg (E0-2) caused approximately a 7-fold reduction in brain 10-FTHF DH activities and approximately a 1.9-fold reduction in brain MTHFR activities as compared to controls at 11 days of development (pbrain taurine levels. In EtOH-treated and EtOH and 5-methyl THF-treated embryos, brain taurine levels decreased by approximately 5.5-fold and 6.2-fold as compared to controls, respectively (pbrain taurine levels at 11 days of development. PMID:20541623

  18. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    SciTech Connect

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

  19. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain.

    PubMed

    Simpson, Tamara; Pase, Matthew; Stough, Con

    2015-01-01

    The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function. PMID:26413126

  20. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

    PubMed Central

    Simpson, Tamara; Pase, Matthew; Stough, Con

    2015-01-01

    The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function. PMID:26413126

  1. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

    PubMed

    McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

    2015-09-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. PMID:25975171

  2. Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment

    PubMed Central

    Hatipoglu, Gökçe; Hock, Stefan W; Weiss, Ruth; Fan, Zheng; Sehm, Tina; Ghoochani, Ali; Buchfelder, Michael; Savaskan, Nicolai E; Eyüpoglu, Ilker Y

    2015-01-01

    Malignant gliomas can be counted to the most devastating tumors in humans. Novel therapies do not achieve significant prolonged survival rates. The cancer cells have an impact on the surrounding vital tissue and form tumor zones, which make up the tumor microenvironment. We investigated the effects of sunitinib, a small molecule multitargeted receptor tyrosine kinase inhibitor, on constituents of the tumor microenvironment such as gliomas, astrocytes, endothelial cells, and neurons. Sunitinib has a known anti-angiogenic effect. We found that sunitinib normalizes the aberrant tumor-derived vasculature and reduces tumor vessel pathologies (i.e. auto-loops). Sunitinib has only minor effects on the normal, physiological, non-proliferating vasculature. We found that neurons and astrocytes are protected by sunitinib against glutamate-induced cell death, whereas sunitinib acts as a toxin towards proliferating endothelial cells and tumor vessels. Moreover, sunitinib is effective in inducing glioma cell death. We determined the underlying pathways by which sunitinib operates as a toxin on gliomas and found vascular endothelial growth factor receptor 2 (VEGFR2, KDR/Flk1) as the main target to execute gliomatoxicity. The apoptosis-inducing effect of sunitinib can be mimicked by inhibition of VEGFR2. Knockdown of VEGFR2 can, in part, foster the resistance of glioma cells to receptor tyrosine kinase inhibitors. Furthermore, sunitinib alleviates tumor-induced neurodegeneration. Hence, we tested whether temozolomide treatment could be potentiated by sunitinib application. Here we show that sunitinib can amplify the effects of temozolomide in glioma cells. Thus, our data indicate that combined treatment with temozolomide does not abrogate the effects of sunitinib. In conclusion, we found that sunitinib acts as a gliomatoxic agent and at the same time carries out neuroprotective effects, reducing tumor-induced neurodegeneration. Thus, this report uncovered sunitinib's actions on the brain tumor microenvironment, revealing novel aspects for adjuvant approaches and new clinical assessment criteria when applied to brain tumor patients. PMID:25458015

  3. A multimodal RAGE-specific inhibitor reduces amyloid ?–mediated brain disorder in a mouse model of Alzheimer disease

    PubMed Central

    Deane, Rashid; Singh, Itender; Sagare, Abhay P.; Bell, Robert D.; Ross, Nathan T.; LaRue, Barbra; Love, Rachal; Perry, Sheldon; Paquette, Nicole; Deane, Richard J.; Thiyagarajan, Meenakshisundaram; Zarcone, Troy; Fritz, Gunter; Friedman, Alan E.; Miller, Benjamin L.; Zlokovic, Berislav V.

    2012-01-01

    In Alzheimer disease (AD), amyloid ? peptide (A?) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates A?-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked A? binding to the V domain of RAGE and inhibited A?40- and A?42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human A?-precursor protein, a transgenic mouse model of AD with established A? pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating A?40 and A?42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited ?-secretase activity and A? production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced A?40 and A?42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of A?-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD. PMID:22406537

  4. Itraconazole associated quadriparesis and edema: a case report

    PubMed Central

    2011-01-01

    Introduction Itraconazole is an anti-fungal agent widely used to treat various forms of mycosis. It is particularly useful in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Side effects are uncommon and usually mild. Mild neuropathy is noted to occur very rarely. We present an unusual and, to the best of our knowledge, as yet unreported case of severe neuropathy and peripheral edema due to itraconazole in the absence of a concomitant risk factor. Case presentation A 72-year-old Caucasian man was started on itraconazole following diagnosis of severe asthma with fungal sensitization. One month later he presented with severe bilateral ankle edema with an elevated serum itraconazole level. The itraconazole dose was reduced but his ankle edema persisted and he developed weakness of all four limbs. Itraconazole was completely stopped leading to improvement in his leg edema but he became bed bound due to weakness. He gradually improved with supportive care and neurorehabilitation. On review at six months, our patient was able to mobilize with the aid of two elbow crutches and power had returned to 5/5 in distal extremities and 4+/5 in proximal extremities. The diagnosis was established based on the classical presentation of drug-induced neuropathy and negative investigatory findings for any alternative diagnoses. Conclusion We report the case of a patient presenting with an unusual complication of severe neuropathy and peripheral edema due to itraconazole. Clinicians should be alert to this association when encountered with neuropathy and/or edema in an itraconazole therapy recipient. PMID:21477327

  5. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo

    PubMed Central

    Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45?50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1? and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain. PMID:26466323

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

    PubMed

    Br?ni?teanu, 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. PMID:26120654

  7. Status Epilepticus Induces Vasogenic Edema via Tumor Necrosis Factor-?/ Endothelin-1-Mediated Two Different Pathways

    PubMed Central

    Kim, Ji-Eun; Ryu, Hea Jin; Kang, Tae-Cheon

    2013-01-01

    Status epilepticus (SE) induces vasogenic edema in the piriform cortex with disruptions of the blood-brain barrier (BBB). However, the mechanisms of vasogenic edema formation following SE are still unknown. Here we investigated the endothelin B (ETB) receptor-mediated pathway of SE-induced vasogenic edema. Following SE, the release of tumor necrosis factor-? (TNF-?) stimulated endothelin-1 (ET-1) release and expression in neurons and endothelial cells. In addition, TNF-?-induced ET-1 increased BBB permeability via ETB receptor-mediated endothelial nitric oxide synthase (eNOS) activation in endothelial cells. ETB receptor activation also increased intracellular reactive oxygen species by NADPH oxidase production in astrocytes. These findings suggest that SE results in BBB dysfunctions via endothelial-astroglial interactions through the TNF-?-ET-1-eNOS/NADPH oxidase pathway, and that these ETB receptor-mediated interactions may be an effective therapeutic strategy for vasogenic edema in various neurological diseases. PMID:24040253

  8. Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients

    PubMed Central

    Mojtahedzadeh, Mojtaba; Ahmadi, Arezoo; Mahmoodpoor, Ata; Beigmohammadi, Mohammad Taghi; Abdollahi, Mohammad; Khazaeipour, Zahra; Shaki, Fatemeh; Kuochaki, Bizhan; Hendouei, Narjes

    2014-01-01

    Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress. Materials and Methods: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days. Results: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004). Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients. PMID:25535502

  9. Catalpol Increases Brain Angiogenesis and Up-Regulates VEGF and EPO in the Rat after Permanent Middle Cerebral Artery Occlusion

    PubMed Central

    Zhu, Hui-Feng; Wan, Dong; Luo, Yong; Zhou, Jia-Li; Chen, Li; Xu, Xiao-Yu

    2010-01-01

    To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately. PMID:20827397

  10. 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

  11. Chronic edema of the lower extremities: international consensus recommendations for compression therapy clinical research trials.

    PubMed

    Stout, N; Partsch, H; Szolnoky, G; Forner-Cordero, I; Mosti, G; Mortimer, P; Flour, M; Damstra, R; Piller, N; Geyer, M J; Benigni, J-P; Moffat, C; Cornu-Thenard, A; Schingale, F; Clark, M; Chauveau, M

    2012-08-01

    Chronic edema is a multifactorial condition affecting patients with various diseases. Although the pathophysiology of edema varies, compression therapy is a basic tenant of treatment, vital to reducing swelling. Clinical trials are disparate or lacking regarding specific protocols and application recommendations for compression materials and methodology to enable optimal efficacy. Compression therapy is a basic treatment modality for chronic leg edema; however, the evidence base for the optimal application, duration and intensity of compression therapy is lacking. The aim of this document was to present the proceedings of a day-long international expert consensus group meeting that examined the current state of the science for the use of compression therapy in chronic edema. An expert consensus group met in Brighton, UK, in March 2010 to examine the current state of the science for compression therapy in chronic edema of the lower extremities. Panel discussions and open space discussions examined the current literature, clinical practice patterns, common materials and emerging technologies for the management of chronic edema. This document outlines a proposed clinical research agenda focusing on compression therapy in chronic edema. Future trials comparing different compression devices, materials, pressures and parameters for application are needed to enhance the evidence base for optimal chronic oedema management. Important outcomes measures and methods of pressure and oedema quantification are outlined. Future trials are encouraged to optimize compression therapy in chronic edema of the lower extremities. PMID:22801397

  12. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling

    PubMed Central

    Hagmann, Patric; Deco, Gustavo

    2015-01-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model’s prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information. PMID:26317432

  13. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    PubMed Central

    2012-01-01

    Correction to Rao J S, Kim H W, Kellom M, Greenstein D, Chen M, Kraft A D, Harry G J, Rapoport S I, Basselin M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. Journal of Neuroinflammation 8:101.

  14. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the

    E-print Network

    Thompson, Paul

    A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume for review September 22, 2009) A recently identified variant within the fat mass and obesity- associated (FTO, in adults and an 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons

  15. Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

    PubMed

    Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

    2015-07-01

    Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease. PMID:25931268

  16. Calcified neurocysticercus, perilesional edema, and histologic inflammation.

    PubMed

    Nash, Theodore E; Bartelt, Luther A; Korpe, Poonum S; Lopes, Beatriz; Houpt, Eric R

    2014-02-01

    Abstract. Here, we present the second report of the histopathology of a Taenia solium calcification giving rise to perilesional edema. This has important implications, because if perilesional edema lesions are inflammatory in character, immunosuppressive or anti-inflammatory medications, not just antiepileptic drugs alone, may be useful to prevent or treat recurring episodes in such patients. PMID:24394477

  17. The effect of inhaled nitric oxide on the carrageenan-induced paw edema.

    PubMed

    Coelho, Carly Faria; Vieira, Rodolfo P; Lopes-Martins, Patrícia Sardinha Leonardo; Teixeira, Simone Aparecida; Borbely, Alexandre Urban; Gouvea, Irene Maria; Frigo, Lucio; Lopes-Martins, Rodrigo Álvaro Brandão

    2015-01-01

    Inhaled nitric oxide therapy reaches not only pulmonary vessels, but also other vasculatures, presenting anti-inflammatory effects. Therefore, this study investigated the effects of inhaled nitric oxide on a mice model of carrageenan-induced paw edema. Paw edema was induced in male Swiss mice (20-30 g) by subplantar injection of carrageenan (0.05 ml of a 1% suspension in 0.9% saline). The evaluation of time-course edema (mililiter) was measured by plethysmometry until 12 h following carrageenan administration. Thirty minutes after carrageenan injection, some groups received inhaled nitric oxide (300 ppm at variable doses and times) or Indometacin (INDO 5 mg/Kg, v.o), while others received sildenafil (1 mg/Kg, i.p) or rolipram (3 mg/Kg, i.p.) with or without inhaled nitric oxide. Paws were assessed for edema levels by plethysmometry, mieloperoxidase activity and histological analysis. Inhaled nitric oxide significantly reduced carrageenan-induced paw edema, mieloperoxidase activity and inflammatory infiltrate, although similar results were also observed in sildenafil and rolipram treated groups. In addition, significant effects between inhaled nitric oxide with pharmacological therapy was observed. Inhaled nitric oxide presents anti-inflammatory effects on carrageenan-induce paw edema, as observed through reduced edema, mieloperoxidase activity and neutrophil infiltration, indicating that inhaled nitric oxide therapy goes beyond lung vascular effects. PMID:25070733

  18. The Inhibitory Effect of Kakkonto, Japanese Traditional (Kampo) Medicine, on Brain Penetration of Oseltamivir Carboxylate in Mice with Reduced Blood-Brain Barrier Function

    PubMed Central

    Ohara, Kousuke; Oshima, Shinji; Fukuda, Nanami; Ochiai, Yumiko; Maruyama, Ayumi; Kanamuro, Aki; Negishi, Akio; Honma, Seiichi; Ohshima, Shigeru; Akimoto, Masayuki; Takenaka, Shingo; Kobayashi, Daisuke

    2015-01-01

    Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression. PMID:25788966

  19. GSK3? inhibition protects the immature brain from hypoxic-ischaemic insult via reduced STAT3 signalling.

    PubMed

    D'Angelo, Barbara; Joakim Ek, C; Sun, Yanyan; Zhu, Changlian; Sandberg, Mats; Mallard, Carina

    2016-02-01

    Hypoxic-ischaemic (HI) injury is an important cause of neurological morbidity in neonates. HI leads to pathophysiological responses, including inflammation and oxidative stress that culminate in cell death. Activation of glycogen synthase kinase 3? (GSK3?) and the signal transducer and activator of transcription (STAT3) promotes brain inflammation. The purpose of this study was to test whether inhibition of GSK3? signalling protects against neonatal HI brain injury. Mice were subjected to HI at postnatal day (PND) 9 and treated with a selective GSK3? inhibitor, SB216763. Brain injury and caspase-3 activation, anti-oxidant and inflammatory mRNA responses and activation of STAT3 were analysed. Our results show that HI reduced phosphorylation of GSK3?, thus promoting its kinase activity. The GSK3? inhibitor reduced caspase-3 activation and neuronal cell death elicited by HI and reverted the effects of HI on gene expression of the anti-oxidant enzyme sod2 and mitochondrial factor pgc1?. The HI insult activated STAT3 in glial cells and GSK3? inhibition attenuated STAT3 phosphorylation and its nuclear translocation following HI. Further, GSK3? inhibition reduced HI-induced gene expression of pro-inflammatory cytokines tnf? and Il-6, while promoted the anti-inflammatory factor Il-10. In summary, data show that GSK3? inhibition is neuroprotective in neonatal HI brain injury likely via reduced pro-inflammatory responses by blocking STAT3 signalling. Our study suggests that pharmacological interventions built upon GSK3? silencing strategies could represent a novel therapy in neonatal brain injury. PMID:26384655

  20. 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

  1. Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro.

    PubMed Central

    Bemis, J C; Seegal, R F

    1999-01-01

    Consumption of contaminated Great Lakes fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, making it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotoxic effects of two of these contaminants--polychlorinated biphenyls (PCBs) and methylmercury (MeHg)--both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changes in media lactate dehydrogenase concentrations. Elevations in both tissue and media 3, 4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contaminants suggests that future revisions of fish-consumption guidelines should consider contaminant interactions. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10544155

  2. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    PubMed

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

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. PMID:23994447

  3. Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats.

    PubMed

    Moretti, R; Zanin, A; Pansiot, J; Spiri, D; Manganozzi, L; Kratzer, I; Favero, G; Vasiljevic, A; Rinaldi, V E; Pic, I; Massano, D; D'Agostino, I; Baburamani, A; La Rocca, M A; Rodella, L F; Rezzani, R; Ek, J; Strazielle, N; Ghersi-Egea, J-F; Gressens, P; Titomanlio, L

    2015-12-17

    The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin. Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18h after ibotenate injection. We determined lesion size at 5days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR. Dextran extravasation was seen 2h after the insult, suggesting a rapid BBB breakdown that was resolved by 4h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin. Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects. PMID:26542996

  4. Reduced brain levels of DHEAS in hepatic coma patients: significance for increased GABAergic tone in hepatic encephalopathy.

    PubMed

    Ahboucha, Samir; Talani, Giuseppe; Fanutza, Tomas; Sanna, Enrico; Biggio, Giovanni; Gamrani, Halima; Butterworth, Roger F

    2012-07-01

    Increased neurosteroids with allosteric modulatory activity on GABA(A) receptors such as 3?-5? tertrahydroprogesterone; allopregnanolone (ALLO), are candidates to explain the phenomenon of "increased GABAergic tone" in hepatic encephalopathy (HE). However, it is not known how changes of other GABA(A) receptor modulators such as dehydroepiandrosterone sulfate (DHEAS) contribute to altered GABAergic tone in HE. Concentrations of DHEAS were measured by radioimmunoassay in frontal cortex samples obtained at autopsy from 11 cirrhotic patients who died in hepatic coma and from an equal number of controls matched for age, gender, and autopsy delay intervals free from hepatic or neurological diseases. To assess whether reduced brain DHEAS contributes to increased GABAergic tone, in vitro patch clamp recordings in rat prefrontal cortex neurons were performed. A significant reduction of DHEAS (5.81±0.88 ng/g tissue) compared to control values (9.70±0.79 ng/g, p<0.01) was found. Brain levels of DHEAS in patients with liver disease who died without HE (11.43±1.74 ng/g tissue), and in a patient who died in uremic coma (12.56 ng/g tissue) were within the control range. Increasing ALLO enhances GABAergic tonic currents concentration-dependently, but increasing DHEAS reduces these currents. High concentrations of DHEAS (50 ?M) reduce GABAergic tonic currents in the presence of ALLO, whereas reduced concentrations of DHEAS (1 ?M) further stimulate these currents. These findings demonstrate that decreased concentrations of DHEAS together with increased brain concentrations of ALLO increase GABAergic tonic currents synergistically; suggesting that reduced brain DHEAS could further increase GABAergic tone in human HE. PMID:22490610

  5. Impact of edema and seed movement on the dosimetry of prostate seed implants

    PubMed Central

    Sloboda, Ron S.; Usmani, N.; Monajemi, T. T.; Liu, D. M-C

    2012-01-01

    This article summarizes current knowledge concerning the characterization of prostatic edema and intra-prostatic seed movement as these relate to dosimetry of permanent prostate implants, and reports the initial application to clinical data of a new edema model used in calculating pre- and post-implant dose distributions. Published edema magnitude and half-life parameters span a broad range depending on implant technique and measurement uncertainty, hence clinically applicable values should be determined locally. Observed intra-prostatic seed movements appear to be associated with particular aspects of implant technique and could be minimized by technique modification. Using an extended AAPM TG-43 formalism incorporating the new edema model, relative dose error RE associated with neglecting edema was calculated for three I-125 seed implants (18.9 cc, 37.6 cc, 60.2 cc) performed at our center. Pre- and post-plan RE average values and ranges in a 50 × 50 × 50 mm3 calculation volume were similar at ~2% and ~0–3.5%, respectively, for all three implants; however, the spatial distribution of RE varied for different seed configurations. Post-plan values of D90 and V100 for prostate were reduced by ~2% and ~1%, respectively. In cases where RE is not clinically negligible as a consequence of large edema magnitude and / or use of Pd-103 seeds, the dose calculation method demonstrated here can be applied to account for edema explicitly and there by improve the accuracy of clinical dose estimates. PMID:22557797

  6. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

    2011-11-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  7. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

    PubMed

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

    2014-01-01

    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content. PMID:24435134

  8. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  9. Xenon improves neurological outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury

    PubMed Central

    Luh, Clara; Gruss, Marco; Radyushkin, Konstantin; Hirnet, Tobias; Werner, Christian; Engelhard, Kristin; Franks, Nicholas P; Thal, Serge C; Dickinson, Robert

    2015-01-01

    Objectives To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury, and to determine whether application of xenon has a clinically relevant therapeutic time window. Design Controlled animal study. Setting University research laboratory. Subjects Male C57BL/6N mice (n=196) Interventions 75% xenon, 50% xenon or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements & Main Results Outcome following trauma was measured using: 1) functional neurological outcome score, 2) histological measurement of contusion volume, 3) analysis of locomotor function and gait. Our study shows that xenon-treatment improves outcome following traumatic brain injury. Neurological outcome scores were significantly (p<0.05) better in xenon-treated groups in the early phase (24 hours) and up to 4 days after injury. Contusion volume was significantly (p<0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p<0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 hour or 3 hours after injury. Neurological outcome was significantly (p<0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p<0.05) were observed in the xenon-treated group, 1 month after trauma. Conclusions These results show for the first time that xenon improves neurological outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in brain trauma patients. PMID:25188549

  10. THYROID HORMONE INSUFFICIENCY DURING BRAIN DEVELOPMENT REDUCES PARVALBUMIN IMMUNOREACTIVITY AND INHIBITORY FUNCTION IN THE HIPPOCAMPUS.

    EPA Science Inventory

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  11. Molecular Signatures of Reduced Nerve Toxicity by CeCl3 in Phoxim-exposed Silkworm Brains

    PubMed Central

    Wang, Binbin; Li, Fanchi; Ni, Min; Zhang, Hua; Xu, Kaizun; Tian, Jianghai; Hu, Jingsheng; Shen, Weide; Li, Bing

    2015-01-01

    CeCl3 can reduce the damage caused by OP pesticides, in this study we used the brain of silkworms to investigate the mechanism of CeCl3 effects on pesticide resistance. The results showed that phoxim treatments led to brain damages, swelling and death of neurons, chromatin condensation, and mitochondrial damage. Normal nerve conduction was severely affected by phoxim treatments, as revealed by: increases in the contents of neurotransmitters Glu, NO, and ACh by 63.65%, 61.14%, and 98.54%, respectively; decreases in the contents of 5-HT and DA by 53.19% and 43.71%, respectively; reductions in the activities of Na+/K+-ATPase, Ca2+/Mg2+-ATPase, and AChE by 85.27%, 85.63%, and 85.63%, respectively; and increase in the activity of TNOS by 22.33%. CeCl3 pretreatment can significantly reduce such damages. Results of DGE and qRT-PCR indicated that CeCl3 treatments significantly upregulated the expression levels of CYP4G23, cyt-b5, GSTs-?1, ace1, esterase-FE4, and ?-esterase 2. Overall, phoxim treatments cause nerve tissue lesions, neuron death, and nerve conduction hindrance, but CeCl3 pretreatments can promote the expression of phoxim resistance-related genes in silkworm brains to reduce phoxim-induced damages. Our study provides a potential new method to improve the resistance of silkworms against OP pesticides. PMID:26227613

  12. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    PubMed

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of GABAA receptor expression in hippocampus. PMID:25541342

  13. Preservation of the Blood Brain Barrier and Cortical Neuronal Tissue by Liraglutide, a Long Acting Glucagon-Like-1 Analogue, after Experimental Traumatic Brain Injury

    PubMed Central

    Hakon, Jakob; Ruscher, Karsten; Tomasevic, Gregor

    2015-01-01

    Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 ?g/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI. PMID:25822252

  14. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus.

    PubMed

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K; Fiacco, Todd A

    2015-09-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1?min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  15. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

    PubMed Central

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K.

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1?min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8–20 weeks old) compared with juvenile (P15–P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  16. Berry fruit and nuts: their role in reducing oxidative stress and inflammation in the aging brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Berry fruits and nuts are nutrient dense and contain a variety of bioactive phytochemicals, specifically polyphenols. A growing body of literature describes pre-clinical research, using both in vitro and in vivo techniques, which show beneficial effects of nut and berry consumption on the brain in ...

  17. An Online Family Intervention to Reduce Parental Distress Following Pediatric Brain Injury

    ERIC Educational Resources Information Center

    Wade, Shari L.; Carey, Joanne; Wolfe, Christopher R.

    2006-01-01

    This study examined whether an online problem-solving intervention could improve parental adjustment following pediatric traumatic brain injury (TBI). Families of children with moderate-to-severe TBI were recruited from the trauma registry of a large children's hospital and randomly assigned to receive online family problem solving therapy (FPS; n…

  18. Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts...

  19. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

    PubMed Central

    Houvenaghel, Jean-François; Le Jeune, Florence; Dondaine, Thibaut; Esquevin, Aurore; Robert, Gabriel Hadrien; Péron, Julie; Haegelen, Claire; Drapier, Sophie; Jannin, Pierre; Lozachmeur, Clément; Argaud, Soizic; Duprez, Joan; Drapier, Dominique; Vérin, Marc; Sauleau, Paul

    2015-01-01

    Objective The decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking. Methods To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism. Results We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency. Conclusions These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms. PMID:26448131

  20. Inhibition of mTOR Pathway by Rapamycin Reduces Brain Damage in Rats Subjected to Transient Forebrain Ischemia

    PubMed Central

    Yang, Xiao; Hei, Changhun; Liu, Ping; Song, Yaozu; Thomas, Taylor; Tshimanga, Sylvie; Wang, Feng; Niu, Jianguo; Sun, Tao; Li, P. Andy

    2015-01-01

    The aims of this study are to clarify the role of mTOR in mediating cerebral ischemic brain damage and the effects of rapamycin on ischemic outcomes. Ten minutes of forebrain ischemia was induced in rats, and their brains were sampled after 3 h, 16 h, and 7 days reperfusion for histology, immunohistochemistry and biochemical analysis. Our data demonstrated that cerebral ischemia resulted in both apoptotic and necrotic neuronal death; cerebral ischemia and reperfusion led to significant increases of mRNA and protein levels of p-mTOR and its downstream p-P70S6K and p-S6; elevation of LC3-II, and release of cytochrome c into the cytoplasm in both the cortex and hippocampus. Inhibition of mTOR by rapamycin markedly reduced ischemia-induced damage; suppressed p-Akt, p-mTOR, p-P70S6K and p-S6 protein levels; decreased LC3-II and Beclin-1; and prevented cytochrome c release in the two structures. All together, these data provide evidence that cerebral ischemia activates mTOR and autophagy pathways. Inhibition of mTOR deactivates the mTOR pathway, suppresses autophagy, prevents cytochrome c release and reduces ischemic brain damage. PMID:26681922

  1. Novel Imaging Markers of Ischemic Cerebral Edema and Its Association with Neurological Outcome.

    PubMed

    Kimberly, W Taylor; Battey, Thomas W K; Wu, Ona; Singhal, Aneesh B; Campbell, Bruce C V; Davis, Stephen M; Donnan, Geoffrey A; Sheth, Kevin N

    2016-01-01

    Ischemic cerebral edema (ICE) is a recognized cause of secondary neurological deterioration after large hemispheric stroke, but little is known about the scope of its impact. To study edema in less severe stroke, our group has developed several markers of cerebral edema using brain magnetic resonance imaging (MRI). These tools, which are based on categorical and volumetric measurements in serial diffusion-weighted imaging (DWI), are applicable to a wide variety of stroke volumes. Further, these metrics provide distinct volumetric measurements attributable to ICE, infarct growth, and hemorrhagic transformation. We previously reported that ICE independently predicted neurological outcome after adjustment for known risk factors. We found that an ICE volume of 11 mL or greater was associated with worse neurological outcome. PMID:26463953

  2. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury.

    PubMed

    Harvey, Lloyd D; Yin, Yan; Attarwala, Insiya Y; Begum, Gulnaz; Deng, Julia; Yan, Hong Q; Dixon, C Edward; Sun, Dandan

    2015-12-01

    We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16?mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1?ml/kg) was administered intraperitonially at 5?min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to ameliorate TBI-induced cellular pathology. PMID:26685193

  3. Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain

    PubMed Central

    Chen, Wanqiu; Guo, Yi; Walker, Espen J.; Shen, Fanxia; Jun, Kristine; Oh, S. Paul; Degos, Vincent; Lawton, Michael T.; Tihan, Tarik; Davalos, Dimitrios; Akassoglou, Katerina; Nelson, Jeffrey; Pile-Spellman, John; Su, Hua; Young, William L.

    2013-01-01

    Objective Vessels in brain arteriovenous malformations (bAVM) are prone to rupture. The underlying pathogenesis is not clear. Hereditary hemorrhagic telangiectasia type 2 (HHT2) patients with activin receptor-like kinase 1 (Alk1) mutation have a higher incidence of bAVM than the general population. We tested the hypothesis that vascular endothelial growth factor (VEGF) impairs vascular integrity in the Alk1-deficient brain through reduction of mural cell-coverage. Methods and Results Adult Alk11f/2f mice (loxP sites flanking exons 4-6) and wild-type (WT) mice were injected with 2×107 PFU Ad-Cre and 2×109 genome copies of AAV-VEGF to induce focal homozygous Alk1 deletion (in Alk11f/2f mice) and angiogenesis. Brain vessels were analyzed eight weeks later. Compared to WT mice, the Alk1-deficient brain had more fibrin (99±30×103 pixels/mm2 vs. 40±13×103, P=0.001), iron deposition (508±506 pixels/mm2 vs. 6 ±49, P=0.04), and Iba1+ microglia/macrophage infiltration (888±420 Iba1+ cells/mm2 vs. 240±104 Iba1+, P=0.001) after VEGF stimulation. In the angiogenic foci, the Alk1-deficient brain had more ?-SMA- vessels (52±9% vs. 12±7%, P<0.001), fewer vascular associated pericytes (503±179/mm2 vs. 931±115, P<0.001), and reduced PDGFR-? expression (26±9%, P<0.001). Conclusion Reduction of mural cell coverage in response to VEGF stimulation is a potential mechanism for the impairment of vessel wall integrity in HHT2-associated bAVM. PMID:23241407

  4. The impact of dietary isoflavonoids on malignant brain tumors

    PubMed Central

    Sehm, Tina; Fan, Zheng; Weiss, Ruth; Schwarz, Marc; Engelhorn, Tobias; Hore, Nirjhar; Doerfler, Arnd; Buchfelder, Michael; Eyüpoglu, IIker Y; Savaskan, Nic E

    2014-01-01

    Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose–response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach. PMID:24898306

  5. Cross-sex hormone treatment in male-to-female transsexual persons reduces serum brain-derived neurotrophic factor (BDNF).

    PubMed

    Fuss, Johannes; Hellweg, Rainer; Van Caenegem, Eva; Briken, Peer; Stalla, Günter K; T'Sjoen, Guy; Auer, Matthias K

    2015-01-01

    Serum levels of brain-derived neurotrophic factor (BDNF) are reduced in male-to-female transsexual persons (MtF) compared to male controls. It was hypothesized before that this might reflect either an involvement of BDNF in a biomechanism of transsexualism or to be the result of persistent social stress due to the condition. Here, we demonstrate that 12 month of cross-sex hormone treatment reduces serum BDNF levels in male-to-female transsexual persons independent of anthropometric measures. Participants were acquired through the European Network for the Investigation of Gender Incongruence (ENIGI). Reduced serum BDNF in MtF thus seems to be a result of hormonal treatment rather than a consequence or risk factor of transsexualism. PMID:25498415

  6. Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice

    PubMed Central

    Fenn, Ashley M.; Skendelas, John P.; Moussa, Daniel N.; Muccigrosso, Megan M.; Popovich, Phillip G.; Lifshitz, Jonathan

    2015-01-01

    Abstract Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15–30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1?d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1?, tumor necrosis factor ?) in enriched microglia/macrophages 1?d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1? and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1–7?d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7?d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. PMID:25070744

  7. Reduced Metabolsim in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-03-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and {sup 18}FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% {+-} 10) whereas males tended to increase it (+5.5% {+-} 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  8. Reduced cerebellar brain activity during reward processing in adolescent binge drinkers.

    PubMed

    Cservenka, Anita; Jones, Scott A; Nagel, Bonnie J

    2015-12-01

    Due to ongoing development, adolescence may be a period of heightened vulnerability to the neurotoxic effects of alcohol. Binge drinking may alter reward-driven behavior and neurocircuitry, thereby increasing risk for escalating alcohol use. Therefore, we compared reward processing in adolescents with and without a history of recent binge drinking. At their baseline study visit, all participants (age=14.86±0.88) were free of heavy alcohol use and completed a modified version of the Wheel of Fortune (WOF) functional magnetic resonance imaging task. Following this visit, 17 youth reported binge drinking on ?3 occasions within a 90 day period and were matched to 17 youth who remained alcohol and substance-naïve. All participants repeated the WOF task during a second visit (age=16.83±1.22). No significant effects were found in a region of interest analysis of the ventral striatum, but whole-brain analyses showed significant group differences in reward response at the second study visit in the left cerebellum, controlling for baseline visit brain activity (p/?<0.05), which was negatively correlated with mean number of drinks consumed/drinking day in the last 90 days. These findings suggest that binge drinking during adolescence may alter brain activity during reward processing in a dose-dependent manner. PMID:26190276

  9. Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model.

    PubMed

    Pakkianathan, Colleen; Benggon, Michael; Khatibi, Nikan H; Chen, Hank; Marcantonio, Suzzanne; Applegate, Richard; Tang, Jiping; Zhang, John

    2016-01-01

    Neurosurgical procedures are associated with unintentional damage to the brain during surgery, known as surgically induced brain injuries (SBI), which have been implicated in orchestrating structural and neurobehavioral deterioration. Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population. Sprague-Dawley rats were treated with low- and high-dose propofol 30 min before SBI. At 24 h post injury, brain water content and neurobehavioral assessment was conducted based on previously established models. In vehicle-treated rats, SBI resulted in significant cerebral edema and higher neurological deficit scores compared with sham-operated rats. Low- or high-dose propofol therapy neither reduced cerebral edema nor improved neurologic function. The results suggest that propofol pretreatment fails to provide neuroprotection in SBI rats. However, it is possible that a SBI model with less magnitude of injury or that propofol re-dosing, given the short-acting pharmacokinetic property of propofol, may be needed to provide definitive conclusions. PMID:26463969

  10. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    NASA Astrophysics Data System (ADS)

    (Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-08-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the ?/? ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

  11. [A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

    PubMed

    Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

    2009-08-01

    A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications. PMID:19764516

  12. Neurovascular protection by telmisartan via reducing neuroinflammation in stroke-resistant spontaneously hypertensive rat brain after ischemic stroke.

    PubMed

    Kono, Syoichiro; Kurata, Tomoko; Sato, Kota; Omote, Yoshio; Hishikawa, Nozomi; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2015-03-01

    Telmisartan is a highly lipid-soluble angiotensin receptor blocker (ARB), which improves insulin sensitivity and reduces triglyceride levels and, thus, is called metabo-sartan. We examined the effects of telmisartan on neurovascular unit (N-acetylglucosamine oligomer [NAGO], collagen IV, and glial fibrillary acidic protein [GFAP]) and neuroinflammation (matrix metalloproteinase-9 [MMP-9] and inflammasome) in brain of stroke-resistant spontaneously hypertensive rat (SHR-SR). At 12 weeks of age, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups, that is, vehicle group, low-dose telmisartan group (.3 mg/kg/d), and high-dose telmisartan group (3 mg/kg/d, postoral). Immunohistologic analysis at ages 6, 12, and 18 months showed progressive decreases of NAGO-positive endothelium and collagen IV-positive basement membrane and progressive increases of MMP-9-positive neurons, GFAP-positive astrocytes, and NLRP3-positive inflammasome in the cerebral cortex of vehicle group. Low-dose telmisartan reduced such changes without lowering blood pressure (BP), and high-dose telmisartan further improved such changes with lowering BP. The present findings suggest that a persistent hypertension caused a long-lasting inflammation after tMCAO in SHR-SR, which accelerated neurovascular disruption and emergent inflammasome, and that telmisartan greatly reduced such inflammation and protected the neurovascular unit via its pleiotropic effects in living hypertensive rat brain after ischemic stroke. PMID:25534368

  13. Reduced Hippocampal Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Rats after Prenatal Exposure to Propylthiouracil (PTU)

    PubMed Central

    Chakraborty, Goutam; Magagna-Poveda, Alejandra; Parratt, Carolyn; Umans, Jason G.; MacLusky, Neil J.

    2012-01-01

    Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy. PMID:22253429

  14. Pyruvate administered to newborn rats with insulin-induced hypoglycemic brain injury reduces neuronal death and cognitive impairment.

    PubMed

    Zhou, Dong; Qian, Jing; Chang, Hong; Xi, Bo; Sun, Ruo-peng

    2012-01-01

    Based on previous studies, we had made a try to administer sodium pyruvate to newborn Wistar rats suffering repetitive and profound hypoglycemia, which can induce brain injury. Fluoro-Jade B was used to marked degenerative neurons 1 day after the third hypoglycemic insult, and Morris water navigation task was performed to assess cognitive function when the rats were 6 weeks old. We found that administration of sodium pyruvate to those rats whose hypoglycemia was terminated by dextrose can reduce neurodegeneration induced by hypoglycemia and improve the cognitive function. Supplementing sodium pyruvate with glucose to terminate severe neonatal hypoglycemia is an effective intervention. PMID:21603897

  15. Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

    PubMed Central

    2013-01-01

    Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

  16. Diabetic macular edema: New promising therapies

    PubMed Central

    Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

    2013-01-01

    The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

  17. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. PMID:24227908

  18. Multimodal MR imaging of acute and subacute experimental traumatic brain injury: Time course and correlation with cerebral energy metabolites

    PubMed Central

    Maegele, Marc; Hoeffgen, Alexander; Uhlenkueken, Ulla; Mautes, Angelika; Schaefer, Nadine; Lippert-Gruener, Marcela; Schaefer, Ute; Hoehn, Mathias

    2015-01-01

    Background Traumatic brain injury (TBI) is one of the leading causes of death and permanent disability world-wide. The predominant cause of death after TBI is brain edema which can be quantified by non-invasive diffusion-weighted magnetic resonance imaging (DWI). Purpose To provide a better understanding of the early onset, time course, spatial development, and type of brain edema after TBI and to correlate MRI data and the cerebral energy state reflected by the metabolite adenosine triphosphate (ATP). Material and Methods The spontaneous development of lateral fluid percussion-induced TBI was investigated in the acute (6?h), subacute (48?h), and chronic (7 days) phase in rats by MRI of quantitative T2 and apparent diffusion coefficient (ADC) mapping as well as perfusion was combined with ATP-specific bioluminescence imaging and histology. Results An induced TBI led to moderate to mild brain damages, reflected by transient, pronounced development of vasogenic edema and perfusion reduction. Heterogeneous ADC patterns indicated a parallel, but mixed expression of vasogenic and cytotoxic edema. Cortical ATP levels were reduced in the acute and subacute phase by 13% and 27%, respectively, but were completely normalized at 7 days after injury. Conclusion The partial ATP reduction was interpreted to be partially caused by a loss of neurons in parallel with transient dilution of the regional ATP concentration by pronounced vasogenic edema. The normalization of energy metabolism after 7 days was likely due to infiltrating glia and not to recovery. The MRI combined with metabolite measurement further improves the understanding and evaluation of brain damages after TBI. PMID:25610615

  19. Therapeutic Hypothermia Reduces Intracranial Pressure and Partial Brain Oxygen Tension in Patients with Severe Traumatic Brain Injury: Preliminary Data from the Eurotherm3235 Trial.

    PubMed

    Flynn, Liam M C; Rhodes, Jonathan; Andrews, Peter J D

    2015-09-01

    Traumatic brain injury (TBI) is a significant cause of disability and death and a huge economic burden throughout the world. Much of the morbidity associated with TBI is attributed to secondary brain injuries resulting in hypoxia and ischemia after the initial trauma. Intracranial hypertension and decreased partial brain oxygen tension (PbtO2) are targeted as potentially avoidable causes of morbidity. Therapeutic hypothermia (TH) may be an effective intervention to reduce intracranial pressure (ICP), but could also affect cerebral blood flow (CBF). This is a retrospective analysis of prospectively collected data from 17 patients admitted to the Western General Hospital, Edinburgh. Patients with an ICP >20?mmHg refractory to initial therapy were randomized to standard care or standard care and TH (intervention group) titrated between 32°C and 35°C to reduce ICP. ICP and PbtO2 were measured using the Licox system and core temperature was recorded through rectal thermometer. Data were analyzed at the hour before cooling, the first hour at target temperature, 2 consecutive hours at target temperature, and after 6 hours of hypothermia. There was a mean decrease in ICP of 4.3±1.6?mmHg (p<0.04) from 15.7 to 11.4?mmHg, from precooling to the first epoch of hypothermia in the intervention group (n=9) that was not seen in the control group (n=8). A decrease in ICP was maintained throughout all time periods. There was a mean decrease in PbtO2 of 7.8±3.1?mmHg (p<0.05) from 30.2 to 22.4?mmHg, from precooling to stable hypothermia, which was not seen in the control group. This research supports others in demonstrating a decrease in ICP with temperature, which could facilitate a reduction in the use of hyperosmolar agents or other stage II interventions. The decrease in PbtO2 is not below the suggested treatment threshold of 20?mmHg, but might indicate a decrease in CBF. PMID:26060880

  20. Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage.

    PubMed

    Lekic, Tim; Flores, Jerry; Klebe, Damon; Doycheva, Desislava; Rolland, William B; Tang, Jiping; Zhang, John H

    2016-01-01

    Germinal matrix hemorrhage (GMH) is the most devastating neurological problem of premature infants. Current treatment strategies are ineffective and brain injury is unpreventable. Insulin-like growth factor 1 (IGF-1) is an endogenous protein shown to have multiple neuroprotective properties. We therefore hypothesized that IGF-1 would reduce brain injury after GMH. Neonatal rats (P7 age) received stereotactic collagenase into the right ganglionic eminence. The following groups were studied: (1) sham, (2) GMH?+?vehicle, (3) GMH?+?intranasal IGF-1. Three days later, the animals were evaluated using the righting-reflex (early neurobehavior), Evans blue dye leakage (blood-brain barrier (BBB) permeability), brain water content (edema), and hemoglobin assay (extent of bleeding). Three weeks later, juvenile rats were tested using a water maze (delayed neurobehavior), and then were sacrificed on day 28 for assessment of hydrocephalus (ventricular size). Intranasal IGF-1 treated animals had improved neurological function, and amelioration of BBB permeability, edema, and re-bleeding. IGF-1 may play a part in protective brain signaling following GMH, and our observed protective effect may offer new promise for treatment targeting this vulnerable patient population. PMID:26463950

  1. Multilevel Segmentation and Integrated Bayesian Model Classification with an Application to Brain Tumor Segmentation

    E-print Network

    Corso, Jason J.

    region membership: or Incorporate models as hidden variables and marginalize over them: brain edema tumor. Typical Example: T1 T1 w/ Contrast Flair T2 Results on Training Set Tumor Edema Algorithm Jac Prec Rec Jac% 76% Model-Based Extractor 62% 75% 81% 54% 66% 72% Results on Testing Set Tumor Edema Algorithm Jac

  2. The effect of sleep-specific brain activity versus reduced stimulus interference on declarative memory consolidation.

    PubMed

    Piosczyk, Hannah; Holz, Johannes; Feige, Bernd; Spiegelhalder, Kai; Weber, Friederike; Landmann, Nina; Kuhn, Marion; Frase, Lukas; Riemann, Dieter; Voderholzer, Ulrich; Nissen, Christoph

    2013-08-01

    Studies suggest that the consolidation of newly acquired memories and underlying long-term synaptic plasticity might represent a major function of sleep. In a combined repeated-measures and parallel-group sleep laboratory study (active waking versus sleep, passive waking versus sleep), we provide evidence that brief periods of daytime sleep (42.1 ± 8.9 min of non-rapid eye movement sleep) in healthy adolescents (16 years old, all female), compared with equal periods of waking, promote the consolidation of declarative memory (word-pairs) in participants with high power in the electroencephalographic sleep spindle (sigma) frequency range. This observation supports the notion that sleep-specific brain activity when reaching a critical dose, beyond a mere reduction of interference, promotes synaptic plasticity in a hippocampal-neocortical network that underlies the consolidation of declarative memory. PMID:23398120

  3. Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model

    PubMed Central

    Melega, William P.; Lacan, Goran; Gorgulho, Alessandra A.; Behnke, Eric J.; De Salles, Antonio A. F.

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n?=?8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n?=?4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID:22295102

  4. Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.

    PubMed

    Melega, William P; Lacan, Goran; Gorgulho, Alessandra A; Behnke, Eric J; De Salles, Antonio A F

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n?=?8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n?=?4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID:22295102

  5. Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Serduc, Raphaël; van de Looij, Yohan; Francony, Gilles; Verdonck, Olivier; van der Sanden, Boudewijn; Laissue, Jean; Farion, Régine; Bräuer-Krisch, Elke; Siegbahn, Erik Albert; Bravin, Alberto; Prezado, Yolanda; Segebarth, Christoph; Rémy, Chantal; Lahrech, Hana

    2008-03-01

    Cerebral edema is one of the main acute complications arising after irradiation of brain tumors. Microbeam radiation therapy (MRT), an innovative experimental radiotherapy technique using spatially fractionated synchrotron x-rays, has been shown to spare radiosensitive tissues such as mammal brains. The aim of this study was to determine if cerebral edema occurs after MRT using diffusion-weighted MRI and microgravimetry. Prone Swiss nude mice's heads were positioned horizontally in the synchrotron x-ray beam and the upper part of the left hemisphere was irradiated in the antero-posterior direction by an array of 18 planar microbeams (25 mm wide, on-center spacing 211 mm, height 4 mm, entrance dose 312 Gy or 1000 Gy). An apparent diffusion coefficient (ADC) was measured at 7 T 1, 7, 14, 21 and 28 days after irradiation. Eventually, the cerebral water content (CWC) was determined by microgravimetry. The ADC and CWC in the irradiated (312 Gy or 1000 Gy) and in the contralateral non-irradiated hemispheres were not significantly different at all measurement times, with two exceptions: (1) a 9% ADC decrease (p < 0.05) was observed in the irradiated cortex 1 day after exposure to 312 Gy, (2) a 0.7% increase (p < 0.05) in the CWC was measured in the irradiated hemispheres 1 day after exposure to 1000 Gy. The results demonstrate the presence of a minor and transient cellular edema (ADC decrease) at 1 day after a 312 Gy exposure, without a significant CWC increase. One day after a 1000 Gy exposure, the CWC increased, while the ADC remained unchanged and may reflect the simultaneous presence of cellular and vasogenic edema. Both types of edema disappear within a week after microbeam exposure which may confirm the normal tissue sparing effect of MRT. For more information on this article, see medicalphysicsweb.org

  6. Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema

    PubMed Central

    WANG, YU; BU, JIMEI; ZHANG, QING; CHEN, KAI; ZHANG, JIHONG; BAO, XIAORONG

    2015-01-01

    The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t-test or the Chi-square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1-positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2-positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1-AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS. PMID:26261083

  7. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis

    PubMed Central

    Karim, Rushmia; Sykakis, Evripidis; Lightman, Susan; Fraser-Bell, Samantha

    2013-01-01

    Background Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. Objectives To assess the effectiveness of interventions in the treatment of uveitic macular edema. Search strategy Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. Selection criteria Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. Data collection and analysis Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. Conclusion More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient. PMID:23807831

  8. Traumatic Brain Injury-Induced Neuronal Apoptosis is Reduced Through Modulation of PI3K and Autophagy Pathways in Mouse by FTY720.

    PubMed

    Zhang, Li; Ding, Ke; Wang, Handong; Wu, Yong; Xu, Jianguo

    2016-01-01

    FTY720 is a synthetic compound produced by modification of metabolite from Isaria sinclairii. It is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues, thereby causing peripheral lymphopenia. Growing evidences have suggested that apoptosis and autophagy were involved in the secondary brain injury after traumatic brain injury (TBI) although FTY720 exerted neuroprotective effects in a variety of neurological diseases except TBI. The present study was aimed to investigate the role of FTY720 in a mouse model of TBI. In experiment 1, ICR mice were divided into four groups: sham group, TBI group, TBI + vehicle group, and TBI + FTY720 group. And the injured cerebral cortex (including both contused and penumbra) was used for analysis. We found that FTY720 administration after TBI improved neurobehavioral function, alleviated brain edema, accompanied by modulation of apoptotic indicators such as Bcl-2, Bcl-xL, Bax, and cytochrome c. In experiment 2, ICR mice were also divided into four groups: sham group, TBI + vehicle group, TBI + FTY720 group, and TBI + FTY720 + inhibitors group. And the injured cerebral cortex (including both contused and penumbra) was used for analysis. We found that FTY720 increased the expression of phospho-protein kinase B (AKT) and some autophagy markers such as LC3 and Beclin 1. In addition, the apoptosis inhibition effect of FTY720 was partly abrogated by the phosphatidylinositide 3-kinases (PI3K)/AKT pathway inhibitor LY294002 and autophagy inhibitor 3-methyladenine. Collectively, our data provide the first evidence that FTY720 exerted neuroprotective effects after TBI, at least in part, through the activation of PI3K/AKT pathway and autophagy. PMID:26099903

  9. 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.

  10. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study

    PubMed Central

    2011-01-01

    Background The phytocannabinoid cannabidiol (CBD) exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS). Methods Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. Results CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. Conclusions These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid. PMID:21244691

  11. Toward reducing impact induced brain injury: Lessons from a computational study of army and football helmet pads

    E-print Network

    Moss, W C; Blackman, E G

    2012-01-01

    We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterize the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the Head Injury Criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry, and material stiffness. We find that: (1) The football pad materials do not outperform the currently used military pad material in militarily-relevant impact scenarios; (2) Optimal material properties for a pad depend on impact energy; and (3) Thicker pads perform better at all velocities. Our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be significantly reduced. Keywords: helmet,...

  12. Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

    PubMed

    Zarubina, I V; Shabanov, P D

    2009-03-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia. PMID:19529857

  13. Reduced complexity of intracranial pressure observed in short time series of intracranial hypertension following traumatic brain injury in adults.

    PubMed

    Soehle, Martin; Gies, Bernadette; Smielewski, Peter; Czosnyka, Marek

    2013-08-01

    Physiological parameters, such as intracranial pressure (ICP), are regulated by interconnected feedback loops, resulting in a complex time course. According to the decomplexification theory, disease is characterised by a loss of feedback loops resulting in a reduced complexity of the time course of physiological parameters. We hypothesized that complexity of the ICP time series is decreased during periods of intracranial hypertension (IHT) following adult traumatic brain injury. In an observational retrospective cohort study, ICP was continuously monitored using intraparenchymally implanted probes and stored using ICM + -software. Periods of IHT (ICP > 25 mmHg for at least 1,024 s), were compared with preceding periods of intracranial normotension (ICP < 20 mmHg) and analysed at 1 s-intervals. ICP data (length = 1,024 s) were normalised (mean = 0, SD = 1) and complexity was estimated using the scaling exponent ? (as derived from detrended fluctuation analysis), sample entropy (SampEn, m = 1, r = 0.2 × SD) and multiscale entropy. 344 episodes were analysed in 22 patients. During IHT (ICP = 31.7 ± 7.8 mmHg, mean ± SD), ? was significantly elevated (? = 1.02 ± 0.22, p < 0.001) and SampEn significantly reduced (SampEn = 1.45 ± 0.46, p = 0.004) as compared to before IHT (ICP = 15.7 ± 3.2 mmHg, ? = 0.81 ± 0.14, SampEn = 1.81 ± 0.24). In addition, MSE revealed a significantly (p < 0.05) decreased entropy at scaling factors ranging from 1 to 10. Both the increase in ? as well as the decrease in SampEn and MSE indicate a loss of ICP complexity. Therefore following traumatic brain injury, periods of IHT seem to be characterised by a decreased complexity of the ICP waveform. PMID:23306818

  14. Cisplatin increases brain 2-arachidonoylglycerol (2-AG) and concomitantly reduces intestinal 2-AG and anandamide levels in the least shrew.

    PubMed

    Darmani, Nissar A; McClanahan, Bryan A; Trinh, Chung; Petrosino, Stefania; Valenti, Marta; Di Marzo, Vincenzo

    2005-09-01

    The chemotherapeutic agent cisplatin may produce emesis via release of several neurotransmitters such as serotonin (5-HT), substance P and/or dopamine as well as production of prostaglandins (PGs). Administration of synthetic 2-arachidonoylglycerol (2-AG) but not of anandamide, which are two putative endocannabinoids, causes vomiting via its downstream metabolites such as arachidonic acid (AA) and PGs in the least shrew (Cryptotis parva). We report here that cisplatin (0, 5, 10 and 20 mg/kg, i.p.) causes dose- and time-dependent increases in brain tissue levels of 2-AG but not anandamide in this vomiting species. Concomitantly, intestinal tissue levels of both endocannabinoids are relatively reduced. Selective inhibitors [arachidonoyl-serotonin (AA-5-HT) and URB597, 0-5 and 0-10 mg/kg, i.p.] of one of the major endocannabinoid metabolic enzymes, the intracellular fatty acid amide hydrolase (FAAH), do not significantly prevent vomiting produced by emetic doses of i.p.-administered 2-AG, cisplatin or the dopamine receptor agonist apomorphine. At large doses (10 and 20 mg/kg, respectively), both FAAH inhibitors caused emesis per se. Administration of one selective uptake inhibitor of endocannabinoids, OMDM1 (0-5 mg/kg, i.p.), also did not significantly prevent emesis by the direct and indirect emetic stimuli, and likewise caused emesis by itself at a high (10 mg/kg) dose. However, another selective uptake inhibitor, VDM11, did not produce significant emesis per se and prevented emesis caused by apomorphine. Both the corticosteroid dexamethasone, and the cyclooxygenase inhibitor indomethacin, reduced vomiting produced by cisplatin. These data: (a) provide the first evidence that cisplatin causes a selective increase in 2-AG levels in the brain, and (b) support the established notion that 2-AG may produce some of its effects, including emesis, via downstream metabolites produced independently of FAAH. PMID:15921709

  15. Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data.

    PubMed

    Greve, Douglas N; Svarer, Claus; Fisher, Patrick M; Feng, Ling; Hansen, Adam E; Baare, William; Rosen, Bruce; Fischl, Bruce; Knudsen, Gitte M

    2014-05-15

    Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([(11)C]SB207145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC. PMID:24361666

  16. Traumatic Brain Injury During Development Reduces Minimal Clonic Seizure Thresholds At Maturity

    PubMed Central

    Statler, Kimberly D.; Swank, Seth; Abildskov, Tracy; Bigler, Erin D.; White, H. Steve

    2008-01-01

    Post-traumatic seizures affect 12 – 35% of children after traumatic brain injury (TBI) and are associated with worse cognitive and functional outcome, even after adjustment for severity of injury. Unfortunately, experimental models of pediatric post-traumatic epilepsy are lacking, and pathogenesis remains poorly understood. We have applied a standard model of TBI in immature rats to determine the effect of TBI on electroconvulsive seizure thresholds later in life. Male rats underwent controlled cortical impact to left parietal cortex on post-natal day (PND) 16-18. Hindbrain, forebrain, and limbic seizure thresholds were assessed, respectively, by tonic hindlimb extension (THE), minimal clonic, and partial psychomotor seizure responses during adolescence (PND 34 - 40) and at maturity (PND 60 - 63). Post-traumatic seizure thresholds were compared to those obtained in age- and litter-matched sham craniotomy and naïve controls. TBI during immaturity had no clear effect on THE seizure thresholds. In contrast, TBI lowered minimal clonic seizure thresholds at maturity (p < 0.05 vs. sham or naïve rats), but not during adolescence. Consequently, minimal clonic seizure thresholds increased with age for sham and naïve rats but remained similar for TBI rats during adolescence and at maturity. TBI also tended to lower partial psychomotor seizure thresholds, which were determined only during adolescence (p < 0.1 vs. naive). Controlled cortical impact causes both focal cortical injury at the site of impact and ipsilateral hippocampal neuronal death. Since minimal clonic seizures are mediated by the forebrain, partial psychomotor seizures by the limbic system, and THE seizures by the brainstem, the observed pattern of changes in post-traumatic seizure thresholds is not surprising. The apparent age-dependent effects of TBI, however, are unexpected and likely due to a combination of attenuated maturational increases and progressive epileptogenesis. Additional study is needed to delineate the relative contributions of these processes. Given the sustained reduction in post-traumatic minimal clonic seizure thresholds, controlled cortical impact may hold promise as an experimental model of pediatric post-traumatic epilepsy. PMID:18490145

  17. The vital role of the right ventricle in the pathogenesis of acute pulmonary edema.

    PubMed

    MacIver, David H; Clark, Andrew L

    2015-04-01

    The development of acute pulmonary edema involves a complex interplay between the capillary hydrostatic, interstitial hydrostatic, and oncotic pressures and the capillary permeability. We review the pathophysiological processes involved and illustrate the concepts in a number of common clinical situations including heart failure with normal and reduced ejection fractions, mitral regurgitation, and arrhythmias. We also describe other rarer causes including exercise, swimming, and diving-induced acute pulmonary edema. We suggest a unifying framework in which the critical abnormality is a mismatch or imbalance between the right and left ventricular stroke volumes. In conclusion, we hypothesize that increased right ventricular contraction is an important contributor to the sudden increase in capillary hydrostatic pressure, and therefore, a central mechanism involved in the development of alveolar edema. PMID:25697920

  18. Emerging Pharmacotherapies for Diabetic Macular Edema

    PubMed Central

    Javey, Golnaz; Schwartz, Stephen G.; Flynn, Harry W.

    2012-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss in patients with diabetes mellitus. Although photocoagulation and intensive control of systemic metabolic factors have been reported to achieve improved outcomes in large randomized clinical trials (RCTs), some patients with DME continue to lose vision despite treatment. Pharmacotherapies for DME include locally and systemically administered agents. We review several agents that have been studied for the treatment of DME. PMID:22474425

  19. Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat

    NASA Technical Reports Server (NTRS)

    Lehnert, Hendrik; Lombardi, Federico; Raeder, Ernst A.; Lorenzo, Antonio V.; Verrier, Richard L.; Lown, Bernard; Wurtman, Richard J.

    1987-01-01

    The effect of administering the serotonin precursor 5-l-hydroxytryptophan, in conjunction with a monamine oxidase inhibitor phenelzine and a l-amino acid decarboxylase inhibitor carbidopa, on neurochemical changes in the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid of the cat were investigated. Results showed that this drug regimen led to increases of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid by 330 and 830 percent, respectively. Concomitantly, the threshold of ventricular fibrillation was found to be elevated by 42 percent and the effective refractory period was prolonged by 7 percent; the efferent sympathetic neural activity was suppressed in the normal heart. The results indicate that the enhancement of central serotoninergic neurotransmission can reduce the susceptibility of the heart to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

  20. DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons.

    PubMed

    Vyjayanti, V N; Rao, Kalluri Subba

    2006-01-23

    Linearised pUC 19 DNA with cohesive, blunt and non-matching ends, generated by prior treatment with different restriction enzymes was presented as substrate to measure the NHEJ activity to repair DNA double strand breaks in extracts prepared from isolated neurons from neonatal, young adult and old rat cerebral cortex. Highest end joining activity was noticed with the substrates having cohesive 3' overhang (PstI) or 5' overhang (EcoRI) ends and this activity is significantly reduced with age. However, blunt and non-matching ends were very poorly repaired at all ages. Further, the end joining activity in neurons is not faithful and sequence changes occur during the repair process. Also, the end joining activity in old neuronal extracts, but not in young extracts, was found to decline very rapidly with time of cold storage. These findings, the first of their kind, thus demonstrate that neuronal cells have the capacity to repair DNA double strand breaks through error prone NHEJ mode and that the cohesive end joining activity decreases with age of the animal. PMID:16226837

  1. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    PubMed Central

    Anderson, Collin J.; Sheppard, Daylan T.; Huynh, Rachel; Anderson, Daria Nesterovich; Polar, Christian A.; Dorval, Alan D.

    2015-01-01

    The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson’s disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms. PMID:26217192

  2. Brain Volume Determination in Subarachnoid Hemorrhage Using Rats.

    PubMed

    Lekic, Tim; Hardy, Maurice; Fujii, Mutsumi; McBride, Devin W; Zhang, John H

    2016-01-01

    Brain edema is routinely measured using the wet-dry method. Volume, however, is the sum total of all cerebral tissues, including water. Therefore, volumetric change following injury may not be adequately quantified using percentage of edema. We thus tested the hypothesis that dried brains can be reconstituted with water and then re-measured to determine the actual volume. Subarachnoid hemorrhage (SAH) was induced by endovascular perforation in adult male Sprague-Dawley rats (n?=?30). Animals were euthanized at 24 and 72 h after evaluation of neurobehavior for determination of brain water content. Dried brains were thereafter reconstituted with equal parts of water (lost from brain edema) and centrifuged to remove air bubbles. The total volume was quantified using hydrostatic (underwater) physics principles that 1 ml water (mass)?=?1 cm(3) (volume). The amount of additional water needed to reach a preset level marked on 2-ml test tubes was added to that lost from brain edema, and from the brain itself, to determine the final volume. SAH significantly increased both brain water and volume while worsening neurological function in affected rats. Volumetric measurements demonstrated significant brain swelling after SAH, in addition to the brain edema approach. This modification of the "wet-dry" method permits brain volume determination using valuable post hoc dried brain tissue. PMID:26463930

  3. GABAergic interneuronal loss and reduced inhibitory synaptic transmission in the hippocampal CA1 region after mild traumatic brain injury.

    PubMed

    Almeida-Suhett, Camila P; Prager, Eric M; Pidoplichko, Volodymyr; Figueiredo, Taiza H; Marini, Ann M; Li, Zheng; Eiden, Lee E; Braga, Maria F M

    2015-11-01

    Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region. We investigated whether mTBI induces morphological and pathophysiological alterations in the CA1 using the controlled cortical impact (CCI) model. Seven days after CCI, animals subjected to mTBI showed cognitive impairment in the passive avoidance test and deficits to long-term potentiation (LTP) of synaptic transmission. Deficiencies in inducing or maintaining LTP were likely due to an observed reduction in the activation of NMDA but not AMPA receptors. Significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs) were also observed 7days after CCI. Design-based stereology revealed that although the total number of neurons was unaltered, the number of GABAergic interneurons is significantly reduced in the CA1 region 7days after CCI. Additionally, the surface expression of ?1, ß2/3, and ?2 subunits of the GABAA receptor were reduced, contributing to a reduced mIPSC frequency and amplitude, respectively. Together, these results suggest that mTBI causes a significant reduction in GABAergic inhibitory transmission and deficits to NMDA receptor mediated currents in the CA1, which may contribute to changes in hippocampal excitability and subsequent cognitive impairments after mTBI. PMID:26238734

  4. Placental ischemia in pregnant rats impairs cerebral blood flow autoregulation and increases blood–brain barrier permeability

    PubMed Central

    Warrington, Junie P.; Fan, Fan; Murphy, Sydney R.; Roman, Richard J.; Drummond, Heather A.; Granger, Joey P.; Ryan, Michael J.

    2014-01-01

    Abstract Cerebrovascular events contribute to ~40% of preeclampsia/eclampsia?related deaths, and neurological symptoms are common among preeclamptic patients. We previously reported that placental ischemia, induced by reducing utero?placental perfusion pressure, leads to impaired myogenic reactivity and cerebral edema in the pregnant rat. Whether the impaired myogenic reactivity is associated with altered cerebral blood flow (CBF) autoregulation and the edema is due to altered blood–brain barrier (BBB) permeability remains unclear. Therefore, we tested the hypothesis that placental ischemia leads to impaired CBF autoregulation and a disruption of the BBB. CBF autoregulation, measured in vivo by laser Doppler flowmetry, was significantly impaired in placental ischemic rats. Brain water content was increased in the anterior cerebrum of placental ischemic rats and BBB permeability, assayed using the Evans blue extravasation method, was increased in the anterior cerebrum. The expression of the tight junction proteins: claudin?1 was increased in the posterior cerebrum, while zonula occludens?1, and occludin, were not significantly altered in either the anterior or posterior cerebrum. These results are consistent with the hypothesis that placental ischemia mediates anterior cerebral edema through impaired CBF autoregulation and associated increased transmission of pressure to small vessels that increases BBB permeability leading to cerebral edema. PMID:25168877

  5. Olive oil-enriched diet reduces brain oxidative damages and ameliorates neurotrophic factor gene expression in different life stages of rats.

    PubMed

    Pase, Camila Simonetti; Teixeira, Angélica Martelli; Roversi, Karine; Dias, Verônica Tironi; Calabrese, Francesca; Molteni, Raffaella; Franchi, Silvia; Panerai, Alberto Emilio; Riva, Marco Andrea; Burger, Marilise Escobar

    2015-11-01

    Our aim was to assess the influence of maternal diet rich in monounsaturated fatty acids on oxidative and molecular parameters in brains of mouse pups as well as their body weight during their lifetime. Female rats received a diet containing 20% of olive oil-enriched diet (OOED) and a standard diet control diet (CD) in different periods: pregnancy, lactation and after weaning until pups' adulthood. On the last prenatal day (Group 1), embryos from OOED group showed smaller body weight, brain weight and lower levels of sulphydryl groups glutathione reduced (GSH) in the brain. On postnatal delay-21 (PND21) (Group 2), pups from OOED group showed higher body weight and brain weight, reduced brain weight/body weight ratio and lower brain lipid peroxidation (LP). On PND70 (Group 3), pups from OOED group showed lower brain LP and higher levels of GSH in prefrontal cortex and lower brain levels of reactive species in the hippocampus. Interestingly, the group of animals whose diet was modified from OOED to CD on PND21 showed greater weight gain compared to the group that remained in the same original diet (OOED) until adulthood. Furthermore, OOED consumption during pregnancy and lactation significantly increased BDNF only, as well as its main transcripts exon IV and VI mRNA levels in the prefrontal cortex. In addition, OOED significantly up-regulated FGF-2 mRNA levels in the prefrontal cortex. These findings open a pioneering line of investigation about dietary adjunctive therapeutic strategies and the potential of healthy dietary habits to prevent neonatal conditions and their influence on adulthood. PMID:26168701

  6. [Pharmacological treatment for diabetic macular edema].

    PubMed

    Fukumoto, Masanori; Ikeda, Tsunehiko

    2015-03-01

    Diabetic macular edema(DME) is a major cause of vision loss and has a remarkable impact on the quality of life of diabetic patients. New pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have recently been developed for the treatment of DME. Even though laser therapy has been the standard treatment for DME, the results of several clinical trials have shown the superiority of some of these new agents to laser therapy. The purpose of this review is to briefly summarize the currently available new pharmacological treatments for DME in Japan. PMID:25812378

  7. Diabetic Retinopathy and Diabetic Macular Edema.

    PubMed

    Cohen, Steven R; Gardner, Thomas W

    2016-01-01

    Diabetic retinopathy and diabetic macular edema result from chronic damage to the neurovascular structures of the retina. The pathophysiology of retinal damage remains uncertain but includes metabolic and neuroinflammatory insults. These mechanisms are addressed by intensive metabolic control of the systemic disease and by the use of ocular anti-inflammatory agents, including vascular endothelial growth factor inhibitors and corticosteroids. Improved understanding of the ocular and systemic mechanisms that underlie diabetic retinopathy will lead to improved means to diagnose and treat retinopathy and better maintain vision. PMID:26501152

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

    PubMed Central

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

    2015-01-01

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

  9. Fecal Impaction Causing Pelvic Venous Compression and Edema.

    PubMed

    Naramore, Sara; Aziz, Faisal; Alexander, Chandran Paul; Methratta, Sosamma; Cilley, Robert; Rocourt, Dorothy

    2015-09-28

    Chronic constipation is a common condition which may result in fecal impaction. A 13-year-old male with chronic constipation and encopresis presented with fecal impaction for three weeks. The impaction caused abdominal pain, distension, encopresis, and decreased oral intake. He was found in severe distress with non-pitting edema of his feet and ankles along with perineal edema. The pedal edema worsened after receiving a fluid bolus, so concern arose for venous compression or a thrombus. A Duplex Ultrasound demonstrated changes in the venous waveforms of the bilateral external iliac and common femoral veins without thrombosis. Manual disimpaction and polyethylene glycol 3350 with electrolytes resolved the pedal and perineal edema. Four months later, he had soft bowel movements without recurrence of the edema. A repeat Duplex Ultrasound was normal. We present a child in whom severe fecal impaction caused pelvic venous compression resulting in bilateral pedal and perineal edema. PMID:26500749

  10. Fecal Impaction Causing Pelvic Venous Compression and Edema

    PubMed Central

    Naramore, Sara; Aziz, Faisal; Alexander, Chandran Paul; Methratta, Sosamma; Cilley, Robert; Rocourt, Dorothy

    2015-01-01

    Chronic constipation is a common condition which may result in fecal impaction. A 13-year-old male with chronic constipation and encopresis presented with fecal impaction for three weeks. The impaction caused abdominal pain, distension, encopresis, and decreased oral intake. He was found in severe distress with non-pitting edema of his feet and ankles along with perineal edema. The pedal edema worsened after receiving a fluid bolus, so concern arose for venous compression or a thrombus. A Duplex Ultrasound demonstrated changes in the venous waveforms of the bilateral external iliac and common femoral veins without thrombosis. Manual disimpaction and polyethylene glycol 3350 with electrolytes resolved the pedal and perineal edema. Four months later, he had soft bowel movements without recurrence of the edema. A repeat Duplex Ultrasound was normal. We present a child in whom severe fecal impaction caused pelvic venous compression resulting in bilateral pedal and perineal edema. PMID:26500749

  11. Towards reducing impact-induced brain injury: lessons from a computational study of army and football helmet pads.

    PubMed

    Moss, William C; King, Michael J; Blackman, Eric G

    2014-01-01

    We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterise the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the head injury criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry and material stiffness. We find that (1) the football pad materials do not outperform the currently used military pad material in militarily relevant impact scenarios; (2) optimal material properties for a pad depend on impact energy and (3) thicker pads perform better at all velocities. Although we considered only the isolated response of pad materials, not entire helmet systems, our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be reduced. PMID:23244512

  12. Angular Impact Mitigation System for Bicycle Helmets to Reduce Head Acceleration and Risk of Traumatic Brain Injury

    PubMed Central

    Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M.; Bottlang, Michael

    2013-01-01

    Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p < 0.001), a 34% reduction in peak angular acceleration (p < 0.001), and a 22% to 32% reduction in neck loading (p < 0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required. PMID:23770518

  13. Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury.

    PubMed

    Lucke-Wold, Brandon P; Naser, Zachary J; Logsdon, Aric F; Turner, Ryan C; Smith, Kelly E; Robson, Matthew J; Bailes, Julian E; Lee, John M; Rosen, Charles L; Huber, Jason D

    2015-12-01

    A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, but available pharmacologic options for the treatment of acute neurotrauma are limited. Oxidative stress is an important secondary mechanism of injury that can lead to neuronal apoptosis and subsequent behavioral changes. Using a clinically relevant and validated rodent blast model, we investigated how nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and associated oxidative stress contribute to cellular apoptosis after single and repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming free radicals at neuronal membranes. Using immunohistochemical-staining methods, we found a visible increase in Nox4 after single blast injury in Sprague Dawley rats. Interestingly, Nox4 was also increased in postmortem human samples obtained from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity correlated with an increase in superoxide formation. Alpha-lipoic acid, an oxidative stress inhibitor, prevented the development of superoxide acutely and increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P < 0.05) and heme oxygenase 1 (t = 8.169, P < 0.001) after single blast. Subacutely, alpha-lipoic acid treatment reduced proapoptotic markers Bax (t = 4.483, P < 0.05), caspase 12 (t = 6.157, P < 0.001), and caspase 3 (t = 4.573, P < 0.01) after repetitive blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like behavior 7 days after repetitive blast injury (t = 3.573, P < 0.05) compared with blast exposed animals without treatment. TBI can cause debilitating symptoms and psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic intervention, and alpha-lipoic acid warrants further investigation as a therapeutic for prevention of chronic neurodegeneration. PMID:26414010

  14. Cellular and regional specific changes in multidrug efflux transporter expression during recovery of vasogenic edema in the rat hippocampus and piriform cortex

    PubMed Central

    Kim, Yeon-Jo; Kim, Ji-Eun; Choi, Hui-Chul; Song, Hong-Ki; Kang, Tae-Cheon

    2015-01-01

    In the present study, we investigated the characteristics of drug efflux transporter expressions following status epilepticus (SE). In the hippocampus and piriform cortex (PC), vasogenic edema peaked 3-4 days after SE. The expression of breast cancer resistance protein (BCRP), multidrug resistance protein-4 (MRP4), and p-glycoprotein (p-GP) were decreased 4 days after SE when vasogenic edema was peaked, but subsequently increased 4 weeks after SE. Multidrug resistance protein-1 (MRP1) expression gradually decreased in endothelial cells until 4 weeks after SE. These findings indicate that SE-induced vasogenic edema formation transiently reduced drug efflux pump expressions in endothelial cells. Subsequently, during recovery of vasogenic edema drug efflux pump expressions were differentially upregulated in astrocytes, neuropils, and endothelial cells. Therefore, we suggest that vasogenic edema formation may be a risk factor in pharmacoresistent epilepsy. [BMB Reports 2015; 48(6): 348-353] PMID:25388209

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

    PubMed

    Shi, Song-Sheng; Zhang, Hua-Bin; Wang, Chun-Hua; Yang, Wei-Zhong; Liang, Ri-Sheng; Chen, Ye; Tu, Xian-Kun

    2015-12-01

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

  16. Autoradiographic localization of a non-reducible somatostatin analog (/sup 125/I-CGP 23996) binding sites in the rat brain: comparison with membrane binding

    SciTech Connect

    Epelbaum, J.; Dussaillant, M.; Enjalbert, A.; Kordon, C.; Rostene, W.

    1985-07-01

    The regional distribution of somatostatin binding sites in the rat brain was determined by quantitative autoradiography, using /sup 125/I-CGP 23996, a non-reducible somatostatin analog. In preliminary experiments, kinetic properties of /sup 125/I-CGP 23996 binding to rat brain membranes and slide mounted frozen brain sections were compared and found similar. In addition, distribution of /sup 125/I-CGP 23996 and /sup 125/I-N-Tyr-SRIF14 binding sites on membrane prepared from 10 different rat brain structures were closely correlated (r = 0.91, 2 p less than 0.01), indicating that the non-reducible analog recognizes the same binding site as the Tyr-extended native peptide. Highest levels of /sup 125/I-CGP 23996 binding sites were found in anterior temporal, frontal and cingular cortex as well as hippocampus. Moderate levels were found in the remaining part of the limbic system including amygdala, olfactory tubercles and bed nucleus of the stria terminalis. In the brain stem, nuclei involved in the auditory system such as the ventral cochlear nucleus and the superior olive nucleus, contained high levels of /sup 125/I-CGP 23996 binding sites. The distribution of /sup 125/I-CGP 23996 binding sites roughly correlated with that of the endogenous peptide in most structures, except in the mediobasal hypothalamus.

  17. Corticosteroid withdrawal precipitates perilesional edema around calcified Taenia solium cysts.

    PubMed

    Mejia, Rojelio; Nash, Theodore E

    2013-11-01

    Calcified Taenia solium granulomas are the focus of repeated episodes of perilesional edema and seizures in 50% of persons with calcifications, history of seizures, and a positive serology for cysticercosis. The pathophysiology is unclear but recent studies suggest the edema is caused by inflammation. We report two new cases and four other published cases where cessation of corticosteroids appeared to result in recurrence or new appearance of perilesional edema around calcifications. This suggests that perilesional edema is an immune-mediated phenomenon. PMID:24002482

  18. [Secondary leg edema--experimental study].

    PubMed

    Gregl, A

    1988-12-01

    Peripheral lymphedema can be induced experimentally by obliteration or destruction of the veins and/or lymphatics, extirpation of the lymph nodes and occlusion of lymphatics, circular incision of the soft tissues, experimentally induced thrombophlebitis and by simultaneous traumatization of the veins and lymphatics. Our own animal experiments were designed to provoke leg edema after ligation of the femoral vein and/or accompanying lymphatics below the inguinal ligament. In 23 animals, only one ligature of the femoral vein was applied, below the inguinal ligament and in 12 animals all accompanying lymphatics were ligated in addition. In all animals, the leg circumferences were measured in three precisely fixed positions before the experiments and daily for 22 days during the experiment. The greatest increase in circumference was found in the lower leg irrespective of the time of measurement. The peak increase of circumference was between the third and sixth day after the operation. Permanent lymph edema has not developed in any of the animals. At the latest after three weeks, the leg circumference has normalized. Additional ligation of the lymphatics merely led to a nonsignificant increase in circumference and to displacement of the maximum point by two to three days. Immediately after the operation, phlebographic and lymphographic control investigations were carried out in all animals. PMID:3245261

  19. Inhibition of Brain Swelling after Ischemia-Reperfusion by ?-Adrenergic Antagonists: Correlation with Increased K+ and Decreased Ca2+ Concentrations in Extracellular Fluid

    PubMed Central

    Xu, Junnan; Du, Ting; Yan, Enzhi; Walz, Wolfgang; Peng, Liang

    2014-01-01

    Infarct size and brain edema following ischemia/reperfusion are reduced by inhibitors of the Na+, K+, 2Cl?, and water cotransporter NKCC1 and by ?1-adrenoceptor antagonists. NKCC1 is a secondary active transporter, mainly localized in astrocytes, driven by transmembrane Na+/K+ gradients generated by the Na+,K+-ATPase. The astrocytic Na+,K+-ATPase is stimulated by small increases in extracellular K+ concentration and by the ?-adrenergic agonist isoproterenol. Larger K+ increases, as occurring during ischemia, also stimulate NKCC1, creating cell swelling. This study showed no edema after 3?hr medial cerebral artery occlusion but pronounced edema after 8?hr reperfusion. The edema was abolished by inhibitors of specifically ?1-adrenergic pathways, indicating failure of K+-mediated, but not ?1-adrenoceptor-mediated, stimulation of Na+,K+-ATPase/NKCC1 transport during reoxygenation. Ninety percent reduction of extracellular Ca2+ concentration occurs in ischemia. Ca2+ omission abolished K+ uptake in normoxic cultures of astrocytes after addition of 5?mM KCl. A large decrease in ouabain potency on K+ uptake in cultured astrocytes was also demonstrated in Ca2+-depleted media, and endogenous ouabains are needed for astrocytic K+ uptake. Thus, among the ionic changes induced by ischemia, the decrease in extracellular Ca2+ causes failure of the high-K+-stimulated Na+,K+-ATPase/NKCC1 ion/water uptake, making ?1-adrenergic activation the only stimulus and its inhibition effective against edema. PMID:25478577

  20. Thrombin Preconditioning in Surgical Brain Injury in Rats.

    PubMed

    Benggon, Michael; Chen, Hank; Applegate, Richard L; Zhang, John

    2016-01-01

    The surgical brain injury model replicates neurosurgical brain parenchymal damage. Postsurgical brain edema correlates with postoperative neurological dysfunction. Intranasal administration is a proven method of delivering therapies to brain tissue. Thrombin preconditioning decreased brain edema and improved neurological outcomes in models of ischemic brain injury. We hypothesized thrombin preconditioning in surgical brain injury may improve postoperative brain edema and neurological outcomes. Adult male Sprague-Dawley rats (n?=?78) weighing 285-355 g were randomly assigned to sham or pre-injury treatment: one-time pretreatment 1 day prior, one-time pretreatment 5 days prior, and daily preconditioning for 5 days prior. Treatment arms were divided into vehicle or thrombin therapies, and subdivided into intranasal (thrombin 5 units/50 ?L 0.9 % saline) or intracerebral ventricular (thrombin 0.1 unit/10 ?L 0.9 % saline) administration. Blinded observers performed neurological testing 24 h after brain injury followed immediately by measurement of brain water content. There was a significant difference in ipsilateral brain water content and neurological outcomes between all treatment groups and the sham group. However, there was no change in brain water content or neurological outcomes between thrombin- and vehicle-treated animals. Thrombin preconditioning did not significantly improve brain edema or neurological function in surgical brain injury in rats. PMID:26463965

  1. ETB receptor-mediated MMP-9 activation induces vasogenic edema via ZO-1 protein degradation following status epilepticus.

    PubMed

    Kim, J Y; Ko, A-R; Hyun, H-W; Kang, T-C

    2015-09-24

    The blood-brain barrier (BBB) is formed by the endothelial cells with specialized tight junctions (TJs) lining the blood vessels and astroglial endfeet surrounding the blood vessels. Although BBB disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process, little is known about the molecular and physiological events concerning vasogenic edema formation. In the present study, status epilepticus (SE) changed the expressions and subcellular localizations of TJ proteins (claudin-5, occludin and zonula occludens-1 (ZO-1)) in endothelial cells of the rat piriform cortex. Among TJ proteins, the alteration in ZO-1 expression was relevant to endothelin B (ETB) receptor-mediated endothelial nitric oxide synthase (eNOS) activation, which increased matrix metalloproteinase-9 (MMP-9) activity. Indeed, BQ788 (an ETB receptor antagonist) effectively attenuated SE-induced vasogenic edema by inhibiting eNOS-mediated MMP-9 activation and ZO-1 protein degradation in endothelial cells, although astroglial endfeet were detached from endothelial cells. Therefore, we suggest that SE-induced ETB receptor/eNOS-mediated MMP-9 activation may lead to impairments of endothelial cell function via TJ protein degradation, which are involved in vasogenic edema formation independent of perivascular astroglial functions. PMID:26232046

  2. Decompressive Craniectomy Increases Brain Lesion Volume and Exacerbates Functional Impairment in Closed Head Injury in Mice.

    PubMed

    Szczygielski, Jacek; Mautes, Angelika E; Müller, Andreas; Sippl, Christoph; Glameanu, Cosmin; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

    2016-01-01

    Decompressive craniectomy has been widely used in patients with head trauma. The randomized clinical trial on an early decompression (DECRA) demonstrated that craniectomy did not improve the neurological outcome, in contrast to previous animal experiments. The goal of our study was to analyze the effect of decompressive craniectomy in a murine model of head injury. Male mice were assigned into the following groups: sham, decompressive craniectomy, closed head injury (CHI), and CHI followed by craniectomy. At 24?h post-trauma, animals underwent the Neurological Severity Score test (NSS) and Beam Balance Score test (BBS). At the same time point, magnetic resonance imaging was performed, and volume of edema and contusion was assessed, followed by histopathological analysis. According to NSS, animals undergoing both trauma and craniectomy presented the most severe neurological impairment. Also, balancing time was reduced in this group compared with sham animals. Both edema and contusion volume were increased in the trauma and craniectomy group compared with sham animals. Histopathological analysis showed that all animals that underwent trauma presented substantial neuronal loss. In animals treated with craniectomy after trauma, a massive increase of edema with hemorrhagic transformation of contusion was documented. Decompressive craniectomy applied after closed head injury in mice leads to additional structural and functional impairment. The surgical decompression via craniectomy promotes brain edema formation and contusional blossoming in our model. This additive effect of combined mechanical and surgical trauma may explain the results of the DECRA trial and should be explored further in experiments. PMID:26102497

  3. Reduced GABAergic inhibition in the basolateral amygdala and the development of anxiety-like behaviors after mild traumatic brain injury.

    PubMed

    Almeida-Suhett, Camila P; Prager, Eric M; Pidoplichko, Volodymyr; Figueiredo, Taiza H; Marini, Ann M; Li, Zheng; Eiden, Lee E; Braga, Maria F M

    2014-01-01

    Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified. We assessed the functional alterations in inhibitory synaptic transmission in the BLA and one mechanism that modulates excitatory synaptic transmission, the ?7 containing nicotinic acetylcholine receptor (?7-nAChR), after mTBI, to shed light on the mechanisms that contribute to increased anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact (CCI) injury, animals displayed significantly greater anxiety-like behavior. This was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the mIPSC amplitude were associated with reduced surface expression of ?1, ?2, and ?2 GABAA receptor subunits. However, significant increases in the surface expression and current mediated by ?7-nAChR, were observed, signifying increases in the excitability of principal neurons within the BLA. These results suggest that mTBI causes not only a significant reduction in inhibition in the BLA, but also an increase in neuronal excitability, which may contribute to hyperexcitability and the development of anxiety disorders. PMID:25047645

  4. Reduced GABAergic Inhibition in the Basolateral Amygdala and the Development of Anxiety-Like Behaviors after Mild Traumatic Brain Injury

    PubMed Central

    Almeida-Suhett, Camila P.; Prager, Eric M.; Pidoplichko, Volodymyr; Figueiredo, Taiza H.; Marini, Ann M.; Li, Zheng; Eiden, Lee E.; Braga, Maria F. M.

    2014-01-01

    Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified. We assessed the functional alterations in inhibitory synaptic transmission in the BLA and one mechanism that modulates excitatory synaptic transmission, the ?7 containing nicotinic acetylcholine receptor (?7-nAChR), after mTBI, to shed light on the mechanisms that contribute to increased anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact (CCI) injury, animals displayed significantly greater anxiety-like behavior. This was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the mIPSC amplitude were associated with reduced surface expression of ?1, ?2, and ?2 GABAA receptor subunits. However, significant increases in the surface expression and current mediated by ?7-nAChR, were observed, signifying increases in the excitability of principal neurons within the BLA. These results suggest that mTBI causes not only a significant reduction in inhibition in the BLA, but also an increase in neuronal excitability, which may contribute to hyperexcitability and the development of anxiety disorders. PMID:25047645

  5. Targeted photocoagulation of peripheral ischemia to treat rebound edema

    PubMed Central

    Singer, Michael A; Tan, Colin S; Surapaneni, Krishna R; Sadda, Srinivas R

    2015-01-01

    Introduction Peripheral retinal ischemia not detectable by conventional fluorescein angiography has been proposed to be a driving force for rebound edema in retinal vein occlusions. In this report, we examine the treatment of peripheral retinal ischemia with targeted retinal photocoagulation (TRP) to manage a patient’s rebound edema. Methods To assess the extent of peripheral nonperfusion, an Optos 200Tx device was used. To target the treatment to peripheral ischemia areas, a Navilas Panretinal Laser was used. Results A 64-year-old male with a central retinal vein occlusion and a visual acuity 20/300, and central macular thickness 318 ?m presented with rubeosis. Angiography revealed extensive peripheral nonperfusion. Despite TRP to areas of irreversible ischemia, after 2 months, he continued show rubeosis and rebound edema. Additional TRP laser was repeatedly added more posteriorly to areas of reversible nonperfusion, resulting in eventual resolution of rubeosis and edema. Conclusion In this study, we demonstrate the use of widefield imaging with targeted photo-coagulation of peripheral ischemia to treat rebound edema, while preserving most peripheral vision. In order to treat rebound edema, extensive TRP, across reversible and nonreversible areas of ischemia, had to be performed – not just in areas of nonreversible peripheral ischemia. These areas need to be mapped during episodes of rebound edema, when ischemia is at its maximum. In this way, by doing the most TRP possible, the cycle of rebound edema can be broken. PMID:25709396

  6. [Papillary edema in Muckle-Wells syndrome].

    PubMed

    Wirths, G; Grenzebach, U; Eter, N

    2015-09-01

    Papillary edema may occur isolated without functional impairment or secondary related to various syndromes, increased intracerebral pressure or associated with medicinal treatment. The Muckle-Wells syndrome is a rare disease, which among many other symptoms can lead to optic disc swelling and recurrent increase in intracerebral pressure. Besides familial cold-induced autoinflammatory syndrome (FCAS) and neonatal onset multisystem inflammatory disease (NOMID), the Muckle-Wells syndrome also belongs to the cryopyrin-associated periodic syndromes (CAPS). In most cases of CAP syndromes there is an underlying genetic disorder that leads to overproduction of interleukin-1? (IL-1?); therefore, typical symptoms include inflammation reactions, such as repeated skin rash, fatigue, fever, joint pain and conjunctivitis. PMID:25614348

  7. 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

  8. Reperfusion pulmonary edema after pulmonary endarterectomy.

    PubMed

    Lee, K C; Cho, Y L; Lee, S Y

    2001-06-01

    Pulmonary artery thromboendarterectomy is a potentially curative procedure in chronic, major vessel thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension and unrelenting reperfusion edema have serious complications, often requiring prolonged mechanical ventilation. A 50-year-old man who was diagnosed with a thromboembolism in both pulmonary arteries underwent a bilateral pulmonary endarterectomy. He received O2-isoflurane-fentanyl anesthesia. When the lungs were reperfused with CPB weaning, massive hemorrhage occurred in the left lung. After the operation, the patient was taken to the intensive care unit. Mechanical ventilation was performed immediately and then both inhaled NO and i.v. furosemide therapies were administered. The patient was discharged from ICU 15 days postoperation. PMID:11475183

  9. Serous retinal detachment and cystoid macular edema in a patient with Wyburn-Mason syndrome.

    PubMed

    Onder, Halil Ibrahim; Alisan, Sibel; Tunc, Murat

    2015-03-01

    Wyburn-Mason syndrome is a rare phacomatosis characterized by unilateral arteriovenous malformations (AVMs) involving the brain, retina, and (rarely) the skin. The diagnosis is concluded with dilated fundus examination and markedly dilated tortuous vascular loops with arteriovenous communications on fluorescent angiography. We present a 14-year-old male patient with Wyburn-Mason syndrome who developed serous macular neuroretinal detachment, cystoid macular edema (CME), and consequent visual deterioration in the left eye. To the best of our knowledge, this is the first report of a patient with Wyburn-Mason syndrome who developed serous retinal detachment and CME. PMID:24171831

  10. 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)

  11. Fumaric Acid Esters Do Not Reduce Inflammatory NF-?B/p65 Nuclear Translocation, ICAM-1 Expression and T-Cell Adhesiveness of Human Brain Microvascular Endothelial Cells.

    PubMed

    Haarmann, Axel; Nehen, Mathias; Deiß, Annika; Buttmann, Mathias

    2015-01-01

    Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 µM blocked the IL-1?-induced nuclear translocation of NF-?B/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1?-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1?-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells. PMID:26287168

  12. Fumaric Acid Esters Do Not Reduce Inflammatory NF-?B/p65 Nuclear Translocation, ICAM-1 Expression and T-Cell Adhesiveness of Human Brain Microvascular Endothelial Cells

    PubMed Central

    Haarmann, Axel; Nehen, Mathias; Deiß, Annika; Buttmann, Mathias

    2015-01-01

    Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 µM blocked the IL-1?-induced nuclear translocation of NF-?B/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1?-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1?-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells. PMID:26287168

  13. Augmentation of M-Type (KCNQ) Potassium Channels as a Novel Strategy to Reduce Stroke-Induced Brain Injury

    PubMed Central

    Bierbower, Sonya M.; Choveau, Frank S.; Lechleiter, James D.

    2015-01-01

    Cerebral ischemic stroke is a worldwide cause of mortality/morbidity and thus an important focus of research to decrease the severity of brain injury. Therapeutic options for acute stroke are still limited. In neurons throughout the brain, “M-type” K+ currents, underlain by KCNQ subunits 2–5, play dominant roles in control over excitability, and are thus implicated in myriad neurological and psychiatric disorders. Although KCNQ channel openers, such as retigabine, have emerged as anti-epilepsy drugs, their effects on ischemic injury remain unknown. Here, we investigated the protective effects of M-channel openers on stroke-induced brain injury in mouse photothrombotic and middle cerebral artery occlusion (MCAo) models. Both photothrombosis and MCAo led to rapid, predictable, and consistently sized necrotic brain lesions, inflammatory responses, and behavioral deficits. Administration of three distinct M-channel openers at 0–6 h after ischemic injury significantly decreased brain infarct size and inflammation, and prevented neurological dysfunction, although they were more effective when administered 0–3 h poststroke. Thus, we show beneficial effects against stroke-induced brain injury and neuronal death through pharmacological regulation of ion channels that control neuronal excitability. PMID:25653366

  14. Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

    PubMed

    Komanapalli, Esther S; Sherchan, Prativa; Rolland, William; Khatibi, Nikan; Martin, Robert D; Applegate, Richard L; Tang, Jiping; Zhang, John H

    2016-01-01

    Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n?=?7), SBI (n?=?7), SBI with low-dose EAA, 150 mg/kg (n?=?7), and SBI with high-dose EAA, 450 mg/kg (n?=?7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models. PMID:26463967

  15. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice.

    PubMed

    Fluiter, Kees; Opperhuizen, Anne Loes; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

    2014-03-01

    Traumatic brain injury (TBI) is the leading cause of disability and death in young adults. The secondary neuroinflammation and neuronal damage that follows the primary mechanical injury is an important cause of disability in affected people. The membrane attack complex (MAC) of the complement system is detected in the traumatized brain early after TBI; however, its role in the pathology and neurologic outcome of TBI has not yet been investigated. We generated a C6 antisense oligonucleotide that blocks MAC formation by inhibiting C6, and we compared its therapeutic effect to that of Ornithodoros moubata complement inhibitor (OmCI), a known inhibitor of C5 activation that blocks generation of the anaphylatoxin C5a and C5b, an essential component of MAC. Severe closed head injury in mice induced abundant MAC deposition in the brain. Treatment with C6 antisense reduced C6 synthesis (85%) and serum levels (90%), and inhibited MAC deposition in the injured brain (91-96%). Treatment also reduced accumulation of microglia/macrophages (50-88%), neuronal apoptosis, axonal loss and weight loss (54-93%), and enhanced neurologic performance (84-92%) compared with placebo-treated controls after injury. These data provide the first evidence, to our knowledge, that inhibition of MAC formation in otherwise complement-sufficient animals reduces neuropathology and promotes neurologic recovery after TBI. Given the importance of maintaining a functional complement opsonization system to fight infections, a critical complication in TBI patients, inhibition of the MAC should be considered to reduce posttraumatic neurologic damage. This work identifies a novel therapeutic target for TBI and will guide the development of new therapy for patients. PMID:24489093

  16. NTCP Modeling of Subacute/Late Laryngeal Edema Scored by Fiberoptic Examination

    SciTech Connect

    Rancati, Tiziana; Fiorino, Claudio; Sanguineti, Giuseppe

    2009-11-01

    Purpose: Finding best-fit parameters of normal tissue complication probability (NTCP) models for laryngeal edema after radiotherapy for head and neck cancer. Methods and Materials: Forty-eight patients were considered for this study who met the following criteria: (1) grossly uninvolved larynx, (2) no prior major surgery except for neck dissection and tonsillectomy, (3) at least one fiberoptic examination of the larynx within 2 years from radiotherapy, (4) minimum follow-up of 15 months. Larynx dose-volume histograms (DVHs) were corrected into a linear quadratic equivalent one at 2 Gy/fr with alpha/beta = 3 Gy. Subacute/late edema was prospectively scored at each follow-up examination according to the Radiation Therapy Oncology Group scale. G2-G3 edema within 15 months from RT was considered as our endpoint. Two NTCP models were considered: (1) the Lyman model with DVH reduced to the equivalent uniform dose (EUD; LEUD) and (2) the Logit model with DVH reduced to the EUD (LOGEUD). The parameters for the models were fit to patient data using a maximum likelihood analysis. Results: All patients had a minimum of 15 months follow-up (only 8/48 received concurrent chemotherapy): 25/48 (52.1%) experienced G2-G3 edema. Both NTCP models fit well the clinical data: with LOGEUD the relationship between EUD and NTCP can be described with TD50 = 46.7 +- 2.1 Gy, n = 1.41 +- 0.8 and a steepness parameter k = 7.2 +- 2.5 Gy. Best fit parameters for LEUD are n = 1.17 +- 0.6, m = 0.23 +- 0.07 and TD50 = 47.3 +- 2.1 Gy. Conclusions: A clear volume effect was found for edema, consistent with a parallel architecture of the larynx for this endpoint. On the basis of our findings, an EUD <30-35 Gy should drastically reduce the risk of G2-G3 edema.

  17. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    PubMed Central

    2011-01-01

    Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins. Methods We measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats. Results Compared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1? and tumor necrosis factor ?, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-?Bp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged. Conclusions HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients. PMID:21846384

  18. Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.

    PubMed

    Zhao, Haiping; Wang, Rongliang; Wu, Xiaoning; Liang, Jia; Qi, Zhifeng; Liu, Xiangrong; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2015-03-01

    Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of two modes of delivery. Neurobehavioral deficits and infarct volume, and the expression of ER stress-associated proteins and apoptosis in brain tissue or isolated microvessels, as well as the transcriptional activity of 16 factors involved in ER stress and the unfolded protein response in brain tissue was asscessed. A higher EPO level in cerebrospinal fluid and brain tissue was observed in rats treated with EPO by MCAI (800 IU/kg) than by SI (5000 IU/kg). Moreover, neurobehavioral deficits and infarct volume were reduced in rats treated with EPO by MCAI and salubrinal. EPO suppressed the expression of ER stress signals glucose-regulated protein 78, activating transcription factor (ATF) 6?, and CCAAT enhancer-binding protein homologous protein (CHOP), as well as that of the pro-apoptotic protein caspase-3 in brain microvessels, and decreased the number of CHOP-positive, apoptotic neurons. EPO treatment also reduced the transcriptional activities of CHOP, forkhead box protein O1, and ATF4. These results provide evidence that low dose EPO treatment via MCAI provides neuroprotection following acute ischemic stroke by inhibiting the ER stress response. PMID:25626440

  19. Clinical trials on corticosteroids for diabetic macular edema

    PubMed Central

    Al Dhibi, Hassan A; Arevalo, J Fernando

    2013-01-01

    Diabetic macular edema (DME) is a common cause of visual impairment in diabetic patients. It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier. The pathogenesis of DME is multifactorial. Several therapeutic modalities have been proposed for the treatment of DME. Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities, due to anti-inflammatory, anti-vascular endothelial growth factor and anti-proliferative effects. Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME. Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease. Steroid-related side effects include elevated intraocular pressure, cataract, and injection related complications such as endophthalmitis, vitreous hemorrhage, and retinal detachment particularly with intravitreal steroid injections. In order to reduce the risks, complications and frequent dosing of intravitreal steroids, intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME. PMID:24379920

  20. 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.

  1. 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

  2. Protective effect of ginsenoside Rb1 on integrity of blood-brain barrier following cerebral ischemia.

    PubMed

    Chen, Wei; Guo, Yijun; Yang, Wenjin; Zheng, Ping; Zeng, Jinsong; Tong, Wusong

    2015-10-01

    Ginsenosides, the major bioactive compounds in ginseng root, have been found to have antioxidant, immunomodulatory, and anti-inflammatory activities. In the present study, we sought to investigate whether and how ginsenoside Rb1 (GS-Rb1), the most abundant ginsenoside, can protect blood-brain barrier (BBB) integrity following cerebral ischemia in middle cerebral artery occlusion (MCAO) animal model. ICR mice underwent MCAO and received GS-Rb1 by intraperitoneal injection at 3 h after reperfusion. We evaluated infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression at 48 h after MCAO. We further examined whether GS-Rb1 protected BBB integrity by suppressing post-ischemic inflammation-induced activity of matrix metalloproteinase-9 (MMP-9) and nicotinamide adenine dinucleotide phosphate oxidase (NOX). First, GS-Rb1 decreased infarction and improved neurological deficits in MCAO animals. In addition, GS-Rb1 reduced EB extravasation and brain edema and preserved expression of tight junction proteins in the ischemic brain. Moreover, GS-Rb1 inhibited expression of pro-inflammatory factors including nitric oxide synthase and IL-1?, but increased expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Consistently, GS-Rb1 attenuated ischemia-induced expression and activity of MMP9. Finally, GS-Rb1 reduced NOX-4 mRNA expression and NOX activity in ischemic brain. These results suggest that GS-Rb1 protects loss of BBB integrity in ischemic stroke by suppressing neuroinflammation induction of MMP-9 and NOX4-derived free radicals, and indicate its potential for treating brain injuries, such as ischemia and stroke. PMID:26070903

  3. Anti-A? single-chain antibody brain delivery via AAV reduces amyloid load but may increase cerebral hemorrhages in an Alzheimer mouse model

    PubMed Central

    Kou, Jinghong; Kim, HongDuck; Pattanayak, Abhinandan; Song, Min; Lim, Jeong-Eun; Taguchi, Hiroaki; Paul, Sudhir; Cirrito, John R.; Ponnazhagan, Selvarangan; Fukuchi, Ken-ichiro

    2013-01-01

    Accumulation of amyloid ?-protein (A?) in the brain is thought to be a causal event in Alzheimer’s disease (AD). Immunotherapy targeting A? holds great promise for reducing A? in the brain. Here, we evaluated the efficacy and safety of anti-A? single-chain antibody (scFv59) delivery via recombinant adeno-associated virus (rAAV) on reducing A? deposits in an AD mouse model (TgAPPswe/PS1dE9). First, delivery of scFv59 to the brain was optimized by injecting rAAV serotypes 1, 2, and 5 into the right lateral ventricle. Symmetrical high expression of scFv59 was found throughout the hippocampus and partly in the neocortex in both hemispheres via rAAV1 or rAAV5 while scFv59 expression via rAAV2 was mostly limited to one hemisphere. rAAV1, however, induced apoptosis and microglial activation but rAAV5 did not. Therefore, rAAV5 was selected for therapeutic scFv59 delivery in TgAPPswe/PS1dE9 mice. rAAV5 was similarly injected into the ventricle of 10-month-old TgAPPswe/PS1dE9 mice and 5 months later its efficacy and safety were evaluated. Immunoreactive A? deposits reduced in the hippocampus. A?42 levels in cerebrospinal fluid (CSF) tended to increase and the A?40:42 ratio decreased in CSF, suggesting that A?42 was relocated from the parenchyma to CSF. Hemorrhages associated with a focal increase in blood vessel amyloid were found in the brain. While immunotherapy has great potential for clearing cerebral A?, caution for cerebrovascular effects should be exercised when rAAV-mediated anti-A? immunotherapy is applied. PMID:21709371

  4. Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.

    PubMed

    Dziennis, Suzan; Mader, Sarah; Akiyoshi, Kozaburo; Ren, Xuefang; Ayala, Patricia; Burrows, Gregory G; Vandenbark, Arthur A; Herson, Paco S; Hurn, Patricia D; Offner, Halina A

    2011-06-01

    Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4 h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4 h after MCAO, with repeated doses every 24 h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96 h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24 h and in cortex at 96 h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24 h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4 h time window through immune regulation of myelin-reactive inflammatory T-cells. PMID:21472429

  5. Toluene exposure during the brain growth spurt reduced behavioral responses to nicotine in young adult rats: a potential role for nicotinic acetylcholine receptors in fetal solvent syndrome.

    PubMed

    Chan, Ming-Huan; Tang, Yu-Chi; Chien, Te-Hsiung; Chen, Hwei-Hsien

    2008-02-01

    Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Toluene has been shown to inhibit the nicotinic acetylcholine receptors. Nicotinic receptors play an important role in brain development during brain growth spurt and early adolescence. The long-term effects of neonatal and adolescent toluene exposure on behavioral responses to nicotine in early adulthood were compared. Sprague-Dawley male and female rats were treated with toluene (500 mg/kg, ip) or corn oil daily over postnatal day (PN) 4-9 or 25-30. Nicotine-induced hypothermia, antinociception, and seizure activity were examined during PN 56-60. Toluene exposure during the brain growth spurt, but not adolescence, reduced the behavioral responses to nicotine in young adult rats. However, the levels of alpha4, alpha7, and beta2 nicotinic receptors were not altered in the frontal cortex, striatum, thalamus, hippocampus, and cerebellum by neonatal toluene exposure. These results indicate that toluene exposure during the brain growth spurt produces long-term changes in nicotine sensitivity, which may be unrelated to the total expression levels of alpha4, alpha7, and beta2 nicotinic receptors. The alterations in nicotine sensitivity may be related to the neurobehavioral disturbance associated with fetal solvent syndrome. PMID:17951610

  6. L-phenylalanine preloading reduces the (10)B(n, ?)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

    PubMed

    Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. PMID:26455769

  7. MR imaging assessment of myocardial edema with T2 mapping.

    PubMed

    Montant, P; Sigovan, M; Revel, D; Douek, P

    2015-09-01

    Cardiac magnetic resonance (CMR) provides a high signal-to-noise ratio, high spatial and temporal resolutions, as well as a delayed-enhancement sequence and is therefore considered a reference technique in the field of cardiac imaging. However, currently available sequences are not adequate to assess some pathologic conditions, such as myocardial edema. T2 mapping sequences generate parametric images that are based on the transverse relaxation time (T2) for each voxel. In case of edema, the T2 relaxation time is longer. This review summarizes current knowledge on CMR T2 mapping for assessing myocardial edema. PMID:25697831

  8. Amiloride-Sensitive Sodium Channels and Pulmonary Edema

    PubMed Central

    Althaus, Mike; Clauss, Wolfgang G.; Fronius, Martin

    2011-01-01

    The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed. PMID:21637371

  9. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    EPA Science Inventory

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  10. The Episodic Engram Transformed: Time Reduces Retrieval-Related Brain Activity but Correlates It with Memory Accuracy

    ERIC Educational Resources Information Center

    Furman, Orit; Mendelsohn, Avi; Dudai, Yadin

    2012-01-01

    We took snapshots of human brain activity with fMRI during retrieval of realistic episodic memory over several months. Three groups of participants were scanned during a memory test either hours, weeks, or months after viewing a documentary movie. High recognition accuracy after hours decreased after weeks and remained at similar levels after…

  11. Reduced permeation of /sup 14/C-sucrose, /sup 3/H-mannitol and /sup 3/H-inulin across blood-brain barrier in nephrectomized rats

    SciTech Connect

    Preston, E.; Haas, N.; Allen, M.

    1984-01-01

    Experiments were carried out to determine if changes in the concentration-time profile of a blood-borne radiotracer such as /sup 14/C-sucrose would spuriously alter measurements of its permeation across the blood-brain barrier (permeability-area product, PA) based on a 2-compartment (plasma/brain) simple diffusion model. Anesthetized rats which were bilaterally nephrectomized and given a standard intravenous bolus injection of /sup 14/C-sucrose, /sup 3/H-mannitol or /sup 3/H-inulin exhibited an elevated plasma tracer concentration compared to control animals. However, tracer concentration measured in brain parenchyma after 30 min was not proportionally elevated, and PA calculated from the ratio, parenchymal tracer concentration: plasma concentration-time integral, was significantly reduced below control values. In control rats, distortion and elevation of the plasma /sup 14/C-sucrose profile by continuous intravenous infusion did not result in lowered PA values. This suggested that the lowering of PA by nephrectomy reflected reduced cerebrovascular permeability or area or other cerebral influence rather than a deficiency in the 2-compartment model for PA measurement.

  12. Decreasing the Cerebral Edema Associated with Traumatic Intracerebral Hemorrhages: Use of a Minimally Invasive Technique.

    PubMed

    Chen, Jeff W; Paff, Michelle R; Abrams-Alexandru, Daniella; Kaloostian, Sean W

    2016-01-01

    Traumatic brain injury (TBI) is a major public health problem worldwide that affects all age groups. In the United States alone, there are approximately 50,000 deaths from severe traumatic brain injuries each year. In most studies, about 40 % of severe TBI have associated traumatic intracerebral hemorrhages (tICHs). The surgical treatment of tICH is debated largely because of its invasive nature, particularly in reaching deep tICHs. tICHs have a clear contribution to mass effect and exacerbate cerebral edema and ICP because of the break-down products of hemorrhage. We introduce a modification of the Mi SPACE technique (Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation) that is applicable to tICH. In brief, this technique utilizes a trans-sulcal, stereotactic-guided technique in which a specially designed cannula is used to introduce a 13.5-mm-diameter tube into the epicenter of the tICH. We identified eight tICHs that were treated entirely or in part with the modified Mi SPACE technique during the time period from August 15, 2014 to December 15, 2014. This modified technique was readily deployed safely and efficaciously with significant removal of the tICH as demonstrated by postoperative CT scans. The removal of tICH using this minimally invasive technique may help with the control of ICP and cerebral edema. PMID:26463961

  13. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

    SciTech Connect

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

    2009-10-15

    Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks {alpha}7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-{beta}-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 {mu}g/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

  14. MicroRNA-339-5p Down-regulates Protein Expression of ?-Site Amyloid Precursor Protein-Cleaving Enzyme 1 (BACE1) in Human Primary Brain Cultures and Is Reduced in Brain Tissue Specimens of Alzheimer Disease Subjects*

    PubMed Central

    Long, Justin M.; Ray, Balmiki; Lahiri, Debomoy K.

    2014-01-01

    Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-? (A?) peptide as neuritic plaques in the brain. The short A? peptide is derived from the large transmembrane A? precursor protein (APP). The rate-limiting step in the production of A? from APP is mediated by the ?-site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to excess A? deposition is implicated in sporadic AD. Thus, elucidating the full complement of regulatory pathways that control BACE1 expression is key to identifying novel drug targets central to the A?-generating process. MicroRNAs (miRNAs) are expected to participate in this molecular network. Here, we identified a known miRNA, miR-339-5p, as a key contributor to this regulatory network. Two distinct miR-339-5p target sites were predicted in the BACE1 3?-UTR by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3?-UTR reporter construct resulted in significant reduction in reporter expression. Mutation of both target sites eliminated this effect. Delivery of the miR-339-5p mimic also significantly inhibited expression of BACE1 protein in human glioblastoma cells and human primary brain cultures. Delivery of target protectors designed against the miR-339-5p BACE1 3?-UTR target sites in primary human brain cultures significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to be significantly reduced in brain specimens isolated from AD patients as compared with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in human brain cells and is most likely dysregulated in at least a subset of AD patients making this miRNA a novel drug target. PMID:24352696

  15. Inhibition of Brain Mitogen-Activated Protein Kinase Signaling Reduces Central Endoplasmic Reticulum Stress and Inflammation and Sympathetic Nerve Activity in Heart Failure Rats.

    PubMed

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-01-01

    Mitogen-activated protein kinase (MAPK) signaling and endoplasmic reticulum (ER) stress in the brain have been implicated in the pathophysiology of hypertension. This study determined whether ER stress occurs in subfornical organ and hypothalamic paraventricular nucleus in heart failure (HF) and how MAPK signaling interacts with ER stress and other inflammatory mediators. HF rats had significantly higher levels of the ER stress biomarkers (glucose-regulated protein 78, activating transcription factor 6, activating transcription factor 4, X-box binding protein 1, P58(IPK), and C/EBP homologous protein) in subfornical organ and paraventricular nucleus, which were attenuated by a 4-week intracerebroventricular infusion of inhibitors selective for p44/42 MAPK (PD98059), p38 MAPK (SB203580), or c-Jun N-terminal kinase (SP600125). HF rats also had higher mRNA levels of tumor necrosis factor-?, interleukin-1?, cyclooxygenase-2, and nuclear factor-?B p65, and a lower mRNA level of I?B-?, in subfornical organ and paraventricular nucleus, compared with SHAM rats, and these indicators of increased inflammation were attenuated in the HF rats treated with the MAPK inhibitors. Plasma norepinephrine level was higher in HF rats than in SHAM rats but was reduced in the HF rats treated with PD98059 and SB203580. A 4-week intracerebroventricular infusion of PD98059 also improved some hemodynamic and anatomic indicators of left ventricular function in HF rats. These data demonstrate that ER stress increases in the subfornical organ and paraventricular nucleus of rats with ischemia-induced HF and that inhibition of brain MAPK signaling reduces brain ER stress and inflammation and decreases sympathetic excitation in HF. An interaction between MAPK signaling and ER stress in cardiovascular regions of the brain may contribute to the development of HF. PMID:26573710

  16. 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.

  17. Diagnosis, prevention and management of postoperative pulmonary edema.

    PubMed

    Bajwa, Sj Singh; Kulshrestha, A

    2012-07-01

    Postoperative pulmonary edema is a well-known postoperative complication caused as a result of numerous etiological factors which can be easily detected by a careful surveillance during postoperative period. However, there are no preoperative and intraoperative criteria which can successfully establish the possibilities for development of postoperative pulmonary edema. The aims were to review the possible etiologic and diagnostic challenges in timely detection of postoperative pulmonary edema and to discuss the various management strategies for prevention of this postoperative complication so as to decrease morbidity and mortality. The various search engines for preparation of this manuscript were used which included Entrez (including Pubmed and Pubmed Central), NIH.gov, Medknow.com, Medscape.com, WebMD.com, Scopus, Science Direct, MedHelp.org, yahoo.com and google.com. Manual search was carried out and various text books and journals of anesthesia and critical care medicine were also searched. From the information gathered, it was observed that postoperative cardiogenic pulmonary edema in patients with serious cardiovascular diseases is most common followed by noncardiogenic pulmonary edema which can be due to fluid overload in the postoperative period or it can be negative pressure pulmonary edema (NPPE). NPPE is an important clinical entity in immediate post-extubation period and occurs due to acute upper airway obstruction and creation of acute negative intrathoracic pressure. NPPE carries a good prognosis if promptly diagnosed and appropriately treated with or without mechanical ventilation. PMID:23439791

  18. Diagnosis, Prevention and Management of Postoperative Pulmonary Edema

    PubMed Central

    Bajwa, SJ Singh; Kulshrestha, A

    2012-01-01

    Postoperative pulmonary edema is a well-known postoperative complication caused as a result of numerous etiological factors which can be easily detected by a careful surveillance during postoperative period. However, there are no preoperative and intraoperative criteria which can successfully establish the possibilities for development of postoperative pulmonary edema. The aims were to review the possible etiologic and diagnostic challenges in timely detection of postoperative pulmonary edema and to discuss the various management strategies for prevention of this postoperative complication so as to decrease morbidity and mortality. The various search engines for preparation of this manuscript were used which included Entrez (including Pubmed and Pubmed Central), NIH.gov, Medknow.com, Medscape.com, WebMD.com, Scopus, Science Direct, MedHelp.org, yahoo.com and google.com. Manual search was carried out and various text books and journals of anesthesia and critical care medicine were also searched. From the information gathered, it was observed that postoperative cardiogenic pulmonary edema in patients with serious cardiovascular diseases is most common followed by noncardiogenic pulmonary edema which can be due to fluid overload in the postoperative period or it can be negative pressure pulmonary edema (NPPE). NPPE is an important clinical entity in immediate post-extubation period and occurs due to acute upper airway obstruction and creation of acute negative intrathoracic pressure. NPPE carries a good prognosis if promptly diagnosed and appropriately treated with or without mechanical ventilation. PMID:23439791

  19. Inter-electrode tissue resistance is not affected by tissue edema when electrically

    E-print Network

    Durfee, William K.

    1 Inter-electrode tissue resistance is not affected by tissue edema when electrically stimulating develop edema. The purpose of this study was to evaluate whether the edema would change inter electrodes. The protocol was administered to nine ICU patients with edema, eight surgical patients without

  20. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    PubMed

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. PMID:24338618

  1. Aggressive Zero Balance Ultrafiltration on CPB in Patients with Renal Failure May Cause Cerebral Edema: A Theoretical Analysis

    PubMed Central

    Fontaine, Eustace J.; Warwick, Richard; Sastry, Priya; Poullis, Michael

    2008-01-01

    Abstract: The objective of this study was to determine the brain volume changes that occur secondary to hemofiltration during cardiopulmonary bypass in patients with renal failure. We hypothesized that in patients with elevated urea levels, quick aggressive hemofiltration could be associated with cerebral edema. We constructed a simple two-compartment model similar to the urea kinetic model developed by Depner. Intracellular urea exit was assumed to be minimal based on known urea redistribution times. Calculations were based on a 70-kg patient, with an intracellular volume of 25 L, extracellular volume of 15 L, and a preoperative urea of 40 mmol/L filtered to a post-procedure urea of 6 mmol/L. Analysis showed that a standard size 1500-mL human brain filtered from a preoperative urea of 40 to 6 mmol/L over a short period will expand by 59 mL secondary to the osmotic disequilibrium secondary to hemofiltration (p < .05). The higher the preoperative urea, the larger the fluid shift. This figure does not include the cerebral edema component that is known to arise secondary to cardiopulmonary bypass. Significant cerebral edema theoretically occurs secondary to hemofiltration during cardiopulmonary bypass. More detailed mathematical urea kinetic analysis and clinical correlation are needed. PMID:19192751

  2. Intracerebroventricularly and systemically delivered inhibitor of brain CYP2B (C8-Xanthate), even following chlorpyrifos exposure, reduces chlorpyrifos activation and toxicity in male rats.

    PubMed

    Khokhar, Jibran Younis; Tyndale, Rachel Fynvola

    2014-07-01

    Chlorpyrifos is a pesticide that is metabolically activated to chlorpyrifos oxon (acetylcholinesterase inhibitor) primarily by the cytochrome P450 2B (CYP2B) enzyme subfamily in the liver and brain. We have previously shown that intracerebroventricular pretreatment with a CYP2B inhibitor, C8-Xanthate, can block chlorpyrifos toxicity. Here, we assessed whether delayed introduction of C8-Xanthate would still reduce toxicity and whether peripheral administration of C8-Xanthate could also inhibit chlorpyrifos activation in the brain and block toxicity. Male rats (N = 4-5/group) were either pretreated with C8-Xanthate (40 ?g intracerebroventricular or 5 mg/kg intraperitoneal), or vehicle (ACSF or saline, respectively), 24 h before chlorpyrifos treatment (125 mg/kg subcutaneous) and then treated daily with inhibitor or vehicle until 7 days post-chlorpyrifos treatment. Additional groups received vehicle pretreatment, switching to C8-Xanthate 1, 2, 3, or 4 days after chlorpyrifos and then continuing with daily C8-Xanthate treatment until 7 days post-chlorpyrifos treatment. Neurotoxicity was assessed at baseline (before chlorpyrifos) and then daily after chlorpyrifos, using behavioral assessments (e.g., gait score). Neurochemical assays (e.g., serum and brain chlorpyrifos) were performed at the end of study. Pretreatment with C8-Xanthate completely prevented chlorpyrifos toxicity, and delayed introduction of C8-Xanthate reduced toxicity, even when started up to 4 days after chlorpyrifos treatment. Discontinuation of C8-Xanthate treatment 7 days post-chlorpyrifos treatment did not result in the reappearance of toxicity, tested through 10 days after chlorpyrifos treatment. These findings suggest that CYP2B inhibitor treatment, even days after chlorpyrifos exposure, and using a peripheral delivery route, may be useful as a therapeutic approach to reduce chlorpyrifos toxicity. PMID:24798379

  3. The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa Patients with or without Cystoid Macular Edema

    PubMed Central

    Sandberg, Michael A.; Pearce, Elizabeth N.; Harper, Shyana; Weigel-DiFranco, Carol; Hart, Lois; Rosner, Bernard; Berson, Eliot L.

    2014-01-01

    Importance Current treatments for cystoid macular edema in retinitis pigmentosa are not always effective, may lead to adverse side effects, and may not restore loss of visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce cystoid macular edema in retinitis pigmentosa. Objective To determine whether central foveal thickness in the presence of cystoid macular edema is related to dietary iodine intake inferred from urinary iodine concentration in non-smoking adults with retinitis pigmentosa. Design Cross-sectional study. Setting Institutional referral center. Participants Non-smoking adult patients with retinitis pigmentosa (n = 212, ages 18 to 69 years) with a visual acuity ? 20/200 in at least one eye. Main outcome measure The relationship of log central foveal thickness measured by optical coherence tomography to urinary iodine concentration measured from multiple spot samples and represented as a 3-level classification variable (< 100 ?g/L, 100 ?g/L - 199 ?g/L, and ? 200 ?g/L), assigning greater weight to patients with more reliable urinary iodine concentration estimates. Results Analyses were limited to 199 patients after excluding 11 patients who failed to return urine samples for measuring urinary iodine concentration and 2 outliers for urinary iodine concentration. Thirty-six percent of these patients had cystoid macular edema in one or both eyes. Although log central foveal thickness was inversely related to urinary iodine concentration based on all patients (p = 0.02), regression of log central foveal thickness on urinary iodine concentration separately for patients with and without cystoid macular edema showed a strong inverse significant relationship for the former group (p < 0.001) and no significant relationship for the latter group as tested (p = 0.66). In contrast, we found no significant association between cystoid macular edema prevalence and urinary iodine concentration based on the entire sample as tested. Conclusions and Relevance A higher urinary iodine concentration in non-smoking adults with retinitis pigmentosa was significantly associated with less central foveal swelling in eyes with cystoid macular edema. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of cystoid macular edema in patients with retinitis pigmentosa. PMID:24993773

  4. Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

    ClinicalTrials.gov

    2014-04-21

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal

  5. Reduction of Pain and Edema of the Legs by Walking Wearing Elastic Stockings

    PubMed Central

    Carvalho, Carlos Alberto; Lopes Pinto, Renata; Guerreiro Godoy, Maria de Fatima; Pereira de Godoy, Jose Maria

    2015-01-01

    Aim. The objective of the current study was to evaluate the reduction of edema and pain with the use of elastic stockings. Method. The effect of walking on a treadmill for 50 minutes in the evening wearing elastic compression stockings on pain and edema was evaluated in a prospective randomized crossover clinical trial. In Assessment 1, the legs of participants were measured by volumetry at 7:00 a.m. and they were asked to perform their normal daily activities and to return at 4:00 p.m. Forty-two legs of 21 female patients with ages of the participants ranged from 32 to 72 years with signs and symptoms of chronic venous disease. The sizes of the legs of all patients were evaluated by water displacement volumetry and a visual analog scale was used to assess pain. Results. After walking for 50 minutes on the treadmill, the volume reduced (paired t-test: p value < 0.03). In relation to pain, there was a reduction in pain after the treadmill session using the elastic stocking (Wilcoxon signed rank test: p value < 0.007). Conclusion. The reduction of edema and pain of the legs during the course of the day can be accomplished with the use of elastic stockings, as well as walking. PMID:26366301

  6. Effect of diclofenac sodium (Voltaren) on hypoxia-induced corneal edema in humans.

    PubMed

    Goldberg, M A; McNamara, N; Nguyen, N T; Lerner, L; Rosenblum, L H; Park, D W; Abbott, R L; Levy, B

    1995-01-01

    We evaluated the effect of diclofenac sodium (Voltaren) drops on patients with hypoxia-induced corneal edema. Thirty age- and sex-matched subjects were randomly assigned to one of three groups. Members of each group received masked solutions of either Voltaren, Voltaren vehicle, or a non-preserved lubricant (Cellufresh) every 6 hours for 24 hours and then hourly for 2 hours immediately prior to inducing corneal edema in the experimental eye. Bilateral ultrasonic pachymetry was performed prior to applying a thick contact lens and light patch on the experimental eye of all subjects for 3 hours. The fellow eye served as the control. Following lens removal, bilateral corneal thickness was measured every 30 minutes. The percentage change in corneal swelling for each subject and group was calculated. The findings were also normalized to the control eye to minimize diurnal and individual variability. The results were plotted both as percentage change from hour 0 and percentage change normalized to the control eye. Corneal swelling ranged from 9-11% in all 3 groups, with recovery at 2-3 hours. No significant difference was found among the three groups (P > 0.05, ANOVA). There was a slight trend toward reduced thickness in the Cellufresh group, but this was not statistically significant. Voltaren does not appear to have an effect on the hypoxia-induced corneal edema associated with the production of arachidonic acid pathway metabolites. PMID:7712610

  7. Effect of transcutaneous electrical stimulation on nociception and edema induced by peripheral serotonin.

    PubMed

    Santos, Cristiane M F; Francischi, Janetti N; Lima-Paiva, Patrícia; Sluka, Kathleen A; Resende, Marcos A

    2013-07-01

    Transcutaneous electrical nerve stimulation (TENS) is defined as the application of an electrical current to the skin through surface electrodes for pain relief. Various theories have been proposed in order to explain the analgesic mechanism of TENS. Recent studies have demonstrated that part of this analgesia is mediated through neurotransmitters acting at peripheral sites. The aim of this study was to investigate the effects of low frequency (LF: 10 HZ) TENS and high frequency (HF: 130 HZ) TENS on hyperalgesia and edema when applied before the serotonin (5-HT) administered into the rat paw. LF and HF TENS were applied to the right paw for 20 min, and 5-HT was administered immediately after TENS. The Hargreaves method was used to measure nociception, while the hydroplethysmometer (Ugo Basile®) was used to measure edema. Neither HF nor LF TENS inhibited 5-HT-induced edema. However, LF TENS, but not HF TENS, completely reduced 5-HT-induced hyperalgesia. Pre-treatment of the paw with naltrexone, prior to application of TENS, (Nx: 50 ?g; I.pl.) showed a complete blockade of the analgesic effect induced by low frequency TENS. Thus, our results confirmed the lack of an anti-inflammatory effect through the use of TENS as well as the participation of peripheral endogenous opioid receptors in LF TENS analgesia in addition to its central action. PMID:23336713

  8. History of mild traumatic brain injury is associated with deficits in relational memory, reduced hippocampal volume, and less neural activity later in life

    PubMed Central

    Monti, Jim M.; Voss, Michelle W.; Pence, Ari; McAuley, Edward; Kramer, Arthur F.; Cohen, Neal J.

    2013-01-01

    Evidence suggests that a history of head trauma is associated with memory deficits later in life. The majority of previous research has focused on moderate-to-severe traumatic brain injury (TBI), but recent evidence suggests that even a mild TBI (mTBI) can interact with the aging process and produce reductions in memory performance. This study examined the association of mTBI with memory and the brain by comparing young and middle-aged adults who have had mTBI in their recent (several years ago) and remote (several decades ago) past, respectively, with control subjects on a face-scene relational memory paradigm while they underwent functional magnetic resonance imaging (fMRI). Hippocampal volumes were also examined from high-resolution structural images. Results indicated middle-aged adults with a head injury in their remote past had impaired memory compared to gender, age, and education matched control participants, consistent with previous results in the study of memory, aging, and TBI. The present findings extended previous results by demonstrating that these individuals also had smaller bilateral hippocampi, and had reduced neural activity during memory performance in cortical regions important for memory retrieval. These results indicate that a history of mTBI may be one of the many factors that negatively influence cognitive and brain health in aging. PMID:23986698

  9. Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain.

    PubMed

    Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Chia-Hsiang

    2015-12-10

    Methamphetamine (METH) is a highly addictive psychostimulant that may cause long-lasting synaptic dysfunction and abnormal gene expression. We aimed to explore the differential expression of synaptic plasticity genes in chronic METH-treated mouse brain. We used the RT(2) Profiler PCR Array and the real-time quantitative PCR to characterize differentially expressed synaptic plasticity genes in the frontal cortex and the hippocampus of chronic METH-treated mice compared with normal saline-treated mice. We further used pyrosequencing to assess DNA methylation changes in the CpG region of the five immediate early genes (IEGs) in chronic METH-treated mouse brain. We detected six downregulated genes in the frontal cortex and the hippocampus of chronic METH-treated mice, including five IEGs (Arc, Egr2, Fos, Klf10, and Nr4a1) and one neuronal receptor gene (Grm1), compared with normal saline-treated group, but only four genes (Arc, Egr2, Fos, and Nr4a1) were confirmed to be different. Furthermore, we found several CpG sites of the Arc and the Fos that had significant changes in DNA methylation status in the frontal cortex of chronic METH-treated mice, while the klf10 and the Nr4a1 that had significant changes in the hippocampus. Our results show that chronic administration of METH may lead to significant downregulation of the IEGs expression in both the frontal cortex and the hippocampus, which may partly account for the molecular mechanism of the action of METH. Furthermore, the changes in DNA methylation status of the IEGs in the brain indicate that an epigenetic mechanism-dependent transcriptional regulation may contribute to METH addiction, which warrants additional study. PMID:26496011

  10. Effect of Fluvoxamine on Carrageenan-Induced Paw Edema in Rats Evaluation of the Action Sites

    PubMed Central

    Hajhashemi, Valiollah; Sadeghi, Hossein; Minaiyan, Mohsen; Movahedian, Ahmad; Talebi, Ardeshir

    2011-01-01

    The present study was designed to explore the anti-inflammatory effect of fluvoxamine, as a selective serotonin reuptake inhibitor (SSRI) anti-depressant, on carrageenan-induced paw edema in more details. At first, fluvoxamine was administered intra-peritoneally (2.5, 12.5, 25 and 50 mg Kg-1) 30 min before the subplantar injection of carrageenan. Fluvoxamine was also injected intra-peritoneally at a dose of 50 mg Kg-1 30 or 90 min after carrageenan injection. Then, fluvoxamine was given intra-cerebroventricularly (25, 50 and 100 ?g/rat) and intra-thecally (25, 50 and 100 ?g/rat) 30 min before the carrageenan challenge. Finally, the effect of mifepristone (5 mg Kg-1), an antagonist of the glucocorticoid receptor, on the anti-edema effect of fluvoxamine (50 mg Kg-1) was investigated. Results showed that intra-peritoneal (IP) administration of fluvoxamine before or after carrageenan injection considerably inhibited paw edema response at 4 h post-carrageenan (p < 0.001), but intra-cerebroventricular (i.c.v.) and intra-thecal (i.t.) injection of fluvoxamine did not alter the degree of paw swelling. The inhibitory effect of fluvoxamine was reduced by the pretreatment of mifepristone (p < 0.01). Our results suggest that IP administration of fluvoxamine produces a noticeable anti-inflammatory effect in the carrageenan-induced paw edema in rats and at least, a part of this effect is mediated through glucocorticoid receptor. Moreover, it seems unlikely that central sites have an important role in this inhibitory effect of fluvoxamine. PMID:24250395

  11. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    SciTech Connect

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  12. Early methyl donor deficiency may induce persistent brain defects by reducing Stat3 signaling targeted by miR-124.

    PubMed

    Kerek, R; Geoffroy, A; Bison, A; Martin, N; Akchiche, N; Pourié, G; Helle, D; Guéant, J-L; Bossenmeyer-Pourié, C; Daval, J-L

    2013-01-01

    The methyl donors folate (vitamin B9) and vitamin B12 are centrepieces of the one-carbon metabolism that has a key role in transmethylation reactions, and thus in epigenetic and epigenomic regulations. Low dietary intakes of folate and vitamin B12 are frequent, especially in pregnant women and in the elderly, and deficiency constitutes a risk factor for various diseases, including neurological and developmental disorders. In this respect, both vitamins are essential for normal brain development, and have a role in neuroplasticity and in the maintenance of neuronal integrity. The consequences of a methyl donor deficiency (MDD) were studied both in vivo in rats exposed in utero, and in vitro in hippocampal progenitors (H19-7 cell line). Deficiency was associated with growth retardation at embryonic day 20 (E20) and postnatally with long-term brain defects in selective areas. mRNA and protein levels of the transcription factor Stat3 were found to be decreased in the brains of deprived fetuses and in differentiating progenitors (62 and 48% for total Stat3 protein, respectively), along with a strong reduction in its phosphorylation at both Tyr??? and Ser?²? residues. Vitamin shortage also affected upstream kinases of Stat3 signaling pathway (phospho-Erk1/2, phospho-Src, phospho-JNK, and phospho-p38) as well as downstream target gene products (Bcl-2 and Bcl-xL), thus promoting apoptosis. Conversely, the expression of the Stat3 regulator miR-124 was upregulated in deficiency conditions (?65%), and its silencing by using siRNA partly restored Stat3 signaling in hippocampal neurons by increasing specifically the phosphorylation of Erk1/2 and Src kinases. Furthermore, miR-124 siRNA improved the phenotype of deprived cells, with enhanced neurite outgrowth. Taken together, our data suggest that downregulation of Stat3 signaling by miR-124 would be a key factor in the deleterious effects of MDD on brain development. PMID:23928694

  13. Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection

    PubMed Central

    Chang, Yin-Shuo; Chang, Chang-Cheng; Shen, Jen-Hsiang; Chen, Yu-Tsung; Chan, Karen Kar-Wun

    2015-01-01

    Abstract Periocular botulinum toxin type A (BoNTA) injections are generally safe. Ptosis is the most common adverse effect, whereas eyelid edema is rarely reported. There is no consensus on the latter's incidence, clinical course, or treatment strategy. Here we managed a 59-year-old woman who received BoNTA injections to her forehead, glabella, and eye corner. At 3-day follow-up, she presented with painless, nonpruritic, bilateral periorbital edema, and erythema. Preliminary diagnosis was a local allergic reaction, and topical corticosteroid was administered, but upon lack of improvement, edema secondary to venous and lymphatic congestion was hypothesized, and she was advised to apply hot pads over her eyes, blink frequently, and massage the area. Her eyelid edema resolved 2 weeks later. At 4-month follow-up, the patient requested and received another course of BoNTA at half the dose. Frequent blinking was instructed, and the patient reported a satisfactory outcome with no adverse effects. In our literature review, incidence of BoNTA-induced eyelid edema was 1.4% and showed Asian tendency. Although rare, BoNTA-induced periorbital edema is self-limiting, and normally resolves in 2 to 4 weeks without medical treatment. Patients at risk for edema, including Asian ethnicity, dermatochalasis, and poor periocular muscle tone, are advised to receive injections at half the dosage. Examination of the function and tone of the orbicularis oculi and levator palpebrae superioris muscles before treatment is recommended, and application of hot pads over the eyes, frequent blinking in the morning, and self-massage of the affected area to increase venous return have demonstrated to improve outcome. PMID:26402825

  14. Aging reduces the GABA-dependent /sup 36/Cl/sup -/ flux in rat brain membrane vesicles

    SciTech Connect

    Concas, A.; Pepitoni, S.; Atsoggiu, T.; Toffano, G.; Biggio, G.

    1988-01-01

    The function of the chloride channel associated to GABA/sub A/ receptor complex was analyzed in the brain of aged rats by measuring the chloride flux across the neuronal membrane and its modulation by drugs acting at the level of the GABA receptor complex and /sup 35/S-TBPS binding. The basal /sup 36/Cl/sup -/ uptake by brain membrane vesicles of aged rats was higher than that observed in those of adult rats. The higher /sup 36/Cl/sup -/ uptake found in cortical membrane vesicles of senescent rats was not sensitive to the action of bicuculline indicating that it was not the consequence of a tonic GABAergic modulation. Moreover, the stimulation of /sup 36/Cl/sup -/ uptake induced by GABA was markedly lower in membrane vesicles of aged rats than that observed in those of adult rats. Accordingly, the stimulation of /sup 36/Cl/sup -/ efflux elicited by GABA and pentobarbital was higher in membrane vesicles of adult rats with respect to that of old rats. Finally a significant decrease of /sup 35/S-TBPS binding was observed in membrane preparation from the cerebral cortex, cerebellum and hippocampus of aged-rats.

  15. Behavioral Differences between Neonatal and Adult 6-Hydroxydopamine-Treated Rats to Dopamine Agonists: Relevance to Neurological Symptoms in Clinical Syndromes with Reduced Brain Dopamine1

    PubMed Central

    BREESE, GEORGE R.; BAUMEISTER, ALAN A.; McCOWN, THOMAS J.; EMERICK, SUSAN G.; FRYE, GERALD D.; CROTTY, KAREN; MUELLER, ROBERT A.

    2011-01-01

    Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding—behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-?-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High closes of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa. The latter findings suggest that these behaviors in neonatal 6-OHDA-treated rats are more associated with D-1 than D-2 receptor function. The age-dependent effects of dopamine agonists observed in these studies provide an explanation for the different symptomatology observed in Lesch-Nyhan patients and Parkinson’s disease—neurological disorders with reduced brain dopamine. PMID:6149306

  16. 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.

  17. 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. PMID:26248532

  18. Neuroprotective effect of phytoceramide against transient focal ischemia-induced brain damage in rats.

    PubMed

    Lee, Hong Kyu; Jang, Ji Yeon; Yoo, Hwan-Su; Seong, Yeon Hee

    2015-12-01

    The present study was conducted to investigate the protective effect of phytoceramide against focal transient ischemic brain damage and the underlying mechanisms. Focal transient ischemic brain damage was produced in rats by occlusion of the middle cerebral artery for 2 h followed by 24 h of reperfusion (MCAO/reperfusion). Orally administered phytoceramide (10, 25, and 50 mg/kg) significantly reduced MCAO/reperfusion-induced brain infarction and edema as well as the development of behavioral disabilities in the animals. Depletion of glutathione levels and lipid peroxidation in brain tissue following MCAO/reperfusion was reduced by administration of phytoceramide. The expressions of phosphorylated extracellular signaling-regulating kinases/mitogen-activated protein kinase (p-ERK1/2 MAPK), inflammatory factors such as cyclooxygenase-2 and inducible nitric oxide synthase, and pro-apoptotic proteins Bax and caspase-3 were increased while the anti-apoptotic protein Bcl-2 was decreased in ischemic brain; these effects were significantly inhibited by treatment with phytoceramide. Furthermore, phytoceramide activated the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway to prevent ischemic brain damage. These results suggest that phytoceramide may help prevent neurodegeneration caused by ischemic stroke due to its anti-oxidant, anti-apoptotic, and anti-inflammatory properties. PMID:26345266

  19. Protective effects of dl-3n-butylphthalide against diffuse brain injury

    PubMed Central

    Zhao, Yaning; Li, Jianmin; Zhang, Pan; Chen, Changxiang; Li, Shuxing

    2013-01-01

    Dl-3n-butylphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. Dl-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es-timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier age and cerebral edema. PMID:25206572

  20. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

    NASA Astrophysics Data System (ADS)

    Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

    2014-12-01

    Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml-1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

  1. Protective role of brain water channel AQP4 in murine cerebral malaria

    PubMed Central

    Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood; Agre, Peter

    2013-01-01

    Tragically common among children in sub-Saharan Africa, cerebral malaria is characterized by rapid progression to coma and death. In this study, we used a model of cerebral malaria appearing in C57BL/6 WT mice after infection with the rodent malaria parasite Plasmodium berghei ANKA. Expression and cellular localization of the brain water channel aquaporin-4 (AQP4) was investigated during the neurological syndrome. Semiquantitative real-time PCR comparing uninfected and infected mice showed a reduction of brain AQP4 transcript in cerebral malaria, and immunoblots revealed reduction of brain AQP4 protein. Reduction of brain AQP4 protein was confirmed in cerebral malaria by quantitative immunogold EM; however, polarized distribution of AQP4 at the perivascular and subpial astrocyte membranes was not altered. To further examine the role of AQP4 in cerebral malaria, WT mice and littermates genetically deficient in AQP4 were infected with P. berghei. Upon development of cerebral malaria, WT and AQP4-null mice exhibited similar increases in width of perivascular astroglial end-feet in brain. Nevertheless, the AQP4-null mice exhibited more severe signs of cerebral malaria with greater brain edema, although disruption of the blood–brain barrier was similar in both groups. In longitudinal studies, cerebral malaria appeared nearly 1 d earlier in the AQP4-null mice, and reduced survival was noted when chloroquine rescue was attempted. We conclude that the water channel AQP4 confers partial protection against cerebral malaria. PMID:23277579

  2. Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage

    PubMed Central

    2013-01-01

    Background Endothelin-1 (ET-1) is a potent vasoconstrictor, and astrocytic ET-1 is reported to play a role in the pathogenesis of cerebral ischemic injury and cytotoxic edema. However, it is still unknown whether astrocytic ET-1 also contributes to vasogenic edema and vasospasm during subarachnoid hemorrhage (SAH). In the present study, transgenic mice with astrocytic endothelin-1 over-expression (GET-1 mice) were used to investigate the pathophysiological role of ET-1 in SAH pathogenesis. Results The GET-1 mice experienced a higher mortality rate and significantly more severe neurological deficits, blood–brain barrier breakdown and vasogenic edema compared to the non-transgenic (Ntg) mice following SAH. Oral administration of vasopressin V1a receptor antagonist, SR 49059, significantly reduced the cerebral water content in the GET-1 mice. Furthermore, the GET-1 mice showed significantly more pronounced middle cerebral arterial (MCA) constriction after SAH. Immunocytochemical analysis showed that the calcium-activated potassium channels and the phospho-eNOS were significantly downregulated, whereas PKC-? expression was significantly upregulated in the MCA of the GET-1 mice when compared to Ntg mice after SAH. Administration of ABT-627 (ETA receptor antagonist) significantly down-regulated PKC-? expression in the MCA of the GET-1 mice following SAH. Conclusions The present study suggests that astrocytic ET-1 involves in SAH-induced cerebral injury, edema and vasospasm, through ETA receptor and PKC-mediated potassium channel dysfunction. Administration of ABT-627 (ETA receptor antagonist) and SR 49059 (vasopressin V1a receptor antagonist) resulted in amelioration of edema and vasospasm in mice following SAH. These data provide a strong rationale to investigate SR 49059 and ABT-627 as therapeutic drugs for the treatment of SAH patients. PMID:24156724

  3. Astragaloside IV alleviates early brain injury following experimental subarachnoid hemorrhage in rats.

    PubMed

    Shao, Anwen; Guo, Songxue; Tu, Sheng; Ammar, Al-baadani; Tang, Junjia; Hong, Yuan; Wu, Haijian; Zhang, Jianmin

    2014-01-01

    Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti-apoptotic effects. PMID:25136262

  4. Astragaloside IV Alleviates Early Brain Injury Following Experimental Subarachnoid Hemorrhage in Rats

    PubMed Central

    Shao, Anwen; Guo, Songxue; Tu, Sheng; Ammar, Al-baadani; Tang, Junjia; Hong, Yuan; Wu, Haijian; Zhang, Jianmin

    2014-01-01

    Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti-apoptotic effects. PMID:25136262

  5. Hepatocyte growth factor suppresses ischemic cerebral edema in rats with microsphere embolism.

    PubMed

    Takeo, Satoshi; Takagi, Norio; Takagi, Keiko; Date, Ichiro; Ishida, Kumi; Besshoh, Shintaro; Nakamura, Toshikazu; Tanonaka, Kouichi

    2008-12-19

    The present study was aimed at determining whether human recombinant hepatocyte growth factor (HGF) ameliorates cerebral edema induced by microsphere embolism (ME). Rats were injected with 700 microspheres (48 microm in diameter). Continuous administration of HGF at 13 microg/3 days/animal into the right ventricle was started from 10 min after embolism to the end of the experiment by using an osmotic pump. On day 3 after the ME, the rats were anesthetized, and their brains were perfused with an isotonic mannitol solution to eliminate constituents in the vascular and extracellular spaces. Thereafter, tissue water and cation contents were determined. A significant increase in tissue water content of the right hemisphere by ME was seen. This ME-induced increase in water content was associated with increases in tissue sodium and calcium ion contents and decreases in tissue potassium and magnesium ion contents of the right hemisphere. The treatment of the animal with HGF suppressed the increases in water and sodium and calcium ion contents, but not the decreases in potassium and magnesium ion contents. These results suggest that HGF suppresses the formation of ischemic cerebral edema provoked intracellularly in rats with ME. PMID:18938210

  6. Effects of Cold and Compression on Edema.

    ERIC Educational Resources Information Center

    Sloan, J. P.; And Others

    1988-01-01

    Investigation of ways to treat artificially induced acute inflammatory reactions in human tissue found that neither cooling or pressure alone reduced the swelling, while a combination of the two methods produced a significant reduction in swelling. (Author/CB)

  7. Characterization of symptoms and edema distribution in premenstrual syndrome

    PubMed Central

    Tacani, Pascale Mutti; Ribeiro, Danielle de Oliveira; Barros Guimarães, Barbara Evelyn; Machado, Aline Fernanda Perez; Tacani, Rogério Eduardo

    2015-01-01

    Background Premenstrual syndrome is a group of symptoms linked to the menstrual cycle, and edema is among these symptoms. Physiotherapy is often sought by many patients for the treatment of edema; however, for an adequate prescription of physiotherapeutic procedures, the distribution of edema throughout the body has yet to be characterized. Objective To determine the most frequent symptoms and body regions that present with edema in women during the premenstrual period. Subjects and methods Sixty women with a mean age of 24.6±4.7 years were evaluated during their premenstrual (between days 21 and 28) and menstrual period (between days 1 and 3), and the collected data included body mass, height, biotype (body-fat distribution), face, breast, limb-circumference measurements, and limb-volume estimate, and an adapted version of the Premenstrual Symptoms Screening Tool was used. Statistical analysis was performed using Student’s t-test and the test for equality of two proportions (P?0.05). Results Premenstrual syndrome was identified in 91.7% of the women, and the most frequent symptoms were irritability (73.33%) and physical symptoms, including swelling (65%), and anxiety (58.3%). Edema was detected in the following areas: facial, epigastric, mammary, umbilical, and pubic, the mid-third of the arms, distal forearm, in both thighs and in the mid-third of the legs determined by circumference measurements, and in both upper and lower limbs, according to the estimated volume. Conclusion In this study population, the most frequent symptoms were irritability, physical symptoms, and anxiety, with distribution of edema in the face, breast, abdomen, pubic area, distal upper limb, and proximal lower limb. PMID:25792857

  8. Quinidine, but Not Eicosanoid Antagonists or Dexamethasone, Protect the Gut from Platelet Activating Factor-Induced Vasoconstriction, Edema and Paralysis

    PubMed Central

    Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

    2015-01-01

    Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 ?M). The COX and LOX inhibitors ASA and AA861 (500 ?M, 10 ?M) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 ?M, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 ?M) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 ?M) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments deserves further study. PMID:25793535

  9. Effects of phase I complex decongestive physiotherapy on physical functions and depression levels in breast cancer related lymph edema

    PubMed Central

    Atalay, Orçin Telli; Özkir, An?l; Çalik, Bilge Ba?akçi; Baskan, Emre; Ta?kin, Harun

    2015-01-01

    [Purpose] Breast cancer-related upper extremity lymph edema is known to cause physical, functional and psychological impairments in women after modified radical mastectomy. The aim of this study was to investigate the effects of phase I Complex Decongestive Physiotherapy (CDP) on physical functions and depression levels in women with breast cancer-related upper extremity lymph edema. [Subjects and Methods] Fifty-eight subjects with breast cancer-related upper extremity lymph edema were the subjects of this study. The arm circumference, shoulder range of motion (ROM), muscle strength and depression levels of the subjects were assessed before and after phase I CDP treatment. [Results] After phase I CDP, there was a statistically significant reduction in circumference measurements at all levels of the affected arm. There was not any statistically significant difference in muscle strength after CDP. The shoulder ROM improved after treatment. There was a significant reduction in the Beck Depression Inventory score. A significant positive correlation was found between depression levels and circumference measurement. [Conclusion] Based on the results we suggest that by reducing limb volume, beside improving physical functions, phase I CDP can affect psychological status, especially depression which is very common in women with breast cancer-related upper extremity lymph edema. PMID:25931748

  10. Effects of phase I complex decongestive physiotherapy on physical functions and depression levels in breast cancer related lymph edema.

    PubMed

    Atalay, Orçin Telli; Özkir, An?l; Çalik, Bilge Ba?akçi; Baskan, Emre; Ta?kin, Harun

    2015-03-01

    [Purpose] Breast cancer-related upper extremity lymph edema is known to cause physical, functional and psychological impairments in women after modified radical mastectomy. The aim of this study was to investigate the effects of phase I Complex Decongestive Physiotherapy (CDP) on physical functions and depression levels in women with breast cancer-related upper extremity lymph edema. [Subjects and Methods] Fifty-eight subjects with breast cancer-related upper extremity lymph edema were the subjects of this study. The arm circumference, shoulder range of motion (ROM), muscle strength and depression levels of the subjects were assessed before and after phase I CDP treatment. [Results] After phase I CDP, there was a statistically significant reduction in circumference measurements at all levels of the affected arm. There was not any statistically significant difference in muscle strength after CDP. The shoulder ROM improved after treatment. There was a significant reduction in the Beck Depression Inventory score. A significant positive correlation was found between depression levels and circumference measurement. [Conclusion] Based on the results we suggest that by reducing limb volume, beside improving physical functions, phase I CDP can affect psychological status, especially depression which is very common in women with breast cancer-related upper extremity lymph edema. PMID:25931748

  11. Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom.

    PubMed

    De Toni, Lanuze G B; Menaldo, Danilo L; Cintra, Adélia C O; Figueiredo, Maria J; de Souza, Anderson R; Maximiano, William M A; Jamur, Maria C; Souza, Glória E P; Sampaio, Suely V

    2015-09-01

    Snake venom metalloproteinases have been described as responsible for several inflammatory effects. In this study, we investigated the edema and hyperalgesia induced in rats by Batroxase, a P-I metalloproteinase from Bothrops atrox venom, along with possible inflammatory mediators involved in these responses. Batroxase or sterile saline was injected into rat paws and the edema and hyperalgesic effects were evaluated for 6h by using a plethysmometer and a Von Frey system, respectively. Batroxase induced significant edematogenic and hyperalgesic peak responses in the first hours after administration. The inflammatory mediators involved in these responses were assayed by pretreatment of animals with synthesis inhibitors or receptor antagonists. Peak responses were significantly reduced by administration of the glucocorticoid dexamethasone, the H1 receptor antagonist diphenhydramine and the FLAP inhibitor MK-886. Rat paws injected with compound 48/80, a mast cell degranulating agent, followed by Batroxase injection resulted in significant reduction of the edema and hyperalgesia. However, Batroxase itself induced minor degranulation of RBL-2H3 mast cells in vitro. Additionally, the inflammatory responses did not seem to be related to prostaglandins, bradykinin or nitric oxide. Our results indicate a major involvement of histamine and leukotrienes in the edema and hyperalgesia induced by Batroxase, which could be related, at least in part, to mast cell degranulation. PMID:26072684

  12. The Effects of Portulaca oleracea on Hypoxia-Induced Pulmonary Edema in Mice.

    PubMed

    Yue, Tan; Xiaosa, Wen; Ruirui, Qi; Wencai, Shi; Hailiang, Xin; Min, Li

    2015-03-01

    Portulaca oleracea L. (PO) is known as "a vegetable for long life" due to its antioxidant, anti-inflammatory, and other pharmacological activities. However, the protective activity of the ethanol extract of PO (EEPO) against hypoxia-induced pulmonary edema has not been fully investigated. In this study, we exposed mice to a simulated altitude of 7000 meters for 0, 3, 6, 9, and 12?h to observe changes in the water content and transvascular leakage of the mouse lung. It was found that transvascular leakage increased to the maximum in the mouse lung after 6?h exposure to hypobaric hypoxia. Prophylactic administration of EEPO before hypoxic exposure markedly reduced the transvascular leakage and oxidative stress, and inhibited the upregulation of NF-kB in the mouse lung, as compared with the control group. In addition, EEPO significantly reduced the levels of proinflammatory cytokines and cell adhesion molecules in the lungs of mice, as compared with the hypoxia group. Our results show that EEPO can reduce initial transvascular leakage and pulmonary edema under hypobaric hypoxia conditions. PMID:25761168

  13. Delayed IGF-1 treatment reduced long-term hypoxia-ischemia-induced brain damage and improved behavior recovery of immature rats.

    PubMed

    Zhong, Jin; Zhao, Limin; Du, Yansheng; Wei, Gang; Yao, Wei-Guo; Lee, Wei-Hua

    2009-06-01

    Cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute newborn mortality and chronic disability. Despite our increasing understanding of the mechanisms of neuronal injury, an effective clinical therapy has yet to be established to mitigate brain damage and improve the prognosis and well-being of these newborn patients. Insulin-like growth factor 1 (IGF-1) is a well-known neurotrophic factor, essential for the survival and functional maturation of immature neurons. This study demonstrated that subcutaneous administration of IGF-1 at 24 and 48 hours of recovery significantly reduced hypoxia-ischemia-induced injury to immature rat brains and improved long-term memory and cognitive behavior. IGF-1's therapeutic effects likely involve its ability to prevent delayed apoptosis, as we demonstrated in primary cortical neuronal cultures under oxygen and glucose deprivation. IGF-1's neuroprotective effects parallel the activities of phosphatidylinositol-3/Akt and its down-stream signaling pathway, suggesting a potential mechanistic link. Overall, evidence from this investigation strongly supports IGF-1's potential therapeutic use in the treatment of hypoxic-ischemic encephalopathy in newborn patients. PMID:19500451

  14. Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.

    PubMed

    Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan

    2011-11-21

    Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion. PMID:22001884

  15. The roles of MMP-9/TIMP-1 in cerebral edema following experimental acute cerebral infarction in rats.

    PubMed

    Li, Dan-Dong; Song, Jin-Ning; Huang, Huan; Guo, Xiao-Ye; An, Ji-Yang; Zhang, Ming; Li, Yu; Sun, Peng; Pang, Hong-Gang; Zhao, Yong-Lin; Wang, Jun-Feng

    2013-08-29

    Matrix metalloproteinases 9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), regulate homeostasis and turnover of the extra cellular matrix (ECM). They play important roles in acute cerebral infarction (ACI). The contributions of MMP-9 and TIMP-1 to the early stages of ACI are not completely understood. This study investigates the time course of MMP-9 and TIMP-1 and their relations to edema after ACI in rats. Serum concentrations of MMP-9 and TIMP-1 protein were measured using ELISA and mRNA level were measured using real-time PCR. Brain samples were harvested and the brain water content (BWC) was measured. Results revealed that MMP-9 concentration increased fast during the first 12 h after ACI, while after 12 h the increase was much slower. The MMP-9 protein concentration was elevated earlier than the mRNA level. BWC increased starting at 6 h after ACI to reach a peak at 12 h and decreased back to normal levels at 72 h. Both the MMP-9 protein and its mRNA were positively correlated with BWC, however no correlation was found between TIMP-1 levels and BWC. The MMP-9/TIMP-1 protein ratio was more closely correlated with BWC than the MMP-9 concentration. These results indicate that brain edema induced by ACI is associated with increased MMP-9 levels and MMP-9/TIMP-1 ratio in serum. PMID:23819982

  16. Brain, Behavior, and Immunity: Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors

    Cancer.gov

    Brain, Behavior, and Immunity 30 (2013) S109–S116 Contents lists available at SciVerse ScienceDirect Brain, Behavior, and Immunity j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y b r b i Reduced hippocampal volume

  17. Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine.

    PubMed

    Breese, G R; Baumeister, A A; McCown, T J; Emerick, S G; Frye, G D; Crotty, K; Mueller, R A

    1984-11-01

    Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6149306

  18. Delayed progesterone treatment reduces brain infarction and improves functional outcomes after ischemic stroke: a time-window study in middle-aged rats.

    PubMed

    Yousuf, Seema; Sayeed, Iqbal; Atif, Fahim; Tang, Huiling; Wang, Jun; Stein, Donald G

    2014-02-01

    We evaluated the neuroprotective effects of delayed progesterone (PROG) treatment against ischemic stroke-induced neuronal death, inflammation, and functional deficits. We induced transient focal cerebral ischemia in male rats and administered PROG (8?mg/kg) or vehicle intraperitoneally at 3, 6, or 24?hours post occlusion, subcutaneously 5?hours later and then every 24?hours for 7 days. Behavioral outcomes were evaluated over 22 days. Infarct size and other biomarkers of injury were evaluated by cresyl violet staining, and matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF) by immunofluorescence. Progesterone treatment started at 3 and 6?hours post occlusion significantly (P<0.05) improved behavioral performance at all time points (74.01%) and reduced infarction volume (61.68%) compared with vehicle. No significant difference was observed between the 3 and 6?hour PROG treatment groups. Matrix metalloproteinase-9 and VEGF were upregulated in the PROG groups compared with vehicle. Glial fibrillary acidic protein expression was increased in the vehicle group but markedly lower in the PROG groups. Treatment delayed for 24?hours did not significantly improve functional outcomes or reduce infarction volume. We conclude that, under the right treatment conditions, PROG treatment delayed up to 6?hours can improve functional deficits and reduce brain infarction, possibly by modulating GFAP, VEGF, and MMP-9 expression. PMID:24301297

  19. Disruption of IP3R2-mediated Ca(2+) signaling pathway in astrocytes ameliorates neuronal death and brain damage while reducing behavioral deficits after focal ischemic stroke.

    PubMed

    Li, Hailong; Xie, Yicheng; Zhang, Nannan; Yu, Yang; Zhang, Qiao; Ding, Shinghua

    2015-12-01

    Inositol trisphosphate receptor (IP3R)-mediated intracellular Ca(2+) increase is the major Ca(2+) signaling pathway in astrocytes in the central nervous system (CNS). Ca(2+) increases in astrocytes have been found to modulate neuronal function through gliotransmitter release. We previously demonstrated that astrocytes exhibit enhanced Ca(2+) signaling in vivo after photothrombosis (PT)-induced ischemia, which is largely due to the activation of G-protein coupled receptors (GPCRs). The aim of this study is to investigate the role of astrocytic IP3R-mediated Ca(2+) signaling in neuronal death, brain damage and behavior outcomes after PT. For this purpose, we conducted experiments using homozygous type 2 IP3R (IP3R2) knockout (KO) mice. Histological and immunostaining studies showed that IP3R2 KO mice were indeed deficient in IP3R2 in astrocytes and exhibited normal brain cytoarchitecture. IP3R2 KO mice also had the same densities of S100?+ astrocytes and NeuN+ neurons in the cortices, and exhibited the same glial fibrillary acidic protein (GFAP) and glial glutamate transporter (GLT-1) levels in the cortices and hippocampi as compared with wild type (WT) mice. Two-photon (2-P) imaging showed that IP3R2 KO mice did not exhibit ATP-induced Ca(2+) waves in vivo in the astrocytic network, which verified the disruption of IP3R-mediated Ca(2+) signaling in astrocytes of these mice. When subject to PT, IP3R2 KO mice had smaller infarction than WT mice in acute and chronic phases of ischemia. IP3R2 KO mice also exhibited less neuronal apoptosis, reactive astrogliosis, and tissue loss than WT mice. Behavioral tests, including cylinder, hanging wire, pole and adhesive tests, showed that IP3R2 KO mice exhibited reduced functional deficits after PT. Collectively, our study demonstrates that disruption of astrocytic Ca(2+) signaling by deleting IP3R2s has beneficial effects on neuronal and brain protection and functional deficits after stroke. These findings reveal a novel non-cell-autonomous neuronal and brain protective function of astrocytes in ischemic stroke, whereby suggest that the astrocytic IP3R2-mediated Ca(2+) signaling pathway might be a promising target for stroke therapy. PMID:26433454

  20. Implications of the lymphatic system in CVI-associated edema.

    PubMed

    Mortimer, P S

    2000-01-01

    Lymph drainage is intimately linked with venous drainage in health and disease. Evidence exists to support the view that lymphatics frequently fail in venous disease, particularly in its advanced stages. The implications of this are to increase the risk of infection and the amount of edema, events which can only further the morbidity of venous disease. PMID:10667636

  1. Hypovolemia and hypotension complicating management of acute cardiogenic pulmonary edema.

    PubMed

    Figueras, J; Weil, M H

    1979-12-01

    After the acute onset of heart failure and in the absence of acute myocardial infarction, plasma volume may occasionally be depleted to the extent that the patient presents with clinical signs of circulatory shock. In five patients, the acute onset of clinical and radiographic signs of cardiogenic pulmonary edema were associated with reduction in arterial blood pressure and cardiac output. The pulmonary arterial wedge pressure was within normal limits but a reduction in plasma volume was demonstrated, which is best explained by the rapid translocation of plasma water that represented pulmonary (and most likely also peripheral) edema fluid. The infusion of 5 percent albumin solution significantly increased cardiac output, mean arterial pressure and cardiac work, reversed lactic acidosis, enhanced furosemide-induced diuresis and was followed by a decrease in both clinical and radiographic signs of pulmonary edema. These observations confirm that volume expansion may constitute appropriate treatment for some patients with cardiogenic pulmonary edema who may present with hypotension and who are unresponsive to conventional therapy. PMID:506939

  2. Lurasidone and fluoxetine reduce novelty-induced hypophagia and NMDA receptor subunit and PSD-95 expression in mouse brain.

    PubMed

    Stan, Tiberiu Loredan; Sousa, Vasco Cabral; Zhang, Xiaoqun; Ono, Michiko; Svenningsson, Per

    2015-10-01

    Lurasidone, a novel second-generation antipsychotic agent, exerts antidepressant actions in patients suffering from bipolar type I disorder. Lurasidone acts as a high affinity antagonist at multiple monoamine receptors, particularly 5-HT2A, 5-HT7, D2 and ?2 receptors, and as a partial agonist at 5-HT1A receptors. Accumulating evidence indicates therapeutic actions by monoaminergic antidepressants are mediated via alterations of glutamate receptor-mediated neurotransmission. Here, we used mice and investigated the effects of chronic oral administration of vehicle, lurasidone (3 or 10mg/kg) or fluoxetine (20mg/kg) in the novelty induced hypophagia test, a behavioral test sensitive to chronic antidepressant treatment. We subsequently performed biochemical analyses on NMDA receptor subunits and associated proteins. Both lurasidone and fluoxetine reduced the latency to feed in the novelty-induced hypophagia test. Western blotting experiments showed that both lurasidone and fluoxetine decreased the total levels of NR1, NR2A and NR2B subunits of NMDA receptors and PSD-95 (PostSynaptic Density-95) in hippocampus and prefrontal cortex. Taken together, these data indicate that antidepressant/anxiolytic-like effects of lurasidone, as well as fluoxetine, could involve reduced NMDA receptor-mediated signal transduction, particularly in pathways regulated by PSD-95, in hippocampus and prefrontal cortex. PMID:26256011

  3. 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. PMID:26355809

  4. Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats.

    PubMed

    Gu, Chi; Wang, Yifei; Li, Jianru; Chen, Jingyin; Yan, Feng; Wu, Cheng; Chen, Gao

    2015-10-22

    Early brain injury (EBI) plays a crucial role in the pathological progress of subarachnoid hemorrhage (SAH). This study was designed to determine whether rosiglitazone protects the brain against EBI in rats, and discuss the role of the anti-apoptotic mechanism mediated by Bcl-2 family proteins in this neuroprotection. 86 male Sprague-Dawley rats were divided into the sham group, the SAH+ vehicle group and the SAH+ rosiglitazone group. SAH was induced via an endovascular perforation technique and rosiglitazone (3mg/kg) or vehicle was administered. Mortality, neurological scores, brain water content, Evans blue dye assay, TUNEL stain assay, Gelatin zymography, and western blot analysis were performed. Rosiglitazone significantly improved mortality, neurological scores, brain water content, blood brain barrier (BBB) and apoptosis compared with the vehicle group within 24h after SAH. The TUNEL staining assay demonstrated that apoptosis was ameliorated. Cleaved Caspase-3 and MMP-9 expression was reduced, whereas Bcl-2 and p-Bad was markedly preserved by rosiglitazone. A significant elevation of p-Akt was detected after rosiglitazone treatment. Our study demonstrated that rosiglitazone plays a neuroprotective role in EBI after SAH via attenuation of BBB disruption, brain edema and apoptosis. PMID:26220473

  5. [Massive gestational vulvar edema. A case report and review of literature].

    PubMed

    Martí-Gamboa, Sabina; Savirón Cornudella, Ricardo; Campillos-Maza, José Manuel

    2014-09-01

    We report the case of a 22-year-old primiparous, admitted to our hospital with a 2-week history of vulvar edema that had evolved within 24 hours to the point of stopping urine flow and hindering ambulation. The only remarkable finding in relation with the edema was hypoalbuminemia for no apparent cause. The correction of hypoalbuminemia and the establishment of diuretic treatment, with the drainage of the edema allowed for a complete resolution of the edema. PMID:25412558

  6. SUSCEPTIBILITY OF EARLY LIFE STAGES OF THE FOWLER'S TOAD (Anaxyrus fowleri) TO THE TADPOLE EDEMA VIRUS

    E-print Network

    Gray, Matthew

    SUSCEPTIBILITY OF EARLY LIFE STAGES OF THE FOWLER'S TOAD (Anaxyrus fowleri) TO THE TADPOLE EDEMA) - Gosner Stage 36 (Rear limb development) - Gosner Stage 42 (Metamorphosis) . Tadpole edema virus (TEV-metamorphic bufonid toads to the tadpole edema virus. 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7 8 9 10 11 12 13

  7. Nasal Administration of Recombinant Osteopontin Attenuates Early Brain Injury after Subarachnoid Hemorrhage

    PubMed Central

    Topkoru, Basak Caner; Altay, Orhan; Duris, Kamil; Krafft, Paul R.; Yan, Junhao; Zhang, John H.

    2013-01-01

    Background and purpose Neuronal apoptosis is a key pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). Given that recombinant osteopontin (rOPN), a promising neuroprotectant, cannot pass through the blood-brain barrier (BBB), we aimed to examine whether nasal administration of rOPN prevents neuronal apoptosis after experimental SAH. Methods Male Sprague-Dawley rats (n=144) were subjected to the endovascular perforation SAH model. rOPN was administered via the nasal route and neurological scores as well as brain water content were evaluated at 24 and 72 hours after SAH-induction. The expressions of cleaved caspase-3 (CC3), phosphorylated focal adhesion kinase (p-FAK), and phosphorylated Akt (p-Akt) were examined using Western blot analysis. Neuronal cell death was demonstrated with terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL). We also administered FAK inhibitor 14 and phosphatidylinositol 3-kinase (PI3K) inhibitor, Wortmannin, prior to rOPN to establish its neuroprotective mechanism. ELISA was used to measure rOPN delivery into the cerebrospinal fluid (CSF). Results CSF level of rOPN increased after its nasal administration. This was associated with improved neurological scores and reduced brain edema at 24 hours after SAH. rOPN increased p-FAK and p-Akt expressions and decreased caspase-3 cleavage, resulting in attenuation of neuronal cell death within the cerebral cortex. These effects were abolished by FAK inhibitor 14 and Wortmannin. Conclusion Nasal administration of rOPN decreased neuronal cell death and brain edema and improved the neurological status in SAH rats, possibly through FAKPI3K-Akt-induced inhibition of capase-3 cleavage. PMID:24008574

  8. Link between D sub 1 and D sub 2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

    SciTech Connect

    Seeman, P.; Niznik, H.B.; Guan, H.C.; Booth, G.; Ulpian, C. )

    1989-12-01

    Dopamine receptor types D{sub 1} and D{sub 2} can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D{sub 1}-D{sub 2} interaction in homogenized tissue as revealed by ligand binding. D{sub 2} agonists lowered the binding of ({sup 3}H)raclopride to D{sub 2} receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D{sub 1}-selective antagonist SCH 23390 prevented the agonist-induced decrease in ({sup 3}H)raclopride binding to D{sub 2} sites in the striatum but not in the anterior pituitary, which has no D{sub 1} receptors. Conversely, a dopamine-induced reduction in the binding of ({sup 3}H)SCH 23390 to D{sub 1} receptors could be prevented by the D{sub 2}-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D{sub 1}-D{sub 2} interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D{sub 2} receptors in the high-affinity state. Thus, the D{sub 1}-D{sub 2} link may be mediated by guanine nucleotide-binding protein components. The link may underlie D{sub 1}-D{sub 2} interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.

  9. Electrical stimulation as a treatment intervention to improve function, edema or pain following acute lateral ankle sprains: A systematic review.

    PubMed

    Feger, Mark A; Goetschius, John; Love, Hailey; Saliba, Sue A; Hertel, Jay

    2015-11-01

    The purpose of this systematic review was to assess whether electrical stimulation (ES), when used in conjunction with a standard treatment, can reduce levels of functional impairment, edema, and pain compared to a standard treatment alone, in patients following a lateral ankle sprain. We searched PubMed, CINAHL, SportDiscus, and Medline (OVID) databases through June 2014 using the terms "ankle sprain or ankle sprains or ligament injury or ligamentous injury," and "electric stimulation or electric stimulation or electrotherapy." Our search identified four randomized control trials, of which, neuromuscular ES and high-voltage pulsed stimulation were the only two ES modalities utilized. Effect sizes and 95% confidence intervals (CI) were estimated using Cohen's d for comparison between treatment groups. Three of four effect sizes for function had 95% CI that crossed zero. Twenty-four of the thirty-two effect sizes for edema had 95% CI that crossed zero. All effect sizes for pain had 95% CI that crossed zero. Therefore, the use of ES is not recommended as a means to improve function, reduce edema, or decrease pain in the treatment of acute lateral ankle sprains. PMID:25791198

  10. Updates in the Management of Diabetic Macular Edema

    PubMed Central

    Mathew, Christopher; Yunirakasiwi, Anastasia; Sanjay, Srinivasan

    2015-01-01

    Diabetes mellitus is a chronic disease which has multiple effects on different end-organs, including the retina. In this paper, we discuss updates on diabetic macular edema (DME) and the management options. The underlying pathology of DME is the leakage of exudates from retinal microaneurysms, which trigger subsequent inflammatory reactions. Both clinical and imaging techniques are useful in diagnosing, classifying, and gauging the severity of DME. We performed a comprehensive literature search using the keywords “diabetes,” “macula edema,” “epidemiology,” “pathogenesis,” “optical coherence tomography,” “intravitreal injections,” “systemic treatment,” “hypertension,” “hyperlipidemia,” “anemia,” and “renal disease” and collated a total of 47 relevant articles published in English language. The main modalities of treatment currently in use comprise laser photocoagulation, intravitreal pharmacological and selected systemic pharmacological options. In addition, we mention some novel therapies that show promise in treating DME. We also review systemic factors associated with exacerbation or improvement in DME. PMID:25984537

  11. Optical Coherence Tomographic Findings in Berlin’s Edema

    PubMed Central

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra; Bouraoui, Rym; Largueche, Leila; Mghaieth, Fatma

    2010-01-01

    Purpose To describe optical coherence tomography (OCT) findings in a patient with Berlin’s edema following blunt ocular trauma. Case Report A 26-year-old man presented with acute loss of vision in his left eye following blunt trauma. He underwent a complete ophthalmologic examination and OCT. Fundus examination revealed abnormal yellow discoloration in the macula. OCT disclosed thickening of outer retinal structures and increased reflectivity in the area of photoreceptor outer segments with preservation of inner retinal architecture. Re-examination was conducted one month later at the time which OCT changes resolved leading to a surprisingly normal appearance. Conclusion OCT can be a useful tool in the diagnosis and follow-up of eyes with Berlin’s edema and may reveal ultrastructural macular changes. PMID:22737342

  12. A case of subretinal tubercular abscess presenting as disc edema.

    PubMed

    Shetty, Sachin Bermu; Bawtag, Mohammad Abdullah; Biswas, Jyotirmay

    2015-02-01

    We report a case of ocular tuberculosis (TB) which initially presented with disc edema and was mistaken for optic neuritis. With no definite pathology being identified, the patient was treated on the lines of optic neuritis with intravenous (IV) steroid with beneficial effect. Ocular TB was suspected when he presented later with a subretinal abscess. Based on positive Mantoux, QuantiFERON TB gold results and radiographic findings, a diagnosis of subretinal abscess of presumed tubercular etiology was made. The patient was successfully treated with anti-tubercular therapy. To the best of our knowledge, this is the first case report of ocular TB presenting as disc edema followed by subretinal abscess. PMID:25827550

  13. 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. PMID:25901618

  14. Postobstructive pulmonary edema after biopsy of a nasopharyngeal mass

    PubMed Central

    Mehta, Keyur Kamlesh; Ahmad, Sabina Qureshi; Shah, Vikas; Lee, Haesoon

    2015-01-01

    We describe a case of 17 year-old male with a nasopharyngeal rhabdomyosarcoma who developed postobstructive pulmonary edema (POPE) after removing the endotracheal tube following biopsy. He developed muffled voice, rhinorrhea, dysphagia, odynophagia, and difficulty breathing through nose and weight loss of 20 pounds in the preceding 2 months. A nasopharyngoscopy revealed a fleshy nasopharyngeal mass compressing the soft and hard palate. Head and neck MRI revealed a large mass in the nasopharynx extending into the bilateral choana and oropharynx. Biopsy of the mass was taken under general anesthesia with endotracheal intubation. Immediately after extubation he developed oxygen desaturation, which did not improve with bag mask ventilation with 100% of oxygen, but improved after a dose of succinylcholine. He was re-intubated and pink, frothy fluid was suctioned from the endotracheal tube. Chest radiograph (CXR) was suggestive of an acute pulmonary edema. He improved with mechanical ventilation and intravenous furosemide. His pulmonary edema resolved over the next 24 h. POPE is a rare but serious complication associated with upper airway obstruction. The pathophysiology of POPE involves hemodynamic changes occurring in the lung and the heart during forceful inspiration against a closed airway due to an acute or chronic airway obstruction. This case illustrates the importance of considering the development of POPE with general anesthesia, laryngospasm and removal of endotracheal tube to make prompt diagnosis and to initiate appropriate management.

  15. Pathogenesis of edema formation in the nephrotic syndrome.

    PubMed

    Palmer, B F; Alpern, R J

    1997-06-01

    The development of edema in the nephrotic syndrome has traditionally been viewed as an underfill mechanism. According to this view, urinary loss of protein results in hypoalbuminemia and decreased plasma oncotic pressure. As a result, plasma water translocates out of the intravascular space and results in a decrease in intravascular volume. In response to the underfilled circulation, effector mechanisms are then activated that signal the kidney to secondarily retain salt and water. While an underfill mechanism may be responsible for edema formation in a minority of patients, recent clinical and experimental findings would suggest that edema formation in most nephrotic patients is the result of primary salt retention. Direct measurements of blood and plasma volume or measurement of neurohumoral markers that indirectly reflect effective circulatory volume are mostly consistent with either euvolemia or a volume expanded state. The ability to maintain plasma volume in the setting of a decreased plasma oncotic pressure is achieved by alterations in transcapillary exchange mechanisms known to occur in the setting of hypoalbuminemia that limit excessive capillary fluid filtration. The intrarenal mechanism responsible for primary sodium retention is not yet known, but may involve tubular resistance to the natriuretic effect of atrial natriuretic peptide. PMID:9185099

  16. Inhibition of surgically induced miosis and prevention of postoperative macular edema with nepafenac

    PubMed Central

    Cervantes-Coste, Guadalupe; Sánchez-Castro, Yuriana G; Orozco-Carroll, Mónica; Mendoza-Schuster, Erick; Velasco-Barona, Cecilio

    2009-01-01

    Objective: To evaluate the effectiveness of prophylactic administration of nepafenac 0.1% in maintaining mydriasis and in preventing postoperative macular edema following cataract surgery. Methods: This was a prospective, randomized, single-masked comparative study in 60 patients undergoing phacoemulsification cataract surgery. Patients were randomized to either the nepafenac or the control group. Nepafenac was administered 3 times daily 1 day before surgery and continued for 6 weeks. The control group received tobramycin-dexamethasone treatment only. Trans-operative mydriasis was measured before surgery, after nuclear emulsification, following cortex aspiration, and at the conclusion of surgery. Macular optical coherence tomography determined central foveal thickness (FT) and total macular volume (TMV) before surgery and at 2 and 6 weeks after surgery. All patients received tobramycin-dexamethasone for 2 weeks after surgery. Results: The difference in mean pupil size, at the end of surgery, between the control group (6.84 ± 0.93 mm) and the nepafenac group (7.91 ± 0.74 mm) was statistically significant (p < 0.001). There were no significant differences in FT values between the two groups at any time point; however, TMV at 2 and at 6 weeks was statistically significantly different (p < 0.001), with higher TMV in the control group. Conclusion: Prophylactic use of nepafenac was effective in reducing macular edema after cataract surgery and in maintaining trans-operative mydriasis. PMID:19668569

  17. Morphological and functional outcomes following modified early treatment diabetic retinopathy study laser in diabetic macular edema

    PubMed Central

    Raman, Rajiv; Santhanam, Kiruthika; Gella, Laxmi; Pal, Bikramjit P.; Sharma, Tarun

    2015-01-01

    Aim: The aim was to report morphological and functional outcomes following modified early treatment diabetic retinopathy study (ETDRS) laser in diabetic macular edema (DME). Materials and Methods: Structural and functional changes using spectral domain optical coherence tomography (OCT) and microperimetry (MP) were studied before and 4 months after laser in 37 eyes with clinically significant macular edema (ME) requiring modified ETDRS laser treatment. Paired t-test was used to compare pre and postlaser outcomes P < 0.05 was considered statistically significant. Results: Central foveal thickness showed a significant reduction after laser P = 0.004. There was a significant reduction in mean retinal thickness (MRT) and retinal volume in all the quadrants of ETDRS except for the temporal and nasal quadrants in outer 6 mm ring. Maximum reduction in MRT was seen in eyes with DME having neurosensory detachment (382.66 ? to 292.61 ?). Retinal sensitivities reduced in all quadrants following laser, however, fixation patterns showed improvements. The change in VA was positively correlated to change in MRT (r = 0.468, P = 0.032). Conclusion: Laser not only causes structural benefits such as reduction of retinal thickness and volume, it also causes improvement of fixation patterns.

  18. Anti-inflammatory activity of betalain-rich dye of Beta vulgaris: effect on edema, leukocyte recruitment, superoxide anion and cytokine production.

    PubMed

    Martinez, Renata M; Longhi-Balbinot, Daniela T; Zarpelon, Ana C; Staurengo-Ferrari, Larissa; Baracat, Marcela M; Georgetti, Sandra R; Sassonia, Rogério C; Verri, Waldiceu A; Casagrande, Rubia

    2015-04-01

    We have recently developed betalain-rich beetroot (Beta vulgaris) dye (betalain) to be used in food products. Betalain (30-300 mg/kg) intraperitoneal (i.p.) treatment diminished carrageenan (100 µg/paw)-induced paw edema and neutrophil migration to the paw skin tissue. Betalain (100 mg/kg) treatment by subcutaneous or per oral routes also inhibited the carrageenan-induced paw edema. Importantly, the post-treatment with betalain (100 mg/kg, i.p.) significantly inhibited carrageenan- and complete Freund's adjuvant (10 µl/paw)-induced paw edema. Betalain (100 mg/kg) also reduced carrageenan (500 µg/cavity)-induced recruitment of total leukocytes, including mononuclear cells and neutrophils, as well as increasing vascular permeability in the peritoneal cavity. Furthermore, betalain significantly reduced carrageenan-induced superoxide anion, tumor necrosis factor-alpha (TNF-?) and interleukin (IL)-1? levels in the peritoneal fluid, as well as augmenting IL-10 levels. Therefore, this compound presents prominent anti-inflammatory effect on carrageenan-induced paw edema and peritonitis by reducing the production of superoxide anion and the cytokines TNF-? and IL-1?, in addition to increasing IL-10 levels. These results suggest that betalain shows therapeutic potential that could be utilized in the treatment of inflammation-associated diseases. PMID:25173360

  19. Strategy for the Management of Macular Edema in Retinal Vein Occlusion: The European VitreoRetinal Society Macular Edema Study

    PubMed Central

    Adelman, Ron A.; Parnes, Aaron J.; Bopp, Silvia; Saad Othman, Ihab; Ducournau, Didier

    2015-01-01

    Objective. To compare the efficacy of different therapies in the treatment of macular edema associated with retinal vein occlusion (RVO). Design. This is a nonrandomized, multicenter collaborative study. Participants. 86 retina specialists from 29 countries provided clinical information, including choice of treatment and outcome, on 2,603 patients with macular edema including 738 cases of RVO. Methods. Reported data included the type and number of treatments performed, visual acuities, and other clinical and diagnostic findings. Main Outcome Measures. The mean increase in visual acuity and mean number of treatments performed. Results. 358 cases of central retinal vein occlusion (CRVO) and 380 cases of branch retinal vein occlusion (BRVO) were included in this investigation. Taking all RVO cases together, pars plana vitrectomy with internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than other therapies. Those treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injection alone showed the second greatest improvement in vision. Dexamethasone intravitreal implant alone and intravitreal triamcinolone alone both resulted in modest visual gains. Conclusions. In the treatment of macular edema in RVO, vitrectomy with ILM peeling may achieve visual improvement and may be a good option for certain cases. Anti-VEGF injection is the most effective of the nonsurgical treatments. PMID:25705695

  20. Purification of Mouse Brain Vessels.

    PubMed

    Boulay, Anne-Cécile; Saubaméa, Bruno; Declèves, Xavier; Cohen-Salmon, Martine

    2015-01-01

    In the brain, most of the vascular system consists of a selective barrier, the blood-brain barrier (BBB) that regulates the exchange of molecules and immune cells between the brain and the blood. Moreover, the huge neuronal metabolic demand requires a moment-to-moment regulation of blood flow. Notably, abnormalities of these regulations are etiological hallmarks of most brain pathologies; including glioblastoma, stroke, edema, epilepsy, degenerative diseases (ex: Parkinson's disease, Alzheimer's disease), brain tumors, as well as inflammatory conditions such as multiple sclerosis, meningitis and sepsis-induced brain dysfunctions. Thus, understanding the signaling events modulating the cerebrovascular physiology is a major challenge. Much insight into the cellular and molecular properties of the various cell types that compose the cerebrovascular system can be gained from primary culture or cell sorting from freshly dissociated brain tissue. However, properties such as cell polarity, morphology and intercellular relationships are not maintained in such preparations. The protocol that we describe here is designed to purify brain vessel fragments, whilst maintaining structural integrity. We show that isolated vessels consist of endothelial cells sealed by tight junctions that are surrounded by a continuous basal lamina. Pericytes, smooth muscle cells as well as the perivascular astrocyte endfeet membranes remain attached to the endothelial layer. Finally, we describe how to perform immunostaining experiments on purified brain vessels. PMID:26574794

  1. THE PERIVASCULAR POOL OF AQUAPORIN-4 MEDIATES THE EFFECT OF OSMOTHERAPY IN POST-ISCHEMIC CEREBRAL EDEMA

    PubMed Central

    Zeynalov, Emil; Chen, Chih-Hung; Froehner, Stanley C.; Adams, Marvin E.; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood; Bhardwaj, Anish

    2009-01-01

    Objective Osmotherapy with hypertonic saline (HS) ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that HS exerts its anti-edema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 (AQP4) pool. We utilized mice with targeted disruption of the gene encoding ?-syntrophin (?-Syn?/?) that lack the perivascular AQP4 pool but retain the endothelial pool of this protein. Design Prospective laboratory animal study. Setting Research laboratory in a university teaching hospital. Measurements and Main Results Halothane-anesthetized adult male wildtype (WT) C57B/6 and ?-Syn?/? mice were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and treated with either a continuous intravenous infusion of 0.9% saline (NS) or 3% HS (1.5 mL/Kg/hr) for 48 hr. In the first series of experiments (n = 59), brain water content analyzed by wet-to-dry ratios in the ischemic hemisphere of WT mice was attenuated after HS (79.9 ± 0.5%mean ± SEM) but not after NS (82.3 ± 1.0%) treatment. In contrast in ?-Syn?/? mice, HS had no effect on the postischemic edema (HS: 80.3 ± 0.7% NS: 80.3 ± 0.4%). In the second series of experiments (n = 31), treatment with HS attenuated post-ischemic BBB disruption at 48 hr in WT mice but not in ?-Syn?/? mice; ?-Syn deletion alone had no effect on BBB integrity. In the third series of experiments (n=34), ?-Syn?/? mice treated with either HS or NS had smaller infarct volume as compared with their WT counterparts. Conclusions These data demonstrate that: 1) osmotherapy with HS exerts anti-edema effects via the perivascular pool of AQP4 2) HS attenuates BBB disruption depending on the presence of perivascular AQP4, and 3) deletion of the perivascular pool of AQP4 alleviates tissue damage following stroke, in mice subjected to osmotherapy as well as in non-treated mice. PMID:18679106

  2. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell

    PubMed Central

    Wilden, Jessica A.; Qing, Kurt Y.; Hauser, Sheketha R.; McBride, William J.; Irazoqui, Pedro P.; Rodd, Zachary A.

    2015-01-01

    Object There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. Methods In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of ?–aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8–10 rats/group), after which the animals were placed in operant chambers containing 2 levers—one used to administer water and the other to administer 15% EtOH—to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat’s left AcbSh. The animals then received 100 or 200 ?A (3–4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. Results In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 ?A of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Conclusions Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism. PMID:24460492

  3. Treatment with harmine ameliorates functional impairment and neuronal death following traumatic brain injury.

    PubMed

    Zhong, Zeqi; Tao, Yuan; Yang, Hui

    2015-12-01

    Traumatic brain injury (TBI) is a leading cause of mortality in young individuals, and results in motor and cognitive deficiency. Excitotoxicity is an important process during neuronal cell death, which is caused by excessive release of glutamate following TBI. Astrocytic glutamate transporters have a predominant role in maintaining extracellular glutamate concentrations below excitotoxic levels, and glutamate transporter 1 (GLT?1) may account for >90% of glutamate uptake in the brain. The ??carboline alkaloid harmine has been demonstrated to exert neuroprotective actions in vivo, and the beneficial effects were specifically due to elevation of GLT?1. However, whether harmine provides neuroprotection following TBI remains to be elucidated. The present study performed intraperitoneal harmine injections in rats (30 mg/kg per day for up to 5 days), in order to investigate whether harmine treatment attenuates brain edema and improves functional recovery in a rat model of TBI. The neuronal survival ratio and the protein expression of apoptosis?associated caspase 3 were also assessed in the hippocampus of the rat brain. Furthermore, the expression levels of GLT?1 and inflammatory cytokines were detected, in order to determine the underlying mechanisms. The results of the present study demonstrated that administration of harmine significantly attenuated cerebral edema, and improved learning and memory ability. In addition, harmine significantly increased the protein expression of GLT?1, and markedly attenuated the expression levels of interleukin?1? and tumor necrosis factor??, thereby attenuating apoptotic neuronal death in the hippocampus. These results provided in vivo evidence that harmine may exert neuroprotective effects by synergistically reducing excitotoxicity and inflammation following TBI. PMID:26496827

  4. Chronic treatment with novel brain-penetrating selective NOP receptor agonist MT-7716 reduces alcohol drinking and seeking in the rat.

    PubMed

    Ciccocioppo, Roberto; Stopponi, Serena; Economidou, Daina; Kuriyama, Makoto; Kinoshita, Hiroshi; Heilig, Markus; Roberto, Marisa; Weiss, Friedbert; Teshima, Koji

    2014-10-01

    Since its discovery, the nociceptin/orphanin FQ (N/OFQ)-NOP receptor system has been extensively investigated as a promising target to treat alcoholism. Encouraging results obtained with the endogenous ligand N/OFQ stimulated research towards the development of novel brain-penetrating NOP receptor agonists with a pharmacological and toxicological profile compatible with clinical development. Here we describe the biochemical and alcohol-related behavioral effects of the novel NOP receptor agonist MT-7716. MT-7716 has high affinity for human NOP receptors expressed in HEK293 cells with a Ki value of 0.21 nM. MT-7716 concentration-dependently stimulated GTP?(35)S binding with an EC50 value of 0.30 nM and its efficacy was similar to N/OFQ, suggesting that MT7716 is a full agonist at NOP receptors. In the two bottle choice test MT-7716 (0, 0.3, 1, and 3 mg/kg, bid) given orally for 14 days dose-dependently decreased voluntary alcohol intake in Marchigian Sardinian rats. The effect became gradually stronger following repeated administration, and was still significant 1 week after discontinuation of the drug. Oral naltrexone (30 mg/kg, bid) for 14 days also reduced ethanol intake; however, the effect decreased over the treatment period and rapidly disappeared when drug treatment was discontinued. MT-7716 is also effective for preventing reinstatement caused by both ethanol-associated environmental stimuli and stress. Finally, to investigate the effect of MT-7716 on alcohol withdrawal symptoms, Wistar rats were withdrawn from a 7-day alcohol liquid diet. MT-7716 significantly attenuated somatic alcohol withdrawal symptoms. Together these findings indicate that MT-7716 is a promising candidate for alcoholism treatment remaining effective with chronic administration. PMID:24863033

  5. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.

    PubMed

    Ho, April J; Stein, Jason L; Hua, Xue; Lee, Suh; Hibar, Derrek P; Leow, Alex D; Dinov, Ivo D; Toga, Arthur W; Saykin, Andrew J; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J; Craig, David W; Gerber, Jill D; Allen, April N; Corneveaux, Jason J; Stephan, Dietrich A; DeCarli, Charles S; DeChairo, Bryan M; Potkin, Steven G; Jack, Clifford R; Weiner, Michael W; Raji, Cyrus A; Lopez, Oscar L; Becker, James T; Carmichael, Owen T; Thompson, Paul M

    2010-05-01

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes-these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

  6. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

    PubMed Central

    Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

    2010-01-01

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

  7. Acute pulmonary edema secondary to hyperbaric oxygen therapy

    PubMed Central

    Obiagwu, Chukwudi; Paul, Vishesh; Chadha, Sameer; Hollander, Gerald; Shani, Jacob

    2015-01-01

    Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of diabetic ulcers, air embolism, carbon monoxide poisoning and gas gangrene with minimal adverse effects. Very few cases of HBOT causing acute pulmonary edema (PE) has been described; with a study on dogs suggesting that a complication of this therapy could be PE. We describe the case of an 80-year-old man with a history of stable systolic heart failure and diabetes mellitus presenting with acute PE following treatment with HBOT for diabetic foot. PMID:25988073

  8. Acute pulmonary edema secondary to hyperbaric oxygen therapy.

    PubMed

    Obiagwu, Chukwudi; Paul, Vishesh; Chadha, Sameer; Hollander, Gerald; Shani, Jacob

    2015-02-01

    Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of diabetic ulcers, air embolism, carbon monoxide poisoning and gas gangrene with minimal adverse effects. Very few cases of HBOT causing acute pulmonary edema (PE) has been described; with a study on dogs suggesting that a complication of this therapy could be PE. We describe the case of an 80-year-old man with a history of stable systolic heart failure and diabetes mellitus presenting with acute PE following treatment with HBOT for diabetic foot. PMID:25988073

  9. Use of antivascular endothelial growth factor for diabetic macular edema

    PubMed Central

    Karim, Rushmia; Tang, Benjamin

    2010-01-01

    Background Diabetic macular edema (DME) is one of the manifestations of diabetic retinopathy leading to loss of central vision and visual acuity. It manifests itself with swelling around the central part of the retina, the area responsible for sharp vision. Current treatment includes laser therapy and intravitreal steroids with preventative measures including diabetes control. No one treatment has guaranteed control of diabetic macular edema which leads to deteriorating visual acuity, function and quality of life in patients. Vascular endothelial growth factor (VEGF) has been shown to be a critical stimulus in the pathogenesis of macular edema secondary to diabetes.1 Antiangiogenic therapy encompassed treatment with anti-VEGF which inhibits VEGF-driven neovascularization hence macular edema leading to decreased visual acuity. Objective For this review, we evaluated the effectiveness of intravitreal anti-VEGF in treating DME. Data sources We identified five trials (n = 525) using electronic databases (Cochrane Central Register of Controlled Trials [Central], Medline®, and Excerpta Medica Database [EMBASE®]) in October 2008, supplemented by hand searching of reference lists, review articles, and conference abstracts. Methods We included all randomized clinical trials (RCTs) evaluating any form of intravitreal anti-VEGF for treating DME. The main outcome factor was change in best-corrected visual acuity and central macular thickness. One author assessed eligibility, methodological quality, and extracted data. Meta analysis was performed when appropriate. Results We included three trials of adequate methodological quality in our meta-analysis. Patients treated with anti-VEGF showed improvement in visual acuity of ?0.17 (95% confidence interval [CI]: ?0.23, ?0.10) and central macular thickness ?84.69 (95% CI: ?117.09, ?52.30). Patients treated with combined anti-VEGF and intravitreal triamcinolone showed improvement of visual acuity of ?0.19 (95% CI: ?0.27, ?0.11) and central macular thickness mean change being –111.20 (95% CI: ?148.13, ?74.28). Conclusions Anti-VEGF has been associated with an improvement in visual acuity and central macular thickness in the analysis, however trial analysis was of a short duration and further research is needed to determine long-term benefits. PMID:20535227

  10. [Acute recurring Quincke edema in allergy to malt extract].

    PubMed

    Wüthrich, B

    1984-02-25

    The case is reported of a 19-year-old patient with recurrent Quincke edema with systemic symptoms. Based on observations of the course, diary entries and specific skin tests (scratch), sensitization to malt extract from germinated barley was diagnosed. The allergic reactions usually occurred after consumption of malt-containing chocolate drinks and malt-containing snack products. In cooperation with Prof. S. G. O. JOHANSSON, Stockholm, we have for the first time identified specific serum IgE antibodies against malt extract. PMID:6710112

  11. Intravitreal Corticosteroids in the Management of Diabetic Macular Edema

    PubMed Central

    Flynn, Harry W.; Scott, Ingrid U.

    2013-01-01

    Diabetic macular edema (DME) remains an important worldwide cause of visual loss. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants. At this time, no steroid is approved by the United States Food and Drug Administration (FDA) for the treatment of DME. PMID:24224143

  12. [Lower limb edema and steatorrhea: value of scintigraphic technics].

    PubMed

    Bourgeois, P; Munck, D; Leduc, O

    2003-04-01

    The authors report the case of a young woman with right lower limb edema who also presented one steatorrhea. Her clinical history is typical for one primary lymphedema and the lymphoscintigraphic investigation of the lower limbs confirms the diagnosis. The scan showed the absence of the right iliac and lomboaortic lymph nodes but also that the thoracic duct was normally present. One C14-triolein breath test is pathological and proves the malabsorption of the fats. The authors discuss the interest of the scintigraphic techniques in such case and review the problem of the association between lower limb lymphedemas and fatty malabsorption. PMID:12806877

  13. Role of histamine receptors in the regulation of edema and circulation postburn.

    PubMed

    Räntfors, Johanna; Cassuto, Jean

    2003-12-01

    Despite histamine being a potent endogenous vasoactive agent released in increasing amounts postburn, its role in postburn oedema formation has been controversial and its effect on burn circulation poorly investigated. The present study investigated the involvement of H(1), H(2) and H(3) receptors in postburn edema in rats exposed to skin and muscle burns and their influence on skin circulation postburn. We used the selective antagonists clemastine (H(1)), ranitidine (H(2)), thioperamide (H(3)) and the selective H(3) receptor agonist, imetit. Results showed that none of the antagonists or the H(3) agonist had significant effect on postburn edema measured by quantitative spectrophotometric analysis of extravasated Evans blue-albumin in the full-thickness burned skin or muscle. Clemastine and thioperamide failed to induce significant effect on blood flow in the partial- or full-thickness skin burn injury as measured by laser Doppler flowmetry, while ranitidine significantly (P<0.01) reduced blood flow in the full-thickness burn. In contrast, the H(3) receptor agonist, imetit, significantly increased blood flow, both in the partial-thickness burn injury (P<0.05) and in the full-thickness burn (P<0.01). Moreover, imetit significantly (P<0.01) increased mean arterial pressure while thioperamide significantly (P<0.01) reduced systemic pressure. In conclusion, H(1), H(2) and H(3) receptors are not important actors in the regulation of vascular patency permeability, whereas H(3) receptors play an important role by increasing skin circulation postburn, presumably by relaxation of vascular smooth muscle and/or by interacting with other inflammatory neurotransmitters. Data also suggest that H(2) receptor blockers may not be best choice for stress ulcer prophylaxis in burn patients. PMID:14636750

  14. Diffusion Imaging of Brain Tumors

    PubMed Central

    Maier, Stephan E.; Sun, Yanping; Mulkern, Robert V.

    2010-01-01

    MR imaging offers a tremendous armamentarium of different methods that can be employed in brain tumor characterization. MR diffusion imaging has become a widely accepted method for probing the presence of fluid pools and molecular tissue water mobility. For most clinical applications of diffusion imaging, it is assumed that the diffusion signal vs diffusion weighting factor b decays monoexponentially. Within this framework, measurement of a single diffusion coefficient in brain tumors permits an approximate categorization of tumor type and for some tumors definitive diagnosis. In most brain tumors, when compared to normal brain tissue, the diffusion coefficient is elevated. The presence of peritumoral edema, which also exhibits an elevated diffusion coefficient, often precludes delineation of the tumor based on diffusion information alone. Serially obtained diffusion data is useful to document and even predict cellular response to drug or radiation therapy. Diffusion measurements in tissues over an extended range of b-factors have clearly shown that the mono-parametric description of the MR diffusion signal decay is incomplete. Very high diffusion weighting on clinical systems requires substantial compromise in spatial resolution. But after suitable analysis, superior separation of malignant brain tumors, peritumoral edema, and normal brain tissue can be achieved. These findings are also discussed in light of tissue-specific differences in membrane structure and the restrictions membranes exert on diffusion. Finally, measurement of the directional dependence of diffusion permits assessment of white matter integrity and dislocation. Such information, particularly in conjunction with advanced post-processing, is considered immensely useful for therapy planning. Diffusion imaging, which permits monoexponential analysis and provides directional diffusion information, is performed routinely in brain tumor patients. More advanced methods require improvement in acquisition speed and spatial resolution to gain clinical acceptance. PMID:20886568

  15. He-Ne laser treatment for 16 cases of nonspecific edema

    NASA Astrophysics Data System (ADS)

    Xia, Wenlou; Liu, Sixian; Cao, Guangyi; Chen, Zhifu; Zhang, Haishui; Wei, Wei; Xia, Xinshe; Sia, Guangyu

    1993-03-01

    Nonspecific edema is a syndrome which is caused by a metabolism disorder of sodium and water. The people who suffer with this are mostly women about 25 - 50 years old. When it happens periodic edema, abdominal distension acratia, and obesity accompany the disease. Through several means of examination, no organic disease was found in the heart, liver, or kidney. Now 16 edema cases have been irradiated with laser and the result is satisfactory. The results are reported in this paper.

  16. In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury

    NASA Astrophysics Data System (ADS)

    Xu, Zhun; Zhu, Quing; Wang, Lihong V.

    2011-06-01

    For the first time, we have implemented photoacoustic tomography (PAT) to image the water content of an edema in vivo. We produced and imaged a cold-induced cerebral edema transcranially, then obtained blood vessel and water accumulation images at 610 and 975 nm, respectively. We tracked the changes at 12, 24, and 36 h after the cold injury. The blood volume decreased after the cold injury, and the maximum area of edema was observed 24 h after the cold injury. We validated PAT of the water content of the edema through magnetic Resonance Imaging and the water spectrum from the spectrophotometric measurement.

  17. Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet.

    PubMed

    Haj-Yasein, Nadia Nabil; Vindedal, Gry Fluge; Eilert-Olsen, Martine; Gundersen, Georg Andreas; Skare, Øivind; Laake, Petter; Klungland, Arne; Thorén, Anna Elisabeth; Burkhardt, John Michael; Ottersen, Ole Petter; Nagelhus, Erlend Arnulf

    2011-10-25

    Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement. PMID:21990350

  18. Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema

    PubMed Central

    Peng, Ying-Jie; Makarenko, Vladislav V.; Nanduri, Jayasri; Vasavda, Chirag; Raghuraman, Gayatri; Yuan, Guoxiang; Gadalla, Moataz M.; Kumar, Ganesh K.; Snyder, Solomon H.; Prabhakar, Nanduri R.

    2014-01-01

    Oxygen (O2) sensing by the carotid body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure. Humans and animals exhibit substantial interindividual variation in this chemosensory reflex response, with profound effects on cardiorespiratory functions. However, the underlying mechanisms are not known. Here, we report that inherent variations in carotid body O2 sensing by carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling contribute to reflex variation in three genetically distinct rat strains. Compared with Sprague-Dawley (SD) rats, Brown-Norway (BN) rats exhibit impaired carotid body O2 sensing and develop pulmonary edema as a consequence of poor ventilatory adaptation to hypobaric hypoxia. Spontaneous Hypertensive (SH) rat carotid bodies display inherent hypersensitivity to hypoxia and develop hypertension. BN rat carotid bodies have naturally higher CO and lower H2S levels than SD rat, whereas SH carotid bodies have reduced CO and greater H2S generation. Higher CO levels in BN rats were associated with higher substrate affinity of the enzyme heme oxygenase 2, whereas SH rats present lower substrate affinity and, thus, reduced CO generation. Reducing CO levels in BN rat carotid bodies increased H2S generation, restoring O2 sensing and preventing hypoxia-induced pulmonary edema. Increasing CO levels in SH carotid bodies reduced H2S generation, preventing hypersensitivity to hypoxia and controlling hypertension in SH rats. PMID:24395806

  19. Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

    PubMed

    Rosas-Hernandez, H; Ramirez, M; Ramirez-Lee, M A; Ali, S F; Gonzalez, C

    2015-08-20

    The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of these effects have been reported in vivo. The aim of this study was to evaluate the role of PRL in the maintenance of the BBB in the rat. Male Wistar rats were treated with Bromocriptine (Bromo) to inhibit PRL production for 28days in the absence or presence of lipopolysaccharide (LPS). BBB permeability was evaluated through the Evans Blue dye and fluorescein-dextran extravasation as well as through edema formation. The expression of claudin-5, occludin, glial fibrillary acidic protein (GFAP) and the PRL receptor (PRLR) was evaluated through western blot. Bromo reduced the physiological levels of PRL at 28days. At the same time, Bromo increased BBB permeability and edema formation associated with a decrement in claudin-5 and occludin and potentiated the increase in BBB permeability induced by LPS. However, no neuroinflammation was detected, since the expression of GFAP was unchanged, as well as the expression of the PRLR. These data provide the first evidence that inhibition of PRL with Bromo affects the maintenance of the BBB through modulating the expression of tight junction proteins in vivo. PMID:26047726

  20. [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced Hypertension].

    PubMed

    Aida, Junko; Okutani, Hiroai; Oda, Yutaka; Okutani, Ryu

    2015-08-01

    A 27-year-old woman with mental retardation was admitted to a nearby hospital for an abrupt onset of seizure. Physical examination revealed remarkable hypertension and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH) accompanied by eclampsia. She was orotracheally intubated because of refractory seizure and hypoxemia, and transferred to our hospital for further treatment. Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the left posterior cerebrum by brain MRI. No abnormal findings were detected in the fetus, with heart rate of 150 beats x min. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean section under general anesthesia was scheduled. A male newborn was delivered with Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of nicardipine for controlling hypertension. Chest X-P on completion of surgery revealed remarkably alleviated pulmonary edema. She received intensive treatment and continued positive pressure ventilation for four days after delivery. She recovered with no neurological deficits and her child was well without any complications. PMID:26442424

  1. Comparison of intravitreal bevacizumab and triamcinolone acetonide theraphies for diffuse diabetic macular edema

    PubMed Central

    Aksoy, Sibel; Yilmaz, Gursel; Akkoyun, Imren; Yazici, Ayse Canan

    2015-01-01

    AIM To compare therapeutic effects of intravitreal triamcinolone acetonide (IVTA) versus intravitreal bevacizumab (IVB) injections for bilateral diffuse diabetic macular edema (DDME). METHODS Forty eyes of 20 patients with bilateral DDME participated in this study. For each patient, 4 mg/0.1 mL IVTA was injected to one eye and 2.5 mg/0.1 mL IVB was injected to the other eye. The effects of injection for diabetic macular edema (DME) were evaluated using best-corrected visual acuity (BCVA), central macular thickness (CMT) by optical coherence tomography (OCT) and intraocular pressure (IOP) by applanation tonometer. Patients underwent eye examinations, including BCVA, CMT, and IOP at pre-injection, 1, 4, 8, 12 and 24wk after injection. During the follow-up, second injections were performed to eyes which have CMT greater than 400 µm at 12wk for salvage therapy. RESULTS BCVA (logarithm of the minimum angle of resolution) at pre-injection, 1, 4, 8, 12 and 24wk after injection was 0.71±0.19, 0.62±0.23, 0.63±0.12, 0.63±0.13, 0.63±0.14 and 0.61±0.24 in the IVTA group and 0.68±0.25, 0.61±0.22, 0.60±0.24, 0.62±0.25, 0.65±0.26 and 0.59±0.25 in the IVB group, respectively. CMT (µm) at pre-injection, 1, 4, 8, 12 and 24wk after injection was 544±125, 383±96, 335±87, 323±87, 333±92, 335±61 in the IVTA group and 514±100, 431±86, 428±107, 442±106, 478±112, 430±88 in the IVB group respectively. Reduction ratios of mean CMT were 29% at 1wk, 38% at 4wk, 40% at 8wk, 38% at 12wk, and 38% at 24wk in the IVTA group. Second IVTA injections were performed to the 6 eyes (30%) at 12wk. Reduction ratios of mean CMT were 16% at 1wk, 17% at 4wk, 14% at 8wk, 7% at 12wk, and 16% at 24wk in the IVB group. Second IVB injections were performed to the 15 eyes (75%) at 12wk. CONCLUSION This study showed earlier and more frequent macular edema recurrences in the eyes treated with bevacizumab compared with the ones treated with triamcinolone acetonide. Triamcinolone acetonide was found to provide more efficient and long-standing effect in terms of reducing CMT compared with the bevacizumab. PMID:26086006

  2. Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Purpose To compare two laser photocoagulation techniques for treatment of diabetic macular edema (DME): modified-ETDRS direct/grid photocoagulation (mETDRS) and a, potentially milder, but potentially more extensive, mild macular grid (MMG) laser technique in which small mild burns are placed throughout the macula, whether or not edema is present, and microaneurysms are not treated directly. Methods 263 subjects (mean age 59 years) with previously untreated DME were randomly assigned to receive laser photocoagulation by mETDRS (N=162 eyes) or MMG (N=161 eyes) technique. Visual acuity, fundus photographs and OCT measurements were obtained at baseline and after 3.5, 8, and 12 months. Treatment was repeated if DME persisted. Main Outcome Measure Change in OCT measures at 12-months follow up. Results From baseline to 12 months, among eyes with baseline central subfield thickness ? 250 microns, central subfield thickening decreased by an average of 88 microns in the mETDRS group and decreased by 49 microns in the MMG group (adjusted mean difference: 33 microns, 95% confidence interval 5 to 61 microns, P=0.02). Weighted inner zone thickening by OCT decreased by 42 and 28 microns, respectively (adjusted mean difference: 14 microns, 95% confidence interval 1 to 27 microns, P=0.04), maximum retinal thickening (maximum of the central and four inner subfields) decreased by 66 and 39 microns, respectively (adjusted mean difference: 27 microns, 95% confidence interval 6 to 47 microns, P=0.01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference: 0.3 mm3, 95% confidence interval 0.02 to 0.53 mm3, P=0.03). At 12 months, the mean change in visual acuity was 0 letters in the mETDRS group and 2 letters worse in the MMG group (adjusted mean difference: 2 letters, 95% confidence interval ?0.5 to 5 letters, P=0.10). Conclusions At 12 months after treatment, the MMG technique is less effective at reducing OCT measured retinal thickening than the more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

  3. VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema

    NASA Technical Reports Server (NTRS)

    Schaffartzik, W.; Poole, D. C.; Derion, T.; Tsukimoto, K.; Hogan, M. C.; Arcos, J. P.; Bebout, D. E.; Wagner, P. D.

    1992-01-01

    Ventilation-perfusion (VA/Q) inequality has been shown to increase with exercise. Potential mechanisms for this increase include nonuniform pulmonary vasoconstriction, ventilatory time constant inequality, reduced large airway gas mixing, and development of interstitial pulmonary edema. We hypothesized that persistence of VA/Q mismatch after ventilation and cardiac output subside during recovery would be consistent with edema; however, rapid resolution would suggest mechanisms related to changes in ventilation and blood flow per se. Thirteen healthy males performed near-maximal cycle ergometry at an inspiratory PO2 of 91 Torr (because hypoxia accentuates VA/Q mismatch on exercise). Cardiorespiratory variables and inert gas elimination patterns were measured at rest, during exercise, and between 2 and 30 min of recovery. Two profiles of VA/Q distribution behavior emerged during heavy exercise: in group 1 an increase in VA/Q mismatch (log SDQ of 0.35 +/- 0.02 at rest and 0.44 +/- 0.02 at exercise; P less than 0.05, n = 7) and in group 2 no change in VA/Q mismatch (n = 6). There were no differences in anthropometric data, work rate, O2 uptake, or ventilation during heavy exercise between groups. Group 1 demonstrated significantly greater VA/Q inequality, lower vital capacity, and higher forced expiratory flow at 25-75% of forced vital capacity for the first 20 min during recovery than group 2. Cardiac index was higher in group 1 both during heavy exercise and 4 and 6 min postexercise. However, both ventilation and cardiac output returned toward baseline values more rapidly than did VA/Q relationships. Arterial pH was lower in group 1 during exercise and recovery. We conclude that greater VA/Q inequality in group 1 and its persistence during recovery are consistent with the hypothesis that edema occurs and contributes to the increase in VA/Q inequality during exercise. This is supported by observation of greater blood flows and acidosis and, presumably therefore, higher pulmonary vascular pressures in such subjects.

  4. Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia

    PubMed Central

    Ren, Changhong; Li, Ning; Wang, Brian; Yang, Yong; Gao, Jinhuan; Li, Sijie; Ding, Yuchuan; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke. PMID:26618042

  5. HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor

    SciTech Connect

    Martin-Garcia, Julio . E-mail: julio.martin-garcia@drexelmed.edu; Cao, Wei; Varela-Rohena, Angel; Plassmeyer, Matthew L.; Gonzalez-Scarano, Francisco

    2006-03-01

    We previously described envelope glycoproteins of an HIV-1 isolate adapted in vitro for growth in microglia that acquired a highly fusogenic phenotype and lower CD4 dependence, as well as resistance to inhibition by anti-CD4 antibodies. Here, we investigated whether similar phenotypic changes are present in vivo. Envelope clones from the brain and spleen of an HIV-1-infected individual with neurological disease were amplified, cloned, and sequenced. Phylogenetic analysis demonstrated clustering of sequences according to the tissue of origin, as expected. Functional clones were then used in cell-to-cell fusion assays to test for CD4 and co-receptor utilization and for sensitivity to various antibodies and inhibitors. Both brain- and spleen-derived envelope clones mediated fusion in cells expressing both CD4 and CCR5 and brain envelopes also used CCR3 as co-receptor. We found that the brain envelopes had a lower CD4 dependence, since they efficiently mediated fusion in the presence of low levels of CD4 on the target cell membrane, and they were significantly more resistant to blocking by anti-CD4 antibodies than the spleen-derived envelopes. In contrast, we observed no difference in sensitivity to the CCR5 antagonist TAK-779. However, brain-derived envelopes were significantly more resistant than those from spleen to the fusion inhibitor T-1249 and concurrently showed slightly greater fusogenicity. Our results suggest an increased affinity for CD4 of brain-derived envelopes that may have originated from in vivo adaptation to replication in microglial cells. Interestingly, we note the presence of envelopes more resistant to a fusion inhibitor in the brain of an untreated, HIV-1-infected individual.

  6. Over-hydration detection in brain by magnetic induction spectroscopy

    NASA Astrophysics Data System (ADS)

    González, César A.; Pérez, María; Hevia, Nidiyare; Arámbula, Fernándo; Flores, Omar; Aguilar, Eliot; Hinojosa, Ivonne; Joskowicz, Leo; Rubinsky, Boris

    2010-04-01

    Detection and continuous monitoring of edema in the brain in early stages is useful for assessment of medical condition and treatment. We have proposed a solution in which the bulk measurements of the tissue electrical properties to detect edema or in general accumulation of fluids are made through measurement of the magnetic induction phase shift between applied and measured currents at different frequencies (Magnetic Induction Spectroscopy; MIS). Magnetic Resonant Imaging (MRI) has been characterized because its capability to detect different levels of brain tissue hydration by differences in diffusion-weighted (DW) sequences and it's involve apparent diffusion coefficient (ADC). The objective of this study was to explore the viability to use measurements of the bulk tissue electrical properties to detect edema or in general accumulation of fluids by MIS. We have induced a transitory and generalized tissue over-hydration condition in ten volunteers ingesting 1.5 to 2 liters of water in ten minutes. Basal and over-hydration conditions were monitored by MIS and MRI. Changes in the inductive phase shift at certain frequencies were consistent with changes in the brain tissue hydration level observed by DW-ADC. The results suggest that MIS has the potential to detect pathologies associated to changes in the content of fluids in brain tissue such as edema and hematomas.

  7. Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Bernstock, Joshua D.; Klimanis, Dace; Wang, Sixian; Spatz, Maria; Maric, Dragan; Johnson, Kory; Klinman, Dennis M.; Li, Xiaohong; Li, Xinhui; Hallenbeck, John M.

    2015-01-01

    The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1?. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1? production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1?, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies. PMID:26473731

  8. Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

    PubMed Central

    Wei, Ji-Fu; Wei, Xiao-Long; Mo, Ya-Zhen; He, Shao-Heng

    2009-01-01

    Background It has been recognized that phospholipase A2 (PLA2) is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA2 provoke inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops mucrosquamatus crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation. Results The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation. Conclusion TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation. PMID:19400930

  9. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    PubMed Central

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ?6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ?6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ?15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ?25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2%). Dexamethasone intravitreal implant offers a viable treatment option for DME, especially in cases that are persistent or treatment (anti-vascular endothelial growth factor/laser) refractory. PMID:26213460

  10. Burn plasma transfer induces burn edema in healthy rats.

    PubMed

    Kremer, Thomas; Abé, Dorotheé; Weihrauch, Marc; Peters, Christopher; Gebhardt, Martha Maria; Germann, Guenter; Heitmann, Christoph; Walther, Andreas

    2008-10-01

    Thermal injuries greater than 20% body surface area (BSA) result in systemic shock with generalized edema in addition to local tissue destruction. Burn shock is induced by a variety of mediators, mainly immunomodulative cytokines. This experimental study evaluates if burn shock can be induced in healthy rats by transfer of burn plasma (BP) with mediators. Thermal injury was induced by hot water (100 degrees C water, 12 s, 30% BSA) in male syngenic Wistar rats. Donor rats were killed 4 h posttrauma, and BP was harvested. Burn plasma was transferred to healthy animals by continuous intravenous infusion in three types of dilution (100%, 10%, and 1%). Positive controls were directly examined 4 h after thermal injury, and negative control rats had a continuous infusion done with sham burn (SB) plasma (37 degrees C water, 12 s, 30% BSA). Afterwards, intravital fluorescence microscopy was performed in postcapillary mesenteric venules at 0, 60, and 120 min. Edema formation was assessed by relative changes over time in fluorescence intensity of fluorescein isothiocyanate-albumin in the intravascular versus the extravascular space. The interactions of leucocytes and endothelium were evaluated by quantification of leukocyte sticking. Additionally, microhemodynamic (volumetric blood flow, erythrocyte velocity, venular wall shear rate, venular diameters) and macrohemodynamic parameters (blood pressure, heart frequency, temperature) were assessed online (arterial catheter). For statistics, an ANOVA was performed with Bonferroni adjustment procedure. Differences were considered significant when P < 0.05. There are no statistically significant differences in microhemodynamics or macrohemodynamics between study groups. Burn plasma infusion and thermal injury lead to significant increases in fluorescein isothiocyanate-albumin extravasation, whereas SB plasma shows no significant changes. Even BP diluted in 0.9% saline (10% and 1%) results in a similar transvascular flux of plasma proteins as direct thermal injury. Differences between positive controls and BP infusion are not significant, whereas all groups are statistically different from the SB group (P<0.05). Leukocyte sticking is significantly increased in all groups except the SB group, and the number of adherent leukocytes is dose dependent. The present study demonstrates that as early as 4 h after thermal injury, there are sufficient factors (e.g., cytokines) in BP to induce systemic burn shock in healthy rats even in diluted plasma (1%). However, the "key" cytokines are not identified at this point. The burned tissue is no longer required for burn shock induction, and the pathophysiologic process seems to be self-perpetuating as early as 4 h posttrauma. Leukocytes are activated by thermal injury and BP infusion. The role of leukocyte-endothelium interactions for edema formation remains uncertain and requires further investigation. PMID:18323747

  11. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema

    PubMed Central

    2015-01-01

    BACKGROUND The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. METHODS At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. RESULTS From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P = 0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P = 0.003 for aflibercept vs. ranibizumab, and P = 0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P = 0.40), hospitalization (P = 0.51), death (P = 0.72), or major cardiovascular events (P = 0.56). CONCLUSIONS Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.) PMID:25692915

  12. A neonate with hand, foot, and mouth disease complicated with brainstem encephalitis and pulmonary edema:A complete recovery

    PubMed Central

    Guo, Shi-Jie; Wang, Dong-Xuan; Dai, Chun-Lai; Wu, Hui

    2014-01-01

    Hand, foot, and mouth disease (HFMD) with serious complications and fatal cases have been reported over the last decade worldwide. The authors report a rare case of HFMD in a neonate complicated with brainstem encephalitis and pulmonary edema. She had fever, lethargy, dyspnea. Physical examination revealed shock signs, fine rales on both lungs, absent Moro reflex. The patient had a rapidly progressive course with seizures, coma, no spontaneous breathing, chemosis. There were some vesicles on left sole and red maculopapular rashes on perianal skin. She had a history of exposure to HFMD. Fecal sample was positive for EV71 RNA by real-time PCR. Chest X-rays showed bilateral pulmonary infiltrates. MRI of the brain showed significant hypointensity in the brainstem on T1WI and hyperintensity on T2WI. She recovered well. This case highlights severe HFMD in neonates is rare. Medical history and physical examination are important in making diagnosis. PMID:25097545

  13. Brain herniation

    MedlinePLUS

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  14. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    SciTech Connect

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-? and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ? Carvedilol possesses promising anti-arthritic properties. ? It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ? It abrogated the leukocyte invasion to air pouch exudates and linings. ? It reduced/normalized oxidative stress markers in sera and exudates of arthritic rats. ? It also mitigated the release of proinflammatory cytokines and eicosanoids.

  15. The Effect of Postsurgical Edema of the Knee Joint on Reflex Inhibition of the Quadriceps Femoris

    E-print Network

    McDonough, Andrew L.; Weir, Joseph P.

    1996-01-01

    The purpose of this case study was to investigate reflex inhibition of the quadriceps femoris in a subject with postsurgical edema of the left knee. The subject was a 45-year-old male with a traumatic knee injury with resultant edema who underwent...

  16. Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits

    SciTech Connect

    Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.

    1981-01-01

    In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a /sup 24/Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

  17. [The diabetic macular edema--new possibilities of the treatment].

    PubMed

    Studnicka, J

    2012-05-01

    The article summarizes data from the literature about new possibilities of the diabetic macular edema treatment. Comparing intravitreal application of triamcinolone and laser photocoagulation, the better effect of the laser treatment with its lower side effects was proven. In combined treatment of triamcinolone and laser photocoagulation comparing with the laser monotherapy, no better effect of the combined therapy was proven. The intravitreal implant releasing fluocinolone acetonide significantly improved the best-corrected visual acuity (BCVA), but caused cataract progression and elevation of the intraocular pressure. Intravitreal application of ranibizumab significantly improved BCVA in the monotherapy, and in the combination with the retinal laser photocoagulation did as well. Intravitreal application of bevacizumab significantly improved BCVA, but its use is off-label only. Aflibercept is in the final stage of clinical trails. PMID:22913868

  18. Diabetic Macular Edema: Pathophysiology and Novel Therapeutic Targets.

    PubMed

    Das, Arup; McGuire, Paul G; Rangasamy, Sampathkumar

    2015-07-01

    Diabetic macular edema (DME) is the major cause of vision loss in diabetic persons. Alteration of the blood-retinal barrier is the hallmark of this disease, characterized by pericyte loss and endothelial cell-cell junction breakdown. Recent animal and clinical studies strongly indicate that DME is an inflammatory disease. Multiple cytokines and chemokines are involved in the pathogenesis of DME, with multiple cellular involvement affecting the neurovascular unit. With the introduction of anti-vascular endothelial growth factor (VEGF) agents, the treatment of DME has been revolutionized, and the indication for laser therapy has been limited. However, the response to anti-VEGF drugs in DME is not as robust as in proliferative diabetic retinopathy, and many patients with DME do not show complete resolution of fluid despite multiple intravitreal injections. Potential novel therapies targeting molecules other than VEGF and using new drug-delivery systems currently are being developed and evaluated in clinical trials. PMID:25935789

  19. Pulmonary embolism presenting as high-altitude pulmonary edema.

    PubMed

    Shlim, D R; Papenfus, K

    1995-05-01

    High-altitude pulmonary edema (HAPE) is a recognized risk of rapid ascent to high altitude. Since the recognition of this entity more than 30 years ago, most pulmonary deaths at high altitude have been attributed to HAPE. However, as the bodies can almost never be recovered for postmortem examination, rare diagnoses that appear clinically similar to HAPE will not be recognized. A 33-year-old woman climbing on Mt. Everest, and taking oral contraceptive pills, developed what seemed to be severe HAPE. Examination after she was evacuated from the mountain revealed a deep venous thrombosis in her left leg and multiple pulmonary emboli. We propose that multiple pulmonary emboli at high altitude can mimic HAPE, and fatal pulmonary embolism may be an explanation for some alleged victims of HAPE who died despite what should have been adequate descent. PMID:11995910

  20. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    PubMed Central

    Dong, Xian-hui; Bai, Jiang-tao; Kong, Wei-na; He, Xiao-ping; Yan, Peng; Shao, Tie-mei; Yu, Wen-guo; Chai, Xi-qing; Wu, Yan-hua; Liu, Cong

    2015-01-01

    Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer’s disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer’s disease patients. An APPswe/PS1?E9 double transgenic mouse model of Alzheimer’s disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer’s disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer’s disease. PMID:26109953

  1. Fluid distribution in progressive pulmonary edema: a low-temperature scanning-electron-microscopy study

    SciTech Connect

    Hook, G.R.

    1981-06-01

    High pressure pulmonary edema is a common medical disorder caused by venous hypertension following left ventricular heart failure. Abnormal fluid accumulation in the alveolar air spaces results in a life-threatening loss of respiratory function. The primary component of the fluid is water and therefore the study of water distribution in the alveolus can provide insight into high pressure pulmonary edema pathology. The new method of freeze-fracture, low temperature SEM has been developed and applied to the study of pulmonary edema. This method combines freeze-fracture sample preservation with SEM observation and retains pulmonary fluids in the frozen hydrated state for direct three-dimensional SEM imaging of alveoli. Quantitative measurements of alveolar structures resulting from high-pressure pulmonary edema were made from SEM micrographs. From these measurements a model for alveolar fluid distribution resulting from progressive high pressure edema was made.

  2. Strong topical steroid, NSAID, and carbonic anhydrase inhibitor cocktail for treatment of cystoid macular edema

    PubMed Central

    Asahi, Masumi G; Bobarnac Dogaru, Gabriela L; Onishi, Spencer M; Gallemore, Ron P

    2015-01-01

    Purpose To report the combination cocktail of strong steroid, non-steroidal anti-inflammatory drug (NSAID), and carbonic anhydrase inhibitor drops for treatment of cystoid macular edema. Methods This is a retrospective case series of patients with cystoid macular edema managed with a topical combination of strong steroid (difluprednate), NSAID, and carbonic anhydrase inhibitor drops. The patients were followed with optical coherence tomography and fluorescein angiography. Results In our six cases, resolution of the cystic edema with improvement in visual acuity was achieved with the use of a combination cocktail of drops. Leakage on fluorescein angiography and cystic edema on optical coherence tomography both responded to treatment with the topical cocktail of drops. Conclusion A topical cocktail of strong steroid, NSAID, and carbonic anhydrase inhibitor drops are effective for managing cystoid macular edema. Further studies comparing this combination with more invasive treatments should be undertaken to determine the efficacy of this cocktail over other treatment options. PMID:26664246

  3. HEME OXYGENASE 2 DEFICIENCY INCREASES BRAIN SWELLING AND INFLAMMATION AFTER INTRACEREBRAL HEMORRHAGE

    PubMed Central

    WANG, J.; DORÉ, S.

    2015-01-01

    Intracerebral hemorrhage (ICH) remains a major medical problem and currently has no effective treatment. Hemorrhaged blood is highly toxic to the brain, and catabolism of the pro-oxidant heme, mainly released from hemoglobin, is critical for the resolution of hematoma after ICH. The degradation of the pro-oxidant heme is controlled by heme oxygenase (HO). We have previously reported a neuroprotective role for HO2 in early brain injury after ICH; however, in vivo data that specifically address the role of HO2 in brain edema and neuroinflammation after ICH are absent. Here, we tested the hypothesis that HO2 deletion would exacerbate ICH-induced brain edema, neuroinflammation, and oxidative damage. We subjected wild-type (WT) and HO2 knockout (?/?) mice to the collagenase-induced ICH model. Interestingly, HO2?/? mice had enhanced brain swelling and neuronal death, although HO2 deletion did not increase collagenase-induced bleeding; the exacerbation of brain injury in HO2?/? mice was also associated with increases in neutrophil infiltration, microglial/macrophage and astrocyte activation, DNA damage, peroxynitrite production, and cytochrome c immunoreactivity. In addition, we found that hemispheric enlargement was more sensitive than brain water content in the detection of subtle changes in brain edema formation in this model. Combined, these novel findings extend our previous observations and demonstrate that HO2 deficiency increases brain swelling, neuroinflammation, and oxidative damage. The results provide additional evidence that HO2 plays a critical protective role against ICH-induced early brain injury. PMID:18674596

  4. Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice.

    PubMed

    Ghosh, Somnath; Canugovi, Chandrika; Yoon, Jeong Seon; Wilson, David M; Croteau, Deborah L; Mattson, Mark P; Bohr, Vilhelm A

    2015-07-01

    Oxidative DNA damage is mainly repaired by base excision repair (BER). Previously, our laboratory showed that mice lacking the BER glycosylases 8-oxoguanine glycosylase 1 (Ogg1) or nei endonuclease VIII-like 1 (Neil1) recover more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model was used to investigate whether loss of 1 of the 2 alleles of X-ray repair cross-complementing protein 1 (Xrcc1), which encodes a nonenzymatic scaffold protein required for BER, alters recovery from stroke. Ischemia and reperfusion caused higher brain damage and lower functional recovery in Xrcc1(+/-) mice than in wild-type mice. Additionally, a greater percentage of Xrcc1(+/-) mice died as a result of the stroke. Brain samples from human individuals who died of stroke and individuals who died of non-neurological causes were assayed for various steps of BER. Significant losses of thymine glycol incision, abasic endonuclease incision, and single nucleotide incorporation activities were identified, as well as lower expression of XRCC1 and NEIL1 proteins in stroke brains compared with controls. Together, these results suggest that impaired BER is a risk factor in ischemic brain injury and contributes to its recovery. PMID:25971543

  5. Lycopene attenuates early brain injury and inflammation following subarachnoid hemorrhage in rats

    PubMed Central

    Wu, An; Liu, Rongcai; Dai, Weimin; Jie, Yuanqing; Yu, Guofeng; Fan, Xiaofeng; Huang, Qiang

    2015-01-01

    Early brain injury (EBI), following subarachnoid hemorrhage (SAH), includes blood-brain barrier (BBB) disruption and consequent edema formation. This study aims to evaluate the effect of lycopene on early brain injury and inflammation in SAH. Neurological deficits, brain water content and Evans blue dye extravasation were evaluated after the treatment with lycopene. Besides neuronal apoptosis,some inflammatory cytokines were also detected. The results suggested that administration of lycopene following SAH significantly ameliorated EBI, including brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In addition, it also ameliorated inflammation triggered by SAH. In conclusion, post-SAH lycopene administration may attenuate EBI in SAH, possibly through ameliorating neuronal apoptosis, maintaining BBB integrity and attenuating inflammation. PMID:26550416

  6. Lymphadiposal Flaps and Lymphaticovenular Anastomoses for Severe Leg Edema: Functional Reconstruction for Lymph Drainage System.

    PubMed

    Koshima, Isao; Narushima, Mitsunaga; Mihara, Makoto; Yamamoto, Takumi; Hara, Hisako; Ohshima, Azusa; Kikuchi, Kazuki; Todokoro, Ken; Seki, Yukio; Iida, Takuya; Nakagawa, Masahiro

    2016-01-01

    Background?Collecting lymphatics have lymph-drainage function with contraction of smooth muscle cells. Patients with edema have lost this drainage function due to degeneration of smooth muscle cells. Lymphaticovenular (LV) anastomosis salvages smooth muscle cells from reversible degeneration (mild edema), but muscle cells cannot be recovered from irreversible degeneration (severe edema). Therefore, in severe edema, LV anastomoses cannot reestablish the drainage function of the lymphatic system.To overcome this weakness of LV bypass methods for severe edema, new methods were instituted for repair of this missing drainage function using a lymphadiposal flap from the contralateral foot for hemilateral edema, or transfer of lateral thoracic lymph nodes for bilateral edema. Methods?A total of 13 cases were repaired with lymphadiposal flaps and additional LV anastomoses. These cases have frequent phlegmon or cellulitis or resisted to previous LV anastomoses and/or compression therapy. The ages ranged from 15 to 75 years. There were four cases of primary edema and nine cases of secondary edema. Results?Regarding the lymphadiposal flap (n?=?8), three cases showed an excellent response (37.5%; no need for compression therapy), four cases had a good response (50%; improvement with compression), one case showed no change (12.5%; no improvement), and there were no cases of deterioration. Regarding the lateral thoracic lymph nodes transfer (n?=?5), two cases had a good response (40%), three showed no improvement (60%), and there were no cases of deterioration. Conclusion?It is concluded that lymphadiposal flap or lymph nodes transfer is suitable for severe edema having frequent cellulitis in unilateral or bilateral lower extremities resisting previous LV anastomoses and/or compression therapy. PMID:26258914

  7. Is genistein neuroprotective in traumatic brain injury?

    PubMed

    Soltani, Zahra; Khaksari, Mohammad; Jafari, Elham; Iranpour, Maryam; Shahrokhi, Nader

    2015-12-01

    The concerns about negative consequences of estrogen therapy have led to introduce other strategies to obtain estrogen's benefits in the brain. The present study tests the hypothesis that a major isoflavone of soy; genistein with estrogen-like activity can be neuroprotective in traumatic brain injury (TBI). The male Wistar rats were randomly divided to four groups: sham, TBI, vehicle and genistein. The TBI was induced by Marmarou method. The brain edema and the disruption of blood-brain-barrier (BBB) were evaluated 48h post-TBI. Genistein (15mg/kg) or dimethyl sulfoxide (DMSO) was injected i.p., twice after TBI. The intracranial pressure (ICP), the motor performance, and the beam-walk task (WB) were determined before trauma, on trauma day (D0), and first (D1) and second (D2) days post-TBI. Genistein inhibited a development of brain edema and a BBB permeability in TBI animals. An increase of ICP and a defect in motor and WB performance were showed following TBI, in all times evaluated. An increase of ICP induced by TBI was suppressed by genistein on D1 and D2 times. Genistein improved a motor disorder induced by TBI, on D1 and D2 times. Also an increase of traversal time in WB task was suppressed by genistein in TBI animals, on D1 and D2 times. The results of this study demonstrated that genistein can be neuroprotective in TBI. Genistein inhibited the disruption of BBB, the brain edema and the increase of ICP, and the disturbance of neurobehavioral performance in TBI. PMID:26367454

  8. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% ({+-}22 SD), and the average change in the FLAIR images was 60% ({+-}18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg ({+-}3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.

  9. Porphyrin-laser photodynamic induction of focal brain necrosis

    SciTech Connect

    Stroop, W.G.; Battles, E.J.; Townsend, J.J.; Schaefer, D.C.; Baringer, J.R.; Straight, R.C. )

    1989-09-01

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

  10. Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-?B 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 ?B (NF-?B) 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-?B mediated inflammatory pathway. PMID:26475978

  11. Macular Edema After Cataract Surgery In Eyes Without Pre-operative Central-involved Diabetic Macular Edema

    PubMed Central

    Baker, Carl W.; Almukhtar, Talat; Bressler, Neil M.; Glassman, Adam R.; Grover, Sandeep; Kim, Stephen J.; Murtha, Timothy J.; Rauser, Michael E.; Stockdale, Cynthia

    2014-01-01

    Objective To estimate the incidence of central-involved macular edema (ME)16 weeks following cataract surgery in eyes with diabetic retinopathy (DR) without definite central-involved diabetic macular edema (DME) preoperatively. Methods In a multicenter, prospective, observational study, participants (N = 293) with DR without definite OCT central subfield (CSF) thickening underwent cataract surgery. The primary outcome was development of central-involved ME defined as; (1) OCT CSF thickness ? 250?m (time domain) or ? 310?m (spectral domain) with ?1 step increase in logOCT CSF thickness pre-operative to the 16-week visit; (2) ?2-step increase in logOCT CSF pre-operative to 16-week visit; or (3) non-topical treatment for ME received before the 16-week visit with either of the OCT criteria met at the time of treatment. Results Median participant age was 64 years with median visual acuity letter score of 69 (Snellen equivalent 20/40). Forty-four percent of eyes had history of prior treatment for DME. Sixteen weeks postoperatively, central-involved ME was noted in 0% (95%CI: 0-20%) of 17 eyes with no pre-operative DME. Of eyes with non-central involved DME, 10% (95%CI: 5-18%) of 97 eyes without central involved DME and 12% (95%CI: 7-19%) of 147 eyes with possible central involved DME at baseline progressed to central-involved ME. History of DME treatment was significantly associated with central-involved ME development (P<0.001). Conclusion In eyes with DR without concurrent central-involved DME, presence of non-central DME immediately prior to cataract surgery, or history of DME treatment, may increase risk of developing central-involved ME 16 weeks after cataract extraction. PMID:23599174

  12. Role of C-fibers during acute and chronic stress on formalin-induced paw edema in rats.

    PubMed

    Sepehri, Zahra; Fereidoni, Masoud; Niazmand, Saeed

    2012-09-01

    Stimulation of peripheral nociceptors leads to releasing of some mediators such as substance P (SP) and Calcitonin gene-related peptide (CGRP) and contributes to the edema formation by vasodilatation induction. On the other hand glucocorticoids have anti-inflammatory action, and they are elevated in the plasma during stress. This communication reports C-fibers inflammatory role and the effects of chronic and acute stress and/or dexamethasone (as stress mimicry) on paw edema induced by formalin at presence/deficit C-fibers rats. Acute stress and dexamethasone and chronic dexamethasone have shown an anti-inflammatory effect in C-normal groups, but chronic stress had no effect on inflammation. C-fibers reduction (C-lesion) had anti-inflammatory effects. In deficit C-fibers rats, acute and chronic stress had not stronger anti-inflammatory effect, but acute dexamethasone reduced the anti-inflammatory effect of C-fibers reduction while in the same condition, chronic dexamethasone induced stronger anti-inflammatory effect. The results show C-fiber nerve produce and release the peripheral inflammatory mediators, "C-fibers reduction" decreased the paw inflammation. Counter adaptation in C-lesion animals may reduce the modulatory effects of dexamethasone on the remaining C-fibers. Acute dexamethasone diminished the "C-fibers reduction" anti-inflammatory effect, but at chronic treatment, the modulatory effects of dexamethasone aggregated and it augmented the C-fibers reduction antiinflammatory effect. PMID:23140021

  13. Astaxanthin Alleviates Early Brain Injury Following Subarachnoid Hemorrhage in Rats: Possible Involvement of Akt/Bad Signaling

    PubMed Central

    Zhang, Xiang-Sheng; Zhang, Xin; Wu, Qi; Li, Wei; Zhang, Qing-Rong; Wang, Chun-Xi; Zhou, Xiao-Ming; Li, Hua; Shi, Ji-Xin; Zhou, Meng-Liang

    2014-01-01

    Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH). Previously, we demonstrated that astaxanthin (ATX) administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt) pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway. PMID:25072152

  14. Role of dietary polyphenols in attenuating brain edema and cell swelling in cerebral ischemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyphenols are natural substances with variable phenolic structures and are enriched in vegetables, fruits, grains, bark, roots, tea, and wine. There are over 8000 polyphenolic structures identified in plants, but edible plants contain only several hundred polyphenolic structures. Recent interest...

  15. Brain Basics: Know Your Brain

    MedlinePLUS

    ... EPUB version (2 MB) MOBI version (4 MB) Brain Basics: Know Your Brain Request free mailed brochure Table of Contents Introduction ... dysfunctional. Image 1 < top > The Architecture of the Brain The brain is like a committee of experts. ...

  16. Anethum graveolens seeds aqueous extract stimulates whole brain 5-hydroxytryptamine metabolism and reduces feeding behavior and body weight in obese rats.

    PubMed

    Bano, Farhat; Ahmed, Afrinah; Ahmed, Maryam; Parveen, Tahira

    2015-01-01

    The percentage of overweight and obese person has increased markedly since several decays. Obesity is associated with increased risked factor for many diseases such as, diabetes, heart complications, arthritis and certain types of cancer. Feeding behavior is in controlled by a major interaction between central nervous system and many organs of the body. The role of serotonin (5-HT) in feeding behavior is well recognized. The aim of present study was to evaluate the effect of Anethum graveolens seeds aqueous extract (AGAE) on food intake, body weight and serotonin metabolism in over weight rats. Five weeks oral administration of AGAE shows significant decrease in body weight, food intake and significant increase in whole brain 5-HT, 5-HIAA and tryptophan level in brain and plasma of experimental animals. Increased level of 5-HT induced satiety and suppressed food intake and result is the reduction in body weight. PMID:25553698

  17. Progesterone reduces inflammation and apoptosis in neonatal rats with hypoxic ischemic brain damage through the PI3K/Akt pathway

    PubMed Central

    Li, Xiaojuan; Zhang, Junhe; Zhu, Xiaoqian; Wang, Ping; Wang, Xiaoyin; Li, Dongliang

    2015-01-01

    A neonatal rat model with hypoxic ischemic brain damage (HIBD) was established. Forty 7-day-old neonatal Wistar rats were randomly divided into four groups: sham operation, model, progesterone and Akt inhibitor. Electron microscopy revealed that the neonatal rats with HIBD showed neuronal changes. The protein expression levels of pAkt, Nuclear factor ?B (NF-?B) and Bcl-2 in the hippocampus were detected by immunohistochemistry and Western blot. The neuronal structure was normal in the sham operation group after HIBD for 24 h. Cavitation change due to hypoxic ischemic brain damage was observed in the neurons of the model group. Progesterone treatment improved neuronal damage and cavitation. Neuronal cavitation was clearly changed in the Akt inhibitor group. The protein expression levels of hippocampal pAkt and Bcl-2 did not significantly change after HIBD, whereas that of NF-?B increased. Progesterone pre-treatment increased the expression levels of pAkt and Bcl-2 but decreased that of NF-?B. The protein expression levels of pAkt and Bcl-2 decreased in the Akt inhibitor group, whereas that of NF-?B increased. This result indicates that progesterone can decrease inflammation in HIBD, inhibit apoptosis and protect the brain by activating the Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway. PMID:26221393

  18. Anti-inflammatory effect of ethanolic extract from Myagropsis myagroides on murine macrophages and mouse ear edema

    PubMed Central

    2012-01-01

    Background This study aims to investigate anti-inflammatory effect of ethanolic extract of Myagropsis myagroides (EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-?B (NF-?B) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance. Results EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-?B by preventing degradation of inhibitor of ?B-? as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6’-bieckol. Conclusions These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-?B pathway in LPS-stimulated macrophages. PMID:23031211

  19. Prostatic edema in {sup 125}I permanent prostate implants: Dynamical dosimetry taking volume changes into account

    SciTech Connect

    Leclerc, Ghyslain; Lavallee, Marie-Claude; Roy, Rene; Vigneault, Eric; Beaulieu, Luc

    2006-03-15

    The purpose of this study is to determine the impact of edema on the dose delivered to the target volume. An evaluation of the edema characteristics was first made, and then a dynamical dosimetry algorithm was developed and used to compare its results to a standard clinical (static) dosimetry. Source positions and prostate contours extracted from 66 clinical cases on images taken at different points in time (planning, implant day, post-implant evaluation) were used, via the mean interseed distance, to characterize edema [initial increase ({delta}r{sub 0}), half-life ({tau})]. An algorithm was developed to take into account the edema by summing a time series of dose-volume histograms (DVHs) with a weight based on the fraction of the dose delivered during the time interval considered. The algorithm was then used to evaluate the impact of edema on the dosimetry of permanent implants by comparing its results to those of a standard clinical dosimetry. The volumetric study yielded results as follows: the initial prostate volume increase was found to be 1.58 (ranging from 1.15 to 2.48) and the edema half-life, approximately 30 days (range: 3 to 170 days). The dosimetric differences in D{sub 90} observed between the dynamic dosimetry and the clinical one for a single case were up to 15 Gy and depended on the edema half-life and the initial volume increase. The average edema half-life, 30 days, is about 3 times longer than the previously reported 9 days. Dosimetric differences up to 10% of the prescription dose are observed, which can lead to differences in the quality assertion of an implant. The study of individual patient edema resorption with time might be necessary to extract meaningful clinical correlation or biological parameters in permanent implants.

  20. Specific antagonist of platelet-activating factor suppresses edema formation in an Arthus reaction but not edema induced by leukocyte chemoattractants in rabbit skin

    SciTech Connect

    Hellewell, P.G.; Williams, T.J.

    1986-07-15

    The properties of a novel platelet-activating factor (PAF) antagonist, L-652731, on edema responses in rabbit skin induced by exogenous inflammatory mediators and by mediators generated endogenously in a reversed passive Arthus reaction have been investigated. Edema responses in the skin were measured by using the local accumulation of i.v. injected /sup 125/I-albumin. The antagonist, mixed with mediators before intradermal injection, caused a dose-dependent suppression of edema responses to PAF. In contrast, responses induced by other directly acting mediators (bradykinin and histamine) and responses induced by PMN leukocyte-dependent mediators (C5a des Arg, N-formyl-methionyl-leucyl-phenylalanine, and keukotriene B/sub 4/) were not suppressed. Thus, a secondary release of PAF does not appear to be involved in mediating the actions of these agents. In a reversed passive Arthus reaction, intradermal injection of L-652731 together with antibody resulted in a significant inhibition of the edema formation measured for 2 hr after i.v. antigen challenge. In contrast, edema responses induced by intradermal injection of performed immune complexes were not affected by the antagonist. These results suggest that the endogenous production of PAF, in close proximity to microvascular endothelial cells, appears to be an important step in the development of an Arthus reaction. The cellular source of PAF is unknown, but one possibility is the PMN leukocyte, which releases PAF during phagocytosis of immune complexes.

  1. [Prehospital treatment of pulmonary edema at the Emergency Medical Services Center in Sarajevo].

    PubMed

    Basi?, A; Kurtuvi?, A

    2000-01-01

    Quality of prehospital treatment of pulmonary edema depends on functioning of emergency medical service, education and level of competence of medical staff, service equipment, suitable transport and work coordination with Emergency Medical Centre of Clinical centre in Sarajevo. In 1998 in Emergency Medical Service Centre (EMSC) 54 patients with pulmonary edema were treated. In different rates pulmonary edema was associated with myocardial infarction, hypertension, hypotension, rhythm disorders, chronic obstructive pulmonary disease and heroin overdose. Out of total number of treated patients three had lethal outcome what indicates good organisation and efficiency of EMSC Sarajevo. PMID:11117036

  2. Characterization of corneal edema by forward and backward second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Hsueh, Chiu-Mei; Lo, Wen; Chen, Wei-Liang; Hovhannisyan, Vladimir A.; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2010-02-01

    We used second harmonic generation (SHG) microscopy to image and quantify the structural changes of bovine corneal edema. Forward SHG (FWSHG) and backward SHG (BWSHG) signals were simultaneously collected from normal and edematous bovine corneas to reveal their morphological differences. In SHG imaging, edematous corneas can be characterized by uneven expansion in the lamellar interspacing and increased lamellar thickness in posterior stroma (depth > 200 ?m), while the anterior stroma composed of interwoven collagen architecture remained unaffected. Our work demonstrate the capability of SHG imaging in providing morphological information for the investigation of corneal edema biophysics and its potential application in the in vivo evaluation of advancing corneal edema.

  3. Acute pulmonary edema during a triathlon occurrence in a trained athlete.

    PubMed

    Boggio-Alarco, José L; Jaume-Anselmi, Francisco; Ramirez-Rivera, Jose

    2006-01-01

    Prolonged, strenuous exercise is associated with muscle injury; this may become permanent if there is insufficient time to rest between bouts of endurance exercise. We present here the experience of a 36 year old athlete who developed myocardial injury and pulmonary edema during a triathlon. Within 24-hours, after receiving furosemide 40 mg every 8 hours and oxygen, his pulmonary edema disappeared. The serum troponin became transiently elevated as it happens with a myocardial infarction but no electrocardiographic changes occurred. It is concluded that strenuous exercises may cause myocardial injury with a transient decrease of ventricular function and pulmonary edema. The possibility of some permanent damage cannot be excluded. PMID:19606798

  4. CONGENITAL MACROVESSEL ASSOCIATED WITH CYSTOID MACULAR EDEMA AND AN IPSILATERAL INTRACRANIAL VENOUS MALFORMATION

    PubMed Central

    Sanfilippo, Christian J.

    2015-01-01

    Background/Purpose: To report a case of congenital retinal macrovessel associated with cystoid macular edema and an ipsilateral intracranial venous malformation. Methods: Case report. Results: A 58-year-old woman with decreased vision was found to have a congenital retinal venous macrovessel associated with cystoid macular edema because of tributary venous occlusion. The patient underwent neuroimaging and an ipsilateral venous malformation of the frontal lobe was discovered. Conclusion: Congenital retinal macrovessel can occasionally be complicated by vascular occlusion and macular edema. The authors report a case of congenital retinal macrovessel associated with an intracranial venous malformation. Clinicians should be aware of this potential association, and further studies are warranted. PMID:26421894

  5. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    PubMed Central

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-01-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples. PMID:26459926

  6. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    NASA Astrophysics Data System (ADS)

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-10-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

  7. Acute Genital Edema during Peritoneal Dialysis: A Review for Surgeons.

    PubMed

    Jorge, Juaquito; Haggerty, Stephen P

    2015-11-01

    Acute genital edema (AGE) is an infrequent but disruptive complication in patients on continuous ambulatory peritoneal dialysis. It is a common manifestation of dialysate leakage caused by inguinal, umbilical, femoral, or incisional hernias; peritoneal tears; leaks around the dialysis catheter; trauma; fluid overload; and malignancy. The evaluation of AGE begins with a history and physical exam. However, the physical exam in these patients is often indeterminate. Several diagnostic measures exist to evaluate and guide management of AGE occurring during continuous ambulatory peritoneal dialysis but little agreement exists on an optimum method. We have conducted a review of the literature on the evaluation and management of AGE and present a summary of the data. CT peritoneography and peritoneal scintigraphy have been used extensively to evaluate AGE although no comparative studies exist. MRI peritoneography has also been described. CT peritoneography offers more anatomical detail but may not be as sensitive as peritoneal scintigraphy in detecting a peritoneal fluid leak as the cause for AGE. CT is also more costly and subjects the patient to more radiation. MRI is a noncontrast study without radiation risk, but has not been studied to the same degree. If testing is equivocal or bilateral hernias are suspected, diagnostic laparoscopy is helpful and can be combined with hernia repair. Whether the etiology is a leak or tear, low-volume peritoneal dialysis (PD) or cessation of PD for two to four weeks will allow closure. However, hernias almost always require operative repair with mesh usually without disrupting PD. PMID:26672592

  8. Cistoid macular edema as first manifestation of sarcoidosis.

    PubMed

    Cabrillo-Estevez, Lucia; de Juan-Marcos, Lourdes; Kyriakou, Danai; Hernández-Galilea, Emiliano

    2014-08-01

    The purpose of this study is to report a case of cystoid macular edema (CME) as a rare first manifestation of ocular sarcoidosis after cataract surgery. A 60-year-old male developed a CME following uneventful phacoemulsification cataract extraction on his left eye. It resolved with conventional medical therapy. One year later the patient was diagnosed with bilateral CME. Oral corticosteroid therapy produced a significant regression. His medical and ocular histories were unremarkable and all tests for etiological diagnosis were negative. There were inflammation recurrences in his left eye, which were also treated with steroids. Optical coherence tomography showed complete resolution of foveal thickening without improvement in vision. Four years later, the patient presented with CME in both eyes. The laboratory tests included high angiotensin-converting enzyme levels and a gallium scan which were also consistent with sarcoidosis. Azathioprine was needed for management of ocular involvement, but it was withheld due to side-effects. At the present time, the CME is controlled with low-dose corticoids. Ocular involvement in sarcoidosis occurs in 20-50 % of patients. CME is not often the initial manifestation of the disease, but ocular sarcoidosis may present with a wide variety of ocular symptoms in all parts of the eye. Therefore, sarcoidosis should be kept in mind when evaluating a patient with ocular inflammation. PMID:24322273

  9. Microcystic macular edema detection in retina OCT images

    NASA Astrophysics Data System (ADS)

    Swingle, Emily K.; Lang, Andrew; Carass, Aaron; Ying, Howard S.; Calabresi, Peter A.; Prince, Jerry L.

    2014-03-01

    Optical coherence tomography (OCT) is a powerful imaging tool that is particularly useful for exploring retinal abnormalities in ophthalmological diseases. Recently, it has been used to track changes in the eye associated with neurological diseases such as multiple sclerosis (MS) where certain tissue layer thicknesses have been associated with disease progression. A small percentage of MS patients also exhibit what has been called microcystic macular edema (MME), where uid collections that are thought to be pseudocysts appear in the inner nuclear layer. Very little is known about the cause of this condition so it is important to be able to identify precisely where these pseudocysts occur within the retina. This identi cation would be an important rst step towards furthering our understanding. In this work, we present a detection algorithm to nd these pseudocysts and to report on their spatial distribution. Our approach uses a random forest classi er trained on manual segmentation data to classify each voxel as pseudocyst or not. Despite having a small sample size of ve subjects, the algorithm correctly identi es 84.6% of pseudocysts as compared to manual delineation. Finally, using our method, we show that the spatial distribution of pseudocysts within the macula are generally contained within an annulus around the fovea.

  10. Lower extremity edema in patients with early ovarian cancer

    PubMed Central

    2014-01-01

    Background The objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in early ovarian cancer. Methods Patients with early ovarian cancer who underwent staging surgery between January 2001 and December 2010. Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated. Results Patients had a median age of 46 years. Twenty-nine patients (40.8%) had past (13 patients, 44.8%) and/or current patient-reported LEE (16 patients, 55.2%). Symptoms reported on the GCLQ in over 20% of respondents were numbness, firmness/tightness, swelling, heaviness, limited movement of knee, and aching. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (25/29, 86.2%) developed within 12 months after surgery and LEE lasted more than 6 months in approximately two-thirds of the patients (18/29, 62.1%). Only half of the patients (52.1%) indicated knowledge of lymphedema: 86.2% of LEE patients and 28.6% of patients with no LEE. Conclusions Although a significant proportion of patients with ovarian cancer have LEE after surgery, most are not aware of lymphedema until they develop. Education and analyses for LEE and lymphedema are needed in patients with ovarian cancer. PMID:24602386

  11. Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute Intracerebral Hemorrhage

    PubMed Central

    Zhu, Ying; Wang, Jia-Lu; He, Zhi-Yi; Jin, Feng; Tang, Ling

    2015-01-01

    Background and Purpose Perihematomal edema (PHE) contributes to secondary brain damage and aggravates patient outcomes after intracerebral hemorrhage (ICH). MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles have fundamental roles in modulating vascular disease. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients. Methods Hematoma and PHE volumes of ICH patients were measured on admission and in follow-up computed tomography scans. Whole-genome miRNA profiles of ICH patients and healthy controls were determined using the Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated dysregulated miRNA target genes and the signaling pathways involved. Results We identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative PHE volume on days 3–4 (r = ?0.714; P<0.001) in patients with ICH. Conclusions ICH patients appear to have a specific miRNA expression profile. Low expression of miR-126 was positively correlated with the extent of PHE, suggesting it may have a pathogenic role in the development of PHE after ICH. PMID:26207814

  12. Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke

    PubMed Central

    2010-01-01

    Background The link between early blood- brain barrier (BBB) breakdown and endothelial cell activation in acute stroke remain poorly defined. We hypothesized that P-selectin, a mediator of the early phase of leukocyte recruitment in acute ischemia is also a major contributor to early BBB dysfunction following stroke. This was investigated by examining the relationship between BBB alterations following transient ischemic stroke and expression of cellular adhesion molecule P-selectin using a combination of magnetic resonance molecular imaging (MRMI), intravital microscopy and immunohistochemistry. MRMI was performed using the contrast, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) conjugated to Sialyl Lewis X (Slex) where the latter is known to bind to activated endothelium via E- or P selectins. Middle cerebral artery occlusion was induced in male C57/BL 6 wild-type (WT) mice and P-selectin-knockout (KO) mice. At 24 hours following middle cerebral artery occlusion, T1 maps were acquired prior to and following contrast injection. In addition to measuring P- and E-selectin expression in brain homogenates, alterations in BBB function were determined immunohistochemically by assessing the extravasation of immunoglobulin G (IgG) or staining for polymorphonuclear (PMN) leukocytes. In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC)-dextran (MW 2000 kDa). Results MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd) demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P < 0.03). In the P selectin KO mice, ? T1 stroke -? T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX) group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB function, in the P-selectin KO mice compared to WT control mice, there was an attenuation in the extravasation of IgG (P < 0.001), a trend for decreased FITC extravasation and less infiltration of PMN leukocytes (P < 0.001) thereby supporting the observed increase in Kgd permeability in stroke brain of WT compared to KO mice. Conclusion P-selectin expression contributes to enhanced BBB dysfunction at 24 hours after transient focal cerebral ischemia. PMID:20122276

  13. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Zhang, Zong-yong; Sun, Bao-liang; Yang, Ming-feng; Li, Da-wei; Fang, Jie; Zhang, Shuai

    2015-03-01

    Carnosine (?-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1?, IL-6, and tumor necrosis factor-? (TNF-?) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models. PMID:25179154

  14. Brain Tumors

    MedlinePLUS

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  15. Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor

    PubMed Central

    Lübker, Carolin; Dove, Stefan; Tang, Wei-Jen; Urbauer, Ramona J. Bieber; Moskovitz, Jackob; Urbauer, Jeffrey L.; Seifert, Roland

    2015-01-01

    Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca2+-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth. Methionine (Met) residues in CaM, important for interactions between CaM and its binding partners, can be oxidized by ROS. We investigated the impact of site-specific oxidation of Met in CaM on EF activation using thirteen CaM-mutants (CaM-mut) with Met to leucine (Leu) substitutions. EF activation shows high resistance to oxidative modifications in CaM. An intact structure in the C-terminal region of oxidized CaM is sufficient for major EF activation despite altered secondary structure in the N-terminal region associated with Met oxidation. The secondary structures of CaM-mut were determined and described in previous studies from our group. Thus, excess cAMP production and the associated impairment of host defence may be afforded even under oxidative conditions in activated neutrophils. PMID:26184312

  16. Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor.

    PubMed

    Lübker, Carolin; Dove, Stefan; Tang, Wei-Jen; Urbauer, Ramona J Bieber; Moskovitz, Jackob; Urbauer, Jeffrey L; Seifert, Roland

    2015-07-01

    Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca2+-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth. Methionine (Met) residues in CaM, important for interactions between CaM and its binding partners, can be oxidized by ROS. We investigated the impact of site-specific oxidation of Met in CaM on EF activation using thirteen CaM-mutants (CaM-mut) with Met to leucine (Leu) substitutions. EF activation shows high resistance to oxidative modifications in CaM. An intact structure in the C-terminal region of oxidized CaM is sufficient for major EF activation despite altered secondary structure in the N-terminal region associated with Met oxidation. The secondary structures of CaM-mut were determined and described in previous studies from our group. Thus, excess cAMP production and the associated impairment of host defence may be afforded even under oxidative conditions in activated neutrophils. PMID:26184312

  17. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Cattle carcasses affected with anasarca or...CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a) Carcasses of cattle found on post-mortem...

  18. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Cattle affected with anasarca and generalized... ANTE-MORTEM INSPECTION § 309.8 Cattle affected with anasarca and generalized edema. All cattle found on ante-mortem inspection to...

  19. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Cattle carcasses affected with anasarca or...CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a) Carcasses of cattle found on post-mortem...

  20. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Cattle carcasses affected with anasarca or...CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a) Carcasses of cattle found on post-mortem...

  1. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Cattle carcasses affected with anasarca or...CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a) Carcasses of cattle found on post-mortem...

  2. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Cattle affected with anasarca and generalized... ANTE-MORTEM INSPECTION § 309.8 Cattle affected with anasarca and generalized edema. All cattle found on ante-mortem inspection to...

  3. 9 CFR 311.8 - Cattle carcasses affected with anasarca or generalized edema.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Cattle carcasses affected with anasarca or...CARCASSES AND PARTS § 311.8 Cattle carcasses affected with anasarca or generalized edema. (a) Carcasses of cattle found on post-mortem...

  4. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Cattle affected with anasarca and generalized... ANTE-MORTEM INSPECTION § 309.8 Cattle affected with anasarca and generalized edema. All cattle found on ante-mortem inspection to...

  5. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Cattle affected with anasarca and generalized... ANTE-MORTEM INSPECTION § 309.8 Cattle affected with anasarca and generalized edema. All cattle found on ante-mortem inspection to...

  6. 9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Cattle affected with anasarca and generalized... ANTE-MORTEM INSPECTION § 309.8 Cattle affected with anasarca and generalized edema. All cattle found on ante-mortem inspection to...

  7. MYELIN BASIC PROTEIN-MESSENGER RNA (MBP-MRNA) EXPRESSION DURING TRIETHYLTIN-INDUCED MYELIN EDEMA

    EPA Science Inventory

    Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. ET has been reported to depress levels of myelin basic protein (MBP), a glycoprot...

  8. Dose calculation for permanent prostate implants incorporating spatially anisotropic linearly time-resolving edema

    SciTech Connect

    Monajemi, T. T.; Clements, Charles M.; Sloboda, Ron S.

    2011-04-15

    Purpose: The objectives of this study were (i) to develop a dose calculation method for permanent prostate implants that incorporates a clinically motivated model for edema and (ii) to illustrate the use of the method by calculating the preimplant dosimetry error for a reference configuration of {sup 125}I, {sup 103}Pd, and {sup 137}Cs seeds subject to edema-induced motions corresponding to a variety of model parameters. Methods: A model for spatially anisotropic edema that resolves linearly with time was developed based on serial magnetic resonance imaging measurements made previously at our center to characterize the edema for a group of n=40 prostate implant patients [R. S. Sloboda et al., ''Time course of prostatic edema post permanent seed implant determined by magnetic resonance imaging,'' Brachytherapy 9, 354-361 (2010)]. Model parameters consisted of edema magnitude, {Delta}, and period, T. The TG-43 dose calculation formalism for a point source was extended to incorporate the edema model, thus enabling calculation via numerical integration of the cumulative dose around an individual seed in the presence of edema. Using an even power piecewise-continuous polynomial representation for the radial dose function, the cumulative dose was also expressed in closed analytical form. Application of the method was illustrated by calculating the preimplant dosimetry error, RE{sub preplan}, in a 5x5x5 cm{sup 3} volume for {sup 125}I (Oncura 6711), {sup 103}Pd (Theragenics 200), and {sup 131}Cs (IsoRay CS-1) seeds arranged in the Radiological Physics Center test case 2 configuration for a range of edema relative magnitudes ({Delta}=[0.1,0.2,0.4,0.6,1.0]) and periods (T=[28,56,84] d). Results were compared to preimplant dosimetry errors calculated using a variation of the isotropic edema model developed by Chen et al. [''Dosimetric effects of edema in permanent prostate seed implants: A rigorous solution,'' Int. J. Radiat. Oncol., Biol., Phys. 47, 1405-1419 (2000)]. Results: As expected, RE{sub preplan} for our edema model indicated underdosage in the calculation volume with a clear dependence on seed and calculation point positions, and increased with increasing values of {Delta} and T. Values of RE{sub preplan} were generally larger near the ends of the virtual prostate in the RPC phantom compared with more central locations. For edema characteristics similar to the population average values previously measured at our center, i.e., {Delta}=0.2 and T=28 d, mean values of RE{sub preplan} in an axial plane located 1.5 cm from the center of the seed distribution were 8.3% for {sup 131}Cs seeds, 7.5% for {sup 103}Pd seeds, and 2.2% for {sup 125}I seeds. Maximum values of RE{sub preplan} in the same plane were about 1.5 times greater. Note that detailed results strictly apply only for loose seed implants where the seeds are fixed in tissue and move in synchrony with that tissue. Conclusions: A dose calculation method for permanent prostate implants incorporating spatially anisotropic linearly time-resolving edema was developed for which cumulative dose can be written in closed form. The method yields values for RE{sub preplan} that differ from those for spatially isotropic edema. The method is suitable for calculating pre- and postimplant dosimetry correction factors for clinical seed configurations when edema characteristics can be measured or estimated.

  9. An evaluation of standing-induced lower leg edema as a function of floor surace 

    E-print Network

    DiSalvi, Lawrence Roberts

    1995-01-01

    Jobs requiring workers to stand for prolonged periods are common in industry. People whose work involves standing frequently complain of discomfort, particularly in the legs. A study was conducted to determine the amount of edema that occurs...

  10. Severe weight gain and generalized insulin edema after the starting of an insulin pump.

    PubMed

    Greco, Domenico

    2015-02-01

    The possibility of the occurrence of a generalized edema after initiation or intensification of insulin treatment in patients with diabetes, although considered a rare event, has long been described in the literature. In this case, a state of clinically significant edema, with a concurrent severe weight gain, occurred in a patient with type 1 diabetes in whom the implantation of an insulin pump resulted in a dramatic and abrupt improvement in glycemic control. PMID:25282002

  11. The Endothelial Glycocalyx: Emerging Concepts in Pulmonary Edema and Acute Lung Injury

    PubMed Central

    Collins, Stephen R.; Blank, Randal S.; Deatherage, Lindy S.; Dull, Randal O.

    2013-01-01

    The endothelial glycocalyx is a dynamic layer of macromolecules at the luminal surface of vascular endothelium that is involved in fluid homeostasis and regulation. Its role in vascular permeability and edema formation is emerging but is still not well understood. In this special article, we highlight key concepts of endothelial dysfunction with regards to the glycocalyx and provide new insights into the glycocalyx as a mediator of processes central to the development of pulmonary edema and lung injury. PMID:23835455

  12. Acute hemorrhagic edema of infancy: report of 4 cases and review of the current literature.

    PubMed

    Karremann, Michael; Jordan, Alexander J; Bell, Nellie; Witsch, Michael; Dürken, Matthias

    2009-04-01

    Acute hemorrhagic edema of infancy (AHEI) is a cutaneous leukocytoclastic vasculitis that usually occurs in children younger than 2 years of age. It is a rare disease characterized by mild fever, a violent onset of hemorrhagic skin lesions, and edema usually followed by a spontaneous and complete recovery. Although the etiology is unknown, AHEI often follows infections, drug treatment, or vaccination. In the present report, the authors describe 4 cases of AHEI and review the relevant literature. PMID:18772356

  13. Brain Malformations

    MedlinePLUS

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections or radiation during pregnancy interferes with brain development. Types of brain malformations include missing parts ...

  14. Brain components

    MedlinePLUS Videos and Cool Tools

    The brain is composed of more than a thousand billion neurons. Specific groups of them, working in concert, provide ... of information. The 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The ...

  15. Brain surgery

    MedlinePLUS

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  16. Clinical correlates of the spectrum of lung microvascular injury in human noncardiac edema

    SciTech Connect

    Sibbald, W.J.; Driedger, A.A.; Wells, G.A.; Koval, J.J.

    1983-02-01

    Researchers measured the clearance from blood to pulmonary edema fluid of a small molecular researchersight hydrophilic radiotracer, Indium-111-DTPA (In-DTPA) and a larger molecular researchrsight radiotracer, Iodine-125-HSA (I-HSA), in patients with pulmonary edema on either a cardiac or noncardiac (permeability) basis. In previous investigations, researchers had noted an apparent relationship between the magnitude of clearance of I-HSA across the alveolocapillary membrane and the severity of noncardiac pulmonary edema. In this study, researchers were able to distinguish at least 2 distinct groups of patients with noncardiac pulmonary edema. Patients with the greatest damage to the alveolo-capillary exchanging membrane, defined by the flux of I-HSA from blood to edema fluid, were significantly differentiated from those with a lesser microvascular injury on the basis of higher mean heart rate (HR), temperature, cardiac index (CI), pulmonary artery pressures, right ventricular stroke work index (RVSWI), and a lower mean total white blood cell count (WBC), among others. Therefore, noncardiac pulmonary edema is characterized by a spectrum of permeability injury to the pulmonary microvasculature which seems to parallel other measurable indices of the severity of the systemic response to the illness.

  17. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.

    PubMed

    Thorneloe, Kevin S; Cheung, Mui; Bao, Weike; Alsaid, Hasan; Lenhard, Stephen; Jian, Ming-Yuan; Costell, Melissa; Maniscalco-Hauk, Kristeen; Krawiec, John A; Olzinski, Alan; Gordon, Earl; Lozinskaya, Irina; Elefante, Lou; Qin, Pu; Matasic, Daniel S; James, Chris; Tunstead, James; Donovan, Brian; Kallal, Lorena; Waszkiewicz, Anna; Vaidya, Kalindi; Davenport, Elizabeth A; Larkin, Jonathan; Burgert, Mark; Casillas, Linda N; Marquis, Robert W; Ye, Guosen; Eidam, Hilary S; Goodman, Krista B; Toomey, John R; Roethke, Theresa J; Jucker, Beat M; Schnackenberg, Christine G; Townsley, Mary I; Lepore, John J; Willette, Robert N

    2012-11-01

    Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major cause of morbidity and mortality in heart failure (HF) patients, but current treatment options demonstrate substantial limitations. Recent evidence from rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels. To examine the therapeutic potential of this mechanism, we evaluated TRPV4 expression in human congestive HF lungs and developed small-molecule TRPV4 channel blockers for testing in animal models of HF. TRPV4 immunolabeling of human lung sections demonstrated expression of TRPV4 in the pulmonary vasculature that was enhanced in sections from HF patients compared to controls. GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. In isolated rodent and canine lungs, TRPV4 blockade prevented the increased vascular permeability and resultant pulmonary edema associated with elevated PVP. Furthermore, in both acute and chronic HF models, GSK2193874 pretreatment inhibited the formation of pulmonary edema and enhanced arterial oxygenation. Finally, GSK2193874 treatment resolved pulmonary edema already established by myocardial infarction in mice. These findings identify a crucial role for TRPV4 in the formation of HF-induced pulmonary edema and suggest that TRPV4 blockade is a potential therapeutic strategy for HF patients. PMID:23136043

  18. Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review.

    PubMed

    Pluijms, Wouter A; van Mook, Walther Nka; Wittekamp, Bastiaan Hj; Bergmans, Dennis Cjj

    2015-01-01

    Endotracheal intubation is frequently complicated by laryngeal edema, which may present as postextubation stridor or respiratory difficulty or both. Ultimately, postextubation laryngeal edema may result in respiratory failure with subsequent reintubation. Risk factors for postextubation laryngeal edema include female gender, large tube size, and prolonged intubation. Although patients at low risk for postextubation respiratory insufficiency due to laryngeal edema can be identified by the cuff leak test or laryngeal ultrasound, no reliable test for the identification of high-risk patients is currently available. If applied in a timely manner, intravenous or nebulized corticosteroids can prevent postextubation laryngeal edema; however, the inability to identify high-risk patients prevents the targeted pretreatment of these patients. Therefore, the decision to start corticosteroids should be made on an individual basis and on the basis of the outcome of the cuff leak test and additional risk factors. The preferential treatment of postextubation laryngeal edema consists of intravenous or nebulized corticosteroids combined with nebulized epinephrine, although no data on the optimal treatment algorithm are available. In the presence of respiratory failure, reintubation should be performed without delay. Application of noninvasive ventilation or inhalation of a helium/oxygen mixture is not indicated since it does not improve outcome and increases the delay to intubation. PMID:26395175

  19. Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema

    PubMed Central

    Kiire, Christine A; Morjaria, Rupal; Rudenko, Anna; Fantato, Alexina; Smith, Lewis; Smith, Amy; Chong, Victor

    2015-01-01

    Purpose Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. Methods Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 ?m on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. Results Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046). Conclusion In this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course. PMID:26715833

  20. The clinical utility of aflibercept for diabetic macular edema

    PubMed Central

    Stewart, Michael W

    2015-01-01

    The treatment of center-involving diabetic macular edema (DME) has improved because of the proven efficacy of drugs that inhibit the effects of vascular endothelial growth factor (VEGF). The newest anti-VEGF drug, aflibercept, has recently been approved by the United States Food and Drug Administration for the treatment of center-involving DME and for diabetic retinopathy in eyes with DME. In the pivotal Phase III VISTA and VIVID trials, intravitreal aflibercept 2 mg injections every 4 or 8 weeks (after 5 monthly loading doses) produced superior gains in BCVA compared to laser/sham injections. In the Diabetic Retinopathy Clinical Research Network Protocol T trial, which featured monthly anti-VEGF monotherapy for 6 months, followed by monthly pro re nata anti-VEGF injections with laser rescue therapy from months 6 through 12, aflibercept 2 mg monthly was superior to bevacizumab 1.25 mg and ranibizumab 0.5 mg in eyes with BCVA of 20/50 or worse (aflibercept versus bevacizumab: P<0.001; aflibercept versus ranibizumab: P=0.003), but the three regimens were comparable for eyes with VA of 20/40 or better. Only in the 20/50 or worse subgroup did aflibercept achieve clinical superiority (>5 letter difference) to bevacizumab. Each treatment regimen led to significant macular thinning, with aflibercept being superior to bevacizumab in both visual acuity subgroups (P<0.001 for each), but it was not statistically superior to ranibizumab in either group. In diabetic patients, aflibercept has an excellent safety profile that does not appear to differ from laser/sham or other VEGF inhibitory drugs. PMID:26425104

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

    PubMed Central

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

    2015-01-01

    To investigate the protective effects of perfluorooctyl-bromide (PFOB) nanoparticles on early brain injury (EBI) following subarachnoid hemorrhage (SAH), a total of 120 rats were randomly assigned to the following groups: Sham operation group (n = 40), SAH group (n = 40), and SAH + PFOB group (n = 40). Endovascular perforation was performed to induce subarachnoid hemorrhage. Brain water content was measured 24 h after surgery. Meanwhile, morphological changes in the rat hippocampal CA1 region were examined using light and transmission electron microscopy. The rate of neuronal apoptosis in rat hippocampal CA1 region was determined using TUNEL assay. Protein and mRNA expression levels of Caspase-3, Bax, and Bcl-2 were measured using western blot and RT-PCR assays 12, 24, 48, and 72 h after surgery. Compared to the SAH group, the SAH + PFOB group had significantly lower brain water content (P<0.01), with alleviated morphological abnormalities in HE-stained neurons and significantly decreased neurons with karyopyknosis and hyperchromatism in the hippocampal CA1 region. Electron microscopy revealed reduction of neuronal apoptosis, alleviation of glial cell swelling, and mitigation of perivascular edema in the hippocampal region. Immunohistochemical analysis showed that the expression of apoptosis-related factors Caspase-3 and Bax was significantly reduced, while that of the anti-apoptotic factor Bcl-2 was significantly increased. TUNEL staining showed that neuronal apoptosis was significantly reduced in the hippocampal CA1 region (P<0.01). RT-PCR and Western-blot data indicated that expressions of Caspase-3 and Bax were both significantly reduced, while bcl-2 expression was increased significantly at 12, 24, 48, and 72 h after SAH (P<0.01). Together, our data support that PFOB nanoparticles with high oxygen content could counteract ischemia and hypoxia, block neuronal apoptotic pathways, reduce neuronal apoptosis, and therefore, achieve neuroprotective effects in EBI following SAH. PMID:26396671

  2. Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

    SciTech Connect

    Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

    2006-04-15

    Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters ({alpha}=0.15 Gy{sup -1} and {alpha}/{beta}=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD{sub 2}) with respect to three effects: edema, RBE, and dose heterogeneity for {sup 125}I and {sup 103}Pd implants. The EUD{sub 2} analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V{sub 100} (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D{sub 90} (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for {sup 125}I and {sup 103}Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for {sup 125}I and 1.3-1.6 for {sup 103}Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies, when the effects of edema, dose heterogeneity, and RBE were all ignored simultaneously, prostate LDR brachytherapy was reported to show an overall similar dose effect as EBRT and HDR brachytherapy, which are independent of edema and RBE effects and have a better dose coverage.

  3. Effects of Intermittent Pneumatic Compression on Reduction of Postoperative Lower Extremity Edema and Normalization of Foot Microcirculation Flow in Patients Undergoing Arterial Revascularization

    PubMed Central

    Pawlaczyk, Katarzyna; Gabriel, Marcin; Urbanek, Tomasz; Dzieciuchowicz, ?ukasz; Krasi?ski, Zbigniew; Gabriel, Zofia; Olejniczak-Nowakowska, Ma?gorzata; Stanisi?, Micha?

    2015-01-01

    Background In patients with chronic leg ischemia, the beneficial effect of arterial revascularization can be significantly decreased due to postoperative leg swelling. The aim of this study was to assess the effects of intermittent pneumatic compression (IPC) on skin flow normalization in patients undergoing revascularization procedures due to chronic leg ischemia. Material/Methods We evaluated 116 patients with chronic leg ischemia. The patients were divided into groups according to the performed treatment (endovascular or surgical) and implementation of IPC postoperatively. The leg edema assessment and microcirculation flow assessment were performed pre- and postoperatively, using percutaneous O2 pressure (TcpO2), cutaneous blood perfusion (CBP) measurements, and skin flow motion assessment. Results In patients who did not receive IPC, a decrease in CBP value was observed in the 1st postoperative assessment. Among patients receiving IPC, the CBD value increased at the 1st and 2nd postoperative measurements, especially in the surgical group. The lowest TcpO2 values were observed in by-pass surgery group without IPC postoperatively. Conclusions The benefits of the by-pass procedure in patients with leg ischemia can be significantly reduced by postoperative edema. Among patients with postoperative leg edema, local tissue blood perfusion can be improved by the use of IPC, which can result in decreased local leg swelling, as well as improved skin blood perfusion and TcpO2. PMID:26690828

  4. The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats

    PubMed Central

    Hajhashemi, Valiollah; Sadeghi, Hossein; Minaiyan, Mohsen; Movahedian, Ahmad; Talebi, Ardeshir

    2010-01-01

    OBJECTIVE: The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats. METHODS: First, amitriptyline was administered intraperitoneally (i.p.) at doses of 20, 40 and 80 mg kg-1, 30 min before subplantar injection of carrageenan. Second, amitriptyline was given intracerebroventriculary or intrathecally at doses of 25, 50 and 100 µg/rat, 30 min prior to carrageenan cha